Responsiveness, Sensitivity, and Minimally Detectable Difference of the Graded and Redefined Assessment of Strength, Sensibility, and Prehension, Version 1.0.

PubMed

Kalsi-Ryan, Sukhvinder; Beaton, Dorcas; Ahn, Henry; Askes, Heather; Drew, Brian; Curt, Armin; Popovic, Milos R; Wang, Justin; Verrier, Mary C; Fehlings, Michael G

2016-02-01

As spinal cord injury (SCI) trials begin to involve subjects with acute cervical SCI, establishing the property of an upper limb outcome measure to detect change over time is critical for its usefulness in clinical trials. The objectives of this study were to define responsiveness, sensitivity, and minimally detectable difference (MDD) of the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP). An observational, longitudinal study was conducted. International Standards of Neurological Classification of SCI (ISNCSCI), GRASSP, Capabilities of Upper Extremity Questionnaire (CUE-Q), and Spinal Cord Independence Measure (SCIM) were administered 0-10 days, 1, 3, 6, and 12 months post-injury. Standardized Response Means (SRM) for GRASSP and ISNCSCI measures were calculated. Longitudinal construct validity was calculated using Pearson correlation coefficients. Smallest real difference for all subtests was calculated to define the MDD values for all GRASSP subtests. Longitudinal construct validity demonstrated GRASSP and all external measures to be responsive to neurological change for 1 year post-injury. SRM values for the GRASSP subtests ranged from 0.25 to 0.85 units greater than that for ISNCSCI strength and sensation, SCIM-SS, and CUE-Q. MDD values for GRASSP subtests ranged from 2-5 points. GRASSP demonstrates good responsiveness and excellent sensitivity that is superior to ISNCSCI and SCIM III. MDD values are useful in the evaluation of interventions in both clinical and research settings. The responsiveness and sensitivity of GRASSP make it a valuable condition-specific measure in tetraplegia, where changes in upper limb neurological and functional outcomes are essential for evaluating the efficacy of interventions.

Association analysis of SIGMAR1 with major depressive disorder and SSRI response.

PubMed

Kishi, Taro; Yoshimura, Reiji; Okochi, Tomo; Fukuo, Yasuhisa; Kitajima, Tsuyoshi; Okumura, Takenori; Tsunoka, Tomoko; Kawashima, Kunihiro; Yamanouchi, Yoshio; Kinoshita, Yoko; Umene-Nakano, Wakako; Naitoh, Hiroshi; Nakamura, Jun; Ozaki, Norio; Iwata, Nakao

2010-06-01

Several investigations have suggested the possible involvement of sigma 1 non-opioid intracellular receptor 1 (sigma 1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma 1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma 1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline). We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis. In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples. Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results. (c) 2010. Published by Elsevier Ltd. All rights reserved.

Lack of association between TPH2 gene polymorphisms with major depressive disorder in multiethnic Malaysian population.

PubMed

Nazree, Nur Elia; Loke, Ai Chin; Zainal, Nor Zuraida; Mohamed, Zahurin

2015-03-01

Numerous association studies of candidate genes studies with major depressive disorder (MDD) have been conducted for many years; however, the evidence of association between genes and the risk of developing MDD still remains inconclusive. In this study, we aimed to investigate the association between the tryptophan hydroxylase 2 (TPH2) gene and MDD in three ethnic groups (Malay, Chinese and Indian) within the Malaysian population. Two hundred and sixty five MDD patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for MDD and 332 healthy controls were recruited for the study. All cases and controls were then genotyped for TPH2 polymorphisms rs1386494, rs1386495 and rs7305115. Single locus analysis in pooled and ethnically stratified subjects revealed no association between each of the three variants of the TPH2 gene with susceptibility to MDD. Strong linkage disequilibrium was detected between rs1386495 and rs1386494 in pooled subjects; however, no significant association was found in the haplotype analysis. In this study, we suggest that in both the Chinese and Indian populations, gender distribution differ significantly between cases and controls, showing that women are more at risk of developing MDD compared with men. Therefore, we suggest that the occurrence of MDD in both Chinese and Indians in the Malaysian population may be influenced by gender. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Optic coherence tomography shows inflammation and degeneration in major depressive disorder patients correlated with disease severity.

PubMed

Kalenderoglu, Aysun; Çelik, Mustafa; Sevgi-Karadag, Ayse; Egilmez, Oguzhan Bekir

2016-11-01

Previous research has consistently detected inflammation in the etiology of depression and neuroimaging studies have demonstrated gray matter abnormalities implying a neurodegenerative process in depression. The aim of this study was to compare ganglion cell layer (GCL), and inner plexiform layer (IPL) volumes and retinal nerve fiber layer (RNFL) thickness between first episode and recurrent major depressive disorder (MDD) patients and controls using optic coherence tomography (OCT) in order to detect findings supporting a degenerative process. Also choroid thicknesses of the same groups were compared to examine effects of inflammation on MDD. This study included 50 recurrent MDD patients, 50 first episode MDD patients and 50 controls. OCT measurements were performed by a spectral OCT device. GCL and IPL volumes and RNFL and choroid thicknesses were measured automatically by the device. GCL and IPL volumes were significantly smaller in recurrent depression patients than first episode patients and in all MDD patients than controls. Also there were significant negative correlations between their volumes and disease severity parameters such as Ham-D and CGI scores, and disease duration. RNFL thicknesses were also lower in recurrent MDD patients than first episode patients and all MDD patients than controls but statistical significance was achieved only for global RNFL and temporal superior RNFL. Mean choroid thickness was higher in MDD patients than controls and in first episode MDD patients than recurrent MDD patients. Cross-sectional design of our study limits conclusions about progressive degeneration during the course of MDD. Lack of a control neuroimaging method like magnetic resonance imaging makes it hard to draw firm conclusions from our results. OCT finding of decreased GCL and IPL volumes supports previous research suggesting degeneration in MDD. OCT may be an important tool to track neurodegeneration in patients with major depression. Considering RNFL to be the latest layer that will be affected during course of degeneration, GCL and IPL volumes appear to be better parameters to follow. In addition, choroid may be an important structure to detect acute attack period and to follow inflammatory process in MDD like in systemic inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

PubMed

Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

2013-10-01

Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression. Copyright © 2013 Elsevier Inc. All rights reserved.

The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls

PubMed Central

Karakula-Juchnowicz, Hanna; Gałęcka, Mirosława; Rog, Joanna; Bartnicka, Anna; Łukaszewicz, Zuzanna; Krukow, Pawel; Morylowska-Topolska, Justyna; Skonieczna-Zydecka, Karolina; Krajka, Tomasz; Jonak, Kamil; Juchnowicz, Dariusz

2018-01-01

There is an increasing amount of evidence which links the pathogenesis of irritable bowel syndrome (IBS) with food IgG hyperreactivity. Some authors have suggested that food IgG hyperreactivity could be also involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to compare levels of serum IgG against 39 selected food antigens between three groups of participants: patients with MDD (MDD group), patients with IBS (IBS group) and healthy controls (HC group). The study included 65 participants (22 in the MDD group, 22 in the IBS group and 21 in the HC group). Serum IgG levels were examined using enzyme-linked immunosorbent assay (ELISA). Medical records, clinical data and laboratory results were collected for the analysis. IgG food hyperreactivity (interpreted as an average of levels of IgG antibodies above 7.5 µg/mL) was detected in 28 (43%) participants, including 14 (64%) from the MDD group, ten (46%) from the IBS group and four (19%) from the HC group. We found differences between extreme IgG levels in MDD versus HC groups and in IBS versus HC groups. Patients with MDD had significantly higher serum levels of total IgG antibodies and IgG against celery, garlic and gluten compared with healthy controls. The MDD group also had higher serum IgG levels against gluten compared with the IBS group. Our results suggest dissimilarity in immune responses against food proteins between the examined groups, with the highest immunoreactivity in the MDD group. Further studies are needed to repeat and confirm these results in bigger cohorts and also examine clinical utility of IgG-based elimination diet in patients with MDD and IBS. PMID:29710769

Preliminary differences in resting state MEG functional connectivity pre- and post-ketamine in major depressive disorder.

PubMed

Nugent, Allison C; Robinson, Stephen E; Coppola, Richard; Zarate, Carlos A

2016-08-30

Functional neuroimaging techniques including magnetoencephalography (MEG) have demonstrated that the brain is organized into networks displaying correlated activity. Group connectivity differences between healthy controls and participants with major depressive disorder (MDD) can be detected using temporal independent components analysis (ICA) on beta-bandpass filtered Hilbert envelope MEG data. However, the response of these networks to treatment is unknown. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects. We obtained MEG recordings before and after open-label infusion of 0.5mg/kg ketamine in MDD subjects (N=13) and examined networks previously shown to differ between healthy individuals and those with MDD. Connectivity between the amygdala and an insulo-temporal component decreased post-ketamine in MDD subjects towards that observed in control subjects at baseline. Decreased baseline connectivity of the subgenual anterior cingulate cortex (sgACC) with a bilateral precentral network had previously been observed in MDD compared to healthy controls, and the change in connectivity post-ketamine was proportional to the change in sgACC glucose metabolism in a subset (N=8) of subjects receiving [11F]FDG-PET imaging. Ketamine appeared to reduce connectivity, regardless of whether connectivity was abnormally high or low compared to controls at baseline. These preliminary findings suggest that sgACC connectivity may be directly related to glutamate levels. Published by Elsevier Ireland Ltd.

Disrupted functional connectivity patterns of the insula subregions in drug-free major depressive disorder.

PubMed

Wang, Chao; Wu, Huawang; Chen, Fangfang; Xu, Jinping; Li, Hongming; Li, Hong; Wang, Jiaojian

2018-07-01

Major depressive disorder (MDD) is characterized by impairments in emotional and cognitive functions. Emerging studies have shown that cognition and emotion interact by reaching identical brain regions, and the insula is one such region with functional and structural heterogeneity. Although previous literatures have shown the role of insula in MDD，it remains unclear whether the insular subregions show differential change patterns in MDD. Using the resting-state fMRI data in a group of 23 drug-free MDD patients and 34 healthy controls (HCs), we investigated whether the abnormal connectivity patterns of insular sub-regions or any behavioural correlates can be detected in MDD. Further hierarchical cluster analysis was used to identify the functional connectivity-clustering patterns of insular sub-regions. Compared with HCs, the MDD exhibited higher connectivities between dorsal agranular insula and inferior parietal lobule and between ventral dysgranular and granular insula and thalamus/habehula, and lower connectivity of hypergranular insula to subgenual anterior cingulate cortex. Moreover, the three subregions with significant group differences were in three separate functional systems along anterior-to-posteior gradient. The anterior and middle insula showed positive correlation with depressive severity, while the posterior insular was to the contrary. The small and unbalanced sample size, only included moderate and severe depression and the possible inter-individual differences may limit the interpretability. These findings provided evidences for the MDD-related effects in functional connectivity patterns of insular subregions, and revealed that the subregions might be involved in different neural circuits associated with the contrary impacts on the depressive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus

PubMed Central

Hagan, Cindy C.; Graham, Julia M.E.; Tait, Roger; Widmer, Barry; van Nieuwenhuizen, Adrienne O.; Ooi, Cinly; Whitaker, Kirstie J.; Simas, Tiago; Bullmore, Edward T.; Lennox, Belinda R.; Sahakian, Barbara J.; Goodyer, Ian M.; Suckling, John

2015-01-01

Objective There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. Method Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. Results Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. Conclusions The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain. PMID:25685707

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

PubMed

Hagan, Cindy C; Graham, Julia M E; Tait, Roger; Widmer, Barry; van Nieuwenhuizen, Adrienne O; Ooi, Cinly; Whitaker, Kirstie J; Simas, Tiago; Bullmore, Edward T; Lennox, Belinda R; Sahakian, Barbara J; Goodyer, Ian M; Suckling, John

2015-01-01

There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.

Plasma glial cell line-derived neurotrophic factor in patients with major depressive disorder: a preliminary study.

PubMed

Lee, Bun-Hee; Hong, Jin-Pyo; Hwang, Jung-A; Na, Kyoung-Sae; Kim, Won-Joong; Trigo, Jose; Kim, Yong-Ku

2016-02-01

Some clinical studies have reported reduced peripheral glial cell line-derived neurotrophic factor (GDNF) level in elderly patients with major depressive disorder (MDD). We verified whether a reduction in plasma GDNF level was associated with MDD. Plasma GDNF level was measured in 23 healthy control subjects and 23 MDD patients before and after 6 weeks of treatment. Plasma GDNF level in MDD patients at baseline did not differ from that in healthy controls. Plasma GDNF in MDD patients did not differ significantly from baseline to the end of treatment. GDNF level was significantly lower in recurrent-episode MDD patients than in first-episode patients before and after treatment. Our findings revealed significantly lower plasma GDNF level in recurrent-episode MDD patients, although plasma GDNF levels in MDD patients and healthy controls did not differ significantly. The discrepancy between our study and previous studies might arise from differences in the recurrence of depression or the ages of the MDD patients.

Structural abnormality of the corticospinal tract in major depressive disorder

PubMed Central

2014-01-01

Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs. PMID:25295159

Antidepressant effect detected on proton magnetic resonance spectroscopy in drug-naïve female patients with first-episode major depression.

PubMed

Kaymak, Semra Ulusoy; Demir, Başaran; Oğuz, Kader Karli; Sentürk, Senem; Uluğ, Berna

2009-06-01

Recent neuroimaging studies support functional and structural alterations in the dorsolateral prefrontal cortex (DLPFC), particularly on the left side in patients with major depressive disorders (MDD). The aim of the present study was to examine the biochemical characteristics of left DLPFC as measured on proton ((1)H) magnetic resonance spectroscopy (MRS) in patients with drug-naïve first-episode MDD and a healthy control group. A second aim was to assess the effect of antidepressant treatment on the metabolites of DLPFC. Short-echo single-voxel (1)H-MRS was done for the left DLPFC in 17 female drug-free MDD patients (mean age +/- SD, 30.9 +/- 6.9 years) and 13 matched control subjects (mean age +/- SD, 29.1 +/- 6.2 years) and was repeated at 8 weeks following antidepressant treatment. Comparison of baseline values indicated that there were no significant differences in any of the metabolite ratios (N-acetyl aspartate/creatine [NAA/Cr], myoinositol [Ino]/Cr, and choline [Cho]/Cr) between patients and controls. Significant differences were detected between pre- and post-treatment Ino/Cr ratios (0.67 +/- 0.13, 0.58 +/- 0.22, P = 0.032, respectively), although there was no difference in NAA/Cr and Cho/Cr ratios. Although no significant metabolic alterations exist in female patients with drug-naïve first-episode MDD as evaluated on (1)H-MRS, an increase in Ino/Cr was observed following 8-week antidepressant treatment. These findings give rise to the possibility that non-neuronal cells, particularly glial cells that are probably damaged, play a role in the action of antidepressant treatment.

Gender differences in brain activity and the relationship between brain activity and differences in prevalence rates between male and female major depressive disorder patients: a resting-state fMRI study.

PubMed

Yao, Zhijian; Yan, Rui; Wei, Maobin; Tang, Hao; Qin, Jiaolong; Lu, Qing

2014-11-01

We examined the gender-difference effect on abnormal spontaneous neuronal activity of male and female major depressive disorder (MDD) patients using the amplitude of low-frequency fluctuation (ALFF) and the further clarified the relationship between the abnormal ALFF and differences in MDD prevalence rates between male and female patients. Fourteen male MDD patients, 13 female MDD patients and 15 male and 15 female well matched healthy controls (HCs) completed this study. The ALFF approach was used, and Pearson correlation was conducted to observe a possible clinical relevance. There were widespread differences in ALFF values between female and male MDD patients, including some important parts of the frontoparietal network, auditory network, attention network and cerebellum network. In female MDD patients, there was a positive correlation between average ALFF values of the left postcentral gyrus and the severity of weight loss symptom. The gender-difference effect leading to abnormal brain activity is an important underlying pathomechanism for different somatic symptoms in MDD patients of different genders and is likely suggestive of higher MDD prevalence rates in females. The abnormal ALFF resulting from the gender-difference effect might improve our understanding of the differences in prevalence rates between male and female MDD patients from another perspective. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Sex differences in gut microbiota in patients with major depressive disorder.

PubMed

Chen, Jian-Jun; Zheng, Peng; Liu, Yi-Yun; Zhong, Xiao-Gang; Wang, Hai-Yang; Guo, Yu-Jie; Xie, Peng

2018-01-01

Our previous studies found that disturbances in gut microbiota might have a causative role in the onset of major depressive disorder (MDD). The aim of this study was to investigate whether there were sex differences in gut microbiota in patients with MDD. First-episode drug-naïve MDD patients and healthy controls were included. 16S rRNA gene sequences extracted from the fecal samples of the included subjects were analyzed. Principal-coordinate analysis and partial least squares-discriminant analysis were used to assess whether there were sex-specific gut microbiota. A random forest algorithm was used to identify the differential operational taxonomic units. Linear discriminant-analysis effect size was further used to identify the dominant sex-specific phylotypes responsible for the differences between MDD patients and healthy controls. In total, 57 and 74 differential operational taxonomic units responsible for separating female and male MDD patients from their healthy counterparts were identified. Compared with their healthy counterparts, increased Actinobacteria and decreased Bacteroidetes levels were found in female and male MDD patients, respectively. The most differentially abundant bacterial taxa in female and male MDD patients belonged to phyla Actinobacteria and Bacteroidia, respectively. Meanwhile, female and male MDD patients had different dominant phylotypes. These results demonstrated that there were sex differences in gut microbiota in patients with MDD. The suitability of Actinobacteria and Bacteroidia as the sex-specific biomarkers for diagnosing MDD should be further explored.

A polymorphism in the microRNA-30e precursor associated with major depressive disorder risk and P300 waveform.

PubMed

Xu, Yong; Liu, Haiying; Li, Fei; Sun, Ning; Ren, Yan; Liu, Zhifen; Cao, Xiaohua; Wang, Yanfang; Liu, Pozi; Zhang, Kerang

2010-12-01

Growing evidence shows that the etiological causes and pathological processes underlying major depressive disorder (MDD) and schizophrenia (SCZ) overlap. Our previous study revealed a strong association between the polymorphism ss178077483 in the miRNA-30e precursor (pre-miR-30e) and the risk of SCZ. We thus hypothesized that this SCZ risk allele at the pre-miR-30e gene also confers risk of MDD. To explore the relationship between miR-30e ss178077483 and MDD, we conducted an association analyses in 1088 MDD patients and 1102 control subjects from the Han Chinese population. We also determined the effects of miR-30e ss178077483 on the development of P300 event-related potential components induced by an auditory odd-ball task. We detected a statistically significant positive association between miR-30e ss178077483 and MDD (allelic P=0.0287; genotypic P=0.0275). Moreover, the P300 latency was associated with miR-30e ss178077483 genotypes and the individuals with the C/T genotype have a longer P300 latency than those carrying the C/C genotype (P=0.009). Larger numbers of subjects and different ethnic groups would confirm and strengthen these preliminary findings. To our knowledge, this is the first evidence to suggest that miRNA polymorphisms may play an important role in MDD susceptibility. These findings also imply that certain miRNAs may be involved in the etiology of MDD. Copyright © 2010 Elsevier B.V. All rights reserved.

Genetic effects influencing risk for major depressive disorder in China and Europe.

PubMed

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-03-28

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log 10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Genetic effects influencing risk for major depressive disorder in China and Europe

PubMed Central

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-01-01

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies. PMID:28350396

Relationship between the prefrontal function and the severity of the emotional symptoms during a verbal fluency task in patients with major depressive disorder: a multi-channel NIRS study.

PubMed

Liu, Xiaomin; Sun, Gaoxiang; Zhang, Xiaoqian; Xu, Bo; Shen, Chenyu; Shi, Lujie; Ma, Xiangyun; Ren, Xiajin; Feng, Kun; Liu, Pozi

2014-10-03

Multi-channel near-infrared spectroscopy (NIRS) is a noninvasive and low-cost functional neuroimaging technique in psychiatric research, and it has been wildly used for detecting the spatiotemporal characteristics of brain activity. In order to evaluate the clinical value of NIRS data in the assistant diagnosis of major depressive disorder (MDD), prefrontal cortex (PFC) hemoglobin concentration exchange of 30 MDD patients combined with anxious and obsessive-compulsive symptom was detected by NIRS under voice fluency task (VFT), then the relationship between the severity of depressive, anxious and obsessive-compulsive symptom assessed by Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with NIRS data in PFC was analyzed. Hypoactivation in lateral and lower PFC of MDD patients was confirmed in this study. Furthermore, Spearman correlation found that oxy-hemoglobin concentration ([oxy-Hb]) exchange in right-lateral PFC was associated with the severity of anxiety, while bilateral PFC and antero-medial PFC were associated with severity of depression. Meanwhile, no statistical correlation was observed on the severity of obsessive-compulsive symptom. The results prompted that MDD patients with anxiety and obsession-compulsion symptom showed a PFC hypoactivation state in NIRS. Furthermore, the function of right-lateral PFC was associated with anxiety symptom, while bilateral PFC and antero-medial PFC were associated with depression symptom. Different from depression and anxiety, obsession-compulsion may have a different biological character in PFC function. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive markers of psychotic unipolar depression: a meta-analytic study.

PubMed

Zaninotto, Leonardo; Guglielmo, Riccardo; Calati, Raffaella; Ioime, Lucia; Camardese, Giovanni; Janiri, Luigi; Bria, Pietro; Serretti, Alessandro

2015-03-15

The goal of the current meta-analysis was to review and examine in detail the features of cognitive performance in psychotic (MDDP) versus non-psychotic (MDD) major depressive disorder. An electronic literature search was performed to find studies comparing cognitive performance in MDDP versus MDD. A meta-analysis of broad cognitive domains (processing speed, reasoning/problem solving, verbal learning, visual learning, attention/working memory) and individual cognitive tasks was conducted on all included studies (n=12). Demographic and clinical features were investigated via meta-regression analysis as moderators of cognitive performance. No difference in socio-demographic and clinical variables was detected between groups. In general, a poorer cognitive performance was detected in MDDP versus MDD subjects (ES=0.38), with a greater effect size in drug-free patients (ES=0.69). MDDP patients were more impaired in verbal learning (ES=0.67), visual learning (ES=0.62) and processing speed (ES=0.71) tasks. A significantly poorer performance was also detected in MDDP patients for individual tasks as Trail Making Test A, WAIS-R digit span backward and WAIS-R digit symbol. Age resulted to have a negative effect on tasks involved in working memory performance. In line with previous meta-analyses, our findings seem to support an association between psychosis and cognitive deficits in the context of affective disorders. Psychosis during the course of MDD is associated with poorer cognitive performance in some specific cognitive domains, such as visual and verbal learning and executive functions. Copyright © 2014 Elsevier B.V. All rights reserved.

Soil carbon inventories under a bioenergy crop (switchgrass): Measurement limitations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garten, C.T. Jr.; Wullschleger, S.D.

Approximately 5 yr after planting, coarse root carbon (C) and soil organic C (SOC) inventories were compared under different types of plant cover at four switchgrass (Panicum virgatum L.) production field trials in the southeastern USA. There was significantly more coarse root C under switchgrass (Alamo variety) and forest cover than tall fescue (Festuca arundinacea Schreb.), corn (Zea mays L.), or native pastures of mixed grasses. Inventories of SOC under switchgrass were not significantly greater than SOC inventories under other plant covers. At some locations the statistical power associated with ANOVA of SOC inventories was low, which raised questions aboutmore » whether differences in SOC could be detected statistically. A minimum detectable difference (MDD) for SOC inventories was calculated. The MDD is the smallest detectable difference between treatment means once the variation, significance level, statistical power, and sample size are specified. The analysis indicated that a difference of {approx}50 mg SOC/cm{sup 2} or 5 Mg SOC/ha, which is {approx}10 to 15% of existing SOC, could be detected with reasonable sample sizes and good statistical power. The smallest difference in SOC inventories that can be detected, and only with exceedingly large sample sizes, is {approx}2 to 3%. These measurement limitations have implications for monitoring and verification of proposals to ameliorate increasing global atmospheric CO{sub 2} concentrations by sequestering C in soils.« less

Sex-related differences in sleep slow wave activity in major depressive disorder: a high-density EEG investigation.

PubMed

Plante, David T; Landsness, Eric C; Peterson, Michael J; Goldstein, Michael R; Riedner, Brady A; Wanger, Timothy; Guokas, Jeffrey J; Tononi, Giulio; Benca, Ruth M

2012-09-18

Sleep disturbance plays an important role in major depressive disorder (MDD). Prior investigations have demonstrated that slow wave activity (SWA) during sleep is altered in MDD; however, results have not been consistent across studies, which may be due in part to sex-related differences in SWA and/or limited spatial resolution of spectral analyses. This study sought to characterize SWA in MDD utilizing high-density electroencephalography (hdEEG) to examine the topography of SWA across the cortex in MDD, as well as sex-related variation in SWA topography in the disorder. All-night recordings with 256 channel hdEEG were collected in 30 unipolar MDD subjects (19 women) and 30 age and sex-matched control subjects. Spectral analyses of SWA were performed to determine group differences. SWA was compared between MDD and controls, including analyses stratified by sex, using statistical non-parametric mapping to correct for multiple comparisons of topographic data. As a group, MDD subjects demonstrated significant increases in all-night SWA primarily in bilateral prefrontal channels. When stratified by sex, MDD women demonstrated global increases in SWA relative to age-matched controls that were most consistent in bilateral prefrontal regions; however, MDD men showed no significant differences relative to age-matched controls. Further analyses demonstrated increased SWA in MDD women was most prominent in the first portion of the night. Women, but not men with MDD demonstrate significant increases in SWA in multiple cortical areas relative to control subjects. Further research is warranted to investigate the role of SWA in MDD, and to clarify how increased SWA in women with MDD is related to the pathophysiology of the disorder.

Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder.

PubMed

Hendriks, Sanne M; Licht, Carmilla M M; Spijker, Jan; Beekman, Aartjan T F; Hardeveld, Florian; de Graaf, Ron; Penninx, Brenda W J H

2014-04-01

This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Data were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the Netherlands Study of Depression and Anxiety (NESDA). The Composite Interview Diagnostic Instrument was used to diagnose MDD and GAD. Cognitive profiles were measured using the Leiden Index of Depression Sensitivity, the Anxiety Sensitivity Index, and the Penn State Worry Questionnaire. Results showed that differences in cognitive profiles between single MDD and single GAD subjects were present: scores on hopelessness/suicidality and rumination were significantly higher in MDD than GAD, whereas anxiety sensitivity for physical concerns and pathological worry were higher in GAD than MDD. The cognitive profile of comorbid MDD/GAD showed more extreme depression cognitions compared to single disorders, and a similar anxiety profile compared to single GAD subjects. Despite the commonalities in cognitive profiles in MDD and GAD, there are differences suggesting that MDD and GAD have disorder-specific cognitive profiles. Findings of this investigation give support for models like the cognitive content-specificity model and the tripartite model and could provide useful handles for treatment focus.

Polygenic risk for depression and the neural correlates of working memory in healthy subjects.

PubMed

Yüksel, Dilara; Dietsche, Bruno; Forstner, Andreas J; Witt, Stephanie H; Maier, Robert; Rietschel, Marcella; Konrad, Carsten; Nöthen, Markus M; Dannlowski, Udo; Baune, Bernhard T; Kircher, Tilo; Krug, Axel

2017-10-03

Major depressive disorder (MDD) patients show impairments of cognitive functioning such as working memory (WM), and furthermore alterations during WM-fMRI tasks especially in frontal and parietal brain regions. The calculation of a polygenic risk score (PRS) can be used to describe the genetic influence on MDD, hence imaging genetic studies aspire to combine both genetics and neuroimaging data to identify the influence of genetic factors on brain functioning. We aimed to detect the effect of MDD-PRS on brain activation during a WM task measured with fMRI and expect healthy individuals with a higher PRS to be more resembling to MDD patients. In total, n=137 (80 men, 57 women, aged 34.5, SD=10.4years) healthy subjects performed a WM n-back task [0-back (baseline), 2-back and 3-back condition] in a 3T-MRI-tomograph. The sample was genotyped using the Infinium PsychArray BeadChip and a polygenic risk score was calculated for MDD using PGC MDD GWAS results. A lower MDD risk score was associated with increased activation in the bilateral middle occipital gyri (MOG), the bilateral middle frontal gyri (MFG) and the right precentral gyrus (PCG) during the 2-back vs. baseline condition. Moreover, a lower PRS was associated with increased brain activation during the 3-back vs. baseline condition in the bilateral cerebellum, the right MFG and the left inferior parietal lobule. A higher polygenic risk score was associated with hyperactivation in brain regions comprising the right MFG and the right supplementary motor area during the 3-back vs. 2-back condition. The results suggest that part of the WM-related brain activation patterns might be explained by genetic variants captured by the MDD-PRS. Furthermore we were able to detect MDD-associated activation patterns in healthy individuals depending on the MDD-PRS and the task complexity. Additional gene loci could contribute to these task-dependent brain activation patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC-MS-based metabonomics.

PubMed

Zheng, P; Chen, J-J; Zhou, C-J; Zeng, L; Li, K-W; Sun, L; Liu, M-L; Zhu, D; Liang, Z-H; Xie, P

2016-11-15

Women are more vulnerable to major depressive disorder (MDD) than men. However, molecular biomarkers of sex differences are limited. Here we combined gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabonomics to investigate sex differences of urinary metabolite markers in MDD, and further explore their potential of diagnosing MDD. Consequently, the metabolite signatures of women and men MDD subjects were significantly different from of that in their respective healthy controls (HCs). Twenty seven women and 36 men related differentially expressed metabolites were identified in MDD. Fourteen metabolites were changed in both women and men MDD subjects. Significantly, the women-specific (m-Hydroxyphenylacetate, malonate, glycolate, hypoxanthine, isobutyrate and azelaic acid) and men-specific (tyrosine, N-acetyl-d-glucosamine, N-methylnicotinamide, indoxyl sulfate, citrate and succinate) marker panels were further identified, which could differentiate men and women MDD patients from their respective HCs with higher accuracy than previously reported sex-nonspecific marker panels. Our findings demonstrate that men and women MDD patients have distinct metabonomic signatures and sex-specific biomarkers have promising values in diagnosing MDD.

Disorganization of white matter architecture in major depressive disorder: a meta-analysis of diffusion tensor imaging with tract-based spatial statistics.

PubMed

Chen, Guangxiang; Hu, Xinyu; Li, Lei; Huang, Xiaoqi; Lui, Su; Kuang, Weihong; Ai, Hua; Bi, Feng; Gu, Zhongwei; Gong, Qiyong

2016-02-24

White matter (WM) abnormalities have long been suspected in major depressive disorder (MDD). Tract-based spatial statistics (TBSS) studies have detected abnormalities in fractional anisotropy (FA) in MDD, but the available evidence has been inconsistent. We performed a quantitative meta-analysis of TBSS studies contrasting MDD patients with healthy control subjects (HCS). A total of 17 studies with 18 datasets that included 641 MDD patients and 581 HCS were identified. Anisotropic effect size-signed differential mapping (AES-SDM) meta-analysis was performed to assess FA alterations in MDD patients compared to HCS. FA reductions were identified in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC) in MDD patients relative to HCS. Descriptive analysis of quartiles, sensitivity analysis and subgroup analysis further confirmed these findings. Meta-regression analysis revealed that individuals with more severe MDD were significantly more likely to have FA reductions in the genu of the CC. This study provides a thorough profile of WM abnormalities in MDD and evidence that interhemispheric connections and frontal-striatal-thalamic pathways are the most convergent circuits affected in MDD.

Differences in social functioning among patients with major psychiatric disorders: Interpersonal communication is impaired in patients with schizophrenia and correlates with an increase in schizotypal traits.

PubMed

Yasuyama, Toshiki; Ohi, Kazutaka; Shimada, Takamitsu; Uehara, Takashi; Kawasaki, Yasuhiro

2017-03-01

Impaired social functioning is a hallmark of major psychiatric disorders. The purpose of this study was to detect a disorder-specific factor of social dysfunction among patients with major psychiatric disorders (PSY), including schizophrenia (SCZ), bipolar disorder (BIP) and major depressive disorder (MDD). Social functioning was assessed in patients with SCZ (n=80), BIP (n=27) or MDD (n=29) and healthy controls (HC, n=68) using the Social Functioning Scale (SFS). Compared to HC, the SCZ, BIP and MDD patient groups showed lower total SFS scores. No differences in the total scores for social functioning were observed between patient groups. We next investigated seven subscales of the SFS among PSY and observed significant diagnostic effects on all subscales of the SFS. Notably, patients with SCZ have poorer interpersonal communication than patients with MDD. Furthermore, the poorer interpersonal communication score was significantly correlated with an increase in schizotypal personality traits, as assessed by the Schizotypal Personality Questionnaire (SPQ) in HC. Although there were no differences in overall social functioning among PSY, disorder-specific factors, such as interpersonal communication, were evident in SCZ. The correlation between poor interpersonal communication and the increase in schizotypal traits suggests that poor interpersonal communication may be an intermediate phenotype of SCZ. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Altered Negative Unconscious Processing in Major Depressive Disorder: An Exploratory Neuropsychological Study

PubMed Central

Yang, Zhi; Zhao, Jinping; Jiang, Yi; Li, Chunbo; Wang, Jijun; Weng, Xuchu; Northoff, Georg

2011-01-01

Objective Major depressive disorder (MDD) has been characterized by abnormalities in emotional processing. However, what remains unclear is whether MDD also shows deficits in the unconscious processing of either positive or negative emotions. We conducted a psychological study in healthy and MDD subjects to investigate unconscious emotion processing and its valence-specific alterations in MDD patients. Methods We combined a well established paradigm for unconscious visual processing, the continuous flash suppression, with positive and negative emotional valences to detect the attentional preference evoked by the invisible emotional facial expressions. Results Healthy subjects showed an attentional bias for negative emotions in the unconscious condition while this valence bias remained absent in MDD patients. In contrast, this attentional bias diminished in the conscious condition for both healthy subjects and MDD. Conclusion Our findings demonstrate for the first time valence-specific deficits specifically in the unconscious processing of emotions in MDD; this may have major implications for subsequent neurobiological investigations as well as for clinical diagnosis and therapy. PMID:21755006

Altered negative unconscious processing in major depressive disorder: an exploratory neuropsychological study.

PubMed

Yang, Zhi; Zhao, Jinping; Jiang, Yi; Li, Chunbo; Wang, Jijun; Weng, Xuchu; Northoff, Georg

2011-01-01

Major depressive disorder (MDD) has been characterized by abnormalities in emotional processing. However, what remains unclear is whether MDD also shows deficits in the unconscious processing of either positive or negative emotions. We conducted a psychological study in healthy and MDD subjects to investigate unconscious emotion processing and its valence-specific alterations in MDD patients. We combined a well established paradigm for unconscious visual processing, the continuous flash suppression, with positive and negative emotional valences to detect the attentional preference evoked by the invisible emotional facial expressions. Healthy subjects showed an attentional bias for negative emotions in the unconscious condition while this valence bias remained absent in MDD patients. In contrast, this attentional bias diminished in the conscious condition for both healthy subjects and MDD. Our findings demonstrate for the first time valence-specific deficits specifically in the unconscious processing of emotions in MDD; this may have major implications for subsequent neurobiological investigations as well as for clinical diagnosis and therapy.

A Biomarker to Differentiate between Primary and Cocaine-Induced Major Depression in Cocaine Use Disorder: The Role of Platelet IRAS/Nischarin (I1-Imidazoline Receptor).

PubMed

Keller, Benjamin; Mestre-Pinto, Joan-Ignasi; Álvaro-Bartolomé, María; Martinez-Sanvisens, Diana; Farre, Magí; García-Fuster, M Julia; García-Sevilla, Jesús A; Torrens, Marta

2017-01-01

The association of cocaine use disorder (CUD) and comorbid major depressive disorder (MDD; CUD/MDD) is characterized by high prevalence and poor treatment outcomes. CUD/MDD may be primary (primary MDD) or cocaine-induced (CUD-induced MDD). Specific biomarkers are needed to improve diagnoses and therapeutic approaches in this dual pathology. Platelet biomarkers [5-HT 2A receptor and imidazoline receptor antisera selected (IRAS)/nischarin] were assessed by Western blot in subjects with CUD and primary MDD ( n  = 16) or CUD-induced MDD ( n  = 9; antidepressant free, AD-; antidepressant treated, AD+) and controls ( n  = 10) at basal level and/or after acute tryptophan depletion (ATD). Basal platelet 5-HT 2A receptor (monomer) was reduced in comorbid CUD/MDD subjects (all patients: 43%) compared to healthy controls, and this down-regulation was independent of AD medication (decreases in AD-: 47%, and in AD+: 40%). No basal differences were found for IRAS/nischarin contents in AD+ and AD- comorbid CUD/MDD subjects. The comparison of IRAS/nischarin in the different subject groups during/after ATD showed opposite modulations (i.e., increases and decreases) in response to low plasma tryptophan levels with significant differences discriminating between the subgroups of CUD with primary MDD and CUD-induced MDD. These specific alterations suggested that platelet IRAS/nischarin might be useful as a biomarker to discriminate between primary and CUD-induced MDD in this dual pathology.

Cerebrospinal fluid D-serine concentrations in major depressive disorder negatively correlate with depression severity.

PubMed

Ishiwata, Sayuri; Hattori, Kotaro; Sasayama, Daimei; Teraishi, Toshiya; Miyakawa, Tomoko; Yokota, Yuuki; Matsumura, Ryo; Nishikawa, Toru; Kunugi, Hiroshi

2018-01-15

D-serine is an endogenous co-agonist of N-methyl-D-aspartate receptor (NMDAR) and plays an important role in glutamate neurotransmission. Several studies suggested the possible involvement of D-serine related in the pathophysiology of psychiatric disorders including major depression disorders (MDD). We tried to examine whether cerebrospinal fluid (CSF) or plasma D-serine concentrations are altered in MDD and whether D-serine concentrations correlated with disease severity. 26 MDD patients and 27 healthy controls matched for age, sex and ethnicity were enrolled. We measured amino acids in these samples using by high-performance liquid chromatography with fluorometric detection. D-serine and L-serine, precursor of D-serine, levels in CSF or plasma were not significantly different in patients of MDD compared to controls. Furthermore, a significant correlation between D-serine levels in CSF and Hamilton Depression Rating Scale (HAMD)-17 score was observed (r = -0.65, p = 0.006). Furthermore, we found a positive correlation between CSF D-serine and HVA concentrations in MDD patients (r = 0.54, p = 0.007). CSF D-serine concentrations were correlated with those of plasma in MDD (r = 0.61, p = 0.01) but not in controls. In CSF, we also confirmed a significant correlation between D-serine and L-serine levels in MDD (r = 0.72, p < 0.0001) and controls (r = 0.70, p < 0.0001). The study has some limitations; sample size was relatively small and most patients were medicated. We revealed that CSF D-serine concentrations were correlated with depression severity and HVA concentrations and further investigation were required to reveal the effect of medication and disease heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

Is recurrence in major depressive disorder related to bipolarity and mixed features? Results from the BRIDGE-II-Mix study.

PubMed

Mazzarini, Lorenzo; Kotzalidis, Georgios D; Piacentino, Daria; Rizzato, Salvatore; Angst, Jules; Azorin, Jean-Michel; Bowden, Charles L; Mosolov, Sergey; Young, Allan H; Vieta, Eduard; Girardi, Paolo; Perugi, Giulio

2018-03-15

Current classifications separate Bipolar (BD) from Major Depressive Disorder (MDD) based on polarity rather than recurrence. We aimed to determine bipolar/mixed feature frequency in a large MDD multinational sample with (High-Rec) and without (Low-Rec) >3 recurrences, comparing the two subsamples. We measured frequency of bipolarity/hypomanic features during current depressive episodes (MDEs) in 2347 MDD patients from the BRIDGE-II-mix database, comparing High-Rec with Low-Rec. We used Bonferroni-corrected Student's t-test for continuous, and chi-squared test, for categorical variables. Logistic regression estimated the size of the association between clinical characteristics and High-Rec MDD. Compared to Low-Rec (n = 1084, 46.2%), High-Rec patients (n = 1263, 53.8%) were older, with earlier depressive onset, had more family history of BD, more atypical features, suicide attempts, hospitalisations, and treatment resistance and (hypo)manic switches when treated with antidepressants, higher comorbidity with borderline personality disorder, and more hypomanic symptoms during current MDE, resulting in higher rates of mixed depression according to both DSM-5 and research-based diagnostic (RBDC) criteria. Logistic regression showed age at first symptoms < 30 years, current MDE duration ≤ 1 month, hypomania/mania among first-degree relatives, past suicide attempts, treatment-resistance, antidepressant-induced swings, and atypical, mixed, or psychotic features during MDE to associate with High-Rec. Number of MDEs for defining recurrence was arbitrary; cross-sectionality did not allow assessment of conversion from MDD to BD. High-Rec MDD differed from Low-Rec group for several clinical/epidemiological variables, including bipolar/mixed features. Bipolarity specifier and RBDC were more sensitive than DSM-5 criteria in detecting bipolar and mixed features in MDD. Copyright © 2017. Published by Elsevier B.V.

Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study.

PubMed

Hashimoto, K; Bruno, D; Nierenberg, J; Marmar, C R; Zetterberg, H; Blennow, K; Pomara, N

2016-03-01

Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N=28; age- and gender-matched comparison group, N=19) at baseline and 3-year follow-up (MDD group, N=19; comparison group, N=17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by high-performance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine-glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression.

State-Dependent Differences in Emotion Regulation Between Unmedicated Bipolar Disorder and Major Depressive Disorder.

PubMed

Rive, Maria M; Mocking, Roel J T; Koeter, Maarten W J; van Wingen, Guido; de Wit, Stella J; van den Heuvel, Odile A; Veltman, Dick J; Ruhé, Henricus G; Schene, Aart H

2015-07-01

Major depressive disorder (MDD) and bipolar disorder (BD) are difficult to distinguish clinically during the depressed or remitted states. Both mood disorders are characterized by emotion regulation disturbances; however, little is known about emotion regulation differences between MDD and BD. Better insight into these differences would be helpful for differentiation based on disorder-specific underlying pathophysiological mechanisms. Previous studies comparing these disorders often allowed medication use, limiting generalizability and validity. Moreover, patients with MDD and BD were mostly compared during the depressed, but not the remitted, state, while state might potentially modulate differences between MDD and BD. To investigate positive and negative emotion regulation in medication-free patients with MDD and BD in 2 mood states: depressed or remitted. A cross-sectional study conducted from May 2009 to August 2013 comparing behavioral and functional magnetic resonance imaging emotion regulation data of 42 patients with MDD, 35 with BD, and 36 healthy control (HC) participants free of psychotropic medication recruited from several psychiatric institutions across the Netherlands. A voluntary emotion regulation functional magnetic resonance imaging task using positive and negative pictures. Behavioral and functional magnetic resonance imaging blood oxygen level-dependent responses during emotion regulation. In the remitted state, only patients with BD showed impaired emotion regulation (t = 3.39; P < .001; Cohen d = 0.70), irrespective of emotion type and associated with increased dorsolateral prefrontal cortex activity compared with those with MDD and healthy control participants (P = .008). In the depressed state, patients with MDD and BD differed with regard to happy vs sad emotion regulation (t = 4.19; P < .001; Cohen d = 1.66) associated with differences in rostral anterior cingulate activity (P < .001). Patients with MDD regulated sad and happy emotions poorly compared with those with BD and healthy control participants, while they demonstrated no rostral anterior cingulate difference between happy and sad emotion regulation. In contrast, patients with BD performed worse than those with MDD on sad emotion regulation but normal on happy emotion regulation, and they demonstrated significantly less rostral anterior cingulate activity while regulating happy compared with sad emotions. Medication-free patients with MDD vs BD appear to differ in brain activations during emotion regulation, both while depressed and in remission. These different neuropathophysiological mechanisms between MDD and BD may be useful for further development of additional diagnostic tools.

Exploring culture-specific differences in beliefs about causes, kinship and the heritability of major depressive disorder: the views of Anglo-Celtic and Chinese-Australians.

PubMed

Xu, Mimi; Zou, Lilian; Wilde, Alex; Meiser, Bettina; Barlow-Stewart, Kristine; Chan, Bibiana; Mitchell, Philip B; Sousa, Mariana S; Schofield, Peter R

2013-10-01

The aim of this study was to explore cultural differences in causal attributions and beliefs about heritability of major depressive disorder (MDD). Face-to-face interviews with Anglo-Celtic- and Chinese-Australians community members with a family history of MDD were conducted and subjected to a rigorous qualitative analysis, using the computer software NVivo. Sixteen Anglo-Celtic-Australians and 16 Chinese-Australians were interviewed. Both groups believed that a combination of genetic and environmental factors contributed to MDD, that stress was an important cause of MDD, and that coping factors were significant moderators of the impact of stress on MDD. Both cultural groups believed that the causes of MDD affecting multiple family members included a shared family environment and a "contagion effect", in addition to genetics. Unique to the Chinese-Australian group was the beliefs that parental pressures to exceed academically contributed to MDD; this cultural group also reported beliefs that depression was due to God's will or alternatively fate, which in turn was related to attributions to feng shui and auspicious dates. This study documented key culture-specific differences in beliefs about causes and inheritance of MDD; such differences have major implications for clinician-patient communication about genetic risk associated with having a family history of MDD.

GENETIC AND ENVIRONMENTAL RISK FOR MAJOR DEPRESSION IN AFRICAN-AMERICAN AND EUROPEAN-AMERICAN WOMEN

PubMed Central

Duncan, Alexis E.; Munn-Chernoff, Melissa A.; Hudson, Darrell L.; Eschenbacher, Michaela A.; Agrawal, Arpana; Grant, Julia D.; Nelson, Elliot C.; Waldron, Mary; Glowinski, Anne L.; Sartor, Carolyn E.; Bucholz, Kathleen K.; Madden, Pamela A.F.; Heath, Andrew C.

2014-01-01

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) DSM-IV MDD prevalence, symptomatology and risk factors and (2) genetic and/or environmental liability to MDD, we analyzed data from a large, population representative sample of twins ascertained from birth records (n= 550 AA and n=3226 EA female twins) aged 18–28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (Odds Ratio = 0.88, 95% confidence interval: 0.67–1.15 ). Most MDD risk factors identified among AAs were also associated with MDD at similar magnitudes among EAs. Although the MDD heritability point estimate was higher among AA than EA women in a model with paths estimated separately by race (56%, 95% CI: 29%–78% vs. 41%, 95% CI: 29%–52%), the best-fitting model was one in which additive genetic and nonshared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33%–53% and E = 57%, 47%–67%). Despite a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women. PMID:24910290

Genetic and environmental risk for major depression in African-American and European-American women.

PubMed

Duncan, Alexis E; Munn-Chernoff, Melissa A; Hudson, Darrell L; Eschenbacher, Michaela A; Agrawal, Arpana; Grant, Julia D; Nelson, Elliot C; Waldron, Mary; Glowinski, Anne L; Sartor, Carolyn E; Bucholz, Kathleen K; Madden, Pamela A F; Heath, Andrew C

2014-08-01

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18-28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67-1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29-78% vs. 41%, 95% CI: 29-52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33-53% and E = 57%, 47-67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women.

Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

PubMed

Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

2013-06-01

Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p < 0.05, corrected) in the left ventral prefrontal cortex, right amygdala, right hippocampus and bilateral caudate when comparing the MDD and HC groups. Posthoc analyzes showed that females with MDD had significant GM decreases in limbic regions (p < 0.05, corrected), compared to female HC; while males with MDD demonstrated significant GM reduction in striatal regions, (p < 0.05, corrected), compared to HC males. The observed sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

Serum brain-derived neurotrophic factor levels in subjects with major depressive disorder with previous suicide attempt: A population-based study.

PubMed

Pedrotti Moreira, Fernanda; Borges, Cristiane Jackson; Wiener, Carolina David; da Silva, Paula Moraes; Portela, Luis Valmor; Lara, Diogo R; da Silva, Ricardo Azevedo; de Mattos Souza, Luciano Dias; Jansen, Karen; Oses, Jean Pierre

2018-04-01

Major depressive disorders (MDD) and suicide are significant public health concerns. Recent studies have been demonstrated that alterations in Brain Derived Neurotrophic Factor (BDNF) can be associated with this psychiatric disorders, MDD and suicide. Thus, the aim of this study was to evaluate differences in serum levels in individuals with MDD and with or without suicide attempt (SA), from a population-based sample. This was a paired cross-sectional study nested in a population-based study. The psychopathology screen was performed with the Mini-International Neuropsychiatric Interview (MINI). The total population of the sample consisted of 147 subjects distributed in three groups: 49 healthy controls, 49 subjects with MDD and 49 subjects with MDD and SA (MDD + SA). The BDNF serum levels were significantly reduced in subjects with MDD and MDD + SA compared to the healthy controls. However, there were no significant differences between the MDD and MDD + SA groups with respect to BDNF serum levels. These results suggest that SA did not interfere in the serum levels of BDNF, indicating that this neurotrophin may be related to the diagnosis of MDD and not to suicide attempt. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex differences in physiological and affective responses to stress in remitted depression.

PubMed

Bagley, Sara L; Weaver, Terri L; Buchanan, Tony W

2011-08-03

Major depressive disorder (MDD) is associated with alterations in stress physiology. Severe melancholic depression is characterized by hypercortisolism, but community dwelling mildly depressed individuals and those with remitted MDD have shown reduced or normal reactivity to stress. There are also pronounced sex differences both in the incidence of MDD and in stress reactivity. To explore the relationships among depression history, sex differences, and stress, we examined stress reactivity in people with and without a history of MDD. Twenty-two participants with remitted MDD (12 men and 10 women) and 36 never depressed comparison participants (22 men and 14 women) participated in the study. Cortisol and alpha-amylase (sAA) were sampled from saliva before, 10 min after, and 30 min after the Trier Social Stress Test (TSST). Participants filled out the Positive Affect Negative Affect Schedule (PANAS) before and after they underwent the TSST. Women with remitted MDD showed reduced cortisol response to the TSST compared with the never MDD women, while men with remitted MDD showed comparable cortisol reactivity to the never depressed men. The groups did not differ on sAA reactivity to stress. The remitted MDD group (overall and men and women separately) reported greater negative affect both before and after stress compared to the never depressed group. Women from both groups reported greater post-stress negative affect than men. In contrast, men from both groups reported higher positive affect before and after stress than women. Given that the sex difference findings were not dependent on depression history, self-reported affective differences in response to stress may predate depressive symptoms and contribute to sex differences in depression incidence. Copyright © 2011 Elsevier Inc. All rights reserved.

Variation in Major Depressive Disorder Onset by Place of Origin Among U.S. Latinos.

PubMed

Lee, Sungkyu; Park, Yangjin

2017-09-01

Using a nationally representative sample of 2514 U.S. Latinos, this study examined the extent to which major depressive disorder (MDD) onset differs by place of origin and the factors associated with it. The Kaplan-Meier method estimated the survival and hazard functions for MDD onset by place of origin, and Cox proportional hazards models identified its associative factors. Approximately 13% of the sample had experienced MDD in their lifetimes. Cuban respondents showed the highest survival function, while Puerto Ricans showed the lowest. With the entire sample, the smoothed hazard function showed that the risk of MDD onset peaked in the late 20s and early 80s. Puerto Rican respondents showed the highest risk of MDD during their 20s and 30s, whereas Cuban respondents showed a relatively stable pattern over time. The results from the Cox proportional hazards model indicated that age, sex, and marital status were significantly related to MDD onset (p < .05). In addition, the effect of U.S.-born status on MDD onset was greater among Mexican respondents than among Puerto Ricans. Findings from the present study demonstrate that different Latino subgroups experience different and unique patterns of MDD onset over time. Future research should account for the role of immigration status in examining MDD onset.

Differences in the clinical characteristics of adolescent depressive disorders.

PubMed

Karlsson, Linnea; Pelkonen, Mirjami; Heilä, Hannele; Holi, Matti; Kiviruusu, Olli; Tuisku, Virpi; Ruuttu, Titta; Marttunen, Mauri

2007-01-01

Our objective was to analyze differences in clinical characteristics and comorbidity between different types of adolescent depressive disorders. A sample of 218 consecutive adolescent (ages 13-19 years) psychiatric outpatients with depressive disorders was interviewed for DSM-IV Axis I and Axis II diagnoses. We obtained data by interviewing the adolescents themselves and collecting additional background information from the clinical records. Lifetime age of onset for depression, current episode duration, frequency of suicidal behavior, psychosocial impairment, and the number of current comorbid psychiatric disorders varied between adolescent depressive disorder categories. The type of co-occurring disorder was mainly consistent across depressive disorders. Minor depression and dysthymia (DY) presented as milder depressions, whereas bipolar depression (BPD) and double depression [DD; i.e., DY with superimposed major depressive disorder (MDD)] appeared as especially severe conditions. Only earlier lifetime onset distinguished recurrent MDD from first-episode MDD, and newly emergent MDD appeared to be as impairing as recurrent MDD. Adolescent depressive disorder categories differ in many clinically relevant aspects, with most differences reflecting a continuum of depression severity. Identification of bipolarity and the subgroup with DD seems especially warranted. First episode MDD should be considered as severe a disorder as recurring MDD. (c) 2006 Wiley-Liss, Inc.

Differences among major depressive disorder with and without co-occurring substance use disorders and substance-induced depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

PubMed

Blanco, Carlos; Alegría, Analucía A; Liu, Shang-Min; Secades-Villa, Roberto; Sugaya, Luisa; Davies, Carrie; Nunes, Edward V

2012-06-01

To investigate the association between substance use disorders (SUDs) and the clinical presentation, risk factors, and correlates of major depressive disorder (MDD) by examining differences among 3 groups: (1) individuals with lifetime MDD and no comorbid SUD (MDD-NSUD); (2) individuals with comorbid MDD and SUD (MDD-SUD); and (3) individuals with substance-induced depressive disorder (SIDD). Data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Diagnoses were made using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. The lifetime prevalence of MDD-NSUD was 7.41%, whereas those of MDD-SUD and SIDD were 5.82% and 0.26%, respectively. Overall, risk factors for MDD were more common among individuals with MDD-SUD and SIDD than among those with MDD-NSUD. Individuals with MDD-SUD and SIDD had similar rates of comorbidity with any psychiatric disorder, but both groups had higher rates than individuals with MDD-NSUD (odds ratio [OR] = 2.3; 95% CI, 1.9-2.7 and OR = 2.5; 95% CI, 1.4-4.4, respectively). Individuals with SIDD were significantly less likely to receive medication than those with MDD-SUD or MDD-NSUD (OR = 0.5; 95% CI, 0.3-0.9 for both groups). MDD-SUD is associated with high overall vulnerability to additional psychopathology, a higher number of and more severe depressive episodes, and higher rates of suicide attempts in comparison to individuals with MDD-NSUD. SIDD has low prevalence in the general population but is associated with increased clinical severity and low rates of medication treatment. Similar patterns of comorbidity and risk factors in individuals with SIDD and those with MDD-SUD suggest that the 2 conditions may share underlying etiologic factors. © Copyright 2012 Physicians Postgraduate Press, Inc.

The relationship of impulsivity and cortical thickness in depressed and non-depressed adolescents.

PubMed

Fradkin, Yuli; Khadka, Sabin; Bessette, Katie L; Stevens, Michael C

2017-10-01

Major Depressive Disorder (MDD) is recognized to be heterogeneous in terms of brain structure abnormality findings across studies, which might reflect previously unstudied traits that confer variability to neuroimaging measurements. The purpose of this study was to examine the relationships between different types of trait impulsivity and MDD diagnosis on adolescent brain structure. We predicted that adolescents with depression who were high on trait impulsivity would have more abnormal cortical structure than depressed patients or non-MDD who were low on impulsivity. We recruited 58 subjects, including 29 adolescents (ages 12-19) with a primary DSM-IV diagnosis of MDD and a history of suicide attempt and 29 demographically-matched healthy control participants. Our GLM-based analyses sought to describe differences in the linear relationships between cortical thickness and impulsivity trait levels. As hypothesized, we found significant moderation effects in rostral middle frontal gyrus and right paracentral lobule cortical thickness for different subscales of the Barratt Impulsiveness Scale. However, although these brain-behavior relationships differed between diagnostic study groups, they were not simple additive effects as we had predicted. For the middle frontal gyrus, non-MDD participants showed a strong positive association between cortical thickness and BIS-11 Motor scores, while MDD-diagnosed participants showed a negative association. For Non-Planning Impulsiveness, paracentral lobule cortical thickness was observed with greater impulsivity in MDD, but no association was found for controls. In conclusion, the findings confirm that dimensions of impulsivity have discrete neural correlates, and show that relationships between impulsivity and brain structure are expressed differently in adolescents with MDD compared to non-MDD.

Are there meaningful differences between major depressive disorder, dysthymic disorder, and their subthreshold variants?

PubMed

Moore, Michael T; Brown, Timothy A

2012-09-01

A number of researchers have proposed adding an increasing number of subthreshold variants of major depressive disorder (MDD) as new mood disorder. However, this research has suffered from a number of theoretical and methodological flaws that the current investigation has attempted to address. Individuals with MDD (n = 470) were compared with individuals with subthreshold MDD (n = 57). Individuals with MDD reported consistently more severe symptoms, albeit of small magnitude, as well as differences in comorbidity with only two disorders. Results also indicated that diagnosis did not significantly predict rate of symptom change when MDD was compared with its subthreshold variant. Taken together, the aforementioned evidence suggests that small differences exist between MDD and its subthreshold variant. In addition, the extent to which the latter serves as useful analogs for the former may depend upon the variables under study.

Comparison of Electroencephalography (EEG) Coherence between Major Depressive Disorder (MDD) without Comorbidity and MDD Comorbid with Internet Gaming Disorder.

PubMed

Youh, Joohyung; Hong, Ji Sun; Han, Doug Hyun; Chung, Un Sun; Min, Kyoung Joon; Lee, Young Sik; Kim, Sun Mi

2017-07-01

Internet gaming disorder (IGD) has many comorbid psychiatric problems including major depressive disorder (MDD). In the present study, we compared the neurobiological differences between MDD without comorbidity (MDD-only) and MDD comorbid with IGD (MDD+IGD) by analyzing the quantitative electroencephalogram (QEEG) findings. We recruited 14 male MDD+IGD (mean age, 20.0 ± 5.9 years) and 15 male MDD-only (mean age, 20.3 ± 5.5 years) patients. The electroencephalography (EEG) coherences were measured using a 21-channel digital EEG system and computed to assess synchrony in the frequency ranges of alpha (7.5-12.5 Hz) and beta (12.5-35.0 Hz) between the following 12 electrode site pairs: inter-hemispheric (Fp1-Fp2, F7-F8, T3-T4, and P3-P4) and intra-hemispheric (F7-T3, F8-T4, C3-P3, C4-P4, T5-O1, T6-O2, P3-O1, and P4-O2) pairs. Differences in inter- and intra-hemispheric coherence values for the frequency bands between groups were analyzed using the independent t-test. Inter-hemispheric coherence value for the alpha band between Fp1-Fp2 electrodes was significantly lower in MDD+IGD than MDD-only patients. Intra-hemispheric coherence value for the alpha band between P3-O1 electrodes was higher in MDD+IGD than MDD-only patients. Intra-hemispheric coherence values for the beta band between F8-T4, T6-O2, and P4-O2 electrodes were higher in MDD+IGD than MDD-only patients. There appears to be an association between decreased inter-hemispheric connectivity in the frontal region and vulnerability to attention problems in the MDD+IGD group. Increased intra-hemisphere connectivity in the fronto-temporo-parieto-occipital areas may result from excessive online gaming. © 2017 The Korean Academy of Medical Sciences.

Challenges in comparing the acute cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) vs. electroconvulsive therapy (ECT) in major depression: A systematic review.

PubMed

Kedzior, Karina Karolina; Schuchinsky, Maria; Gerkensmeier, Imke; Loo, Colleen

2017-08-01

The present study aimed to systematically compare the cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) in head-to-head studies with major depression (MDD) patients. A systematic literature search identified six studies with 219 MDD patients that were too heterogeneous to reliably detect meaningful differences in acute cognitive outcomes after ECT vs. HF-rTMS. Cognitive effects of brain stimulation vary depending on the timeframe and methods of assessment, stimulation parameters, and maintenance treatment. Thus, acute and longer-term differences in cognitive outcomes both need to be investigated at precisely defined timeframes and with similar instruments assessing comparable functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatial affect learning restricted in major depression relative to anxiety disorders and healthy controls.

PubMed

Gollan, Jackie K; Norris, Catherine J; Hoxha, Denada; Irick, John Stockton; Hawkley, Louise C; Cacioppo, John T

2014-01-01

Detecting and learning the location of unpleasant or pleasant scenarios, or spatial affect learning, is an essential skill that safeguards well-being (Crawford & Cacioppo, 2002). Potentially altered by psychiatric illness, this skill has yet to be measured in adults with and without major depressive disorder (MDD) and anxiety disorders (AD). This study enrolled 199 adults diagnosed with MDD and AD (n=53), MDD (n=47), AD (n=54), and no disorders (n=45). Measures included clinical interviews, self-reports, and a validated spatial affect task using affective pictures (IAPS; Lang, Bradley, & Cuthbert, 2005). Participants with MDD showed impaired spatial affect learning of negative stimuli and irrelevant learning of pleasant pictures compared with non-depressed adults. Adults with MDD may use a "GOOD is UP" heuristic reflected by their impaired learning of the opposite correlation (i.e., "BAD is UP") and performance in the pleasant version of the task.

Impact of culture on autobiographical life structure in depression.

PubMed

Jobson, Laura; Miskon, Nazleen; Dalgleish, Tim; Hitchcock, Caitlin; Hill, Emma; Golden, Ann-Marie; Zulkefly, Nor Sheereen; Mukhtar, Firdaus

2018-03-23

Distortions in autobiographical memory have been implicated in major depressive disorder (MDD). Those with MDD demonstrate a 'depressogenic' autobiographical life structure. Research has not examined how culture influences this process. We investigated whether Malay individuals (members of an interdependent culture) with MDD demonstrated a 'depressogenic' autobiographical life structure similar to that of British individuals (members of an independent culture) with MDD. A 2 (Culture; Malay, British) × 2 (Mood; depressed, control) cross-sectional design using a card sort task and self-report measures was used. Malay individuals with MDD or no history of MDD completed the life-structure card-sorting task, which provided a novel method for investigating organizational structure of the life narrative. These data were compared to previously collected data in which British individuals with MDD or without MDD had completed the same task within the same experimental protocol. Pan-culturally those with MDD had greater negativity (i.e., used more negative attributes), negative redundancy (i.e., used the same negative attributes repeatedly across life chapters) and negative emodiversity (i.e., had greater variety and relative abundance of negative attributes), and reduced positive redundancy (i.e., used the same positive attributes repeatedly across chapters) in their structuring relative to controls. While the British MDD group had greater compartmentalization (i.e., the negative and positive attributes were clustered separately across different chapters) than British controls, the Malay MDD group had lower levels of compartmentalization than Malay controls. The findings suggest culture may shape aspects of the autobiographical life structure in MDD. The majority of the literature investigating depression pertains to individuals from European Western cultures, despite recognition that depression ranks as one of the most debilitating diseases worldwide. This raises questions as to whether current depression models and interventions can be applied universally or whether they are limited to European Western groups. The current study found that pan-culturally those with MDD had similar structuring of their life story relative to controls. However, there were some cultural differences that need to be considered (e.g., Malay individuals provided less detailed, less elaborate and less emotionally diverse life stories and while the British MDD group had greater compartmentalization than British controls, the Malay MDD group had lower levels of compartmentalization than Malay controls). Limitations of the study included group differences in gender and mood at the time of testing. Cultural differences in the number of attributes used may have influenced findings. Only the Malay group completed the individualism-collectivism measure. © 2018 The British Psychological Society.

Anhedonia among patients with Major Depressive Disorder: A comparison between patients on escitalopram and healthy controls.

PubMed

Ng, C G; Wong, S K; Loh, H S; Yee, A

Escitalopram has widely been recognized as one of the most frequently used antidepressants, with superior tolerability and great efficacy in preventing major depressive disorder (MDD) relapse and recurrence. However, anhedonia, which is a core symptom of MDD, remains difficult to treat. This study investigates the hedonic levels of MDD patients treated with Escitalopram. A total of 108 participants, 26 of whom with MDD on Escitalopram, were recruited in this cross sectional study. They were evaluated using the Snaith-Hamilton Pleasure Scale (SHAPS) and Beck Depression Inventory (BDI) questionnaires to assess their hedonic state, general mental health condition and level of depression. Our study shows that most items in the SHAPS scores are significantly different between MDD patients on Escitalopram and the controls. The hedonic capacity remains different between the two groups despite patients with MDD are put on Escitalopram treatment. Escitalopram fails to alleviate the hedonic state of MDD patients. Antidepressants that improve both depressive symptoms and hedonic states should be considered when treating MDD patients in clinical settings.

Neural response to reward anticipation in those with depression with and without panic disorder.

PubMed

Gorka, Stephanie M; Huggins, Ashley A; Fitzgerald, Daniel A; Nelson, Brady D; Phan, K Luan; Shankman, Stewart A

2014-08-01

One of the hallmark features of major depressive disorder (MDD) is reduced reward anticipation. There have been mixed findings in the literature as to whether reward anticipation deficits in MDD are related to diminished mesolimbic activation and/or enhanced dorsal anterior cingulate activation (dACC). One of the reasons for these mixed findings is that these studies have typically not addressed the role of comorbid anxiety, a class of disorders which frequently co-occur with depression and have a common neurobiology. The aim of the current study was to examine group differences in neural responses to reward anticipation in 40 adults with either: (1) current MDD with no lifetime diagnosis of an anxiety disorder (MDD-only), (2) current MDD with comorbid panic disorder (MDD-PD), or (3) no lifetime diagnosis of psychopathology. All participants completed a passive slot machine task during a functional magnetic resonance imaging (fMRI) scan. Analyses indicated that there were no group differences in activation of mesolimbic reward regions; however, the MDD-only group exhibited greater dACC activation during the anticipation of rewards compared with the healthy controls and the comorbid MDD-PD group (who did not differ from each other). The sample size was small which limits generalizability. These findings provide preliminary support for the role of hyperactive dACC functioning in reduced reward anticipation in MDD. They also indicate that comorbid anxiety may alter the association between MDD and neural responding to reward anticipation. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of major depressive disorder among the long-term unemployed.

PubMed

Nurmela, Kirsti; Mattila, Aino; Heikkinen, Virpi; Uitti, Jukka; Ylinen, Aarne; Virtanen, Pekka

2018-01-01

Depression is a common mental health disorder among the unemployed, but research on identifying their depression in health care is scarce. The present study aimed to explore the identification of major depressive disorder (MDD) in health care on long-term unemployed and find out if the duration of unemployment correlates with the risk for unidentified MDD. The study sample consisted the patient files of long-term unemployed people (duration of unemployment 1-35 years, median 11 years), who in a screening project diagnosed with MDD (n = 243). The MDD diagnosis was found in the health care records of 101. Binomial logistic regression models were used to explore the effect of the duration of unemployment, as a discrete variable, to the identification of MDD in health care. MDD was appropriately identified in health care for 42% (n = 101) of the participants with MDD. The odds ratio for unidentified MDD in health care was 1.060 (95% confidence interval 1.011; 1.111, p = 0.016) per unemployment year. When unemployment had continued, for example, for five years the odds ratio for having unidentified MDD was 1.336. The association remained significant throughout adjustments for the set of background factors (gender, age, occupational status, marital status, homelessness, criminal record, suicide attempts, number of health care visits). This study among depressed long-term unemployed people indicates that the longer the unemployment period has lasted, the more commonly these people suffer from unidentified MDD. Health services should be developed with respect to sensitivity to detect signs of depression among the long-term unemployed.

A preliminary study of the influence of age of onset and childhood trauma on cortical thickness in major depressive disorder.

PubMed

Jaworska, Natalia; MacMaster, Frank P; Gaxiola, Ismael; Cortese, Filomeno; Goodyear, Bradley; Ramasubbu, Rajamannar

2014-01-01

Major depressive disorder (MDD) neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Adults with MDD (N=36) and controls (HC; N=18) underwent magnetic resonance imaging. Twenty patients had MDD onset<24 years of age (pediatric onset) and 16 had onset>25 years of age (adult onset). The MDD group was also subdivided into those with (N=12) and without (N=19) physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with FreeSurfer software. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently), particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.

Clinical features of patients with dysthymia in a large cohort of Han Chinese women with recurrent major depression.

PubMed

Wu, Wenqing; Wang, Zhoubing; Wei, Yan; Zhang, Guanghua; Shi, Shenxun; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Liu, Ying; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S; Flint, Jonathan; Zhang, Zhen

2013-01-01

Dysthymia is a form of chronic mild depression that has a complex relationship with major depressive disorder (MDD). Here we investigate the role of environmental risk factors, including stressful life events and parenting style, in patients with both MDD and dysthymia. We ask whether these risk factors act in the same way in MDD with and without dysthymia. We examined the clinical features in 5,950 Han Chinese women with MDD between 30-60 years of age across China. We confirmed earlier results by replicating prior analyses in 3,950 new MDD cases. There were no significant differences between the two data sets. We identified sixteen stressful life events that significantly increase the risk of dysthymia, given the presence of MDD. Low parental warmth, from either mother or father, increases the risk of dysthymia. Highly threatening but short-lived threats (such as rape) are more specific for MDD than dysthymia. While for MDD more severe life events show the largest odds ratio versus controls, this was not seen for cases of MDD with or without dysthymia. There are increased rates of stressful life events in MDD with dysthymia, but the impact of life events on susceptibility to dysthymia with MDD differs from that seen for MDD alone. The pattern does not fit a simple dose-response relationship, suggesting that there are moderating factors involved in the relationship between environmental precipitants and the onset of dysthymia. It is possible that severe life events in childhood events index a general susceptibility to chronic depression, rather than acting specifically as risk factors for dysthymia.

The high price of depression: Family members' health conditions and health care costs.

PubMed

Ray, G Thomas; Weisner, Constance M; Taillac, Cosette J; Campbell, Cynthia I

2017-05-01

To compare the health conditions and health care costs of family members of patients diagnosed with a Major Depressive Disorder (MDD) to family members of patients without an MDD diagnosis. Using electronic health record data, we identified family members (n=201,914) of adult index patients (n=92,399) diagnosed with MDD between 2009 and 2014 and family members (n=187,011) of matched patients without MDD. Diagnoses, health care utilization and costs were extracted for each family member. Logistic regression and multivariate models were used to compare diagnosed health conditions, health services cost, and utilization of MDD and non-MDD family members. Analyses covered the 5years before and after the index patient's MDD diagnosis. MDD family members were more likely than non-MDD family members to be diagnosed with mood disorders, anxiety, substance use disorder, and numerous other conditions. MDD family members had higher health care costs than non-MDD family members in every period analyzed, with the highest difference being in the year before the index patient's MDD diagnosis. Family members of patients with MDD are more likely to have a number of health conditions compared to non-MDD family members, and to have higher health care cost and utilization. Copyright © 2017. Published by Elsevier Inc.

Uric acid levels may be a biological marker for the differentiation of unipolar and bipolar disorder: the role of affective temperament.

PubMed

Kesebir, Sermin; Tatlıdil Yaylacı, Elif; Süner, Ozgür; Gültekin, Bülent Kadri

2014-08-01

The aim of this study was to investigate whether uric acid levels are different between patients with remission period of bipolar disorder type I (BD) and patients with remission period of major depressive disorder (MDD). For this aim 41 patients diagnosed with BD and 30 patients diagnosed with recurrent MDD according to DSM-IV who were in remission period for at least 8 weeks were evaluated consecutively. The median age and gender distribution of the two groups were similar. Subjects with comorbid psychiatric diagnosis and/or severe medical illnesses were excluded. Affective temperament was evaluated with TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire). Plasma uric acid levels were recorded in mg/dl. The uric acid levels of BD patients were found higher than patients with MDD and healthy controls. Additionally uric acid levels of MDD patients were lower than patients with BD and healthy subjects (F=4.183, p=0.039). A moderate correlation between hyperthymic and irritable temperament scores and uric acid levels was detected in both patient groups and in healthy controls. A negative correlation was observed between depressive temperament and uric acid levels only in MDD group. The measurements of temperament were estimated depending on the patient׳s statement. The medications that patients used were not controlled. There is a purinergic dysfunction not only in BD but also in MDD patients. High uric acid levels are associated with hyperthymic and irritable temperament scores whereas low uric acid levels are associated with depressive temperament scores. Copyright © 2014 Elsevier B.V. All rights reserved.

What is the impact of child abuse on gray matter abnormalities in individuals with major depressive disorder: a case control study.

PubMed

Ahn, Sung Jun; Kyeong, Sunghyon; Suh, Sang Hyun; Kim, Jae-Jin; Chung, Tae-Sub; Seok, Jeong-Ho

2016-11-14

Patients with major depressive disorder (MDD) present heterogeneous clinical symptoms, and childhood abuse is associated with deepening of psychopathology. The aim of this study was to identify structural brain abnormalities in MDD and to assess further differences in gray matter density (GMD) associated with childhood abuse in MDD. Differences in regional GMD between 34 MDD patients and 26 healthy controls were assessed using magnetic resonance imaging and optimized voxel-based morphometry. Within the MDD group, further comparisons were performed focusing on the experience of maltreatment during childhood (23 MDD with child abuse vs 11 MDD without child abuse). Compared with healthy controls, the MDD patient group showed decreased GMD in the bilateral orbitofrontal cortices, right superior frontal gyrus, right posterior cingulate gyrus, bilateral middle occipital gyri, and left cuneus. In addition, the patient group showed increased GMD in bilateral postcentral gyri, parieto-occipital cortices, putamina, thalami, and hippocampi, and left cerebellar declive and tuber of vermis. Within the MDD patient group, the subgroup with abuse showed a tendency of decreased GMD in right orbitofrontal cortex, but showed increased GMD in the left postcentral gyrus compared to the subgroup without abuse. Our findings suggest a complicated dysfunction of networks between cortical-subcortical circuits in MDD. In addition, increased GMD in postcentral gyrus and a possible reduction of GMD in the orbitofrontal cortex of MDD patients with abuse subgroup may be associated with abnormalities of body perception and emotional dysregulation.

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals - a proof of concept study.

PubMed

Sheldrick, A; Camara, S; Ilieva, M; Riederer, P; Michel, T M

2017-10-01

The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8±5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant treatment and overall age 84.3±5 years versus 14 unaffected subjects at age 70.3±13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample size in this proof of concept study corroborates data from previous studies, which show that treatment with antidepressants mediates alterations in neuroplasticity via the action of NTF. However, more research using post-mortem brain tissue with larger samples needs to be carried out as well as longitudinal studies to further verify these results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Childhood adversity impacts on brain subcortical structures relevant to depression.

PubMed

Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J

2017-03-01

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. Copyright © 2016. Published by Elsevier Ltd.

Brief Report: Overgeneral Autobiographical Memory in Adolescent Major Depressive Disorder

PubMed Central

Champagne, Katelynn; Burkhouse, Katie L.; Woody, Mary L.; Feurer, Cope; Sosoo, Effua; Gibb, Brandon E.

2016-01-01

The current study examined whether overgeneral autobiographical memory (OGM) bias serves as a state-like marker of major depressive disorder (MDD) in adolescence or whether it would also be observed in currently nondepressed adolescents with a history of MDD. We examined differences in OGM to positive and negative cue words between adolescents (aged 11–18 years) with current MDD (n = 15), remitted MDD (n = 25), and no history of any depressive disorder (n = 25). Youth and their parents were administered a structured diagnostic interview and adolescents completed the autobiographical memory test. Compared to never depressed adolescents, adolescents with current or remitted MDD recalled less specific memories in response to positive and negative cue words. The difference between the two MDD groups was small and nonsignificant. These findings suggest that OGM is not simply a state-like marker in currently depressed adolescents, but is also evident in adolescents with remitted MDD, indicating that it may represent a trait-like vulnerability that increases risk for relapse. PMID:27498000

Does major depressive disorder in parents predict specific fears and phobias in offspring?

PubMed

Biel, Matthew G; Klein, Rachel G; Mannuzza, Salvatore; Roizen, Erica R; Truong, Nhan L; Roberson-Nay, Roxann; Pine, Daniel S

2008-01-01

Evidence suggests a relationship between parental depression and phobias in offspring as well as links between childhood fears and risk for major depression. This study examines the relationship between major depressive disorder (MDD) and anxiety disorders in parents and specific fears and phobias in offspring. Three hundred and eighteen children of parents with lifetime MDD, anxiety disorder, MDD+anxiety disorder, or neither were psychiatrically assessed via parent interview. Rates of specific phobias in offspring did not differ significantly across parental groups. Specific fears were significantly elevated in offspring of parents with MDD+anxiety disorder relative to the other groups (MDD, anxiety disorder, and controls, which did not differ). We failed to find increased phobias in offspring of parents with MDD without anxiety disorder. Elevated rates of specific fears in offspring of parents with MDD+anxiety disorder may be a function of more severe parental psychopathology, increased genetic loading, or unmeasured environmental influences. (c) 2007 Wiley-Liss, Inc.

Pain and major depressive disorder: Associations with cognitive impairment as measured by the THINC-integrated tool (THINC-it).

PubMed

Cha, Danielle S; Carmona, Nicole E; Mansur, Rodrigo B; Lee, Yena; Park, Hyun Jung; Rodrigues, Nelson B; Subramaniapillai, Mehala; Rosenblat, Joshua D; Pan, Zihang; Lee, Jae Hon; Lee, JungGoo; Almatham, Fahad; Alageel, Asem; Shekotikhina, Margarita; Zhou, Aileen J; Rong, Carola; Harrison, John; McIntyre, Roger S

2017-04-01

To examine the role of pain on cognitive function in adults with major depressive disorder (MDD). Adults (18-65) with a Diagnostic and Statistical Manual - Fifth Edition (DSM-5)-defined diagnosis of MDD experiencing a current major depressive episode (MDE) were enrolled (n MDD =100). All subjects with MDD were matched in age, sex, and years of education to healthy controls (HC) (n HC =100) for comparison. Cognitive function was assessed using the recently validated THINC-integrated tool (THINC-it), which comprises variants of the choice reaction time (i.e., THINC-it: Spotter), One-Back (i.e., THINC-it: Symbol Check), Digit Symbol Substitution Test (i.e., THINC-it: Codebreaker), Trail Making Test - Part B (i.e., THINC-it: Trails), as well as the Perceived Deficits Questionnaire for Depression - 5-item (i.e., THINC-it: PDQ-5-D). A global index of objective cognitive function was computed using objective measures from the THINC-it, while self-rated cognitive deficits were measured using the PDQ-5-D. Pain was measured using a Visual Analogue Scale (VAS). Regression analyses evaluated the role of pain in predicting objective and subjective cognitive function. A significant between-group differences on the VAS was observed (p<0.001), with individuals with MDD reporting higher pain severity as evidenced by higher scores on the VAS than HC. Significant interaction effects were observed between self -rated cognitive deficits and pain ratings (p<0.001) on objective cognitive performance (after adjusting for MADRS total score), suggesting that pain moderates the association between self-rated and objective cognitive function. Results indicated that pain is associated with increased self-rated and objective cognitive deficits in adults with MDD. The study herein provides preliminary evidence demonstrating that adults with MDD reporting pain symptomatology and poorer subjective cognitive function is predictive of poorer objective cognitive performance. THINC-it is capable of detecting cognitive dysfunction amongst adults with MDD and pain. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Differences of biased recall memory for emotional information among children and adolescents of mothers with MDD, children and adolescents with MDD, and normal controls.

PubMed

Fattahi Asl, Abouzar; Ghanizadeh, Ahmad; Mollazade, Javad; Aflakseir, Abdolaziz

2015-08-15

This study examines explicit memory bias for emotional information in children and adolescents with major depressive disorder (MDD). Participants were a convenient sample of 28 children and adolescents of mothers with MDD, 28 children and adolescents with MDD, and 29 healthy controls. Their age range was 11-17 years old. The groups were matched for gender ratio, mean age, and the years of educational level. They were assessed by the Recall Task. Emotional stimuli consisted of three sets of words namely sad, happy, and neutral words. Children and adolescents of mothers with MDD similar to children and adolescents with MDD recalled more sadness stimuli in comparison with the controls. In other words, they showed an explicit memory bias towards sad stimuli. Also, healthy children significantly recalled more happy words than the other two groups. There was no significant difference among the three groups for the recall of neutral stimuli. Current findings support that there is a recall memory bias for emotional information in children with MDD. These children more than healthy children recall sad words. Moreover, healthy children recall happy words more than children with MDD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Combined Pathway and Regional Heritability Analysis Indicates NETRIN1 Pathway Is Associated With Major Depressive Disorder.

PubMed

Zeng, Yanni; Navarro, Pau; Fernandez-Pujals, Ana M; Hall, Lynsey S; Clarke, Toni-Kim; Thomson, Pippa A; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Wray, Naomi R; Deary, Ian J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2017-02-15

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have identified few significant associations. Testing the aggregation of genetic variants, in particular biological pathways, may be more powerful. Regional heritability analysis can be used to detect genomic regions that contribute to disease risk. We integrated pathway analysis and multilevel regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS samples [Generation Scotland: The Scottish Family Health Study (GS:SFHS, N = 6455) and Psychiatric Genomics Consortium (PGC:MDD) (N = 18,759)]. A polygenic risk score (PRS) composed of single nucleotide polymorphisms from the pathway most consistently associated with MDD was created, and its accuracy to predict MDD, using area under the curve, logistic regression, and linear mixed model analyses, was tested. In GS:SFHS, four pathways were significantly associated with MDD, and two of these explained a significant amount of pathway-level regional heritability. In PGC:MDD, one pathway was significantly associated with MDD. Pathway-level regional heritability was significant in this pathway in one subset of PGC:MDD. For both samples the regional heritabilities were further localized to the gene and subregion levels. The NETRIN1 signaling pathway showed the most consistent association with MDD across the two samples. PRSs from this pathway showed competitive predictive accuracy compared with the whole-genome PRSs when using area under the curve statistics, logistic regression, and linear mixed model. These post-GWAS analyses highlight the value of combining multiple methods on multiple GWAS data for the identification of risk pathways for MDD. The NETRIN1 signaling pathway is identified as a candidate pathway for MDD and should be explored in further large population studies. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Gender Differences in Depressive Symptom Profile: Results from Nationwide General Population Surveys in Korea.

PubMed

Kim, Ji-Hyun; Cho, Maeng Je; Hong, Jin Pyo; Bae, Jae Nam; Cho, Seong-Jin; Hahm, Bong-Jin; Lee, Dong-Woo; Park, Jong-Ik; Lee, Jun-Young; Jeon, Hong Jin; Chang, Sung Man

2015-11-01

This study investigated gender differences in symptom profiles of major depressive disorder (MDD) in the Korean general population. Data were pooled from the series of nationwide Korean Epidemiologic Catchment Area surveys conducted in 2001, 2006 and 2011, respectively. Of the 18,807 participants, 507 (397 women and 110 men) were diagnosed with MDD within the prior 12 months. In agreement with previous studies, women with MDD appeared to be more vulnerable to experiencing atypical depressive episodes defined as depression with two or more symptoms of fatigue, increased appetite and hypersomnia (P < 0.001). In terms of individual symptoms, female gender was significantly related with higher prevalence of fatigue (P = 0.008), hypersomnia (P = 0.001), noticeable psychomotor retardation (P = 0.029) and suicidal attempts (P = 0.016) with adjustment for birth cohort effect, partner status, and employment status. In the same analysis, men with MDD appeared more vulnerable to decreased libido than women (P = 0.009). This is the first report to demonstrate gender differences in symptomatology of MDD in the general Korean population, and the results are comparable to previous investigations from western societies. Assumingly, the intercultural similarity in female preponderance to atypical depression might reflect the common biological construct underlying the gender difference in mechanism of MDD. In clinical settings, gender differences of MDD should be carefully considered, because these features could be related with treatment response and drug side effects.

Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder.

PubMed

Simas, Tiago; Chattopadhyay, Shayanti; Hagan, Cindy; Kundu, Prantik; Patel, Ameera; Holt, Rosemary; Floris, Dorothea; Graham, Julia; Ooi, Cinly; Tait, Roger; Spencer, Michael; Baron-Cohen, Simon; Sahakian, Barbara; Bullmore, Ed; Goodyer, Ian; Suckling, John

2015-01-01

The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD) time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric), such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric), where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC) and major depressive disorder (MDD). Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome. These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders.

Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder

PubMed Central

Simas, Tiago; Chattopadhyay, Shayanti; Hagan, Cindy; Kundu, Prantik; Patel, Ameera; Holt, Rosemary; Floris, Dorothea; Graham, Julia; Ooi, Cinly; Tait, Roger; Spencer, Michael; Baron-Cohen, Simon; Sahakian, Barbara; Bullmore, Ed; Goodyer, Ian; Suckling, John

2015-01-01

Introduction The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD) time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric), such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric), where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC) and major depressive disorder (MDD). Results Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome. Conclusion These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders. PMID:26308854

Major Depression and Treatment Response in Adolescents with ADHD and Substance Use Disorder

PubMed Central

Warden, Diane; Riggs, Paula D.; Min, Sung-Joon; Mikulich-Gilbertson, Susan K.; Tamm, Leanne; Trello-Rishel, Kathlene; Winhusen, Theresa

2011-01-01

Background Major depressive disorder (MDD) frequently co-occurs in adolescents with substance use disorders (SUD) and attention deficit hyperactivity disorder (ADHD), but the impact of MDD on substance treatment and ADHD outcomes and implications for clinical practice are unclear. Methods Adolescents (n=303; ages 13-18) meeting DSM-IV criteria for ADHD and SUD were randomized to Osmotic Release Methylphenidate (OROS-MPH) or placebo and 16 weeks of cognitive behavioral therapy (CBT). Adolescents with (n=38) and without (n=265) MDD were compared on baseline demographic and clinical characteristics as well as non-nicotine substance use and ADHD treatment outcomes. Results Adolescents with MDD reported more non-nicotine substance use days at baseline and continued using more throughout treatment compared to those without MDD (p<0.0001 based on Timeline Followback; p<0.001 based on urine drug screens). There was no difference between adolescents with and without MDD in retention or CBT sessions attended. ADHD symptom severity (based on DSM-IV ADHD Rating Scale) followed a slightly different course of improvement although with no difference between groups in baseline or 16-week symptom severity or 16 week symptom reduction. There was no difference in days of substance use or ADHD symptom outcomes over time in adolescents with MDD or those without MDD treated with OROS-MPH or placebo. Depressed adolescents were more often female, older, and not court ordered. Conclusions These preliminary findings suggest that compared to non-depressed adolescents with ADHD and SUD, those with co-occurring MDD have more severe substance use at baseline and throughout treatment. Such youth may require interventions targeting depression. PMID:21885210

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls.

PubMed

Simon, Naomi M; Walton, Zandra E; Bui, Eric; Prescott, Jennifer; Hoge, Elizabeth; Keshaviah, Aparna; Schwarz, Noah; Dryman, Taylor; Ojserkis, Rebecca A; Kovachy, Benjamin; Mischoulon, David; Worthington, John; De Vivo, Immaculata; Fava, Maurizio; Wong, Kwok-Kin

2015-08-01

Leukocyte telomere length (LTL) is a marker of cellular turnover and oxidative stress. Studies suggest major depressive disorder (MDD) is associated with oxidative stress, but examinations of MDD and LTL have yielded mixed results, likely because of differences in measurement methods and unmeasured confounding. This study examined LTL and telomerase activity in 166 individuals with MDD compared to 166 age- and gender-matched matched controls free of any psychiatric disorder, using well-validated assays and clinical assessment methods, and controlling for a range of potential confounders. Subjects aged 18 to 70 were evaluated by trained raters and provided blood for LTL and telomerase activity measurement. LTL was assayed using Southern blot and replicated with qPCR, and telomerase activity was assayed with a repeat amplification protocol using a commercial kit. There was no significant difference in telomere length for individuals with MDD [mean (SD)=9.1 (3.0)kbp] compared to controls [mean(SD)=8.9(2.5)kbp] measured by Southern blot (p=0.65) or by confirmatory qPCR (p=0.91) assays. Controlling for potential confounders did not alter the results. Telomerase activity did not differ by MDD diagnosis overall (p=0.40), but the effect of MDD was significantly modified by gender (t(299)=2.67, p=0.0079) even after controlling for potential confounders, with telomerase activity significantly greater only in males with MDD versus controls. Our well-characterized, well-powered examination of concurrently assessed telomere length and telomerase activity in individuals with clinically significant, chronic MDD and matched controls failed to provide strong evidence of an association of MDD with shorter LTL, while telomerase activity was higher in men with MDD [corrected]. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder

PubMed Central

Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

2016-01-01

Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients. PMID:27271861

Demographic Correlates of DSM-IV Major Depressive Disorder among Older African Americans, Black Caribbeans, and Non-Hispanic Whites: Results from the National Survey of American Life

PubMed Central

Aranda, María P.; Chae, David H.; Lincoln, Karen D.; Taylor, Robert Joseph; Woodward, Amanda Toler; Chatters, Linda M.

2012-01-01

Objectives To examine the demographic correlates of lifetime and 12-month prevalence of major depressive disorder (MDD) among older African Americans, Black Caribbeans, and non-Hispanic Whites. Methods Data are from adults age 55 years and older (n = 1439) recruited to the National Survey of American Life (NSAL; 2001–2003). The DSM-IV World Mental Health Composite International Diagnostic Interview was used to assess 12-month and lifetime MDD. Weighted logistic regression was used to model demographic correlates of MDD. Results The population prevalence of lifetime and 12-month MDD were 11.2% and 4.1%, respectively. Bivariate analyses revealed that younger respondents and those with greater disability had a higher prevalence of both lifetime and 12-month MDD compared to those who were older and had lower disability. Multivariable logistic regressions controlling for demographic characteristics revealed that non-Hispanic Whites had the greatest odds of lifetime MDD (OR = 2.27, 95% CI = 1.32, 3.93). Women had significantly greater odds of lifetime MDD compared to men (OR = 2.49, 95% CI = 1.14, 5.41); there were no gender differences in 12-month MDD. Other significant predictors of MDD were marital status and region of residence. Conclusions The distribution, correlates, and nature of associations with MDD vary as a function of whether we examined lifetime vs. 12-month MDD. Future work should account for within group differences among older adults with depression. Understanding MDD correlates and the nature of intergroup diversity can inform the identification of particularly vulnerable subgroups as well as appropriate treatment approaches. PMID:22038674

Persistent decrease in alpha current density in fully remitted subjects with major depressive disorder treated with fluoxetine: A prospective electric tomography study.

PubMed

Almeida Montes, Luis Guillermo; Prado Alcántara, Hugo; Portillo Cedeño, Bertha Alicia; Hernández García, Ana Olivia; Fuentes Rojas, Patricia Elisa

2015-06-01

Major depressive disorder (MDD) is recurrent, and its pathophysiology is not fully understood. Studies using electric tomography (ET) have identified abnormalities in the current density (CD) of MDD subjects in regions associated with the neurobiology of MDD, such as the anterior cingulate cortex (ACC) and medial orbitofrontal cortex (mOFC). However, little is known regarding the long-term CD changes in MDD subjects who respond to antidepressants. The aim of this study was to compare CD between healthy and MDD subjects who received 1-year open-label treatment with fluoxetine. Thirty-two-channel electroencephalograms (EEGs) were collected from 70 healthy controls and 74 MDD subjects at baseline (pre-treatment), 1 and 2weeks and 1, 2, 6, 9 and 12months. Variable-resolution ET (VARETA) was used to assess the CD between subject groups at each time point. The MDD group exhibited decreased alpha CD (αCD) in the occipital and parietal cortices, ACC, mOFC, thalamus and caudate nucleus at each time point. The αCD abnormalities persisted in the MDD subjects despite their achieving full remission. The low sub-alpha band was different between the healthy and MDD subjects. Differences in the amount of αCD between sexes and treatment outcomes were observed. Lack of a placebo arm and the loss of depressed patients to follow-up were significant limitations. The persistence of the decrease in αCD might suggest that the underlying pathophysiologic mechanisms of MDD are not corrected despite the asymptomatic state of MDD subjects, which could be significant in understanding the highly recurrent nature of MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical Features of Patients with Dysthymia in a Large Cohort of Han Chinese Women with Recurrent Major Depression

PubMed Central

Wu, Wenqing; Wang, Zhoubing; Wei, Yan; Zhang, Guanghua; Shi, Shenxun; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Liu, Ying; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S.; Flint, Jonathan; Zhang, Zhen

2013-01-01

Background Dysthymia is a form of chronic mild depression that has a complex relationship with major depressive disorder (MDD). Here we investigate the role of environmental risk factors, including stressful life events and parenting style, in patients with both MDD and dysthymia. We ask whether these risk factors act in the same way in MDD with and without dysthymia. Results We examined the clinical features in 5,950 Han Chinese women with MDD between 30–60 years of age across China. We confirmed earlier results by replicating prior analyses in 3,950 new MDD cases. There were no significant differences between the two data sets. We identified sixteen stressful life events that significantly increase the risk of dysthymia, given the presence of MDD. Low parental warmth, from either mother or father, increases the risk of dysthymia. Highly threatening but short-lived threats (such as rape) are more specific for MDD than dysthymia. While for MDD more severe life events show the largest odds ratio versus controls, this was not seen for cases of MDD with or without dysthymia. Conclusions There are increased rates of stressful life events in MDD with dysthymia, but the impact of life events on susceptibility to dysthymia with MDD differs from that seen for MDD alone. The pattern does not fit a simple dose-response relationship, suggesting that there are moderating factors involved in the relationship between environmental precipitants and the onset of dysthymia. It is possible that severe life events in childhood events index a general susceptibility to chronic depression, rather than acting specifically as risk factors for dysthymia. PMID:24386213

Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

PubMed Central

Yao, Shun; Zhong, Yi; Xu, Yuhao; Qin, Jiasheng; Zhang, Ningning; Zhu, Xiaolan; Li, Yuefeng

2017-01-01

Previous studies have detected abnormal serum ferritin levels in patients with depression; however, the results have been inconsistent. This study used quantitative susceptibility mapping (QSM) for the first time to examine brain iron concentration in depressed patients and evaluated whether it is related to severity. We included three groups of age- and gender-matched participants: 30 patients with mild-moderate depression (MD), 14 patients with major depression disorder (MDD) and 20 control subjects. All participants underwent MR scans with a 3D gradient-echo sequence reconstructing for QSM and performed the 17-item Hamilton Depression Rating Scale (HDRS) test. In MDD, the susceptibility value in the bilateral putamen was significantly increased compared with MD or control subjects. In addition, a significant difference was also observed in the left thalamus in MDD patients compared with controls. However, the susceptibility values did not differ between MD patients and controls. The susceptibility values positively correlated with the severity of depression as indicated by the HDRS scores. Our results provide evidence that brain iron deposition may be associated with depression and may even be a biomarker for investigating the pathophysiological mechanism of depression. PMID:28900391

Comparison of major depressive disorder onset among foreign-born Asian Americans: Chinese, Filipino, and Vietnamese ethnic groups.

PubMed

Lee, Sungkyu; Choi, Sunha; Matejkowski, Jason

2013-11-30

Using a nationally representative sample of 1280 Asian Americans, we examined the extent to which major depressive disorder (MDD) onset differs by ethnicity and its associated factors for each of the three ethnic groups: Vietnamese, Filipino, and Chinese. We employed the Kaplan-Meier method to estimate the survival and hazard functions for MDD onset by ethnicity, and cox proportional hazards models to identify socio-demographic and immigration-related factors associated with MDD onset. Approximately 7% of the entire sample had experienced MDD onset in their lifetime. Filipino immigrants showed the highest survival function, followed by Vietnamese immigrants over time. Those who were never-married or divorced were more likely to experience MDD onset when compared to their married or cohabiting counterparts. Those who immigrated at a younger age were more likely to experience MDD onset than were those who immigrated at an older age. However, there were ethnic variations in terms of the risk factors that were associated with MDD onset across these three ethnic groups. Findings from this study signal the importance of understanding the differing experiences of MDD onset by ethnicity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Heterogeneity of amygdala response in major depressive disorder: the impact of lifetime subthreshold mania.

PubMed

Fournier, J C; Keener, M T; Mullin, B C; Hafeman, D M; Labarbara, E J; Stiffler, R S; Almeida, J; Kronhaus, D M; Frank, E; Phillips, M L

2013-02-01

Patients with major depressive disorder (MDD) present with highly heterogeneous symptom profiles. We aimed to examine whether individual differences in amygdala activity to emotionally salient stimuli were related to heterogeneity in lifetime levels of depressive and subthreshold manic symptoms among adults with MDD. We compared age- and gender-matched adults with MDD (n = 26) with healthy controls (HC, n = 28). While undergoing functional magnetic resonance imaging, participants performed an implicit emotional faces task: they labeled a color flash superimposed upon initially neutral faces that dynamically morphed into one of four emotions (angry, fearful, sad, happy). Region of interest analyses examined group differences in amygdala activity. For conditions in which adults with MDD displayed abnormal amygdala activity versus HC, within-group analyses examined amygdala activity as a function of scores on a continuous measure of lifetime depression-related and mania-related pathology. Adults with MDD showed significantly greater right-sided amygdala activity to angry and happy conditions than HC (p < 0.05, corrected). Multiple regression analyses revealed that greater right-amygdala activity to the happy condition in adults with MDD was associated with higher levels of subthreshold manic symptoms experienced across the lifespan (p = 0.002). Among depressed adults with MDD, lifetime features of subthreshold mania were associated with abnormally elevated amygdala activity to emerging happy faces. These findings are a first step toward identifying biomarkers that reflect individual differences in neural mechanisms in MDD, and challenge conventional mood disorder diagnostic boundaries by suggesting that some adults with MDD are characterized by pathophysiological processes that overlap with bipolar disorder.

Pericardial adipose tissue and the metabolic syndrome is increased in patients with chronic major depressive disorder compared to acute depression and controls.

PubMed

Kahl, K G; Herrmann, J; Stubbs, B; Krüger, T H C; Cordes, J; Deuschle, M; Schweiger, U; Hüper, K; Helm, S; Birkenstock, A; Hartung, D

2017-01-04

Major depressive disorder (MDD) is associated with an estimated fourfold risk for premature death, largely attributed to cardiovascular disorders. Pericardial adipose tissue (PAT), a fat compartment surrounding the heart, has been implicated in the development of coronary artery disease. An unanswered question is whether people with chronic MDD are more likely to have elevated PAT volumes versus acute MDD and controls (CTRL). The study group consists of sixteen patients with chronic MDD, thirty-four patients with acute MDD, and twenty-five CTRL. PAT and adrenal gland volume were measured by magnetic resonance tomography. Additional measures comprised factors of the metabolic syndrome, cortisol, relative insulin resistance, and pro-inflammatory cytokines (interleukin-6; IL-6 and tumor necrosis factor-α, TNF-α). PAT volumes were significantly increased in patients with chronic MDD>patients with acute MDD>CTRL. Adrenal gland volume was slightly enlarged in patients with chronic MDD>acute MDD>CTRL, although this difference failed to reach significance. The PAT volume was correlated with adrenal gland volume, and cortisol concentrations were correlated with depression severity, measured by BDI-2 and MADRS. Group differences were found concerning the rate of the metabolic syndrome, being most frequent in chronic MDD>acute MDD>CTRL. Further findings comprised increased fasting cortisol, increased TNF-α concentration, and decreased physical activity level in MDD compared to CTRL. Our results extend the existing literature in demonstrating that patients with chronic MDD have the highest risk for developing cardiovascular disorders, indicated by the highest PAT volume and prevalence of metabolic syndrome. The correlation of PAT with adrenal gland volume underscores the role of the hypothalamus-pituitary-adrenal system as mediator for body-composition changes. Metabolic monitoring, health advices and motivation for the improvement of physical fitness may be recommended in depressed patients, in particular in chronic depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

PubMed Central

Ligthart, Lannie; Hottenga, Jouke-Jan; Lewis, Cathryn M.; Farmer, Anne E.; Craig, Ian W.; Breen, Gerome; Willemsen, Gonneke; Vink, Jacqueline M.; Middeldorp, Christel M.; Byrne, Enda M.; Heath, Andrew C.; Madden, Pamela A.F.; Pergadia, Michele L.; Montgomery, Grant W.; Martin, Nicholas G.; Penninx, Brenda W.J.H.; McGuffin, Peter; Boomsma, Dorret I.; Nyholt, Dale R.

2013-01-01

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6350) included 2825 migraine cases and 3525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3230) included 1636 MDD cases and 1594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2966), which included 1476 MDD cases and 1058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the ‘pure’ forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. PMID:24081561

Considering sex differences clarifies the effects of depression on facial emotion processing during fMRI.

PubMed

Jenkins, L M; Kendall, A D; Kassel, M T; Patrón, V G; Gowins, J R; Dion, C; Shankman, S A; Weisenbach, S L; Maki, P; Langenecker, S A

2018-01-01

Sex differences in emotion processing may play a role in women's increased risk for Major Depressive Disorder (MDD). However, studies of sex differences in brain mechanisms involved in emotion processing in MDD (or interactions of sex and diagnosis) are sparse. We conducted an event-related fMRI study examining the interactive and distinct effects of sex and MDD on neural activity during a facial emotion perception task. To minimize effects of current affective state and cumulative disease burden, we studied participants with remitted MDD (rMDD) who were early in the course of the illness. In total, 88 individuals aged 18-23 participated, including 48 with rMDD (32 female) and 40 healthy controls (HC; 25 female). fMRI revealed an interaction between sex and diagnosis for sad and neutral facial expressions in the superior frontal gyrus and left middle temporal gyrus. Results also revealed an interaction of sex with diagnosis in the amygdala. Data was from two sites, which might increase variability, but it also increases power to examine sex by diagnosis interactions. This study demonstrates the importance of taking sex differences into account when examining potential trait (or scar) mechanisms that could be useful in identifying individuals at-risk for MDD as well as for evaluating potential therapeutic innovations. Copyright © 2017 Elsevier B.V. All rights reserved.

Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in major depressive disorder and schizophrenia?

PubMed

Szczypiński, Jan Józef; Gola, Mateusz

2018-03-24

Abnormalities in reward processing are crucial symptoms of major depressive disorder (MDD) and schizophrenia (SCH). Recent neuroscientific findings regarding MDD have led to conclusions about two different symptoms related to reward processing: motivational and consummatory anhedonia, corresponding, respectively, to impaired motivation to obtain rewards ('wanting'), and diminished satisfaction from consuming them ('liking'). One can ask: which of these is common for MDD and SCH. In our review of the latest neuroscientific studies, we show that MDD and SCH do not share consummatory anhedonia, as SCH patients usually have unaltered liking. Therefore, we investigated whether motivational anhedonia is the common symptom across MDD and SCH. With regard to the similarities and differences between the neural mechanisms of MDD and SCH, here we expand the current knowledge of motivation deficits and present the common underlying mechanism of motivational anhedonia - the dopamine dysregulation hypothesis - stating that any prolonged dysregulation in tonic dopamine signaling that exceeds the given equilibrium can lead to striatal dysfunction and motivational anhedonia. The implications for further research and treatment of MDD and SCH are also discussed.

Brief report: Overgeneral autobiographical memory in adolescent major depressive disorder.

PubMed

Champagne, Katelynn; Burkhouse, Katie L; Woody, Mary L; Feurer, Cope; Sosoo, Effua; Gibb, Brandon E

2016-10-01

The current study examined whether overgeneral autobiographical memory (OGM) bias serves as a state-like marker of major depressive disorder (MDD) in adolescence or whether it would also be observed in currently nondepressed adolescents with a history of MDD. We examined differences in OGM to positive and negative cue words between adolescents (aged 11-18 years) with current MDD (n = 15), remitted MDD (n = 25), and no history of any depressive disorder (n = 25). Youth and their parents were administered a structured diagnostic interview and adolescents completed the autobiographical memory test. Compared to never depressed adolescents, adolescents with current or remitted MDD recalled less specific memories in response to positive and negative cue words. The difference between the two MDD groups was small and nonsignificant. These findings suggest that OGM is not simply a state-like marker in currently depressed adolescents, but is also evident in adolescents with remitted MDD, indicating that it may represent a trait-like vulnerability that increases risk for relapse. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Comparison of suicide attempts in schizophrenia and major depressive disorder: an exploratory study.

PubMed

Banwari, Girish H; Vankar, Ganpat K; Parikh, Minakshi N

2013-12-01

Schizophrenia and major depressive disorder (MDD) are among the most common psychiatric diagnoses associated with suicide. There is a dearth of published research systematically comparing suicidal behavior in schizophrenia and MDD. The present study aimed to compare suicide attempts in schizophrenia and MDD. In this hospital-based, cross-sectional study, 50 outpatients each of schizophrenia and MDD were evaluated for their sociodemographic characteristics. In subjects with a history of suicide attempt(s), additional information related to the attempt(s) was obtained. Suicide Intent Scale (SIS) was used to assess the suicidal intent and Mini International Neuropsychiatric Interview (MINI) was used to measure the current suicidal risk. Thirty-four percent and 44% of patients with schizophrenia and MDD, respectively, attempted suicide. The attempters in schizophrenia compared to those in MDD were younger and more likely to be single (unmarried, separated or divorced). Suicidal intent was stronger in schizophrenia, while the attempters with MDD were more often preoccupied with a death wish and reported that stressful life events influenced the attempt. There were no differences in the attempt methods of the two groups. Current suicidal risk was higher in attempters compared to the non-attempters in schizophrenia as well as MDD. Suicide attempts in schizophrenia and MDD have similar features, with quite a few notable differences, which have been discussed at length in the present paper. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Symptom profile of major depressive disorder in women with eating disorders.

PubMed

Fernandez-Aranda, Fernando; Pinheiro, Andrea Poyastro; Tozzi, Federica; Thornton, Laura M; Fichter, Manfred M; Halmi, Katherine A; Kaplan, Allan S; Klump, Kelly L; Strober, Michael; Woodside, D Blake; Crow, Scott; Mitchell, James; Rotondo, Alessandro; Keel, Pamela; Plotnicov, Katherine H; Berrettini, Wade H; Kaye, Walter H; Crawford, Steven F; Johnson, Craig; Brandt, Harry; La Via, Maria; Bulik, Cynthia M

2007-01-01

Based on the well-documented association between eating disorders (EDs) and affective disorders, the patterns of comorbidity of EDs and major depressive disorder (MDD) were investigated. The temporal relation between EDs and MDD onset was analyzed to determine differences in the course and nature of MDD when experienced prior to versus after the onset of the ED. Lifetime MDD and depressive symptoms were assessed in 1371 women with a history of ED. The prevalence of MDD was first explored across ED subtypes, and ages of onset of MDD and EDs were compared. Depressive symptoms were examined in individuals who developed MDD before and after ED onset. The lifetime prevalence of MDD was 72.9%. Among those with lifetime MDD (n =963), 34.5% reported MDD onset before the onset of ED. Those who experienced MDD first reported greater psychomotor agitation (OR =1.53; 95%CI =1.14-2.06), and thoughts of own death (but not suicide attempts or ideation; OR =1.73; 95%CI =1.31-2.30). Among individuals who had MDD before ED, 26.5% had the MDD onset during the year before the onset of ED; 67% of individuals had the onset of both disorders within the same 3 year window. Clinicians treating individuals with new-onset ED or MDD should remain vigilant for the emergence of additional psychopathology, especially during the initial 3 year window following the onset of the first disorder.

Gender Differences in Depressive Symptom Profile: Results from Nationwide General Population Surveys in Korea

PubMed Central

Kim, Ji-Hyun; Cho, Maeng Je; Hong, Jin Pyo; Bae, Jae Nam; Cho, Seong-Jin; Hahm, Bong-Jin; Lee, Dong-Woo; Park, Jong-Ik; Lee, Jun-Young; Jeon, Hong Jin

2015-01-01

This study investigated gender differences in symptom profiles of major depressive disorder (MDD) in the Korean general population. Data were pooled from the series of nationwide Korean Epidemiologic Catchment Area surveys conducted in 2001, 2006 and 2011, respectively. Of the 18,807 participants, 507 (397 women and 110 men) were diagnosed with MDD within the prior 12 months. In agreement with previous studies, women with MDD appeared to be more vulnerable to experiencing atypical depressive episodes defined as depression with two or more symptoms of fatigue, increased appetite and hypersomnia (P < 0.001). In terms of individual symptoms, female gender was significantly related with higher prevalence of fatigue (P = 0.008), hypersomnia (P = 0.001), noticeable psychomotor retardation (P = 0.029) and suicidal attempts (P = 0.016) with adjustment for birth cohort effect, partner status, and employment status. In the same analysis, men with MDD appeared more vulnerable to decreased libido than women (P = 0.009). This is the first report to demonstrate gender differences in symptomatology of MDD in the general Korean population, and the results are comparable to previous investigations from western societies. Assumingly, the intercultural similarity in female preponderance to atypical depression might reflect the common biological construct underlying the gender difference in mechanism of MDD. In clinical settings, gender differences of MDD should be carefully considered, because these features could be related with treatment response and drug side effects. PMID:26539012

Preferences regarding targeted education and risk assessment in people with a family history of major depressive disorder.

PubMed

Quinn, Veronica; Meiser, Bettina; Wilde, Alex; Cousins, Zoe; Barlow-Stewart, Kristine; Mitchell, Philip B; Schofield, Peter R

2014-10-01

Genetic testing for susceptibility to major depressive disorder (MDD) is not available for clinical use at present. Given this, family history remains the best predictor for development of MDD, and family-history-based risk assessment and information about familial aspects of MDD may be useful to clients at increased risk for MDD attending for genetic counseling. This study uses a mixed-methods design to assess the information needs and preferences of people at increased familial risk for MDD. Telephone interviews were conducted with 23 individuals, who had at least one first-degree relative with MDD and were recruited through advertisements placed on depression education websites. The most preferred way to access depression information was via the internet (87 % of participants), although this preference may have been due to the internet-based recruitment method. The second most preferred dissemination strategy (56 %) was face-to-face delivery through a health professional, including genetic counselors. Individuals reported a need for information about etiology and development of MDD, reproductive decision-making, early detection of symptoms and risk-reducing strategies. Nearly all participants expressed an interest in risk assessment. The present study found evidence of a high level of interest for information targeted to people at increased familial risk for MDD. Genetic counselors are likely to be called upon increasingly to provide supportive counseling to assist clients at increased familial risk in interpreting and contextualizing such information once it becomes available.

Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil.

PubMed

de Almeida, Sergio Monteiro; Barbosa, Francisco Jaime; Kamat, Rujvi; de Pereira, Ana Paula; Raboni, Sonia Mara; Rotta, Indianara; Ribeiro, Clea Elisa; Cherner, Mariana; Ellis, Ronald J; Atkinson, Joseph Hampton

2016-12-01

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV- and higher in HIV subtype B compared with C. Individuals with HIV (n = 39) as well as seronegative controls (n = 22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV- group: current MDD, 15 (38.5 %) vs. 0 (0 %), p = 0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p = 0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV- (13 (8-27.5) vs. 2.5 (1-5.5); p < 0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p = 0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV-. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.

Epidemiology and Heritability of Major Depressive Disorder, Stratified by Age of Onset, Sex, and Illness Course in Generation Scotland: Scottish Family Health Study (GS:SFHS).

PubMed

Fernandez-Pujals, Ana Maria; Adams, Mark James; Thomson, Pippa; McKechanie, Andrew G; Blackwood, Douglas H R; Smith, Blair H; Dominiczak, Anna F; Morris, Andrew D; Matthews, Keith; Campbell, Archie; Linksted, Pamela; Haley, Chris S; Deary, Ian J; Porteous, David J; MacIntyre, Donald J; McIntosh, Andrew M

2015-01-01

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.

Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

PubMed

Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

2015-09-29

Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are involved in MDD's etiology. These same mechanisms, however, are less important in clinical progression from first to later MDD episodes and toward chronicity.

Low serotonin1B receptor binding potential in the anterior cingulate cortex in drug-free patients with recurrent major depressive disorder.

PubMed

Tiger, Mikael; Farde, Lars; Rück, Christian; Varrone, Andrea; Forsberg, Anton; Lindefors, Nils; Halldin, Christer; Lundberg, Johan

2016-07-30

The pathophysiology of major depressive disorder (MDD) is not fully understood and the diagnosis is largely based on history and clinical examination. So far, several lines of preclinical data and a single imaging study implicate a role for the serotonin1B (5-HT1B) receptor subtype. We sought to study 5-HT1B receptor binding in brain regions of reported relevance in patients with MDD. Subjects were examined at the Karolinska Institutet PET centre using positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369. Ten drug-free patients with recurrent MDD and ten control subjects matched for age and sex were examined. The main outcome measure was [(11)C]AZ10419369 binding in brain regions of reported relevance in the pathophysiology of MDD. The [(11)C]AZ10419369 binding potential was significantly lower in the MDD group compared with the healthy control group in the anterior cingulate cortex (20% between-group difference), the subgenual prefrontal cortex (17% between-group difference), and in the hippocampus (32% between-group difference). The low anterior cingulate [(11)C]AZ10419369 binding potential in patients with recurrent MDD positions 5-HT1B receptor binding in this region as a putative biomarker for MDD and corroborate a role of the anterior cingulate cortex and associated areas in the pathophysiology of recurrent MDD. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A Randomized, Controlled, Pilot Study of Acamprosate Added to Escitalopram in Adults With Major Depressive Disorder and Alcohol Use Disorder

PubMed Central

Witte, Janet; Bentley, Kate; Eden Evins, Anne; Clain, Alisabet J.; Baer, Lee; Pedrelli, Paola; Fava, Maurizio; Mischoulon, David

2013-01-01

We sought to examine the efficacy and safety of acamprosate augmentation of escitalopram in patients with concurrent major depressive disorder (MDD) and alcohol use disorders. Twenty-three adults (43% female; mean ± SD age, 46 ± 14 years) were enrolled and received 12 weeks of treatment with psychosocial support; escitalopram, 10 to 30 mg/d; and either acamprosate, 2000 mg/d (n = 12), or identical placebo (n = 11). Outcomes included change in clinician ratings of depressive symptoms, MDD response and remission rates, changes in frequency and intensity of alcohol use, retention rates, and adverse events. Twelve subjects (acamprosate, n = 7; placebo, n = 5) completed the study. There was significant mean reduction in ratings of depressive symptoms from baseline in both treatment arms (P < 0.05), with no significant difference between the groups. Those in the acamprosate group had a 50% MDD response rate and a 42% remission rate, whereas those in the placebo arm had a 36% response and remission rate (not significant). Those assigned to acamprosate had significant reduction in number of drinks per week and drinks per month during the trial, whereas those assigned to placebo demonstrated no significant change in any alcohol use parameter, but the between-group difference was not significant. There were no significant associations between change in depressive symptoms and change in alcohol use. Attrition rates did not differ significantly between the 2 arms. Acamprosate added to escitalopram in adults with MDD and alcohol use disorders was associated with reduction in the frequency of alcohol use. The present study was not powered to detect superiority versus placebo. Further study in a larger sample is warranted. PMID:23131884

The Oft-Neglected Role of Parietal EEG Asymmetry and Risk for Major Depressive Disorder

PubMed Central

Stewart, Jennifer L.; Towers, David N.; Coan, James A.; Allen, John J.B.

2010-01-01

Relatively less right parietal activity may reflect reduced arousal and signify risk for major depressive disorder (MDD). Inconsistent findings with parietal electroencephalographic (EEG) asymmetry, however, suggest issues such as anxiety comorbidity and sex differences have yet to be resolved. Resting parietal EEG asymmetry was assessed in 306 individuals (31% male) with (n = 143) and without (n = 163) a DSM-IV diagnosis of lifetime MDD and no comorbid anxiety disorders. Past MDD+ women displayed relatively less right parietal activity than current MDD+ and MDD- women, replicating prior work. Recent caffeine intake, an index of arousal, moderated the relationship between depression and EEG asymmetry for women and men. Findings suggest that sex differences and arousal should be examined in studies of depression and regional brain activity. PMID:20525011

Discrimination in the workplace, reported by people with major depressive disorder: a cross-sectional study in 35 countries

PubMed Central

Brouwers, E P M; Mathijssen, J; Van Bortel, T; Knifton, L; Wahlbeck, K; Van Audenhove, C; Kadri, N; Chang, Ch; Goud, B R; Ballester, D; Tófoli, LF; Bello, R; Jorge-Monteiro, M F; Zäske, H; Milaćić, I; Uçok, A; Bonetto, C; Lasalvia, A; Thornicroft, G; Van Weeghel, J

2016-01-01

Objective Whereas employment has been shown to be beneficial for people with Major Depressive Disorder (MDD) across different cultures, employers’ attitudes have been shown to be negative towards workers with MDD. This may form an important barrier to work participation. Today, little is known about how stigma and discrimination affect work participation of workers with MDD, especially from their own perspective. We aimed to assess, in a working age population including respondents with MDD from 35 countries: (1) if people with MDD anticipate and experience discrimination when trying to find or keep paid employment; (2) if participants in high, middle and lower developed countries differ in these respects; and (3) if discrimination experiences are related to actual employment status (ie, having a paid job or not). Method Participants in this cross-sectional study (N=834) had a diagnosis of MDD in the previous 12 months. They were interviewed using the Discrimination and Stigma Scale (DISC-12). Analysis of variance and generalised linear mixed models were used to analyse the data. Results Overall, 62.5% had anticipated and/or experienced discrimination in the work setting. In very high developed countries, almost 60% of respondents had stopped themselves from applying for work, education or training because of anticipated discrimination. Having experienced workplace discrimination was independently related to unemployment. Conclusions Across different countries and cultures, people with MDD very frequently reported discrimination in the work setting. Effective interventions are needed to enhance work participation in people with MDD, focusing simultaneously on decreasing stigma in the work environment and on decreasing self-discrimination by empowering workers with MDD. PMID:26908523

Discrimination in the workplace, reported by people with major depressive disorder: a cross-sectional study in 35 countries.

PubMed

Brouwers, E P M; Mathijssen, J; Van Bortel, T; Knifton, L; Wahlbeck, K; Van Audenhove, C; Kadri, N; Chang, Ch; Goud, B R; Ballester, D; Tófoli, L F; Bello, R; Jorge-Monteiro, M F; Zäske, H; Milaćić, I; Uçok, A; Bonetto, C; Lasalvia, A; Thornicroft, G; Van Weeghel, J

2016-02-23

Whereas employment has been shown to be beneficial for people with Major Depressive Disorder (MDD) across different cultures, employers' attitudes have been shown to be negative towards workers with MDD. This may form an important barrier to work participation. Today, little is known about how stigma and discrimination affect work participation of workers with MDD, especially from their own perspective. We aimed to assess, in a working age population including respondents with MDD from 35 countries: (1) if people with MDD anticipate and experience discrimination when trying to find or keep paid employment; (2) if participants in high, middle and lower developed countries differ in these respects; and (3) if discrimination experiences are related to actual employment status (ie, having a paid job or not). Participants in this cross-sectional study (N=834) had a diagnosis of MDD in the previous 12 months. They were interviewed using the Discrimination and Stigma Scale (DISC-12). Analysis of variance and generalised linear mixed models were used to analyse the data. Overall, 62.5% had anticipated and/or experienced discrimination in the work setting. In very high developed countries, almost 60% of respondents had stopped themselves from applying for work, education or training because of anticipated discrimination. Having experienced workplace discrimination was independently related to unemployment. Across different countries and cultures, people with MDD very frequently reported discrimination in the work setting. Effective interventions are needed to enhance work participation in people with MDD, focusing simultaneously on decreasing stigma in the work environment and on decreasing self-discrimination by empowering workers with MDD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Resting state synchrony in long-term abstinent alcoholics: Effects of a current major depressive disorder diagnosis.

PubMed

Fein, George; Camchong, Jazmin; Cardenas, Valerie A; Stenger, Andy

2017-03-01

Alcoholism is characterized by a lack of control over an impulsive and compulsive drive toward excessive alcohol consumption despite significant negative consequences; our previous work demonstrated that successful abstinence is characterized by decreased resting-state synchrony (RSS) as measured with functional magnetic resonance imaging (fMRI), within appetitive drive networks and increased RSS in emotion regulation and inhibitory executive control networks. Our hypothesis is that LTAA (Long-Term Abstinent Alcoholics) with a current major depressive disorder (MDD) drank primarily to deal with the negative affect associated with their MDD and not because of a heightened externalizing diathesis (including heightened appetitive drive), and consequently, in achieving and maintaining abstinence, such individuals would not exhibit the RSS adaptations characteristic of pure alcoholics. We studied 69 NSAC (Non Substance Abusing Controls) and 40 LTAA (8 with current MDD, 32 without a current MDD) using resting-state fMRI and seed based connectivity analyses. In the inhibitory executive control network (nucleus accumbens vs. left dorsolateral prefrontal cortex), LTAA with a current MDD showed increased synchrony compared to NSAC. In the emotion regulation executive control network (subgenual anterior cingulate cortex vs. right dorsolateral prefrontal cortex), LTAA with current MDD did not show increased RSS. In the appetitive drive networks (nucleus accumbens vs, aspects of the caudate nucleus and thalamus), LTAA with a current MDD did not show a reduction of RSS compared to NSAC, but LTAA without a current MDD did. These results suggest different pathways to their alcohol dependence in LTAA with vs. without a current MDD, and different patterns of brain activity in long-term abstinence, suggesting different treatment needs. Copyright © 2016 Elsevier Inc. All rights reserved.

Resting state synchrony in long-term abstinent alcoholics: Effects of a current major depressive disorder diagnosis

PubMed Central

Fein, George; Camchong, Jazmin; Cardenas, Valerie A.; Stenger, Andy

2017-01-01

Alcoholism is characterized by a lack of control over an impulsive and compulsive drive toward excessive alcohol consumption despite significant negative consequences; our previous work demonstrated that successful abstinence is characterized by decreased resting-state synchrony (RSS) as measured with functional magnetic resonance imaging (fMRI), within appetitive drive networks and increased RSS in emotion regulation and inhibitory executive control networks. Our hypothesis is that LTAA (Long-Term Abstinent Alcoholics) with a current major depressive disorder (MDD) drank primarily to deal with the negative affect associated with their MDD and not because of a heightened externalizing diathesis (including heightened appetitive drive), and consequently, in achieving and maintaining abstinence, such individuals would not exhibit the RSS adaptations characteristic of pure alcoholics. We studied 69 NSAC (Non Substance Abusing Controls) and 40 LTAA (8 with current MDD, 32 without a current MDD) using resting-state fMRI and seed based connectivity analyses. In the inhibitory executive control network (nucleus accumbens vs. left dorsolateral prefrontal cortex), LTAA with a current MDD showed increased synchrony compared to NSAC. In the emotion regulation executive control network (subgenual anterior cingulate cortex vs. right dorsolateral prefrontal cortex), LTAA with current MDD did not show increased RSS. In the appetitive drive networks (nucleus accumbens vs, aspects of the caudate nucleus and thalamus), LTAA with a current MDD did not show a reduction of RSS compared to NSAC, but LTAA without a current MDD did. These results suggest different pathways to their alcohol dependence in LTAA with vs. without a current MDD, and different patterns of brain activity in long-term abstinence, suggesting different treatment needs. PMID:28262184

Gender differences in alpha-[(11)C]MTrp brain trapping, an index of serotonin synthesis, in medication-free individuals with major depressive disorder: a positron emission tomography study.

PubMed

Frey, Benicio N; Skelin, Ivan; Sakai, Yojiro; Nishikawa, Masami; Diksic, Mirko

2010-08-30

Women are at higher risk than men for developing major depressive disorder (MDD), but the mechanisms underlying this higher risk are unknown. Here, we report proportionally normalized alpha-[(11)C]methyl-L-tryptophan brain trapping constant (alpha-[(11)C]MTrp K*(N)), an index of serotonin synthesis, in 25 medication-free individuals with MDD and in 25 gender- and age-matched healthy subjects who were studied using positron emission tomography (PET). Comparisons of alpha-[(11)C]MTrp K*(N) values between the men and women were conducted at the voxel and cluster levels using Statistical Parametric Mapping 2 (SPM2) analysis. In addition, the alpha-[(11)C]MTrp K*(N) values on both sides of the brain were extracted and compared to identify the left to right differences, as well as the gender differences. Women with MDD displayed higher alpha-[(11)C]MTrp K*(N) than men in the inferior frontal gyrus, anterior cingulate cortex (ACC), parahippocampal gyrus, precuneus, superior parietal lobule, and occipital lingual gyrus. In a matched group of normal subjects the gender differences were opposite from those found in MDD patients. Significant hemispheric differences in fronto-limbic structures between men and women with MDD were also observed. The K*(N) extracted from the volumes identified in MDD patients and in male and female normal subjects suggested no significant differences between males and females. In conclusion, depressed women have higher serotonin synthesis in multiple regions of the prefrontal cortex and limbic system involved with mood regulation, as compared with depressed men. Gender differences in brain serotonin synthesis may be related to higher risk for MDD in women. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

The THINC-Integrated Tool (THINC-it) Screening Assessment for Cognitive Dysfunction: Validation in Patients With Major Depressive Disorder.

PubMed

McIntyre, Roger S; Best, Michael W; Bowie, Christopher R; Carmona, Nicole E; Cha, Danielle S; Lee, Yena; Subramaniapillai, Mehala; Mansur, Rodrigo B; Barry, Harry; Baune, Bernhard T; Culpepper, Larry; Fossati, Philippe; Greer, Tracy L; Harmer, Catherine; Klag, Esther; Lam, Raymond W; Wittchen, Hans-Ulrich; Harrison, John

2017-07-01

To validate the THINC-integrated tool (THINC-it)-a freely available, patient-administered, computerized screening tool integrating subjective and objective measures of cognitive function in adults with major depressive disorder (MDD). Subjects aged 18 to 65 years (n = 100) with recurrent MDD experiencing a major depressive episode of at least moderate severity were evaluated and compared to age-, sex-, and education-matched healthy controls (n = 100). Between January and June 2016, subjects completed the THINC-it, which includes variants of the Choice Reaction Time Identification Task (IDN), One-Back Test, Digit Symbol Substitution Test, Trail Making Test-Part B, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). The THINC-it required approximately 10 to 15 minutes for administration and was capable of detecting cognitive deficits in adults with MDD. A total of 44.4% of adults with MDD exhibited cognitive performance at ≥ 1.0 SD below that of healthy controls on standardized mean scores of the THINC-it. Concurrent validity of the overall tool, based on a calculated composite score, was acceptable (r = 0.539, P < .001). Concurrent validity of the component tests ranged from -0.083 (IDN) to 0.929 (PDQ-5-D). Qualitative survey results indicated that there was a high level of satisfaction and perceived value in administering the THINC-it regarding its impact on the appropriateness and quality of care being received. The THINC-it is a valid and sensitive tool for detecting cognitive dysfunction in adults with MDD that is free, easy to use, and rapidly administered. The THINC-it should be incorporated into the assessment and measurement of all patients with MDD, particularly among those with enduring functional impairment. ClinicalTrials.gov identifier: NCT02508493. © Copyright 2017 Physicians Postgraduate Press, Inc.

Serum levels of nerve growth factor (NGF) in patients with major depression disorder and suicide risk.

PubMed

Wiener, Carolina David; de Mello Ferreira, Sharon; Pedrotti Moreira, Fernanda; Bittencourt, Guilherme; de Oliveira, Jacqueline Flores; Lopez Molina, Mariane; Jansen, Karen; de Mattos Souza, Luciano Dias; Rizzato Lara, Diogo; Portela, Luiz Valmor; da Silva, Ricardo Azevedo; Oses, Jean Pierre

2015-09-15

Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigating the genetic variation underlying episodicity in major depressive disorder: suggestive evidence for a bipolar contribution.

PubMed

Ferentinos, Panagiotis; Rivera, Margarita; Ising, Marcus; Spain, Sarah L; Cohen-Woods, Sarah; Butler, Amy W; Craddock, Nicholas; Owen, Michael J; Korszun, Ania; Jones, Lisa; Jones, Ian; Gill, Michael; Rice, John P; Maier, Wolfgang; Mors, Ole; Rietschel, Marcella; Lucae, Susanne; Binder, Elisabeth B; Preisig, Martin; Tozzi, Federica; Muglia, Pierandrea; Breen, Gerome; Craig, Ian W; Farmer, Anne E; Müller-Myhsok, Bertram; McGuffin, Peter; Lewis, Cathryn M

2014-02-01

Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. Episode count was self-reported and, therefore, subject to recall bias. Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts. © 2013 Published by Elsevier B.V.

Mismatch negativity of sad syllables is absent in patients with major depressive disorder.

PubMed

Pang, Xiaomei; Xu, Jing; Chang, Yi; Tang, Di; Zheng, Ya; Liu, Yanhua; Sun, Yiming

2014-01-01

Major depressive disorder (MDD) is an important and highly prevalent mental disorder characterized by anhedonia and a lack of interest in everyday activities. Additionally, patients with MDD appear to have deficits in various cognitive abilities. Although a number of studies investigating the central auditory processing of low-level sound features in patients with MDD have demonstrated that this population exhibits impairments in automatic processing, the influence of emotional voice processing has yet to be addressed. To explore the automatic processing of emotional prosodies in patients with MDD, we analyzed the ability to detect automatic changes using event-related potentials (ERPs). This study included 18 patients with MDD and 22 age- and sex-matched healthy controls. Subjects were instructed to watch a silent movie but to ignore the afferent acoustic emotional prosodies presented to both ears while continuous electroencephalographic activity was synchronously recorded. Prosodies included meaningless syllables, such as "dada" spoken with happy, angry, sad, or neutral tones. The mean amplitudes of the ERPs elicited by emotional stimuli and the peak latency of the emotional differential waveforms were analyzed. The sad MMN was absent in patients with MDD, whereas the happy and angry MMN components were similar across groups. The abnormal sad emotional MMN component was not significantly correlated with the HRSD-17 and HAMA scores, respectively. The data indicate that patients with MDD are impaired in their ability to automatically process sad prosody, whereas their ability to process happy and angry prosodies remains normal. The dysfunctional sad emotion-related MMN in patients with MDD were not correlated with depression symptoms. The blunted MMN of sad prosodies could be considered a trait of MDD.

An exploratory analysis of Go/Nogo event-related potentials in major depression and depression following traumatic brain injury.

PubMed

Bailey, Neil W; Hoy, Kate E; Maller, Jerome J; Segrave, Rebecca A; Thomson, Richard; Williams, Nicholas; Daskalakis, Zafiris J; Fitzgerald, Paul B

2014-12-30

Rates of major depressive disorder (MDD) following traumatic brain injury (TBI) are estimated to be between 20% and 45%, a higher prevalence than that seen in the general population. These increased rates may be due to specific changes in brain function following TBI. Event related potentials (ERPs) are well suited for measuring the electrophysiological differences between groups in areas of cognitive processing impaired in both MDD and TBI, such as response inhibition. The current study presented an emotional Go/Nogo task (with schematic emotional faces as stimuli) to participants with TBI, participants with MDD, and participants with both TBI and MDD (TBI-MDD). Topographical distribution of activity and global field power comparisons were made across stimulus-locked epochs between these groups and healthy controls. The results indicated that ERPs were not altered by TBI alone. Both MDD and TBI-MDD groups showed similar alterations in topographical distribution and global field power in the N2 window, as well as late epoch alterations. The MDD and TBI-MDD groups showed significantly less fronto-central negativity during the N2 window in Nogo trials compared with the control group. The MDD and TBI-MDD groups also showed significantly less global field power in Nogo trials than Go trials during the N2 window while the control group showed the opposite pattern. The MDD and TBI-MDD groups showed no mood-congruent bias in behavioural or ERP measures. The results suggest that TBI-MDD displays similar electrophysiological changes to those found in the MDD group without TBI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Multi-dose drug dispensing as a tool to improve medication adherence: A study in patients using vitamin K antagonists.

PubMed

van Rein, Nienke; de Geus, Kristel S; Cannegieter, Suzanne C; Reitsma, Pieter H; van der Meer, Felix J M; Lijfering, Willem M

2018-01-01

Multi-dose drug dispensing (MDD) is a dosing aid that provides patients with disposable bags containing all drugs intended for 1 dosing moment. MDD is believed to increase medication adherence, but studies are based on self-reported data, and results may depend on socially desirable answers. Therefore, our purpose was to determine the effect of MDD on medication adherence in non-adherent patients taking vitamin K antagonists (VKAs), and to compare with instructing patients on medication use. We conducted a before-after study in non-adherent patients where MDD was the exposure and change in adherence after MDD initiation was the outcome (within patient comparison). Time in therapeutic range (TTR) was selected as a measure for adherence, as this reflects stability of VKA treatment. To analyze whether MDD improved adherence as compared with standard care (ie, letters or calls from nurses of the anticoagulation clinic), non-adherent patients without MDD were also followed to estimate their TTR change over time (between patient comparison). Eighty-three non-adherent VKA patients started using MDD. The median TTR was 63% before MDD and 73% 6 months after MDD. The within patient TTR increased on average by 13% (95%CI 6% to 21%) within 1 month after starting MDD and remained stable during the next 5 months. The TTR of MDD-patients increased 10% (95%CI 2% to 19%) higher as compared with non-MDD patients within 1 month but was similar after 4 months (TTR difference 3%, 95%CI -2% to 9%). Adherence improved after initiation of MDD. Compared with instructing patients, MDD was associated with better adherence within 1 month but was associated with similar improvement after 4 months. Copyright © 2017 John Wiley & Sons, Ltd.

EFFICACY AND LONG-TERM CLINICAL OUTCOME OF COMORBID POSTTRAUMATIC STRESS DISORDER AND MAJOR DEPRESSIVE DISORDER AFTER ELECTROCONVULSIVE THERAPY.

PubMed

Ahmadi, Naser; Moss, Lori; Simon, Edwin; Nemeroff, Charles B; Atre-Vaidya, Nutan

2016-07-01

Many patients fulfill criteria for both posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Electroconvulsive therapy (ECT) is generally acknowledged to be the most-effective treatment for refractory MDD. This study investigated the efficacy of ECT on long-term clinical outcome of comorbid PTSD and MDD. This retrospective nested matched case-control study is inclusive of 22,164 subjects [3,485 with comorbid MDD and PTSD (92 with ECT and 3,393 without ECT) and 18,679 without MDD and PTSD]. Using the clinical global impression scale (CGI) to assess efficacy, more-robust improvement of PTSD and MDD symptoms was observed with ECT (90%), compared to antidepressant-treatment alone(50%) (P = 0.001). During the median of 8 years of follow-up, the death-rate was 8% in subjects without PTSD and MDD, 9.7% in PTSD and MDD treated with ECT and 18% in PTSD and MDD without ECT (P < 0.05). The suicide-rate was 2.2 and 5.9% in PTSD and MDD with and without ECT-treatment, respectively (P < 0.05). Survival-analyses revealed that the relative-risk of cardiovascular and all-cause mortality is not significantly different in patients with comorbid MDD and PTSD treated with ECT, compared to a matched-cohort without PTSD and MDD (P > 0.05). The relative risk of suicidality, all-cause, and cardiovascular mortality was reduced 64, 65, and 46% in MDD and PTSD patients treated with ECT, compared to those without ECT (P < 0.05). ECT is associated with a significant reduction of symptoms of PTSD and MDD, as well as reduction in risk of suicidality, cardiovascular, and all-cause mortality in MDD and PTSD, an effect more robust than antidepressant-therapy alone. © 2015 Wiley Periodicals, Inc.

Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder.

PubMed

Inkster, Becky; Nichols, Thomas E; Saemann, Philipp G; Auer, Dorothee P; Holsboer, Florian; Muglia, Pierandrea; Matthews, Paul M

2009-07-01

Indirect evidence suggests that the glycogen synthase kinase-3beta (GSK3beta) gene might be implicated in major depressive disorder (MDD). We evaluated 15 GSK3beta single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD x genotype interactions by including a matched control group without any psychiatric disorder, including MDD. General linear model with nonstationary cluster-based inference. Munich, Germany. Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). Associations between GSK3beta polymorphisms and regional GM volume differences. Variation in GM volume was associated with GSK3beta polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP x MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). The GSK3beta gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3beta genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3beta polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.

Epidemiology of major depression in four cities in Mexico.

PubMed

Slone, Laurie B; Norris, Fran H; Murphy, Arthur D; Baker, Charlene K; Perilla, Julia L; Diaz, Dayna; Rodriguez, Francisco Gutiérrez; Gutiérrez Rodriguez, José de Jesús

2006-01-01

Analyses were conducted to estimate lifetime and current prevalence of major depressive disorder (MDD) for four representative cities of Mexico, to identify variables that influence the probability of MDD, and to further describe depression in Mexican culture. A multistage probability sampling design was used to draw a sample of 2,509 adults in four different regions of Mexico. MDD was assessed according to DSM-IV criteria by using the Composite International Diagnostic Interview collected by trained lay interviewers. The prevalence of MDD in these four cities averaged 12.8% for lifetime and 6.1% for the previous 12 months. MDD was highly comorbid with other mental disorders. Women were more likely to have lifetime MDD than were men. Being divorced, separated, or widowed (compared to married or never married) and having experienced childhood trauma were related to higher lifetime prevalence but not to current prevalence. In addition, age and education level were related to current 12-month MDD. Data on the profile of MDD in urban Mexico are provided. This research expands our understanding of MDD across cultures.

13C-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder

PubMed Central

Teraishi, Toshiya; Hori, Hiroaki; Sasayama, Daimei; Matsuo, Junko; Ogawa, Shintaro; Ota, Miho; Hattori, Kotaro; Kajiwara, Masahiro; Higuchi, Teruhiko; Kunugi, Hiroshi

2015-01-01

Altered tryptophan–kynurenine (KYN) metabolism has been implicated in major depressive disorder (MDD). The l-[1-13C]tryptophan breath test (13C-TBT) is a noninvasive, stable-isotope tracer method in which exhaled 13CO2 is attributable to tryptophan catabolism via the KYN pathway. We included 18 patients with MDD (DSM-IV) and 24 age- and sex-matched controls. 13C-tryptophan (150 mg) was orally administered and the 13CO2/12CO2 ratio in the breath was monitored for 180 min. The cumulative recovery rate during the 180-min test (CRR0–180; %), area under the Δ13CO2-time curve (AUC; %*min), and the maximal Δ13CO2 (Cmax; %) were significantly higher in patients with MDD than in the controls (p = 0.004, p = 0.008, and p = 0.002, respectively). Plasma tryptophan concentrations correlated negatively with Cmax in both the patients and controls (p = 0.020 and p = 0.034, respectively). Our results suggest that the 13C-TBT could be a novel biomarker for detecting a subgroup of MDD with increased tryptophan–KYN metabolism. PMID:26524975

Temperamental commonalities and differences in euthymic mood disorder patients, creative controls, and healthy controls.

PubMed

Nowakowska, Cecylia; Strong, Connie M; Santosa, Claudia M; Wang, Po W; Ketter, Terence A

2005-03-01

Understanding of mood disorders can be enhanced through assessment of temperamental traits. We explored temperamental commonalities and differences among euthymic bipolar (BP) and unipolar (MDD) mood disorder patients, creative discipline graduate student controls (CC), and healthy controls (HC). Forty-nine BP, 25 MDD, 32 CC, and 47 HC completed self-report temperament/personality measures including: The Affective Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A); the Revised NEO Personality Inventory (NEO-PI-R); and the Temperament and Character Inventory (TCI). Euthymic BP, MDD, and CC, compared to HC, had significantly increased cyclothymia, dysthymia and irritability scores on TEMPS-A; increased neuroticism and decreased conscientiousness on NEO-PI-R; and increased harm avoidance and novelty seeking as well as decreased self-directedness on TCI. TEMPS-A cyclothymia scores were significantly higher in BP than in MDD. NEO-PI-R openness was increased in BP and CC, compared to HC, and in CC compared to MDD. TCI self-transcendence scores in BP were significantly higher than in MDD, CC, and HC. Most of the subjects were not professional artists, and represented many fields; temperament might be different in different art fields. Euthymic BP, MDD, and CC compared to HC, had prominent temperamental commonalities. However, BP and CC had the additional commonality of increased openness compared to HC. BP had particularly high Cyclothymia scores that were significantly higher then those of MDD. The prominent BP-CC overlap suggests underlying neurobiological commonalities between people with mood disorders and individuals involved in creative disciplines, consistent with the notion of a temperamental contribution to enhanced creativity in individuals with bipolar disorders.

Amygdala and whole-brain activity to emotional faces distinguishes major depressive disorder and bipolar disorder.

PubMed

Fournier, Jay C; Keener, Matthew T; Almeida, Jorge; Kronhaus, Dina M; Phillips, Mary L

2013-11-01

It can be clinically difficult to distinguish depressed individuals with bipolar disorder (BD) and major depressive disorder (MDD). To examine potential biomarkers of difference between the two disorders, the current study examined differences in the functioning of emotion-processing neural regions during a dynamic emotional faces task. During functional magnetic resonance imaging, healthy control adults (HC) (n = 29) and depressed adults with MDD (n = 30) and BD (n = 22) performed an implicit emotional-faces task in which they identified a color label superimposed on neutral faces that dynamically morphed into one of four emotional faces (angry, fearful, sad, happy). We compared neural activation between the groups in an amygdala region-of-interest and at the whole-brain level. Adults with MDD showed significantly greater activity than adults with BD in the left amygdala to the anger condition (p = 0.01). Results of whole-brain analyses (at p < 0.005, k ≥ 20) revealed that adults with BD showed greater activity to sad faces in temporoparietal regions, primarily in the left hemisphere, whereas individuals with MDD demonstrated greater activity than those with BD to displays of anger, fear, and happiness. Many of the observed BD-MDD differences represented abnormalities in functioning compared to HC. We observed a dissociation between depressed adults with BD and MDD in the processing of emerging emotional faces. Those with BD showed greater activity during mood-congruent (i.e., sad) faces, whereas those with MDD showed greater activity for mood-incongruent (i.e., fear, anger, and happy) faces. Such findings may reflect markers of differences between BD and MDD depression in underlying pathophysiological processes. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Population-based Longitudinal Study on Work Environmental Factors and the Risk of Major Depressive Disorder

PubMed Central

Wang, JianLi; Patten, Scott B.; Currie, Shawn; Sareen, Jitender; Schmitz, Norbert

2012-01-01

To investigate the relation between work environmental factors and the risk of major depressive disorder (MDD) over 1 year, the authors conducted a population-based longitudinal study of randomly selected employees in Alberta, Canada (January 2008 to November 2011). Participants without a current or lifetime diagnosis of MDD at baseline (n = 2,752) were followed for 1 year. MDD was assessed using the World Health Organization’s Composite International Diagnostic Interview-Auto 2.1. The overall 1-year incidence of MDD was 3.6% (95% confidence interval: 2.8, 4.6); it was 2.9% (95% confidence interval: 1.9, 4.2) in men and 4.5% (95% confidence interval: 3.3, 6.2) in women. The relations between work environmental factors and MDD differed by sex. In men, high job strain increased the risk of MDD in those who worked 35–40 hours per week; job insecurity and family-to-work conflict were predictive of MDD. Women who worked 35–40 hours per week and reported job insecurity, a high effort-reward imbalance, and work-to-family conflict were at a higher risk of developing MDD. Job strain, effort-reward imbalance, job insecurity, and work-to-family conflicts are important risk factors for the onset of MDD and should be targets of primary prevention. However, these work environmental factors appear to operate differently in men and in women. PMID:22556191

Bipolar I disorder and major depressive disorder show similar brain activation during depression.

PubMed

Cerullo, Michael A; Eliassen, James C; Smith, Christopher T; Fleck, David E; Nelson, Erik B; Strawn, Jeffrey R; Lamy, Martine; DelBello, Melissa P; Adler, Caleb M; Strakowski, Stephen M

2014-11-01

Despite different treatments and courses of illness, depressive symptoms appear similar in major depressive disorder (MDD) and bipolar I disorder (BP-I). This similarity of depressive symptoms suggests significant overlap in brain pathways underlying neurovegetative, mood, and cognitive symptoms of depression. These shared brain regions might be expected to exhibit similar activation in individuals with MDD and BP-I during functional magnetic resonance imaging (fMRI). fMRI was used to compare regional brain activation in participants with BP-I (n = 25) and MDD (n = 25) during a depressive episode as well as 25 healthy comparison (HC) participants. During the scans, participants performed an attentional task that incorporated emotional pictures. During the viewing of emotional images, subjects with BP-I showed decreased activation in the middle occipital gyrus, lingual gyrus, and middle temporal gyrus compared to both subjects with MDD and HC participants. During attentional processing, participants with MDD had increased activation in the parahippocampus, parietal lobe, and postcentral gyrus. However, among these regions, only the postcentral gyrus also showed differences between MDD and HC participants. No differences in cortico-limbic regions were found between participants with BP-I and MDD during depression. Instead, the major differences occurred in primary and secondary visual processing regions, with decreased activation in these regions in BP-I compared to major depression. These differences were driven by abnormal decreases in activation seen in the participants with BP-I. Posterior activation changes are a common finding in studies across mood states in participants with BP-I. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genome-wide association analysis of gender differences in major depressive disorder in the Netherlands NESDA and NTR population-based samples.

PubMed

Aragam, Nagesh; Wang, Ke-Sheng; Pan, Yue

2011-10-01

Major depressive disorder (MDD) is a universally prevalent, genetic, and environment dependent mental condition that disables people of every culture, race, gender, and age. While the gender differences for MDD have been widely reported in literature, few genome-wide analyses of gender differences have been reported to date. We conducted a genome-wide association analysis of gender differences for MDD using the Netherlands NESDA and NTR population-based samples (1726 cases and 1630 controls). PLINK software was used to analyze the genome-wide association data of Perlegen 600 K SNP Chips. We identified 40 male-specific and 56 female-specific MDD associated SNPs with P-values less than 10(-4). The best male-specific SNP was rs9352774 (P=2.26 × 10(-6)) within LGSN gene while the best female-specific SNP was rs2715148 (P=5.64 × 10(-7)) within PCLO gene. We also found 38 SNPs showing gene × gender interactions in influencing MDD (P<10(-4)). The best SNP was rs12692709 (P=5.75 × 10(-6)) near FIGN gene at 2q24.3 while the next best SNP was rs11039588 (P=1.16 × 10(-5)) within OR4B1 gene. The findings from this study need be replicated in other populations. These results provide genetic basis for gender differences in MDD and will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in MDD. Copyright © 2011 Elsevier B.V. All rights reserved.

Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

PubMed Central

Darcet, Flavie; Gardier, Alain M.; Gaillard, Raphael; David, Denis J.; Guilloux, Jean-Philippe

2016-01-01

Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID:26901205

The PHF21B gene is associated with major depression and modulates the stress response.

PubMed

Wong, M-L; Arcos-Burgos, M; Liu, S; Vélez, J I; Yu, C; Baune, B T; Jawahar, M C; Arolt, V; Dannlowski, U; Chuah, A; Huttley, G A; Fogarty, R; Lewis, M D; Bornstein, S R; Licinio, J

2017-07-01

Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, <0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD.

Adolescent Major Depressive Disorder: Neuroimaging Evidence of Sex Difference during an Affective Go/No-Go Task.

PubMed

Chuang, Jie-Yu; Hagan, Cindy C; Murray, Graham K; Graham, Julia M E; Ooi, Cinly; Tait, Roger; Holt, Rosemary J; Elliott, Rebecca; van Nieuwenhuizen, Adrienne O; Bullmore, Edward T; Lennox, Belinda R; Sahakian, Barbara J; Goodyer, Ian M; Suckling, John

2017-01-01

Compared to female major depressive disorder (MDD), male MDD often receives less attention. However, research is warranted since there are significant sex differences in the clinical presentation of MDD and a higher rate of suicide in depressed men. To the best of our knowledge, this is the first functional magnetic resonance imaging (fMRI) study with a large sample addressing putative sex differences in MDD during adolescence, a period when one of the most robust findings in psychiatric epidemiology emerges; that females are twice as likely to suffer from MDD than males. Twenty-four depressed and 10 healthy male adolescents, together with 82 depressed and 24 healthy female adolescents, aged 11-18 years, undertook an affective go/no-go task during fMRI acquisition. In response to sad relative to neutral distractors, significant sex differences (in the supramarginal gyrus) and group-by-sex interactions (in the supramarginal gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to the healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with a significant group-by-age interaction in connectivity. Future research may consider altered developmental trajectories and the possible implications of sex-specific treatment and prevention strategies for MDD.

Quantifying the impact of chronic conditions on a diagnosis of major depressive disorder in adults: a cohort study using linked electronic medical records.

PubMed

Ryu, Euijung; Chamberlain, Alanna M; Pendegraft, Richard S; Petterson, Tanya M; Bobo, William V; Pathak, Jyotishman

2016-04-26

Major depressive disorder (MDD) is often comorbid with other chronic mental and physical health conditions. Although the literature widely acknowledges the association of many chronic conditions with the risk of MDD, the relative importance of these conditions on MDD risk in the presence of other conditions is not well investigated. In this study, we aimed to quantify the relative contribution of selected chronic conditions to identify the conditions most influential to MDD risk in adults and identify differences by age. This study used electronic health record (EHR) data on patients empanelled with primary care at Mayo Clinic in June 2013. A validated EHR-based algorithm was applied to identify newly diagnosed MDD patients between 2000 and 2013. Non-MDD controls were matched 1:1 to MDD cases on birth year (±2 years), sex, and outpatient clinic visits in the same year of MDD case diagnosis. Twenty-four chronic conditions defined by Chronic Conditions Data Warehouse were ascertained in both cases and controls using diagnosis codes within 5 years of index dates (diagnosis dates for cases, and the first clinic visit dates for matched controls). For each age group (45 years or younger, between 46 and 60, and over 60 years), conditional logistic regression models were used to test the association between each condition and subsequent MDD risk, adjusting for educational attainment and obesity. The relative influence of these conditions on the risk of MDD was quantified using gradient boosting machine models. A total of 11,375 incident MDD cases were identified between 2000 and 2013. Most chronic conditions (except for eye conditions) were associated with risk of MDD, with different association patterns observed depending on age. Among 24 chronic conditions, the greatest relative contribution was observed for diabetes mellitus for subjects aged ≤ 60 years and rheumatoid arthritis/osteoarthritis for those over 60 years. Our results suggest that specific chronic conditions such as diabetes mellitus and rheumatoid arthritis/osteoarthritis may have greater influence than others on the risk of MDD.

Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression

PubMed Central

Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

2015-01-01

Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic–pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18–65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are involved in MDD’s etiology. These same mechanisms, however, are less important in clinical progression from first to later MDD episodes and toward chronicity. PMID:26418277

Ethnic Differences in Separate and Additive Effects of Anxiety and Depression on Self-rated Mental Health Among Blacks.

PubMed

Assari, Shervin; Dejman, Masoumeh; Neighbors, Harold W

2016-09-01

The aim of this study was to explore ethnic differences in the separate and additive effects of anxiety and depression on self-rated mental health (SRMH) of Blacks in the USA. With a cross-sectional design, we used data from a national household probability sample of African Americans (n = 3570) and Caribbean Blacks (n = 1621) who participated in the National Survey of American Life, 2001-2003. Demographic factors, socio-economic factors, 12-month general anxiety disorder (GAD) and major depressive disorder (MDD), and current SRMH were measured. In each ethnic group, three logistic regressions were used to assess the effects of GAD, MDD, and their combinations on SRMH. Among African Americans, GAD and MDD had separate effects on SRMH. Among Caribbean Blacks, only MDD but not GAD had separate effect on SRMH. Among African Americans, when the combined effects of GAD and MDD were tested, GAD but not MDD was associated with SRMH. The separate and additive effects of GAD and MDD on SRMH among Blacks depend on ethnicity. Although single-item SRMH measures are easy methods for the screening of mental health need, community-based programs that aim to meet the need for mental health services among Blacks in the USA should consider within-race ethnic differences in the applicability of such instruments.

Gender-specific disruptions in emotion processing in younger adults with depression.

PubMed

Wright, Sara L; Langenecker, Scott A; Deldin, Patricia J; Rapport, Lisa J; Nielson, Kristy A; Kade, Allison M; Own, Lawrence S; Akil, Huda; Young, Elizabeth A; Zubieta, Jon-Kar

2009-01-01

One of the principal theories regarding the biological basis of major depressive disorder (MDD) implicates a dysregulation of emotion-processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. This study sought to explore how gender and depression status relate to emotion processing. This study employed a 2 (MDD status) x 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N=151). For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did nondepressed women and men with MDD, particularly for fearful and sad stimuli (Ps <.02), which they were likely to misinterpret as angry (Ps <.04). There was also an interaction of diagnosis and gender for response cost for negative stimuli, with significantly greater interference from negative faces present in women with MDD compared to nondepressed women (P=.01). Men with MDD, conversely, performed similarly to control men (P=.61). These results provide novel and intriguing evidence that depression in younger adults (<35 years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men. (c) 2009 Wiley-Liss, Inc.

Impulsivity in adolescents with major depressive disorder: A comparative tunisian study.

PubMed

Khemakhem, Khaoula; Boudabous, Jaweher; Cherif, Leila; Ayadi, Hela; Walha, Adel; Moalla, Yousr; Hadjkacem, Imen; Ghribi, Farhat

2017-08-01

The association between impulsivity and depressive disorders in adolescence has been little studied at the literature and in our country, yet impulsivity is a major risk factor for suicide. Thus we aimed on this study to evaluate impulsivity in 25 adolescents with Major Depressive Disorder MDD compared to a control sample and to analyze the correlations between impulsivity and clinical features of MDD. Employing a matched case-control design, participants included 25 adolescents with MDD and 75 controls. We have administered the Barratt Impulsivity Scale BIS-11 for the two groups to evaluate impulsivity. Semi structured interviews according DSM 5 criteria were conducted for adolescents with MDD. The Child Depressive Inventory CDI was used to measure depressive symptoms in the control sample. Adolescents with MDD were more impulsive compared to controls according to the BIS-11 in its three domains: motor (24.96±6.26 against 20.6±4.84; p=0.000), attentional (20.88±5.03 against 16.64±3.2; p=0.000) and non planning (28.2±7.26 against 24.44±4.32; p=0.02). Impulsivity was not correlated with clinical features of MDD (suicide attempts, psychiatric comorbidities, antidepressant medication …). Adolescents with MDD seem to be more impulsive than control subjects regardless their clinical features. Whether it is a specific characteristic or a symptom among others of MDD, impulsivity predicts health-related behaviors and associated damage that need to be detected and prevented in time. Copyright © 2017 Elsevier B.V. All rights reserved.

Alterations of microRNA-124 expression in peripheral blood mononuclear cells in pre- and post-treatment patients with major depressive disorder.

PubMed

He, Shen; Liu, Xiaohua; Jiang, Kaida; Peng, Daihui; Hong, Wu; Fang, Yiru; Qian, Yiping; Yu, Shunying; Li, Huafang

2016-07-01

Recently, increasing evidence has indicated that dysfunction of microRNA-124 (miR-124) might be involved in the pathophysiology and treatment of major depressive disorder (MDD) in some animal models of depression. However, the role of miR-124 in MDD patients remains unclear. The objective of this study was to investigate whether the miR-124 expression levels in peripheral blood mononuclear cells (PBMCs) were associated with MDD and to evaluate the effects of antidepressant treatment on miR-124 levels. Quantitative real-time PCR was applied to detect miR-124 expression in 32 pre- and post-treatment MDD patients and 30 healthy controls. Our results showed that expression levels of miR-124 from PBMCs in MDD patients were significantly higher than those in healthy controls (p < 0.001), and that the area under the curve of miR-124 from ROC analysis was 0.762 with a sensitivity of 83.33% and specificity of 66.67% in distinguishing MDD patients from healthy controls. In addition, the expression levels of miR-124 were significantly down-regulated after eight weeks of treatment (p < 0.001). MiRNA target gene prediction and functional annotation analysis indicated that altered miR-124 was involved in affecting some important biological processes and pathways related to MDD. These results provide new information on miR-124 involvement in the biological alterations of MDD and in antidepressant effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

PubMed

Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

2017-02-15

Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10 -11 ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in major depressive disorder patients.

PubMed

Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Kawano, Aimi; Ando, Tomoko; Okamoto, Shizuko; Kanehisa, Masayuki; Higuma, Haruka; Ninomiya, Taiga; Tsuru, Jusen; Hanada, Hiroaki; Kodama, Kensuke; Isogawa, Koichi; Akiyoshi, Jotaro

2012-03-30

Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress. In comparison, psychosocial stress-induced activation of salivary α-amylase (sAA) functions as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in MDD patients. The present study measured sAA and salivary cortisol levels in patients with MDD. The authors determined Profile of Mood State (POMS) and State-Trait anxiety Inventory (STAI) scores, Heart Rate Variability (HRV), and sAA and salivary cortisol levels in 88 patients with MDD and 41 healthy volunteers following the application of electrical stimulation stress. Patients with major depressive disorder were 8 points or more on Hamilton Depression Scale (HAM-D) scores. Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores in patients with major depressive disorder were significantly increased compared to healthy controls. In contrast, Vigor scores in patients with MDD were significantly decreased compared with healthy controls. There was no difference in heart rate variability measures between MDD patients and healthy controls. The threshold of electrical stimulation applied in MDD patients was lower than that in healthy controls. SAA levels in female MDD patients were significantly elevated relative to controls both before and after electrical stimulation. Finally, there were no differences in salivary cortisol levels between major depressive patients and controls. In the present study only three time points were explored. Furthermore, the increased secretion of sAA before and after stimulation could allude to an increased responsiveness of novel and uncontrollable situations in patients with MDD. These preliminary results suggest that sAA might be a useful biological marker of MDD. Copyright © 2011 Elsevier Inc. All rights reserved.

Comorbidity and its relevance on general hospital based mortality in major depressive disorder: a naturalistic 12-year follow-up in general hospital admissions.

PubMed

Schoepf, Dieter; Uppal, Hardeep; Potluri, Rahul; Chandran, Suresh; Heun, Reinhard

2014-05-01

Major depressive disorder (MDD) is associated with physical comorbidity, but the risk factors of general hospital-based mortality are unclear. Consequently, we investigated whether the burden of comorbidity and its relevance on in-hospital death differs between patients with and without MDD in a 12-year follow-up in general hospital admissions. During 1 January 2000 and 30 June 2012, 9604 MDD patients were admitted to three General Manchester Hospitals. All comorbidities with a prevalence ≥1% were compared with those of 96,040 age-gender matched hospital controls. Risk factors of in-hospital death were identified using multivariate logistic regression analyses. Crude hospital-based mortality rates within the period under observation were 997/9604 (10.4%) in MDD patients and 8495/96,040 (8.8%) in controls. MDD patients compared to controls had a substantial higher burden of comorbidity. The highest comorbidities included hypertension, asthma, and anxiety disorders. Subsequently, twenty-six other diseases were disproportionally increased, many of them linked to chronic lung diseases and to diabetes. In deceased MDD patients, chronic obstructive pulmonary disease and type-2 diabetes mellitus were the most common comorbidities, contributing to 18.6% and 17.1% of deaths. Furthermore, fifteen physical diseases contributed to in-hospital death in the MDD population. However, there were no significant differences in their impact on mortality compared to controls in multivariate logistic regression analyses. Thus in one of the largest samples of MDD patients in general hospitals, MDD patients have a substantial higher burden of comorbidity compared to controls, but they succumb to the same physical diseases as their age-gender matched peers without MDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

PSYCHIATRIC COMORBIDITY DOES NOT ONLY DEPEND ON DIAGNOSTIC THRESHOLDS: AN ILLUSTRATION WITH MAJOR DEPRESSIVE DISORDER AND GENERALIZED ANXIETY DISORDER.

PubMed

van Loo, Hanna M; Schoevers, Robert A; Kendler, Kenneth S; de Jonge, Peter; Romeijn, Jan-Willem

2016-02-01

High rates of psychiatric comorbidity are subject of debate: To what extent do they depend on classification choices such as diagnostic thresholds? This paper investigates the influence of different thresholds on rates of comorbidity between major depressive disorder (MDD) and generalized anxiety disorder (GAD). Point prevalence of comorbidity between MDD and GAD was measured in 74,092 subjects from the general population (LifeLines) according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria. Comorbidity rates were compared for different thresholds by varying the number of necessary criteria from ≥ 1 to all nine symptoms for MDD, and from ≥ 1 to all seven symptoms for GAD. According to DSM thresholds, 0.86% had MDD only, 2.96% GAD only, and 1.14% both MDD and GAD (odds ratio (OR) 42.6). Lower thresholds for MDD led to higher rates of comorbidity (1.44% for ≥ 4 of nine MDD symptoms, OR 34.4), whereas lower thresholds for GAD hardly influenced comorbidity (1.16% for ≥ 3 of seven GAD symptoms, OR 38.8). Specific patterns in the distribution of symptoms within the population explained this finding: 37.3% of subjects with core criteria of MDD and GAD reported subthreshold MDD symptoms, whereas only 7.6% reported subthreshold GAD symptoms. Lower thresholds for MDD increased comorbidity with GAD, but not vice versa, owing to specific symptom patterns in the population. Generally, comorbidity rates result from both empirical symptom distributions and classification choices and cannot be reduced to either of these exclusively. This insight invites further research into the formation of disease concepts that allow for reliable predictions and targeted therapeutic interventions. © 2015 Wiley Periodicals, Inc.

Characterizing Emotional Dysfunction in Borderline Personality, Major Depression, and their Co-occurrence

PubMed Central

Dixon-Gordon, Katherine L.; Weiss, Nicole H.; Tull, Matthew T.; DiLillo, David; Messman-Moore, Terri; Gratz, Kim L.

2015-01-01

This research aimed to characterize patterns of emotional reactivity and dysregulation in borderline personality, depression, and their co-occurrence. In Study 1, 488 young adult women from the community were categorized into four groups based on self-reported major depressive disorder (MDD) and borderline personality disorder (BPD) symptoms (Low BPD/Low MDD; Low BPD/High MDD; High BPD/Low MDD; High BPD/High MDD). Immediate and prolonged subjective emotional reactivity to a laboratory stressor were assessed, and participants completed self-report and behavioral measures of emotion dysregulation. Study 2 extended these findings, examining emotional reactivity and dysregulation in a clinical population of 176 substance dependent patients with diagnoses of BPD and MDD and including a biological index of emotional reactivity. Results revealed greater prolonged fear reactivity in the High BPD/High MDD (vs. Low BPD/Low MDD) group in Study 1, and greater prolonged anxiety and negative affect reactivity in both High BPD groups (vs. Low BPD/Low MDD and Low BPD/High MDD groups) in Study 2 (but no differences in cortisol reactivity). Results also demonstrated greater subjective (but not behavioral) emotion dysregulation in the High BPD/High MDD (vs. Low BPD/Low MDD) group in Study 1 and both High BPD groups (vs. both Low BPD groups) in Study 2. Finally, the High BPD/High MDD group reported greater difficulties controlling impulsive behaviors compared with all other groups in Study 1 and the Low BPD groups in Study 2. Findings suggest that BPD pathology (but not MDD pathology alone) is characterized by greater prolonged emotional (especially anxiety/fear-related) reactivity and heightened emotion dysregulation. PMID:26343484

Complement factor H and susceptibility to major depressive disorder in Han Chinese.

PubMed

Zhang, Chen; Zhang, Deng-Feng; Wu, Zhi-Guo; Peng, Dai-Hui; Chen, Jun; Ni, Jianliang; Tang, Wenxin; Xu, Lin; Yao, Yong-Gang; Fang, Yi-Ru

2016-05-01

Accumulating evidence suggests that altered immunity contributes to the development of major depressive disorder (MDD). To examine whether complement factor H (CFH), a regulator of activation of the alternative pathway of the complement cascade, confers susceptibility to MDD. Expression analyses were tested in 53 unmedicated people with MDD and 55 healthy controls. A two-stage genetic association analysis was performed in 3323 Han Chinese with or without MDD. Potential associations between CFH single nucleotide polymorphisms and age at MDD onset were evaluated. CFH levels were significantly lower in the MDD group at both protein and mRNA levels (P = 0.009 and P = 0.014 respectively). A regulatory variant in the CFH gene, rs1061170, showed statistically significant genotypic and allelic differences between the MDD and control groups (genotypic P = 0.0005, allelic P = 0.0001). Kaplan-Meier survival analysis showed that age at onset of MDD was significantly associated with the C allele of rs1061170 (log rank statistic χ(2) = 6.82, P = 0.009). The C-allele carriers had a younger age at onset of MDD (22.2 years, s.d. = 4.0) than those without the C allele (23.6 years, s.d. = 4.3). CFH is likely to play an important role in the development of MDD. rs1061170 has an important effect on age at onset of MDD in Han Chinese and may therefore be related to early pathogenesis of MDD, although further study is needed. © The Royal College of Psychiatrists 2016.

How many different symptom combinations fulfil the diagnostic criteria for major depressive disorder? Results from the CRESCEND study.

PubMed

Park, Seon-Cheol; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

2017-04-01

The polythetic nature of major depressive disorder (MDD) in DSM- IV and DSM-5 inevitably leads to diagnostic heterogeneity. This study aimed to identify the number of depressive symptom combinations actually fulfilling the DSM-IV diagnostic criteria that can be found in Korean MDD patients and the relative frequencies of each combination. Using the data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, we enrolled 853 MDD patients diagnosed using DSM-IV and scored as 8 or more on the Hamilton Depression Rating Scale (HAMD). Descriptive statistical analyses were performed to reveal the degree of diagnostic heterogeneity of the MDD. This study identified 119 different depressive symptom combinations. The most common combination consisted of all nine depressive symptom profiles, and nine different combinations were each present in more than 3% of the patients. The findings support the criticism that the diagnosis of MDD is not based on a single mental process, but on a set of 'family resemblances'.

Clinical features of emergency department patients with depression who had attempted to commit suicide by poisoning.

PubMed

Wee, J H; Park, J H; Choi, S P; Woo, S H; Lee, W J; So, B H; Park, K N

2016-01-01

Many patients present to the emergency department (ED) complaining of intentional poisoning. Of those, some have major depressive disorder (MDD) in their medical history. The aim of this study was to investigate the prevalence of MDD patients who were treated for poisoning in the ED. A retrospective review was performed on 268 patients who were treated with poisoning between July 2007 and November 2011. Of these patients, we only included those who were over 18 years of age. Information regarding age, gender, cause, time of ingestion, type of drug, history of attempting suicide, and outcome, among other characteristics, was collected and compared to patients who did not have MDD. A total of 244 patients were included in this study. Of those, 52 patients (21.3%) had a history of MDD. Compared to non-MDD patients, a majority (34.6% vs. 19.8%) of those in the MDD group had a history of suicide attempts (P = 0.027), and 34 (65.4% in the MDD group vs. 34.4% in the non-MDD group) took more than two types of drugs (P < 0.001). There were no differences in age, sex, time of ingestion or disease severity between MDD and non-MDD patients. In poisoning patients with MDD, physicians in the ED must consider that they have a higher tendency to show suicidal behavior and to have ingested multiple types of drugs.

Recollection deficiencies in patients with major depressive disorder.

PubMed

Drakeford, Justine L; Edelstyn, Nicola M J; Oyebode, Femi; Srivastava, Shrikant; Calthorpe, William R; Mukherjee, Tirthankar

2010-02-28

Neuropsychological research suggests that recognition memory (RM) and recall memory are impaired in patients with a major depressive disorder or a dysphoric mood state. This study examines the proposal that abnormalities in recollection (a form of recall) result from a breakdown in frontal strategic memory processes involved in encoding and retrieval, and executive functions linked to reality monitoring, planning, problem-solving, reasoning and decision-making. We investigated two predictions arising from this theory. Firstly, patients diagnosed with a major depressive disorder (MDD) will display a dissociation between (deficient) recollection and (preserved) familiarity. Secondly, if recollection impairments are indicative of a breakdown in prefrontal strategic memory processes which are dependent, at least in part, on executive processes, then an explicit correlational approach predicts that recollection will be positively associated with the severity of executive dysfunction in MDD patients. The remember/know paradigm was used to investigate RM for words and neutral faces in 16 MDD patients and 16 healthy volunteers, matched for age, gender and estimates of premorbid IQ. Measures of executive function included working memory, reasoning and decision-making. Applying the Dual Process Signal Detection interpretation of the remember/know data, the MDD group displayed significant impairments in RM and recollection rates for both verbal and neutral facial memoranda. In contrast, familiarity-aware rates were preserved. There was no evidence of executive dysfunction in the patient group, and little evidence that recollection rates correlated with executive function. Furthermore, a single process signal detection approach suggested that the MDD patients displayed a reduction in sensitivity for RM and remember rates but not know responses. The criteria for detecting studied from unstudied items, and remembering from knowing, were the same in both patient and healthy control groups. Taken together, these findings are consistent with the view that MDD is marked by a decline in RM, which is underpinned by an impairment in recollection rather than familiarity processes. The extent to which the recollection deficiencies arise from disruption of strategic memory and executive processes requires further investigation. 2008 Elsevier Ireland Ltd. All rights reserved.

What is the best screening test for depression in chronic spinal pain patients?

PubMed

Choi, YunHee; Mayer, Tom G; Williams, Mark J; Gatchel, Robert J

2014-07-01

High prevalence rates of depression have been found in patients with chronic spinal disorder (CSD). The biopsychosocial model has become widely adopted and, with it, the role of psychopathology in the development and/or exacerbation of CSD has become increasingly recognized. Standardized diagnostic criteria, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), have been used to diagnose major depressive disorder (MDD). Many measures of MDD (and depressive symptom inventories) have been developed during the past 50 years, but their comparative utility in CSD populations is still unclear. To systemically compare the performance of depression screening questionnaires in detecting MDD among a large sample of patients with CSD. Prospective cohort study comparing the screening ability of four popular depression measures for diagnosing MDD against the "gold standard" Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), using a receiver operating characteristic (ROC) analysis in a CSD population. A consecutive cohort of 546 patients with CSD admitted to an interdisciplinary functional restoration program. Sensitivity, specificity, ROC curves, area under the curve (AUC), and optimal cutoff points that are most closely related to the prevalence rates of MDD, with balanced sensitivity and specificity analysis. Using the SCID-I diagnosis as a "gold standard," the ability of four screening measures in detecting MDD were compared. These included: the Beck Depression Inventory (BDI); Hamilton Rating Scale for Depression (HRSD); 9-Item Patient Health Questionnaire Depression Module (PHQ-9); and the Short Form-36 (SF-36). Of 542 CSD patients, 331 (61.1%) were diagnosed with MDD by the SCID-I. Results of the ROC analysis revealed that the BDI (AUC 0.768), HRSD (AUC 0.796), and PHQ-9 (AUC 0.768) have similar abilities to discriminate between depressed and nondepressed patients in this population. These depression measures outperformed the two mental health scales derived from the SF-36 (Mental Component Summary score/5-Item Mental Health Index; AUC 0.679-0.715). The optimal cut-off scores of 15 (for the BDI), 17 (for the HRSD), and 10 (for the PHQ-9) were also determined. Although the greatest overall accuracy (sensitivity of 81.3% and specificity of 65.4%) was obtained with the HRSD, it is the only clinician-administered instrument. Self-report measures of depression (the BDI and PHQ-9) showed comparable abilities to detect depression, only slightly less than the HRSD. Compared to the HRSD, both BDI and PHQ-9 are relatively short and easy to self-administer. The cut-off scores established in this study may be used to reliably determine whether a person should be evaluated more thoroughly for an MDD diagnosis. Using an acknowledged "gold standard," the HRSD, BDI and PHQ-9 showed similar validity to recommend their use for future clinical and research purposes. The SF-36 is less appropriate for diagnosing MDD. Copyright © 2014 Elsevier Inc. All rights reserved.

Major Depressive Disorder Among Preadolescent Canadian Children: Rare Disorder or Rarely Detected?

PubMed

Korczak, Daphne J; Ofner, Marianna; LeBlanc, John; Wong, Sam; Feldman, Mark; Parkin, Patricia C

2017-03-01

Despite agreement that preadult onset of depression is associated with greater illness severity, and that children can meet the diagnostic criteria for major depressive disorder (MDD), few studies have examined the presentation of MDD among young children. This is the first nationwide study of MDD among preadolescent children in Canada. Pediatrician members (2500) of a Canadian pediatric surveillance network were surveyed monthly over 3 years to report new cases of MDD among 5- to 12-year-olds. Survey response and questionnaire completion rates were 80% and 85%, respectively. Symptom presentation and duration, impairment, medical and psychiatric history, and management were reported. Twenty-nine new cases of MDD were identified by pediatricians. Of these, 23 (79%) experienced symptoms for >6 months before presentation with global functional impairment. Parental depression or anxiety, commonly maternal, was present in 21 cases (72%). Twenty-two children (76%) reported suicidal ideation; 6 (21%) had attempted suicide. Twenty-three children (79%) were treated with medication. Thirteen children (45%) were treated with 2 or more medications. Children with MDD frequently had a parental history of mood disorders, experienced long-standing symptom presence, high symptom burden and functional impairment prior to presentation; and commonly treatment with polypharmacy. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

The course of major depressive disorder from childhood to young adulthood: Recovery and recurrence in a longitudinal observational study.

PubMed

Kovacs, Maria; Obrosky, Scott; George, Charles

2016-10-01

The episodic nature of major depressive disorder (MDD) in clinically referred adults has been well-characterized, particularly by the NIMH Collaborative Depression Study. Previous work has established that MDD also is episodic prior to adulthood, but no study has yet provided comprehensive information on the actual course of MDD in clinically referred juveniles. Thus, the present investigation sought to characterize recovery, recurrence, and their predictors across multiple episodes of MDD in initially 8- to 13-year-old outpatients (N=102), and to estimate freedom from morbidity ("well-time") across the years. Clinically referred youngsters with MDD were repeatedly assessed in an observational study across two decades (median follow up length: 15 years). Survival analytic techniques served to model recovery from the 1st, 2nd and 3rd lifetime episodes of MDD, the risk of developing the 2nd, 3rd, and 4th episodes, and the effects of traditional psychosocial and clinical predictors of outcomes. "Well-time" across the follow-up and its predictors also were examined. Recovery rates ranged from 96% to 100% across MDD episodes; episode lengths ranged from 6 to 7 months. Up to 72% of those recovered from the first episode of MDD had a further episode; median inter-episode intervals were about 3-5 years. No single demographic, social, or clinical variable, nor treatment, consistently predicted recovery/recurrence. Psychiatric morbidity over time derived mostly from non-affective disorders, which, however, did not alter the course of MDD. The sample was relatively small and power to detect small effects further declined with each MDD episode recurrence. Echoing findings on adults, the course of pediatric-onset MDD in this clinical sample was unequivocally episodic. Traditional course predictors had limited temporal stability, highlighting the need to examine novel predictor variables. The ongoing risk of depression episodes into the second and third decades of life suggests that prevention efforts should start in late childhood. Copyright © 2016 Elsevier B.V. All rights reserved.

Ventromedial Prefrontal Cortex Thinning in Preschool-Onset Depression

PubMed Central

Marrus, Natasha; Belden, Andrew; Nishino, Tomoyuki; Handler, Ted; Ratnanather, J Tilak; Miller, Michael; Barch, Deanna; Luby, Joan; Botteron, Kelly

2016-01-01

Background The ventromedial prefrontal cortex (VMPFC) is a key center of affect regulation and processing, fundamental aspects of emotional competence which are disrupted in mood disorders. Structural alterations of VMPFC have consistently been observed in adult major depression and are associated with depression severity, yet it is unknown whether young children with depression demonstrate similar abnormalities. We investigated cortical thickness differences in the VMPFC of children with a history of preschool-onset depression (PO-MDD). Methods Participants in a longitudinal study of PO-MDD underwent structural brain imaging between the ages of 7 to 12 years. Using local cortical distance metrics, cortical thickness of the VMPFC was compared in children with and without a history of PO-MDD. Results Children previously diagnosed with PO-MDD (n=34) had significantly thinner right VMPFC versus children without a history of PO-MDD [(n=95); F(1,126)=5.97, p=0.016)]. This effect was specific to children with a history of PO-MDD vs. other psychiatric conditions and was independent of comorbid anxiety or externalizing disorders. Decreases in right VMPFC thickness were predicted by preschool depressive symptoms independent of depressive symptoms in school age. Limitations Results are cross-sectional and cannot distinguish whether thinner right VMPFC represents a vulnerability marker of MDD, consequence of MDD, or marker of remitted MDD. Longitudinal imaging is needed to contextualize how this difference relates to normative VMPFC structural development. Conclusions Onset of depression at preschool age was associated with decreased cortical thickness of right VMPFC. This finding implicates the VMPFC in depression from very early stages of brain development. PMID:25881284

A COMPREHENSIVE EXAMINATION OF WHITE MATTER TRACTS AND CONNECTOMETRY IN MAJOR DEPRESSIVE DISORDER

PubMed Central

Delaparte, Lauren; Yeh, Fang‐Cheng; DeLorenzo, Christine; McGrath, Patrick J.; Weissman, Myrna M.; Adams, Phillip; Fava, Maurizio; Deckersbach, Thilo; McInnis, Melvin G.; Carmody, Thomas J.; Cooper, Crystal M.; Kurian, Benji T.; Lu, Hanzhang; Toups, Marisa S.; Trivedi, Madhukar H.; Parsey, Ramin V.

2015-01-01

Background Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI). Methods 139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract‐based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD. Results There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry. Conclusions The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts. PMID:26477532

Prevalence of depression-PTSD comorbidity: implications for clinical practice guidelines and primary care-based interventions.

PubMed

Campbell, Duncan G; Felker, Bradford L; Liu, Chuan-Fen; Yano, Elizabeth M; Kirchner, JoAnn E; Chan, Domin; Rubenstein, Lisa V; Chaney, Edmund F

2007-06-01

Compared to those with depression alone, depressed patients with posttraumatic stress disorder (PTSD) experience more severe psychiatric symptomatology and factors that complicate treatment. To estimate PTSD prevalence among depressed military veteran primary care patients and compare demographic/illness characteristics of PTSD screen-positive depressed patients (MDD-PTSD+) to those with depression alone (MDD). Cross-sectional comparison of MDD patients versus MDD-PTSD+ patients. Six hundred seventy-seven randomly sampled depressed patients with at least 1 primary care visit in the previous 12 months. Participants composed the baseline sample of a group randomized trial of collaborative care for depression in 10 VA primary care practices in 5 states. The Patient Health Questionnaire-9 assessed MDD. Probable PTSD was defined as a Primary Care PTSD Screen > or = 3. Regression-based techniques compared MDD and MDD-PTSD+ patients on demographic/illness characteristics. Thirty-six percent of depressed patients screened positive for PTSD. Adjusting for sociodemographic differences and physical illness comorbidity, MDD-PTSD+ patients reported more severe depression (P < .001), lower social support (P < .001), more frequent outpatient health care visits (P < .001), and were more likely to report suicidal ideation (P < .001) than MDD patients. No differences were observed in alcohol consumption, self-reported general health, and physical illness comorbidity. PTSD is more common among depressed primary care patients than previously thought. Comorbid PTSD among depressed patients is associated with increased illness burden, poorer prognosis, and delayed response to depression treatment. Providers should consider recommending psychotherapeutic interventions for depressed patients with PTSD.

A multicenter study of major depressive disorder among emergency department patients in Latin-American countries.

PubMed

Castilla-Puentes, Ruby C; Secin, Ricardo; Grau, Arturo; Galeno, Roxanna; Feijo de Mello, Marcelo; Pena, Nuri; Sanchez-Russi, Carlos A

2008-01-01

This multicenter study estimated the prevalence of major depressive disorder (MDD) among emergency department patients in Latin America. To identify patients with MDD, we used a combination of DSM IV- criteria interview and a questionnaire screen including the center for Epidemiological Studies Depression Scale. We analyzed data from consecutive adult patients from hospitals in Argentina, Brazil, Chile, Colombia, and Mexico and described the demographic and health status differences between MDD and non-MDD patients. Prevalence of MDD ranges from 23.0 to 35.0%. The estimates are based on a total of 1,835 patients aged 18 years and over, with response rates of 83.0%. Compared to non-MDD patients, MDD patients were more likely to be middle-aged, female, smokers, of lower socioeconomic status, and to report a diagnosis of asthma or arthritis/rheumatism. Multivariate analysis identified a lower level of education, smoking, and self-reported anxiety, chronic fatigue, and back problems to be independently associated with MDD. Our data suggest that the prevalence of MDD is elevated among emergency department patients in Latin American countries. The integration of depression screening into routine emergency care merits serious consideration, especially if such screening can be linked to psychiatric treatment.

Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

PubMed

Devanand, D P; Adorno, Elizabeth; Cheng, Jocelyn; Burt, Tal; Pelton, G H Gregory H; Roose, S P Steven P; Sackeim, H A Harold A

2004-03-01

Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. Academic clinic sample results may not generalize to community populations. In the elderly, late-onset DD is typically different from early onset DD. Cerebrovascular disease appears to play a role in the etiology of late onset DD. The similarities between late onset DD and late onset MDD suggest a single condition along a continuum.

Personality-related core beliefs in patients diagnosed with fibromyalgia plus depression: A comparison with depressed and healthy control groups.

PubMed

Taymur, Ibrahim; Ozdel, Kadir; Gundogdu, Ibrahim; Efe, Canan; Tulaci, Riza Gokcer; Kervancioglu, Aysegul

2015-07-01

Personality has an important role in understanding both fibromyalgia syndrome (FMS) and major depressive disorder (MDD). This study considers the question that specific personality features may characterize depressed FMS patients. To this end, 125 individuals were included in the study: 40 of them diagnosed with FMS+ MDD, 40 with MDD only and 45 healthy controls. Individual Beck Depression Inventory (BDI) and Personality Belief Questionnaire-Short Form (PBQ-SF) scores were compared between the three groups. The mean scores for each personality domain of the PBQ-SF were the highest in the MDD group and the lowest mean scores appeared in the control group. Dependent personality and obsessive-compulsive personality scores were higher in the MDD group (t = 2.510, P = 0.014 and t = 2.240, P = 0.028, respectively) in comparison with the FM+ MDD group. However, this difference disappeared when PBQ-SF scores were controlled for depression severity. Although some common personality features are evident in FMS patients, it seems that the differences identified are primarily related to depression symptom severity.

Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.

PubMed

Wray, N R; Pergadia, M L; Blackwood, D H R; Penninx, B W J H; Gordon, S D; Nyholt, D R; Ripke, S; MacIntyre, D J; McGhee, K A; Maclean, A W; Smit, J H; Hottenga, J J; Willemsen, G; Middeldorp, C M; de Geus, E J C; Lewis, C M; McGuffin, P; Hickie, I B; van den Oord, E J C G; Liu, J Z; Macgregor, S; McEvoy, B P; Byrne, E M; Medland, S E; Statham, D J; Henders, A K; Heath, A C; Montgomery, G W; Martin, N G; Boomsma, D I; Madden, P A F; Sullivan, P F

2012-01-01

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

Psychophysiological Correlates of Generalized Anxiety Disorder with or without Comorbid Depression

PubMed Central

Hofmann, Stefan G.; Schulz, Stefan M.; Heering, Sanna; Muench, Frederick; Bufka, Lynn F.

2010-01-01

It remains uncertain whether generalized anxiety disorder (GAD) and major depressive disorder (MDD) represent two separate diagnostic entities. The goal of this study was to examine whether comorbid MDD distinguishes individuals with GAD on a psychophysiological level during an experimentally-induced worrying procedure. Participants included 39 individuals with GAD, 14 of whom met criteria for MDD. During the experimental procedure, participants were asked to worry or relax after an initial baseline phase while measuring their heart rate, high frequency heart rate variability (HF-HRV), skin conductance level, and subjective level of anxiety. The two groups did not differ in their subjective anxiety, heart rate response, and skin conductance levels. However, participants with comorbid MDD had greater HF-HRV values throughout the experiment than did those without MDD. At baseline, HF-HRV was significantly correlated with a self-report measure of depression. These results suggest that individuals with comorbid GAD and MDD can be distinguished based on HF-HRV from individuals with GAD but without MDD. These results support the distinction between GAD and MDD. PMID:20093149

Melancholic features and hostility are associated with suicidality risk in Asian patients with major depressive disorder.

PubMed

Jeon, Hong Jin; Peng, Daihui; Chua, Hong Choon; Srisurapanont, Manit; Fava, Maurizio; Bae, Jae-Nam; Man Chang, Sung; Hong, Jin Pyo

2013-06-01

Suicide rates are higher in East-Asians than other populations, and especially high in Koreans. However, little is known about suicidality risk and melancholic features in Asian patients with major depressive disorder (MDD). Drug-free MDD outpatients were included from 13 centers across five ethnicities consisting of Chinese (n=290), Korean (n=101), Thai (n=102), Indian (n=27), and Malay (n=27). All were interviewed using the Mini-International Neuropsychiatric Interview (M.I.N.I.), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Symptoms Checklist 90-Revised (SCL-90-R). Of 547 subjects, 177 MDD patients showed melancholic features (32.4%). These melancholic MDD patients revealed significantly higher suicidality risk (p<0.0001), hostility (p=0.037), and severity of depression (p<0.0001) than those MDD patients without melancholic features. Suicidality risk was significantly higher in MDD with melancholic features than those without in subjects with lower hostility, whereas it showed no difference in higher hostility. Adjusted odds ratios of melancholic features and hostility for moderate to high suicidality risk were 1.79 (95% CI=1.15-2.79) and 2.45 (95% CI=1.37-4.38), after adjusting for age, sex, education years, and depression severity. Post-hoc analyses showed that suicidality risk was higher in Korean and Chinese than that of Thai, Indian and Malay in MDD subjects with melancholic features, although depression severity showed no significant differences among the ethnicities. Suicidality risk is associated with both melancholic features and hostility and it shows cross-ethnic differences in Asian MDD patients, independent of depression severity. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparing Neural Correlates of REM Sleep in Posttraumatic Stress Disorder and Depression: A Neuroimaging Study

PubMed Central

Ebdlahad, Sommer; Nofzinger, Eric A.; James, Jeffrey A.; Buysse, Daniel J.; Price, Julie C.; Germain, Anne

2013-01-01

Rapid eye movement (REM) sleep disturbances predict poor clinical outcomes in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In MDD, REM sleep is characterized by activation of limbic and paralimbic brain regions compared to wakefulness. The neural correlates of PTSD during REM sleep remain scarcely explored, and comparisons of PTSD and MDD have not been conducted. The present study sought to compare brain activity patterns during wakefulness and REM sleep in 13 adults with PTSD and 12 adults with MDD using [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET). PTSD was associated with greater increases in relative regional cerebral metabolic rate of glucose (rCMRglc) in limbic and paralimbic structures in REM sleep compared to wakefulness. Post-hoc comparisons indicated that MDD was associated with greater limbic and paralimbic rCMRglc during wakefulness but not REM sleep compared to PTSD. Our findings suggest that PTSD is associated with increased REM sleep limbic and paralimbic metabolism, whereas MDD is associated with wake and REM hypermetabolism in these areas. These observations suggest that PTSD and MDD disrupt REM sleep through different neurobiological processes. Optimal sleep treatments between the two disorders may differ: REM-specific therapy may be more effective in PTSD. PMID:24367137

Association of Major Depressive Disorder with Serum Myeloperoxidase and other Markers of Inflammation: A Twin Study

PubMed Central

Vaccarino, Viola; Brennan, Marie-Luise; Miller, Andrew H.; Bremner, J. Douglas; Ritchie, James C.; Lindau, Frauke; Veledar, Emir; Su, Shaoyong; Murrah, Nancy V.; Jones, Linda; Jawed, Farhan; Dai, Jun; Goldberg, Jack; Hazen, Stanley L.

2008-01-01

Background Major depressive disorder (MDD) has been linked to inflammation, but this association may be due to common precursors to both depression and inflammation. Myeloperoxidase (MPO) is an inflammatory enzyme produced by activated leukocytes which predicts risk of coronary heart disease. We sought to examine whether MPO and other markers of inflammation are associated with MDD, and whether the association is confounded by genetic or other shared familial factors. Methods We examined 178 monozygotic and dizygotic middle-aged male twin pairs. We assessed MDD with the Structured Clinical Interview for Psychiatry Disorders. Blood markers of inflammation included MPO, interleukin-6, white blood cell count, C-reactive protein, tumor necrosis factor (TNF)-α, the TNF-α soluble receptor II, and fibrinogen. Analyses were conducted in the overall sample and among 67 twin pairs discordant for MDD using mixed effects regression. Results Twins with a history of MDD had 32% higher levels of MPO (p<0.0001); this difference persisted after adjusting for other risk factors. Among dizygotic MDD-discordant twin pairs, twins with MDD had 77% higher MPO than their brothers without MDD after adjusting for other factors (p<0.0001). In contrast, no significant association was found in monozygotic twins (p=0.13). Similar, but weaker, associations were found between MDD and other inflammatory biomarkers. Conclusion MPO is a useful biomarker of immune activation in MDD. However, the association between inflammation and MDD is largely due to common genetic liability. Our results are consistent with the hypothesis that genes promoting inflammation are involved in the pathogenesis of MDD. PMID:18514165

Demographic variables, design characteristics, and effect sizes of randomized, placebo-controlled, monotherapy trials of major depressive disorder and bipolar depression.

PubMed

Papakostas, George I; Martinson, Max A; Fava, Maurizio; Iovieno, Nadia

2016-05-01

The aim of this work is to compare the efficacy of pharmacologic agents for the treatment of major depressive disorder (MDD) and bipolar depression. MEDLINE/PubMed databases were searched for studies published in English between January 1980 and September 2014 by cross-referencing the search term placebo with each of the antidepressant agents identified and with bipolar. The search was supplemented by manual bibliography review. We selected double-blind, randomized, placebo-controlled trials of antidepressant monotherapies for the treatment of MDD and of oral drug monotherapies for the treatment of bipolar depression. 196 trials in MDD and 19 trials in bipolar depression were found eligible for inclusion in our analysis. Data were extracted by one of the authors and checked for accuracy by a second one. Data extracted included year of publication, number of patients randomized, probability of receiving placebo, duration of the trial, baseline symptom severity, dosing schedule, study completion rates, and clinical response rates. Response rates for drug versus placebo in trials of MDD and bipolar depression were 52.7% versus 37.5% and 54.7% versus 40.5%, respectively. The random-effects meta-analysis indicated that drug therapy was more effective than placebo in both MDD (risk ratio for response = 1.373; P < .001) and bipolar depression (risk ratio = 1.257; P < .001) trials. The meta-regression analysis suggested a statistically significant difference in the risk ratio of responding to drug versus placebo between MDD and bipolar depression trials in favor of MDD (P = .008). Although a statistically significantly greater treatment effect size was noted in MDD relative to bipolar depression studies, the absolute magnitude of the difference was numerically small. Therefore, the present study suggests no clinically significant differences in the overall short-term efficacy of pharmacologic monotherapies for MDD and bipolar depression. © Copyright 2016 Physicians Postgraduate Press, Inc.

Neurostructural impact of co-occurring anxiety in pediatric patients with major depressive disorder: a voxel-based morphometry study.

PubMed

Wehry, Anna M; McNamara, Robert K; Adler, Caleb M; Eliassen, James C; Croarkin, Paul; Cerullo, Michael A; DelBello, Melissa P; Strawn, Jeffrey R

2015-01-15

Depressive and anxiety disorders are among the most frequently occurring psychiatric conditions in children and adolescents and commonly present occur together. Co-occurring depression and anxiety is associated with increased functional impairment and suicidality compared to depression alone. Despite this, little is known regarding the neurostructural differences between anxiety disorders and major depressive disorder (MDD). Moreover, the neurophysiologic impact of the presence of anxiety in adolescents with MDD is unknown. Using voxel-based morphometry, gray matter volumes were compared among adolescents with MDD (and no co-morbid anxiety disorders, n=14), adolescents with MDD and co-morbid anxiety ("anxious depression," n=12), and healthy comparison subjects (n=41). Patients with anxious depression exhibited decreased gray matter volumes in the dorsolateral prefrontal cortex (DLPFC) compared to patients with MDD alone. Compared to healthy subjects, adolescents with anxious depression had increased gray matter volumes in the pre- and post-central gyri. The current sample size was small and precluded an analysis of multiple covariates which may influence GMV. Gray matter deficits in the DLPFC in youth with anxious depression compared to patients with MDD and no co-occurring anxiety may reflect the more severe psychopathology in these patients. Additionally, the distinct gray matter fingerprints of MDD and anxious depression (compared to healthy subjects) suggest differing neurophysiologic substrates for these conditions, though the etiology and longitudinal trajectory of the differences remain to be determined. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE), but not S100B in major depressive disorder.

PubMed

Schmidt, Frank Martin; Mergl, Roland; Stach, Barbara; Jahn, Ina; Schönknecht, Peter

2015-02-01

Alterations in neuronal and glial integrity are considered to be of pathogenic impact on major depressive disorder (MDD). For MDD, data on cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) are lacking and scarce for glial protein S100B. We measured CSF levels of NSE and S100B in 31 patients with MDD and 32 mentally healthy controls using electrochemiluminescence immunoassays (ECLIA). Adjusted means of NSE were significantly elevated in the MDD patients (11.73 ng/ml (9.95-13.52 95% CI) compared to the controls (6.17 ng/ml (4.55-7.78), F = 9.037, P = 0.004. Effect size for adjusted mean group difference of 5.57 ng/ml was found invariably high (Cohen's d = 1.23). Differentiating MDD from controls, a NSE cut-off of 7.94 ng/ml showed sensitivity of 81% (95% CI 63.7-90.8) and specificity of 75% (95% CI 57.9-86.7). Adjusted levels of S100B did not differ significantly between the two groups (1.12 ng/ml (0.77-1.48) in MDD, 0.97 ng/ml (0.64-1.30) in controls). Our results of elevated CSF-NSE levels support neuronal pathology in MDD and the potential use of CSF-NSE as marker in clinical diagnostics. Missing group differences in S100B do not promote a specific glial pathology in depressive disorders.

Gender Differences in the Relationships Among Major Depressive Disorder, Heavy Alcohol Use, and Mental Health Treatment Engagement Among College Students.

PubMed

Pedrelli, Paola; Borsari, Brian; Lipson, Sarah Ketchen; Heinze, Justin E; Eisenberg, Daniel

2016-07-01

Although major depressive disorder (MDD) and heavy episodic drinking (HED, 4+/5+ drinks in a single sitting for women/men) are common among young adults in college, the relationship between the two remains unclear. This study examined the association between MDD and HED in this population, the effect of gender on this association, and whether comorbid MDD and heavy alcohol use are associated with higher rates of mental health treatment engagement. The study comprised 61,561 (65.3% female) undergraduate students who answered an online survey on depression, alcohol use, and treatment engagement in the past year. Hierarchical linear regressions examined the association between MDD and alcohol use (HED and peak blood alcohol concentration [pBAC]) and whether gender moderated these associations. Logistic regressions were then conducted to examine the influence of MDD, heavy alcohol use, and gender on treatment engagement. Students with MDD reported more frequent HED and higher pBAC than did students without MDD; this was especially true for female students. Rates of treatment engagement were higher among women than men, among students with MDD than students without MDD, and among female students with HED than women without HED. The presence of an association between MDD and heavy alcohol use suggests the need for systematic screenings of both conditions. Low rates of treatment engagement in college students with MDD and heavy alcohol use calls for the development of strategies to engage this high-risk group in treatment.

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

PubMed Central

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-01-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

PubMed

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-04-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

Increased Treatment Complexity for Major Depressive Disorder for Inpatients With Comorbid Personality Disorder.

PubMed

Wiegand, Hauke F; Godemann, Frank

2017-05-01

The study examined inpatient treatment for major depressive disorder (MDD) when it is complicated by comorbid personality disorder. In this descriptive analysis of a large data sample from 2013 (German VIPP data set) of 58,913 cases from 75 hospitals, three groups were compared: patients with MDD, patients with MDD and a comorbid personality disorder, and patients with a main diagnosis of personality disorder. Compared with MDD patients, those with comorbid personality disorder had higher rates of recurrent depression and nearly twice as many readmissions within one year, despite longer mean length of stay. Records of patients with comorbidities more often indicated accounting codes for "complex diagnostic procedures," "crisis intervention," and "constant observation." Patients with comorbid disorders differed from patients with a main diagnosis of personality disorder in treatment indicator characteristics and distribution of personality disorder diagnoses. Personality disorder comorbidity made MDD treatment more complex, and recurrence of MDD episodes and hospital readmission occurred more often than if patients had a sole MDD diagnosis.

Prefrontal activation in response to emotional words in patients with bipolar disorder and major depressive disorder.

PubMed

Matsubara, Toshio; Matsuo, Koji; Nakashima, Mami; Nakano, Masayuki; Harada, Kenichiro; Watanuki, Toshio; Egashira, Kazuteru; Watanabe, Yoshifumi

2014-01-15

Abnormal emotional processing is involved in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether the neural mechanism underlying this deficit is a trait characteristic of BD and MDD is unclear. The aim of this study was to elucidate the similarities and differences in processing of emotional stimuli between patients with BD and MDD in remission, using functional near-infrared spectroscopy (fNIRS). Thirty-two patients (16 with BD and 16 with MDD) and 20 healthy control subjects matched for age, sex, handedness, and years of education were included. An emotional Stroop task, including happy, sad, and threat words, was used. The relative oxygenated and deoxygenated hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) changes in the frontal region were measured using 52-channels of NIRS. During the threat task, compared to healthy control subjects, patients with BD showed significantly increased [oxy-Hb] in the left inferior frontal region whereas patients with MDD showed significantly increased [oxy-Hb] in the left middle frontal region. During the happy task, compared to healthy control subjects, patients with BD showed significantly decreased [oxy-Hb] in the middle frontal region in both hemispheres. Moreover, patients with BD exhibited decreased [oxy-Hb] and increased [deoxy-Hb] in the superior frontal and middle frontal regions compared to MDD in response to the happy stimulus. No significant differences in [oxy-Hb] or [deoxy-Hb] were seen between the groups during the sad task. These results suggest that abnormal neural responses to emotional stimuli in patients with mood disorders in remission may be a trait characteristic, that negative emotional stimuli are associated with similar prefrontal responses, and that positive emotional stimuli are associated with different prefrontal responses in patients with BD and MDD. These findings indicate that different neural circuits play a role in emotional processing in BD and MDD; this may aid the elucidation of the pathophysiology of these two disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Neurocognitive impairment in adolescent major depressive disorder: state vs. trait illness markers.

PubMed

Maalouf, Fadi T; Brent, David; Clark, Luke; Tavitian, Lucy; McHugh, Rebecca Munnell; Sahakian, Barbara J; Phillips, Mary L

2011-10-01

Current treatment outcomes of Major Depressive Disorder (MDD) in adolescents remain suboptimal. Discriminating between state and trait markers of MDD in adolescents would help identify markers that may guide choice of appropriate interventions and help improve longer-term outcome for individuals with the illness. We compared neurocognitive performance in executive function, sustained attention and short-term memory in 20 adolescents with MDD in acute episode (MDDa), 20 previously depressed adolescents in remission (MDDr) and 17 healthy control participants (HC). There was a group difference that emerged for executive function with increasing task difficulty (p=0.033). MDDa showed impaired executive function, as measured by using more moves to solve 4-move problems on a forward planning task, relative to MDDr and HC (p=0.01, d=0.94 and p=0.015, d=0.77 respectively). MDDa showed more impulsivity as measured by lower response bias (B″) on a sustained attention task than both MDDr and HC (p=0.01, d=0.85 and p=0.008, d=0.49 respectively). Higher impulsivity was associated with more severe depression (r=-0.365, p=0.022) and earlier age of onset of depression (r=0.402, p=0.012) and there was a trend for a correlation between more executive dysfunction and more severe depression (r=0.301 p=0.059) in MDDa and MDDr combined. The three groups did not differ significantly on short-term memory or target detection on the sustained attention task. These results need to be replicated in the future with a larger sample size. Executive dysfunction and impulsivity appear to be state-specific markers of MDD in adolescents that are related to depression severity and not present in remission. Copyright © 2011 Elsevier B.V. All rights reserved.

Major depressive disorder with subthreshold hypomanic (mixed) features: A real-world assessment of treatment patterns and economic burden.

PubMed

McIntyre, Roger S; Ng-Mak, Daisy; Chuang, Chien-Chia; Halpern, Rachel; Patel, Pankaj A; Rajagopalan, Krithika; Loebel, Antony

2017-03-01

To compare outcomes for individuals with major depressive disorder (MDD) with or without subthreshold hypomania (mixed features) in naturalistic settings. Using the Optum Research Database (1/1/2009─10/31/2014), a retrospective analysis of individuals newly diagnosed with MDD was conducted. Continuous enrollment for 12-months before and after the initial MDD diagnosis was required. MDD with subthreshold hypomania (mixed features) (MDD-MF) was defined based on ≥1 hypomania diagnosis within 30 days after an MDD diagnosis during the one-year follow-up period, in the absence of bipolar I diagnoses. Psychiatric medication use, healthcare utilization, and costs during the one-year follow-up period were compared using multivariate logistic and gamma regressions, controlling for baseline differences. Of 130,626 MDD individuals, 652 (0.5%) met the operational definition of MDD-MF. Compared to the MDD-only group, the MDD-MF group had more suicidality (2.0% vs. 0.5%), anxiety disorders (46.8% vs. 34.0%), and substance use disorders (15.5% vs. 6.1%, all P<0.001). More individuals with MDD-MF were treated with antidepressants (83.6% vs. 71.6%), mood stabilizers (50.5% vs. 2.7%), atypical antipsychotics (39.0% vs. 5.5%), and polypharmacy with multiple drug classes (72.1% vs. 22.7%, all P<0.001). Individuals with MDD-MF had higher hospitalizations rates (24.2% vs. 10.5%) and total healthcare costs (mean: $15,660 vs. $10,744, all P<0.001). The commercial claims data used were not collected for research purposes and may over- or under-represent certain populations. No specific claims-based diagnostic code for MDD with mixed features exists. Greater use of mood stabilizers, atypical antipsychotics, polypharmacy, and healthcare resources provides evidence of the complexity and severity of MDD-MF. Identifying optimal treatment regimens for this population represents a major unmet medical need. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative analysis of affective temperament in patients with difficult-to-treat and easy-to-treat major depression and bipolar disorder: Possible application in clinical settings.

PubMed

Takeshima, Minoru; Oka, Takashi

2016-04-01

Difficult-to-treat major depressive disorder (MDD-DT), which involves antidepressant refractoriness or antidepressant-related adverse psychiatric effects, is bipolar in nature; therefore, it may share common temperamental features with bipolar disorder. To examine this hypothesis, affective temperament was compared between MDD-DT, easy-to-treat major depressive disorder (MDD-ET), and bipolar disorder. Affective temperament was measured in 320 patients (69, 56, and 195 with MDD-ET, MDD-DT, and bipolar disorder, respectively) using the self-rated questionnaire version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A), with between-group differences examined using multiple logistic regression analysis controlling for confounders. Optimal cut-off points for TEMPS-A scores to discriminate between diagnostic groups were determined using receiver-operating characteristic analysis. Of the five temperamental domains, the mode for cyclothymic temperament score was highest, followed by those of bipolar disorder, MDD-DT, and MDD-ET. The cyclothymic temperament score discriminated significantly between bipolar disorder and MDD-DT (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.04-1.20, p=0.0022), MDD-DT and MDD-ET (OR: 1.15, 95% CI: 1.01-1.31, p=0.0334), and bipolar and major depressive disorders (OR: 1.17, 95% CI: 1.07-1.28, p=0.0003). Optimal cut-off points for the cyclothymic temperament scores to discriminate between bipolar disorder and major depressive disorder and MDD-DT and MDD-ET were 9 (sensitivity: 64.6%, specificity: 76.0%) and 6 (66.1%, 62.3%), respectively. MDD-DT has a quantitatively stronger bipolar temperamental feature, cyclothymic temperament, relative to that of MDD-ET. Cut-off points determined in this study could be clinically helpful. Because of our study design, longitudinal changes in temperamental scores during treatment cannot be fully excluded. Copyright © 2016 Elsevier Inc. All rights reserved.

The combined effects of the 5-HTTLPR and 5-HTR1A genes modulates the relationship between negative life events and major depressive disorder in a Chinese population.

PubMed

Zhang, Kerang; Xu, Qi; Xu, Yong; Yang, Hong; Luo, Jinxiu; Sun, Yan; Sun, Ning; Wang, Shan; Shen, Yan

2009-04-01

Serotonin transporter (5-HTT) and 5-HT receptor (5-HTR) involved in the neurotransmission of 5-HT may play an important role in the development of major depression disorder (MDD). Several lines of evidence suggested that the gene-environment interaction may confer susceptibility to depression. The aim of this study is to analyze the combined effect of four serotonin-related genes and two environmental factors on MDD in a Chinese population. This study recruited a total of 401 patients with MDD and 391 age- and gender-matched control subjects. They were all Chinese Han origin. Negative life events and objective social supports were assessed using standard rating scales. Six polymorphisms in the four serotonin-related genes (5-HTT, 5-HTR1A, 5-HTR1B and 5-HTR2A) were selected to detect. The analyses of the gene-environment interactions were performed by the Multifactor Dimensionality Reduction (MDR). Allelic associations between patients with MDD and controls were observed for the polymorphism of 5-HTTLPR and for rs6295 at the 5-HTR1A locus. The 5-HTTLPR polymorphism was associated with negative life events on MDD. A three-way interaction between the 5-HTTLPR polymorphism, rs6295 and negative life events on MDD was found in the individuals aged from 20 years to 29 years. In addition, the individuals carrying the L/L genotype of 5-HTTLPR could be susceptible to MDD when exposed to negative life events. The 5-HTTLPR polymorphism may modify the interaction between negative life events and MDD in the Chinese population. To our knowledge, this is the first report on the combined effect for the 5-HTTLPR polymorphism and 5-HTR1A genes on modifying the response to negative life events conferring susceptibility to MDD in the 20-29 year group.

Disorder-specific volumetric brain difference in adolescent major depressive disorder and bipolar depression.

PubMed

MacMaster, Frank P; Carrey, Normand; Langevin, Lisa Marie; Jaworska, Natalia; Crawford, Susan

2014-03-01

Structural abnormalities in frontal, limbic and subcortical regions have been noted in adults with both major depressive disorder (MDD) and bipolar disorder (BD). In the current study, we examined regional brain morphology in youth with MDD and BD as compared to controls. Regional brain volumes were measured in 32 MDD subjects (15.7 ± 2.1 years), 14 BD subjects (16.0 ± 2.4 years) and 22 healthy controls (16.0 ± 2.8 years) using magnetic resonance imaging (MRI). Regions of interest included the hippocampus, dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), caudate, putamen and thalamus. Volumetric differences between groups were significant (F26,80 = 1.80, p = 0.02). Post-hoc analyses indicated that individuals with MDD showed reduced left hippocampus volumes (p = 0.048) as well as right ACC white and gray matter volumes (p = 0.003; p = 0.01) compared to controls. BD participants also displayed reduced left hippocampal and right/left putamen volumes compared to controls (p < 0.001; p = 0.015; p = 0.046 respectively). Interestingly, right and left ACC white matter volumes were smaller in MDD than in BD participants (p = 0.019; p = 0.045 respectively). No volumetric group differences were observed for the DLPFC and thalamus. Discriminant analysis was able to correctly classify 81.0 % of subjects as having BD or as MDD based on imaging data. Confirmation and extension of our findings requires larger sample sizes. Our findings provide new evidence of distinct, specific regional brain volumetric differences between MDD and BD that may be used to distinguish the two disorders.

Ego-rotation and object-rotation in major depressive disorder.

PubMed

Chen, Jiu; Yang, Laiqi; Ma, Wentao; Wu, Xingqu; Zhang, Yan; Wei, Dunhong; Liu, Guangxiong; Deng, Zihe; Hua, Zhen; Jia, Ting

2013-08-30

Mental rotation (MR) performance provides a direct insight into a prototypical higher-level visuo-spatial cognitive operation. Previous studies suggest that progressive slowing with an increasing angle of orientation indicates a specific wing of object-based mental transformations in the psychomotor retardation that occurs in major depressive disorder (MDD). It is still not known, however, whether the ability of object-rotation is associated with the ability of ego-rotation in MDD. The present study was designed to investigate the level of impairment of mental transformation abilities in MDD. For this purpose we tested 33 MDD (aged 18-52 years, 16 women) and 30 healthy control subjects (15 women, age and education matched) by evaluating the performance of MDD subjects with regard to ego-rotation and object-rotation tasks. First, MDD subjects were significantly slower and made more errors than controls in mentally rotating hands and letters. Second, MDD and control subjects displayed the same pattern of response times to stimuli at various orientations in the letter task but not the hand task. Third, in particular, MDD subjects were significantly slower and made more errors during the mental transformation of hands than letters relative to control subjects and were significantly slower and made more errors in physiologically impossible angles than physiologically possible angles in the mental rotation hand task. In conclusion, MDD subjects present with more serious mental rotation deficits specific to the hand than the letter task. Importantly, deficits were more present during the mental transformation in outward rotation angles, thus suggesting that the mental imagery for hands and letters relies on different processing mechanisms which suggest a module that is more complex for the processing of human hands than for letters during mental rotation tasks. Our study emphasises the necessity of distinguishing different levels of impairment of action in MDD subjects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Functional anatomy of autobiographical memory recall deficits in depression

PubMed Central

Young, K. D.; Erickson, K.; Nugent, A. C.; Fromm, S. J.; Mallinger, A. G.; Furey, M. L.; Drevets, W. C.

2012-01-01

Background Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall. Method Participants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings. Results Behavioral results showed that relative to controls, the patients with MDD had fewer specific (p=0.013), positive (p=0.030), highly arousing (p=0.036) and recent (p=0.020) AMs, and more categorical (p<0.001) AMs. The blood oxygen level-dependent (BOLD) response in the parahippocampus and hippocampus was higher for memory recall versus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD. Conclusions We replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD. PMID:21798113

Methylation of the tryptophan hydroxylase‑2 gene is associated with mRNA expression in patients with major depression with suicide attempts.

PubMed

Zhang, Yuqi; Chang, Zaohuo; Chen, Jionghua; Ling, Yang; Liu, Xiaowei; Feng, Zhang; Chen, Caixia; Xia, Minghua; Zhao, Xingfu; Ying, Wang; Qing, Xu; Li, Guilin; Zhang, Changsong

2015-08-01

Tryptophan hydroxylase-2 (TPH2) contributes to alterations in the function of neuronal serotonin (5-HT), which are associated with various psychopathologies, including major depressive disorder (MDD) or suicidal behavior. The methylation of a single CpG site in the promoter region of TPH2 affects gene expression. Suicide and MDD are strongly associated and genetic factors are at least partially responsible for the variability in suicide risk. The aim of the present study was to investigate whether variations in TPH2 methylation in peripheral blood samples may predispose patients with MDD to suicide attempts. TPH2 mRNA expression levels differed significantly between 50 patients with MDD who had attempted suicide (MDD + suicide group) and 75 control patients with MDD (MDD group); TPH2 expression levels were significantly decreased (P=0.0005) in the patients who had attempted suicide. Furthermore, the frequency of TPH2 methylation was 36.0% in the MDD + suicide group, while it was 13.0% in the MDD group. The results of the present study demonstrated that methylation in the promoter region of TPH2 significantly affected the mRNA expression levels of TPH2, thus suggesting that methylation of the TPH2 promoter may silence TPH2 mRNA expression in MDD patients with or without suicidal behavior. In addition, there was a significant correlation between the methylation status of the TPH2 promoter and depression, hopelessness and cognitive impairment in the MDD + suicide group. In conclusion, the present study demonstrated that TPH2 expression was regulated by DNA methylation of the TPH2 promoter region in patients with MDD.

Lifetime suicidal ideation and attempt in adults with full major depressive disorder versus sustained depressed mood.

PubMed

Yoo, Hye Jin; Hong, Jin Pyo; Cho, Maeng Je; Fava, Maurizio; Mischoulon, David; Heo, Jung-Yoon; Kim, Kiwon; Jeon, Hong Jin

2016-10-01

Major depressive disorder (MDD) is a well-known risk factor for suicidality, but depressed mood has been used non-specifically to describe the emotional state. We sought to compare influence of MDD versus sustained depressed mood on suicidality. A total of 12,532 adults, randomly selected through the one-person-per-household method, completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) and a questionnaire for lifetime suicidal ideation (LSI) and lifetime suicidal attempt (LSA). Of 12,361 adults, 565 were assessed as 'sustained depressed mood group' having depressed mood for more than two weeks without MDD (4.6%), and 810 adults were assessed as having full MDD (6.55%) which consisted of 'MDD with depressed mood group' (6.0%) and 'MDD without depressed mood group' (0.5%). The MDD with depressed mood group showed higher odds ratios for LSI and LSA than the sustained depressed mood group. Contrarily, no significant differences were found in LSI and LSA between the MDD group with and without depressed mood. MDD showed significant associations with LSI (AOR=2.83, 95%CI 2.12-3.78) and LSA (AOR=2.17, 95%CI 1.34-3.52), whereas sustained depressed mood showed significant associations with neither LSI nor LSA after adjusting for MDD and other psychiatric comorbidities. Interaction effect of sustained depressed mood with MDD was significant for LSI but not for LSA. Sustained depressed mood was not related to LSI and LSA after adjusting for psychiatric comorbidities, whereas MDD was significantly associated with both LSI and LSA regardless of the presence of sustained depressed mood. Copyright © 2016 Elsevier B.V. All rights reserved.

Gender Differences in the Relationships Among Major Depressive Disorder, Heavy Alcohol Use, and Mental Health Treatment Engagement Among College Students

PubMed Central

Pedrelli, Paola; Borsari, Brian; Lipson, Sarah Ketchen; Heinze, Justin E.; Eisenberg, Daniel

2016-01-01

Objective: Although major depressive disorder (MDD) and heavy episodic drinking (HED, 4+/5+ drinks in a single sitting for women/men) are common among young adults in college, the relationship between the two remains unclear. This study examined the association between MDD and HED in this population, the effect of gender on this association, and whether comorbid MDD and heavy alcohol use are associated with higher rates of mental health treatment engagement. Method: The study comprised 61,561 (65.3% female) undergraduate students who answered an online survey on depression, alcohol use, and treatment engagement in the past year. Hierarchical linear regressions examined the association between MDD and alcohol use (HED and peak blood alcohol concentration [pBAC]) and whether gender moderated these associations. Logistic regressions were then conducted to examine the influence of MDD, heavy alcohol use, and gender on treatment engagement. Results: Students with MDD reported more frequent HED and higher pBAC than did students without MDD; this was especially true for female students. Rates of treatment engagement were higher among women than men, among students with MDD than students without MDD, and among female students with HED than women without HED. Conclusions: The presence of an association between MDD and heavy alcohol use suggests the need for systematic screenings of both conditions. Low rates of treatment engagement in college students with MDD and heavy alcohol use calls for the development of strategies to engage this high-risk group in treatment. PMID:27340967

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards

PubMed Central

Smoski, Moria J.; Rittenberg, Alison; Dichter, Gabriel S.

2011-01-01

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during fMRI scanning to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and thirteen affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. PMID:22079658

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

PubMed

Smoski, Moria J; Rittenberg, Alison; Dichter, Gabriel S

2011-12-30

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. 2011 Elsevier Ireland Ltd. All rights reserved.

Vulnerability for new episodes in recurrent major depressive disorder: protocol for the longitudinal DELTA-neuroimaging cohort study

PubMed Central

Mocking, Roel J T; Figueroa, Caroline A; Rive, Maria M; Geugies, Hanneke; Servaas, Michelle N; Assies, Johanna; Koeter, Maarten W J; Vaz, Frédéric M; Wichers, Marieke; van Straalen, Jan P; de Raedt, Rudi; Bockting, Claudi L H; Harmer, Catherine J; Schene, Aart H; Ruhé, Henricus G

2016-01-01

Introduction Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission. Methods and analysis In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35–65 years) with ≥2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5 years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3 T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We will integrate measures to test: (1) differences between MDD-participants and controls; (2) associations of baseline measures with retro/prospective recurrence-rates; and (3) repeated measures changes during follow-up recurrence. This data set will allow us to study different predictors of recurrence in combination. Ethics and dissemination The local ethics committee approved this study (AMC-METC-Nr.:11/050). We will submit results for publication in peer-reviewed journals and presentation at (inter)national scientific meetings. Trial registration number NTR3768. PMID:26932139

Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder.

PubMed

Keating, Charlotte; Dawood, Tye; Barton, David A; Lambert, Gavin W; Tilbrook, Alan J

2013-04-29

Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. These outcomes demonstrate that symptoms of MDD were reduced following effective treatment with an SSRI, and further, stress physiology was unlikely to be a key factor in this outcome. Further research is required to discriminate potential differences in underlying stress physiology for individuals with MDD who respond to antidepressant treatment, relative to those who experience treatment resistance.

Sex Differences in Serum Markers of Major Depressive Disorder in the Netherlands Study of Depression and Anxiety (NESDA).

PubMed

Ramsey, Jordan M; Cooper, Jason D; Bot, Mariska; Guest, Paul C; Lamers, Femke; Weickert, Cynthia S; Penninx, Brenda W J H; Bahn, Sabine

2016-01-01

Women have a consistently higher prevalence of major depressive disorder (MDD) than men. Hypotheses implicating hypothalamic-pituitary -adrenal, -gonadal, and -thyroid axes, immune response, genetic factors, and neurotransmitters have emerged to explain this difference. However, more evidence for these hypotheses is needed and new explanations must be explored. Here, we investigated sex differences in MDD markers using multiplex immunoassay measurements of 171 serum molecules in individuals enrolled in the Netherlands Study of Depression and Anxiety (NMDD = 231; Ncontrol = 365). We found 28 sex-dependent markers of MDD, as quantified by a significant interaction between sex and log2-transformed analyte concentration in a logistic regression with diagnosis (MDD/control) as the outcome variable (p<0.05; q<0.30). Among these were a number of male-specific associations between MDD and elevated levels of proteins involved in immune response, including C-reactive protein, trefoil factor 3, cystatin-C, fetuin-A, β2-microglobulin, CD5L, FASLG receptor, and tumor necrosis factor receptor 2. Furthermore, only male MDD could be classified with an accuracy greater than chance using the measured serum analytes (area under the ROC curve = 0.63). These findings may have consequences for the generalization of inflammatory hypotheses of depression to males and females and have important implications for the development of diagnostic biomarker tests for MDD. More studies are needed to validate these results, investigate a broader range of biological pathways, and integrate this data with brain imaging, genetic, and other relevant data.

Reactive heart rate variability in male patients with first-episode major depressive disorder.

PubMed

Liang, Chih-Sung; Lee, Jia-Fu; Chen, Chia-Chi; Chang, Yue-Cune

2015-01-02

The association between cardiovascular reactivity and major depressive disorder (MDD) remains unclear. This study aimed to examine this association via reactive heart rate variability (HRV) in a well-diagnosed first-episode MDD group and a control group. A total of 160 physically healthy, drug-naive patients presenting with their first-episode MDD and 50 healthy controls were recruited. All participants underwent a 5-min electrocardiography at rest and during a mental arithmetic task. Depression severity was assessed using the Beck Depression Inventory II (BDI). HRV measures that showed between-group differences at rest did not reached significance during mental stress. In contrast, HRV measures that revealed between-group differences during stress did not reach significance at rest. In response to mental stress, HRV measures did not significantly change in both group. However, LF and HF in response to stress were different between groups. Patients with MDD revealed an increasing trend in HF and a decreasing trend in LF; conversely, healthy controls had a decreasing trend in HF and an increasing trend in LF. BDI scores correlated with changes in heart rate in the control group. The fundamental change to reactive HRV in patients with first-episode MDD appears qualitative, not quantitative. A distinctly reverse trend in reactive HRV measures were evident between these two groups. Moreover, patients with MDD showed entirely distinct changes in reactive HRV from those in resting HRV. We suggest that in patients with MDD, autonomic system shifts to sympathetic dominance at rest but toward parasympathetic dominance in response to stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Gender differences in serum testosterone and cortisol in patients with major depressive disorder compared with controls.

PubMed

Matsuzaka, Hisashi; Maeshima, Hitoshi; Kida, Sayaka; Kurita, Hirofumi; Shimano, Takahisa; Nakano, Yoshiyuki; Baba, Hajime; Suzuki, Toshihito; Arai, Heii

2013-01-01

Testosterone may have a role distinct from cortisol in the pathophysiology of depression. The hypothalamus-pituitary-adrenal (HPA) axis affects the functions of sex steroid hormones through interaction with corticotropin-releasing hormone (CRH) and gonadotropin-releasing hormone (GnRH). The objective of this study was to investigate differences in serum levels of testosterone and cortisol in male and female patients with major depressive disorder (MDD). Participants included 87 inpatients with MDD at Juntendo University Koshigaya Hospital. Serum levels of testosterone and cortisol were assessed at admission. Matched controls included 128 healthy individuals. Data from MDD patients and controls were compared separately for men and women. Correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients were assessed by sex. Effects of various factors on testosterone and cortisol were analyzed using multiple regression analysis. In male patients with MDD, a significant negative correlation was seen between testosterone levels and the "retardation" score of HAM-D. However, serum testosterone levels were not significantly different in either male or female MDD patients compared with controls. Serum testosterone was negatively associated with the number of depressive episodes in male patients with MDD. Serum cortisol levels in female patients were significantly increased compared with female controls with no significant correlations between cortisol levels and HAM-D scores. The negative correlation between the sub-score of the HAM-D and testosterone may be associated with the biological pathophysiology of male depression. Findings of serum cortisol levels in women may suggest distinct characteristics of these hormones in men and women with MDD.

Sex Differences in Serum Markers of Major Depressive Disorder in the Netherlands Study of Depression and Anxiety (NESDA)

PubMed Central

Ramsey, Jordan M.; Cooper, Jason D.; Bot, Mariska; Guest, Paul C.; Lamers, Femke; Weickert, Cynthia S.

2016-01-01

Women have a consistently higher prevalence of major depressive disorder (MDD) than men. Hypotheses implicating hypothalamic-pituitary -adrenal, -gonadal, and -thyroid axes, immune response, genetic factors, and neurotransmitters have emerged to explain this difference. However, more evidence for these hypotheses is needed and new explanations must be explored. Here, we investigated sex differences in MDD markers using multiplex immunoassay measurements of 171 serum molecules in individuals enrolled in the Netherlands Study of Depression and Anxiety (NMDD = 231; Ncontrol = 365). We found 28 sex-dependent markers of MDD, as quantified by a significant interaction between sex and log2-transformed analyte concentration in a logistic regression with diagnosis (MDD/control) as the outcome variable (p<0.05; q<0.30). Among these were a number of male-specific associations between MDD and elevated levels of proteins involved in immune response, including C-reactive protein, trefoil factor 3, cystatin-C, fetuin-A, β2-microglobulin, CD5L, FASLG receptor, and tumor necrosis factor receptor 2. Furthermore, only male MDD could be classified with an accuracy greater than chance using the measured serum analytes (area under the ROC curve = 0.63). These findings may have consequences for the generalization of inflammatory hypotheses of depression to males and females and have important implications for the development of diagnostic biomarker tests for MDD. More studies are needed to validate these results, investigate a broader range of biological pathways, and integrate this data with brain imaging, genetic, and other relevant data. PMID:27232630

Multivariate pattern analysis strategies in detection of remitted major depressive disorder using resting state functional connectivity.

PubMed

Bhaumik, Runa; Jenkins, Lisanne M; Gowins, Jennifer R; Jacobs, Rachel H; Barba, Alyssa; Bhaumik, Dulal K; Langenecker, Scott A

2017-01-01

Understanding abnormal resting-state functional connectivity of distributed brain networks may aid in probing and targeting mechanisms involved in major depressive disorder (MDD). To date, few studies have used resting state functional magnetic resonance imaging (rs-fMRI) to attempt to discriminate individuals with MDD from individuals without MDD, and to our knowledge no investigations have examined a remitted (r) population. In this study, we examined the efficiency of support vector machine (SVM) classifier to successfully discriminate rMDD individuals from healthy controls (HCs) in a narrow early-adult age range. We empirically evaluated four feature selection methods including multivariate Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net feature selection algorithms. Our results showed that SVM classification with Elastic Net feature selection achieved the highest classification accuracy of 76.1% (sensitivity of 81.5% and specificity of 68.9%) by leave-one-out cross-validation across subjects from a dataset consisting of 38 rMDD individuals and 29 healthy controls. The highest discriminating functional connections were between the left amygdala, left posterior cingulate cortex, bilateral dorso-lateral prefrontal cortex, and right ventral striatum. These appear to be key nodes in the etiopathophysiology of MDD, within and between default mode, salience and cognitive control networks. This technique demonstrates early promise for using rs-fMRI connectivity as a putative neurobiological marker capable of distinguishing between individuals with and without rMDD. These methods may be extended to periods of risk prior to illness onset, thereby allowing for earlier diagnosis, prevention, and intervention.

IRRITABLE MOOD IN ADULT MAJOR DEPRESSIVE DISORDER: RESULTS FROM THE WORLD MENTAL HEALTH SURVEYS

PubMed Central

Kovess-Masfety, Viviane; Alonso, Jordi; Angermeyer, Matthias; Bromet, Evelyn; de Girolamo, Giovanni; de Jonge, Peter; Demyttenaere, Koen; Florescu, Silvia E.; Gruber, Michael J.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Karam, Elie G.; Jin, Robert; Lépine, Jean-Pierre; Levinson, Daphna; McLaughlin, Katie A.; Medina-Mora, María E.; O’Neill, Siobhan; Ono, Yutaka; Posada-Villa, José A.; Sampson, Nancy A.; Scott, Kate M.; Shahly, Victoria; Stein, Dan J.; Viana, Maria C.; Zarkov, Zahari; Kessler, Ronald C.

2014-01-01

Background Although irritability is a core symptom of DSM-IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression-equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross-national community-based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729). Methods The assessment of MDD in the WHO Composite International Diagnostic Interview includes one question about persistent irritability. We examined two expansions of the definition of MDD involving this question: (1) cases with dysphoria and/or anhedonia and exactly four of nine Criterion A symptoms plus irritability; and (2) cases with two or more weeks of irritability plus four or more other Criterion A MDD symptoms in the absence of dysphoria or anhedonia. Results Adding irritability as a tenth Criterion A symptom increased lifetime prevalence by 0.4% (from 11.2 to 11.6%). Adding episodes of persistent irritability increased prevalence by an additional 0.2%. Proportional prevalence increases were significantly higher, but nonetheless small, among males compared to females. Rates of severe role impairment were significantly lower among respondents with this irritable depression who did not meet conventional DSM-IV criteria than those with DSM-IV MDD. Conclusion Although limited by the superficial assessment in this single question on irritability, results do not support expanding adult MDD criteria to include irritable mood. PMID:23364997

A sex-specific comparison of major depressive disorder symptomatology in the canadian forces and the general population.

PubMed

Erickson, Julie; Kinley, D Jolene; Bolton, James M; Zamorski, Mark A; Enns, Murray W; Sareen, Jitender

2014-07-01

To compare major depressive disorder (MDD) symptomatology within men and women in a large, representative sample of Canadian military personnel and civilians. We used the Canadian Community Health Survey: Mental Health and Well-Being (Cycle 1.2 and Canadian Forces Supplement) (n = 36 984 and n = 8441, respectively) to compare past-year MDD symptomatology among military and civilian women, and military and civilian men. Logistic regression models were used to determine differences in the types of depressive symptoms endorsed in each group. Men in the military with MDD were at lower odds than men in the general population to endorse numerous symptoms of depression, such as hopelessness (adjusted odds ratio [AOR] 0.44; 99% CI 0.23 to 0.83) and inability to cope (AOR 0.53; 99% CI 0.31 to 0.92). Military women with MDD were at lower odds of thinking about their death (AOR 0.52; 99% CI 0.32 to 0.86), relative to women with MDD in the general population. Different MDD symptomatology among males and females in the military, compared with those in the general population, may reflect selection effects (for example, personality characteristics and patterns of comorbidity) or occupational experiences unique to military personnel. Future research examining the mechanisms behind MDD symptomatology in military personnel and civilians is required.

A Sex-Specific Comparison of Major Depressive Disorder Symptomatology in the Canadian Forces and the General Population

PubMed Central

Erickson, Julie; Kinley, D Jolene; Bolton, James M; Zamorski, Mark A; Enns, Murray W; Sareen, Jitender

2014-01-01

Objective: To compare major depressive disorder (MDD) symptomatology within men and women in a large, representative sample of Canadian military personnel and civilians. Method: We used the Canadian Community Health Survey: Mental Health and Well-Being (Cycle 1.2 and Canadian Forces Supplement) (n = 36 984 and n = 8441, respectively) to compare past-year MDD symptomatology among military and civilian women, and military and civilian men. Logistic regression models were used to determine differences in the types of depressive symptoms endorsed in each group. Results: Men in the military with MDD were at lower odds than men in the general population to endorse numerous symptoms of depression, such as hopelessness (adjusted odds ratio [AOR] 0.44; 99% CI 0.23 to 0.83) and inability to cope (AOR 0.53; 99% CI 0.31 to 0.92). Military women with MDD were at lower odds of thinking about their death (AOR 0.52; 99% CI 0.32 to 0.86), relative to women with MDD in the general population. Conclusion: Different MDD symptomatology among males and females in the military, compared with those in the general population, may reflect selection effects (for example, personality characteristics and patterns of comorbidity) or occupational experiences unique to military personnel. Future research examining the mechanisms behind MDD symptomatology in military personnel and civilians is required. PMID:25007423

Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity

PubMed Central

Pantazatos, Spiro P.; Huang, Yung-yu; Rosoklija, Gorazd B.; Dwork, Andrew J.; Arango, Victoria; Mann, J. John

2016-01-01

Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing (NGS) approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden-death medication-free individuals postmortem. Using small RNA-seq, we also examined miRNA expression (9 samples per group). DeSeq2 identified thirty-five genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted p<0.1). In depression, altered genes include humanin like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted p<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted p<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorders. PMID:27528462

Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity.

PubMed

Pantazatos, S P; Huang, Y-Y; Rosoklija, G B; Dwork, A J; Arango, V; Mann, J J

2017-05-01

Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted P<0.1). In depression, altered genes include humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted P<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted P<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorders.

Neutral face distractors differentiate performance between depressed and healthy adolescents during an emotional working memory task.

PubMed

Tavitian, Lucy R; Ladouceur, Cecile D; Nahas, Ziad; Khater, Beatrice; Brent, David A; Maalouf, Fadi T

2014-08-01

The aim of the present study is to examine the effect of neutral and emotional facial expressions on voluntary attentional control using a working memory (WM) task in adolescents with major depressive disorder (MDD). We administered the Emotional Face n-back (EFNBACK) task, a visual WM task with neutral, happy and angry faces as distractors to 22 adolescents with MDD (mean age 15.7 years) and 21 healthy controls (HC) (mean age 14.7 years). There was a significant group by distractor type interaction (p = 0.045) for mean percent accuracy rates. Group comparisons showed that MDD youth were less accurate on neutral trials than HC (p = 0.027). The two groups did not differ on angry, happy and blank trials (p > 0.05). Reaction time did not differ across groups. In addition, when comparing the differences between accuracies on neutral trials and each of the happy and angry trials, respectively [(HAP-NEUT) and (ANG-NEUT)], there was a group effect on (HAP-NEUT) where the difference was larger in MDD than HC (p = 0.009) but not on ANG-NEUT (p > 0.05). Findings were independent of memory load. Findings indicate that attentional control to neutral faces is impaired and negatively affected performance on a WM task in adolescents with MDD. Such an impact of neutral faces on attentional control in MDD may be at the core of the social-cognitive impairment observed in this population.

Differences in serotonin transporter binding affinity in patients with major depressive disorder and night eating syndrome.

PubMed

Lundgren, J D; Amsterdam, J; Newberg, A; Allison, K C; Wintering, N; Stunkard, A J

2009-03-01

We examined serotonin transporter (SERT) binding affinity using single photon emission computed tomography (SPECT) in patients with major depressive disorder (MDD) and night eating syndrome (NES). There are similarities between MDD and NES in affective symptoms, appetite disturbance, nighttime awakenings, and, particularly, response to selective serotonin reuptake inhibitors (SSRIs). Six non-depressed patients with NES and seven patients with MDD underwent SPECT brain imaging with 123I-ADAM, a radiopharmaceutical agent selective for SERT sites. Uptake ratios of 123I-ADAM SERT binding were obtained for the midbrain, basal ganglia, and temporal lobe regions compared to the cerebellum reference region. Patients with NES had significantly greater SERT uptake ratios (effect size range 0.64-0.84) in the midbrain, right temporal lobe, and left temporal lobe regions than those with MDD whom we had previously studied. Pathophysiological differences in SERT uptake between patients with NES and MDD suggest these are distinct clinical syndromes.

Daily emotional dynamics in depressed youth: a cell phone ecological momentary assessment study.

PubMed

Silk, Jennifer S; Forbes, Erika E; Whalen, Diana J; Jakubcak, Jennifer L; Thompson, Wesley K; Ryan, Neal D; Axelson, David A; Birmaher, Boris; Dahl, Ronald E

2011-10-01

This study used a new cell phone ecological momentary assessment approach to investigate daily emotional dynamics in 47 youths with major depressive disorder (MDD) and 32 no-psychopathology controls (CON) (ages 7-17 years). Information about emotional experience in the natural environment was obtained using answer-only cell phones, while MDD youths received an 8-week course of cognitive behavioral therapy and/or psychopharmacological treatment. Compared with CON youths, MDD youths reported more intense and labile global negative affect; greater sadness, anger, and nervousness; and a lower ratio of positive to negative affect. These differences increased with pubertal maturation. MDD youths spent more time alone and less time with their families than CON youths. Although differences in emotional experiences were found across social contexts, MDD youths were more negative than CON youths in all contexts examined. As the MDD participants progressed through treatment, diagnostic group differences in the intensity and lability of negative affect decreased, but there were no changes in the ratio of positive to negative affect or in measures of social context. We discuss methodological innovations and advantages of this approach, including improved ecological validity and access to information about variability in emotions, change in emotions over time, the balance of positive and negative emotions, and the social context of emotional experience. Copyright © 2010 Elsevier Inc. All rights reserved.

[Affective and cognitive decision making in major depression: influence of the prefrontal cortex, serotonin transporter genotype and personality traits].

PubMed

Must, Anita; Horváth, Szatmár; Janka, Zoltán

2008-05-30

Patients with major depressive disorder (MDD) show neuropsychological impairments, including deficient executive functions and suboptimal decision-making strategies, which are mediated by several brain regions. In the development of these symptoms the pathology of the prefrontal cortex (PFC), including the dorsolateral, ventromedial and orbitofrontal regions, may also play an important role. Neuropsychological assessment is a useful tool in detecting and measuring these deficiencies, showing that patients with MDD exhibit altered sensitivity to reward and punishment. However, impairment of emotional decision-making strategies in MDD is influenced by genetic variations (5-HTTLPR polymorphism) and personality traits, which seem to have a higher predictive value on decision making performance than the clinical symptoms.

The Role of Attention to Emotion in Recovery from Major Depressive Disorder

PubMed Central

Thompson, Renee J.; Mata, Jutta; Jaeggi, Susanne M.; Buschkuehl, Martin; Jonides, John; Gotlib, Ian H.

2013-01-01

Major Depressive Disorder (MDD) is characterized by several emotional disturbances. One possible but not well-examined disturbance is in attention to emotion, an important facet of emotional awareness. We examined whether attention to emotion predicted recovery from MDD. Fifty-three adults with current MDD completed a week of experience sampling (Time 1). At each prompt, participants reported attention to emotion, negative affect (NA), and positive affect (PA). Approximately one year later (Time 2), the depressive status of 27 participants was reassessed. Participants who had recovered from MDD (n = 8) indicated paying less attention to their emotions at Time 1 than did participants who had not fully recovered (n = 19). Attention to emotion was better predictor of recovery than was severity of MDD, NA, or PA at Time 1. Levels of attention to emotion at Time 1 in participants who recovered from MDD did not differ significantly from the levels reported by 53 never-depressed individuals who had participated in the experience sampling. Findings indicate that high levels of an otherwise adaptive emotional facet can adversely affect the course of MDD. PMID:23853719

Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: (18)F-florbetapir (AV-45/Amyvid) PET study.

PubMed

Wu, Kuan-Yi; Liu, Chia-Yih; Chen, Cheng-Sheng; Chen, Chia-Hsiang; Hsiao, Ing-Tsung; Hsieh, Chia-Ju; Lee, Chin-Pang; Yen, Tzu-Chen; Lin, Kun-Ju

2016-06-01

The objective of this study was to evaluate the amyloid burden, as assessed by (18)F-florbetapir (AV-45/Amyvid) positron emission tomography PET, in patients with major depressive disorder (MDD) with different subtypes of mild cognitive impairment (MCI) and the relationship between amyloid burden and cognition in MDD patients. The study included 55 MDD patients without dementia and 21 healthy control subjects (HCs) who were assessed using a comprehensive cognitive test battery and (18)F-florbetapir PET imaging. The standardized uptake value ratios (SUVR) in eight cortical regions using the whole cerebellum as reference region were determined and voxel-wise comparisons between the HC and MDD groups were performed. Vascular risk factors, serum homocysteine level and the apolipoprotein E (ApoE) genotype were also determined. Among the 55 MDD patients, 22 (40.0 %) had MCI, 12 (21.8 %) non-amnestic MCI (naMCI) and 10 (18.2 %) amnestic MCI (aMCI). The MDD patients with aMCI had the highest relative (18)F-florbetapir uptake in all cortical regions, and a significant difference in relative (18)F-florbetapir uptake was found in the parietal region as compared with that in naMCI subjects (P < 0.05) and HCs (P < 0.01). Voxel-wise analyses revealed significantly increased relative (18)F-florbetapir uptake in the MDD patients with aMCI and naMCI in the frontal, parietal, temporal and occipital areas (P < 0.005). The global cortical SUVR was significantly negatively correlated with MMSE score (r = -0.342, P = 0.010) and memory function (r = -0.328, P = 0.015). The negative correlation between the global SUVR and memory in the MDD patients remained significant in multiple regression analyses that included age, educational level, ApoE genotype, and depression severity (β = -3.607, t = -2.874, P = 0.006). We found preliminary evidence of brain beta-amyloid deposition in MDD patients with different subtypes of MCI. Our findings in MDD patients support the hypothesis that a higher amyloid burden is associated with a poorer memory performance. We also observed a high prevalence of MCI among elderly depressed patients, and depressed patients with MCI exhibited heterogeneously elevated (18)F-florbetapir retention as compared with depressed patients without MCI. The higher amyloid burden in the aMCI patients suggests that these patients may also be more likely to develop Alzheimer's disease than other patients diagnosed with major depression.

Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

PubMed Central

Chen, Jian-Huai; Yao, Zhi-Jian; Qin, Jiao-Long; Yan, Rui; Hua, Ling-Ling; Lu, Qing

2016-01-01

Background: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. Methods: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. Results: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network. PMID:26960371

DNA methylation and expression of stress related genes in PBMC of MDD patients with and without serious suicidal ideation.

PubMed

Roy, Bhaskar; Shelton, Richard C; Dwivedi, Yogesh

2017-06-01

Stress plays an important role in major depressive disorder (MDD) and is one of the state dependent factors in suicidal behavior. A dysfunctional hypothalamic-pituitary-adrenal axis is a common feature in this disorder. The involvement of environmental factors has added additional complexity to understanding depression or suicidal behavior. In this regard, epigenetic regulation has been considered a mechanistic interface between environmental stress stimuli and altered functioning of underlying gene network that may increase susceptibility to depression or suicidal behavior. The present study examined whether epigenetic modifications of stress related genes are associated with MDD and whether there are differences in these epigenetic marks between depressed individuals with and without serious suicidal ideation. Using MeDIP analysis in genomic DNA isolated from peripheral blood mononuclear cells (PBMC) of healthy controls (n = 20), MDD patients with (n = 14) or without serious suicidal ideation (n = 10), we studied methylation of the stress-associated genes, Brain Derived Neurotrophic Factor (BDNF), Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1), FK506 Binding Protein 5 (FKBP5), Corticotropin Releasing Hormone Binding Protein (CRHBP), and Corticotropin Releasing Hormone Receptor 1 (CRHR1). In addition, we determined their transcript levels in RNAs isolated from the same PBMC. We found that BDNF, FKBP5, CRHBP, and NR3C1 gene promoters were significantly hypermethylated in MDD patients with and without suicidal ideation. We also found concomitant reductions in expression of BDNF, FKBP5 transcript variants (1, 2 and 3), and NR3C1 genes in these patients, suggesting that promoter hypermethylation in these genes may functionally be associated with their observed downregulation in MDD patients. In a secondary analysis, methylation of these genes was compared between MDD patients with or without serious suicidal ideation and controls. The MDD with serious suicidal ideation were significantly different from controls while the MDD without were not, although MDD with or without suicidal ideation were not different from each other, likely owning to a relatively small sample size. Thus, our findings underline the importance of epigenetic modifications of stress-associated genes in depression and, possibly, suicidal behavior, which, in future, needs to be confirmed in a larger patient population. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Mistreatment of Major Depressive Disorder

PubMed Central

Paris, Joel

2014-01-01

Objective: To examine the effects of classification on treatment in major depressive disorder (MDD). Method: This is a narrative review. Results: MDD is a highly heterogeneous category, leading to problems in classification and in specificity of treatment. Current models classify all depressions within a single category. However, the construct of MDD obscures important differences between severe disorders that require pharmacotherapy, and mild-to-moderate disorders that can respond to psychotherapy or remit spontaneously. Patients with mild-to-moderate MDD are being treated with routine or overly aggressive pharmacotherapy. Conclusions: The current classification fails to address the heterogeneity of depression, leading to mistreatment. PMID:24881163

Association of Symptom Network Structure With the Course of [corrected] Depression.

PubMed

van Borkulo, Claudia; Boschloo, Lynn; Borsboom, Denny; Penninx, Brenda W J H; Waldorp, Lourens J; Schoevers, Robert A

2015-12-01

Major depressive disorder (MDD) is a heterogeneous condition in terms of symptoms, course, and underlying disease mechanisms. Current classifications do not adequately address this complexity. In novel network approaches to psychopathology, psychiatric disorders are conceptualized as complex dynamic systems of mutually interacting symptoms. This perspective implies that a more densely connected network of symptoms is indicative of a poorer prognosis, but, to date, no previous study has examined whether network structure is indeed associated with the longitudinal course of MDD. To examine whether the baseline network structure of MDD symptoms is associated with the longitudinal course of MDD. In this prospective study, in which remittent and persistent MDD was defined on the basis of a follow-up assessment after 2 years, 515 patients from the Netherlands Study of Depression and Anxiety with past-year MDD (established with the Composite International Diagnostic Interview) and at least moderate depressive symptoms (assessed with the Inventory of Depressive Symptomatology [IDS]) at baseline were studied. Baseline starting and ending dates were September 1, 2004, through February 28, 2007. Follow-up starting and ending dates were September 1, 2006, through February 28, 2009. Analysis was conducted August 2015. The MDD was considered persistent if patients had at least moderate depressive symptoms (IDS) at 2-year follow-up; otherwise, the MDD was considered remitted. Sparse network structures of baseline MDD symptoms assessed via IDS were computed. Global and local connectivity of network structures were compared across persisters and remitters using a permutation test. Among the 515 patients, 335 (65.1%) were female, mead (SD) age was 40.9 (12.1) years, and 253 (49.1%) had persistent MDD at 2-year follow-up. Persisters (n = 253) had a higher baseline IDS sum score than remitters (n = 262) (mean [SD] score, 40.2 [8.9] vs 35.1 [7.1]; the test statistic for the difference in IDS sum score was 22 027; P < .001). The test statistic for the difference in network connectivity was 1.79 (P = .01) for the original data, 1.55 for data matched on IDS sum score (P = .04), and 1.65 for partialed out data (P = .02). At the symptom level, fatigue or loss of energy and feeling guilty had the largest difference in importance in persisters' network compared with that of remitters (Cohen d = 1.13 and 1.18, respectively). This study reports that symptom networks of patients with MDD are related to longitudinal course: persisters exhibited a more densely connected network at baseline than remitters. More pronounced associations between symptoms may be an important determinant of persistence in MDD.

Personality in remitted major depressive disorder with single and recurrent episodes assessed with the Temperament and Character Inventory.

PubMed

Teraishi, Toshiya; Hori, Hiroaki; Sasayama, Daimei; Matsuo, Junko; Ogawa, Shintaro; Ishida, Ikki; Nagashima, Anna; Kinoshita, Yukiko; Ota, Miho; Hattori, Kotaro; Higuchi, Teruhiko; Kunugi, Hiroshi

2015-01-01

Previous studies consistently reported increased harm avoidance (HA) assessed with the Temperament and Character Inventory (TCI) in patients with major depressive disorder (MDD). However, such findings may have been related with depression severity and number of depressive episodes. The aims of the present study were twofold: to examine TCI personality profile in remitted MDD (DSM-IV) patients and to compare TCI personality between MDD patients with single episode (SGL-MDD) and those with recurrent episodes (REC-MDD) in order to elucidate personality profile associated with recurrence. TCI was administered to 86 outpatients with remitted SGL-MDD (12 male and 17 female patients; mean age 43.2 ± 12.1 years) and REC-MDD (26 male and 31 female patients; 40.3 ± 11.6 years), and 529 healthy controls (225 men and 304 women; 43.4 ± 15.5 years), matched for age, sex and education years. Logistic regression analyses were performed in which single/recurrent episodes of depression were the dependent variable and age, sex, age of onset, family history of psychiatric disease and TCI scores were entered as possible predictors. The remitted MDD patients had significantly higher scores on HA (P < 0.001) and lower scores on self-directedness (P < 0.001), compared with the controls. HA (P = 0.03), its subscore, fatigability (P = 0.03), and family history of psychiatric disease were found to be positive predictors for recurrence. There are differences in personality profile between remitted MDD patients and controls, and between remitted REC-MDD and SGL-MDD patients, suggesting that they are trait markers. HA and fatigability might be useful to assess risk for recurrence of depression. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Examining the latent structure mechanisms for comorbid posttraumatic stress disorder and major depressive disorder.

PubMed

Hurlocker, Margo C; Vidaurri, Desirae N; Cuccurullo, Lisa-Ann J; Maieritsch, Kelly; Franklin, C Laurel

2018-03-15

Posttraumatic stress disorder (PTSD) is a complex psychiatric illness that can be difficult to diagnose, due in part to its comorbidity with major depressive disorder (MDD). Given that researchers have found no difference in prevalence rates of PTSD and MDD after accounting for overlapping symptoms, the latent structures of PTSD and MDD may account for the high comorbidity. In particular, the PTSD Negative Alterations in Cognition and Mood (NACM) and Hyperarousal factors have been characterized as non-specific to PTSD. Therefore, we compared the factor structures of the Diagnostic and Statistical Manual of Mental Disorders, 5 th edition (DSM-5) PTSD and MDD and examined the mediating role of the PTSD NACM and Hyperarousal factors on the relationship between MDD and PTSD symptom severity. Participants included 598 trauma-exposed veterans (M age = 48.39, 89% male) who completed symptom self-report measures of DSM-5 PTSD and MDD. Confirmatory factor analyses indicated an adequate-fitting four-factor DSM-5 PTSD model and two-factor MDD model. Compared to other PTSD factors, the PTSD NACM factor had the strongest relationship with the MDD Affective factor, and the PTSD NACM and Hyperarousal factors had the strongest association with the MDD Somatic factor. Further, the PTSD NACM factor explained the relationship between MDD factors and PTSD symptom severity. More Affective and Somatic depression was related to more NACM symptoms, which in turn were related to increased severity of PTSD. Limitations include the reliance on self-report measures and the use of a treatment-seeking, trauma-exposed veteran sample which may not generalize to other populations. Implications concerning the shared somatic complaints and psychological distress in the comorbidity of PTSD and MDD are discussed. Published by Elsevier B.V.

Dissection of major depressive disorder using polygenic risk scores for schizophrenia in two independent cohorts.

PubMed

Whalley, H C; Adams, M J; Hall, L S; Clarke, T-K; Fernandez-Pujals, A M; Gibson, J; Wigmore, E; Hafferty, J; Hagenaars, S P; Davies, G; Campbell, A; Hayward, C; Lawrie, S M; Porteous, D J; Deary, I J; McIntosh, A M

2016-11-01

Major depressive disorder (MDD) is known for its substantial clinical and suspected causal heterogeneity. It is characterized by low mood, psychomotor slowing and increased levels of the personality trait neuroticism; factors also associated with schizophrenia (SCZ). It is possible that some cases of MDD may have a substantial genetic loading for SCZ. The presence of SCZ-like MDD subgroups would be indicated by an interaction between MDD status and polygenic risk of SCZ on cognitive, personality and mood measures. Here, we hypothesized that higher SCZ polygenic risk would define larger MDD case-control differences in cognitive ability, and smaller differences in distress and neuroticism. Polygenic risk scores (PRSs) for SCZ and their association with cognitive variables, neuroticism, mood and psychological distress were estimated in a large population-based cohort (Generation Scotland: Scottish Family Health Study, GS:SFHS). The individuals were divided into those with, and without, depression (n=2587 and n=16 764, respectively) to test for the interactions between MDD status and schizophrenia risk. Replication was sought in UK Biobank (UKB; n=6049 and n=27 476 cases and controls, respectively). In both the cohorts, we found significant interactions between SCZ-PRS and MDD status for measures of psychological distress (β GS =-0.04, P GS =0.014 and β UKB =-0.09, P UKB ⩽0.001 for GS:SFHS and UKB, respectively) and neuroticism (β GS =-0.04, P GS =0.002 and β UKB =-0.06, P UKB =0.023). In both the cohorts, there was a reduction of case-control differences on a background of higher genetic risk of SCZ. These findings suggest that depression on a background of high genetic risk for SCZ may show attenuated associations with distress and neuroticism. This may represent a causally distinct form of MDD more closely related to SCZ.

Implicit and Explicit Self-Esteem in Current, Remitted, Recovered, and Comorbid Depression and Anxiety Disorders: The NESDA Study.

PubMed

van Tuijl, Lonneke A; Glashouwer, Klaske A; Bockting, Claudi L H; Tendeiro, Jorge N; Penninx, Brenda W J H; de Jong, Peter J

2016-01-01

Dual processing models of psychopathology emphasize the relevance of differentiating between deliberative self-evaluative processes (explicit self-esteem; ESE) and automatically-elicited affective self-associations (implicit self-esteem; ISE). It has been proposed that both low ESE and ISE would be involved in major depressive disorder (MDD) and anxiety disorders (AD). Further, it has been hypothesized that MDD and AD may result in a low ISE "scar" that may contribute to recurrence after remission. However, the available evidence provides no straightforward support for the relevance of low ISE in MDD/AD, and studies testing the relevance of discrepant SE even showed that especially high ISE combined with low ESE is predictive of the development of internalizing symptoms. However, these earlier findings have been limited by small sample sizes, poorly defined groups in terms of comorbidity and phase of the disorders, and by using inadequate indices of discrepant SE. Therefore, this study tested further the proposed role of ISE and discrepant SE in a large-scale study allowing for stricter differentiation between groups and phase of disorder. In the context of the Netherlands Study of Depression and Anxiety (NESDA), we selected participants with current MDD (n = 60), AD (n = 111), and comorbid MDD/AD (n = 71), remitted MDD (n = 41), AD (n = 29), and comorbid MDD/AD (n = 14), recovered MDD (n = 136) and AD (n = 98), and never MDD or AD controls (n = 382). The Implicit Association Test was used to index ISE and the Rosenberg Self-Esteem Scale indexed ESE. Controls reported higher ESE than all other groups, and current comorbid MDD/AD had lower ESE than all other clinical groups. ISE was only lower than controls in current comorbid AD/MDD. Discrepant self-esteem (difference between ISE and ESE) was not associated with disorder status once controlling for ESE. Cross-sectional design limits causal inferences. Findings suggest a prominent role for ESE in MDD and AD, while in comorbid MDD/AD negative self-evaluations are also present at the implicit level. There was no evidence to support the view that AD and MDD would result in a low ISE "scar".

Learning from negative feedback in patients with major depressive disorder is attenuated by SSRI antidepressants

PubMed Central

Herzallah, Mohammad M.; Moustafa, Ahmed A.; Natsheh, Joman Y.; Abdellatif, Salam M.; Taha, Mohamad B.; Tayem, Yasin I.; Sehwail, Mahmud A.; Amleh, Ivona; Petrides, Georgios; Myers, Catherine E.; Gluck, Mark A.

2013-01-01

One barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs. learning from negative feedback (punishment). Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject’s relative sensitivity to positive vs. negative feedback showed that both the medicated MDD and HC groups conform to Kahneman and Tversky’s (1979) Prospect Theory, which expects losses (negative feedback) to loom psychologically slightly larger than gains (positive feedback). However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not “normal” when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the cognitive consequences of MDD from those of SSRI treatment, and from cognitive evaluation of MDD subjects in a medication-naïve state before the administration of antidepressants. Future research is needed to correlate the mood-elevating effects and the cognitive balance between reward- and punishment-based learning related to SSRIs. PMID:24065894

Learning from negative feedback in patients with major depressive disorder is attenuated by SSRI antidepressants.

PubMed

Herzallah, Mohammad M; Moustafa, Ahmed A; Natsheh, Joman Y; Abdellatif, Salam M; Taha, Mohamad B; Tayem, Yasin I; Sehwail, Mahmud A; Amleh, Ivona; Petrides, Georgios; Myers, Catherine E; Gluck, Mark A

2013-01-01

One barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs. learning from negative feedback (punishment). Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject's relative sensitivity to positive vs. negative feedback showed that both the medicated MDD and HC groups conform to Kahneman and Tversky's (1979) Prospect Theory, which expects losses (negative feedback) to loom psychologically slightly larger than gains (positive feedback). However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not "normal" when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the cognitive consequences of MDD from those of SSRI treatment, and from cognitive evaluation of MDD subjects in a medication-naïve state before the administration of antidepressants. Future research is needed to correlate the mood-elevating effects and the cognitive balance between reward- and punishment-based learning related to SSRIs.

Abnormal Functional Brain Asymmetry in Depression: Evidence of Biologic Commonality Between Major Depression and Dysthymia

PubMed Central

Bruder, Gerard E.; Stewart, Jonathan W.; Hellerstein, David; Alvarenga, Jorge E.; Alschuler, Daniel; McGrath, Patrick J.

2012-01-01

Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having “pure” dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or “pure” dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening. PMID:22397909

Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

PubMed

Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J

2012-04-30

Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The intra-day dynamics of affect, self-esteem, tiredness, and suicidality in Major Depression.

PubMed

Crowe, Eimear; Daly, Michael; Delaney, Liam; Carroll, Susan; Malone, Kevin M

2018-02-21

Despite growing interest in the temporal dynamics of Major Depressive Disorder (MDD), we know little about the intra-day fluctuations of key symptom constructs. In a study of momentary experience, the Experience Sampling Method captured the within-day dynamics of negative affect, positive affect, self-esteem, passive suicidality, and tiredness across clinical MDD (N= 31) and healthy control groups (N= 33). Ten symptom measures were taken per day over 6 days (N= 2231 observations). Daily dynamics were modeled via intra-day time-trends, variability, and instability in symptoms. MDD participants showed significantly increased variability and instability in negative affect, positive affect, self-esteem, and suicidality. Significantly different time-trends were found in positive affect (increased diurnal variation and an inverted U-shaped pattern in MDD, compared to a positive linear trend in controls) and tiredness (decreased diurnal variation in MDD). In the MDD group only, passive suicidality displayed a negative linear trend and self-esteem displayed a quadratic inverted U trend. MDD and control participants thus showed distinct dynamic profiles in all symptoms measured. As well as the overall severity of symptoms, intra-day dynamics appear to define the experience of MDD symptoms. Copyright © 2018 Elsevier B.V. All rights reserved.

Elevated Hippocampal Cholinergic Neurostimulating Peptide precursor protein (HCNP-pp) mRNA in the amygdala in major depression.

PubMed

Bassi, Sabrina; Seney, Marianne L; Argibay, Pablo; Sibille, Etienne

2015-04-01

The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N = 16 pairs; males: N = 12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N = 6 pairs; males: N = 6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p < 0.0001), but not males, and of UCMS-exposed mice (males and females; p = 0.037). HCNP-pp protein levels were investigated in the human female cohort, but no difference was found. There were no differences in gene expression of acetylcholinesterase (AChE), muscarinic (mAChRs) or nicotinic receptors (nAChRs) between MDD subjects and controls or UCMS and control mice, except for an up-regulation of AChE in UCMS-exposed mice (males and females; p = 0.044). Exploratory analyses revealed a baseline expression difference of cholinergic signaling-related genes between women and men (p < 0.0001). In conclusion, elevated amygdala HCNP-pp expression may contribute to mechanisms of MDD in women, potentially independently from regulating the cholinergic system. The differential expression of genes between women and men could also contribute to the increased vulnerability of females to develop MDD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression.

PubMed

Lirng, Jiing-Feng; Chen, Hung-Chieh; Fuh, Jong-Ling; Tsai, Chia-Fen; Liang, Jen-Feng; Wang, Shuu-Jiun

2015-07-01

Although the comorbidity between migraine and major depressive disorder (MDD) has been recognized, the pathophysiology remains unclear. The dorsolateral prefrontal cortex (DLPFC) is a well-known neural substrate for MDD. We investigated the relationship between brain metabolites in DLPFC and comorbid MDD in migraine patients. We recruited migraine patients from a tertiary headache clinic. A board-certified psychiatrist conducted a structured interview for MDD diagnosis. The severity of depression was evaluated by the Beck Depression Inventory (BDI). Thirty migraine patients (five men, 25 women; mean age: 40.4 ± 12.4 years) completed the study, and 16 of them were diagnosed with MDD. All patients underwent a magnetic resonance spectroscopy (MRS) examination focusing on bilateral DLPFC. The ratios of N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI) to total creatine (tCr) were compared between migraine patients with and without MDD, and were correlated with BDI scores. Relative to patients without MDD, migraine patients with MDD had higher mI/tCr ratios in the bilateral DLPFC (p = 0.02, left; p = 0.02, right, Mann-Whitney U test). The mI/tCr ratios in the right DLPFC were positively correlated with BDI scores (r = 0.52, p = 0.003). The NAA/tCr and Cho/tCr ratios did not differ between migraine patients with and without MDD. Increased mI/tCr within the DLPFC might be associated with the presence of MDD in migraine patients. © International Headache Society 2014.

The gender-specific association of rs334558 in GSK3β with major depressive disorder.

PubMed

Liu, Sha; Wang, Le; Sun, Ning; Yang, Chunxia; Liu, Zhifen; Li, Xinrong; Cao, Xiaohua; Xu, Yong; Zhang, Kerang

2017-01-01

Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with a heritability ranging from 40% to 50%. The single nucleotide polymorphism (SNP) rs334558 on the glycogen synthase kinase-3β (GSK3β) gene has been identified as a genetic risk loci associated with schizophrenia and bipolar disorder. However, results from replication studies examining the association between rs334558 and MDD remain inconsistent.In the present study, first, we conducted a meta-analysis of the association between rs334558 and MDD by combining 5 available case-control samples totaling 2311 cases and 2535 controls. Second, genotyping data from patients with MDD at our institution, after further stratification by gender, were analyzed to determine the association between rs334558 and MDD.All studies retrieved and included in the meta-analysis were from Korea and China. The meta-analysis suggested that the functional polymorphism rs334558 within the GSK3β promoter region was associated with MDD risk (P < 0.05). The associations were observed both in the allelic and genetic models. Analysis of the genotyping data extracted from our hospital database revealed that rs334558 exhibited exclusive association with MDD in female patients (P=0.015).Our findings suggest that GSK3β rs334558 polymorphisms might be a potential risk for MDD, and females with GSK3β rs334558 polymorphisms might have higher penetrance of MDD. If validated in larger scale samples and in different ethnic populations, these findings might be of value as diagnostic references for MDD.

Different patterns of local field potentials from limbic DBS targets in patients with major depressive and obsessive compulsive disorder

PubMed Central

Neumann, W-J; Huebl, J; Brücke, C; Gabriëls, L; Bajbouj, M; Merkl, A; Schneider, G-H; Nuttin, B; Brown, P; Kühn, AA

2016-01-01

The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8–14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n = 14, r = 0.55, P = 0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD. PMID:24514569

Chronic and Episodic Stress in Children of Depressed Mothers.

PubMed

Feurer, Cope; Hammen, Constance L; Gibb, Brandon E

2016-01-01

The goal of this study was to examine chronic and episodic stress in children of mothers with and without a history of major depressive disorder (MDD) during the children's lives. Participants were 255 mothers selected according to their history of MDD (present vs. absent during child's life) and their children (age 8-14; 53% girls, 81% Caucasian). Mothers' and children's histories of MDD were assessed using diagnostic interviews, and their depressive symptoms were assessed via self-report measures. Children's levels of chronic and episodic stress were assessed using a semistructured contextual threat interview. Children of mothers with a history of recurrent MDD, compared to single MDD or no depression, experienced more chronic stress within several domains including peers, mother-child relations, and other family member relations as well as greater episodic dependent interpersonal stress. Each of these group differences was maintained after excluding children with a history of MDD themselves and controlling for their current depressive symptoms. However, only the group difference in chronic peer stress was maintained when controlling for mothers' current depression. The results suggest that children exposed to recurrent maternal MDD experience higher levels of both chronic and episodic stress, at least some of which they contribute to themselves (dependent interpersonal stress) and which is at least partially independent of the effects of children's depression. In addition, much of this stress is associated primarily with current depression in the mother, though it appears that chronic peer stress may remain elevated even after the remission of maternal depression.

Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder

PubMed Central

Kitzlerová, Eva; Lelková, Petra; Jirák, Roman; Zvěřová, Martina; Hroudová, Jana; Manukyan, Ada; Martásek, Pavel; Raboch, Jiří

2018-01-01

Background Several genetic susceptibility loci for major depressive disorder (MDD) or Alzheimer’s disease (AD) have been described. Interactions among polymorphisms are thought to explain the differences between low- and high-risk groups. We tested for the contribution of interactions between multiple functional polymorphisms in the risk of MDD or AD. Material/Methods A genetic association case-control study was performed in 68 MDD cases, 84 AD cases (35 of them with comorbid depression), and 90 controls. The contribution of 7 polymorphisms from 5 genes (APOE, HSPA1A, SLC6A4, HTR2A, and BDNF) related to risk of MDD or AD development was analyzed. Results Significant associations were found between MDD and interactions among polymorphisms in HSPA1A, SLC6A4, and BDNF or HSPA1A, BDNF, and APOE genes. For polymorphisms in the APOE gene in AD, significant differences were confirmed on the distributions of alleles and genotype rates compared to the control or MDD. Increased probability of comorbid depression was found in patients with AD who do not carry the ɛ4 allele of APOE. Conclusions Assessment of the interactions among polymorphisms of susceptibility loci in both MDD and AD confirmed a synergistic effect of genetic factors influencing inflammatory, serotonergic, and neurotrophic pathways at these heterogenous complex diseases. The effect of interactions was greater in MDD than in AD. A presence of the ɛ4 allele was confirmed as a genetic susceptibility factor in AD. Our findings indicate a role of APOE genotype in onset of comorbid depression in a subgroup of patients with AD who are not carriers of the APOE ɛ4 allele. PMID:29703883

Stability and change in etiological factors for alcohol use disorder and major depression.

PubMed

Torvik, Fartein Ask; Rosenström, Tom Henrik; Ystrom, Eivind; Tambs, Kristian; Røysamb, Espen; Czajkowski, Nikolai; Gillespie, Nathan; Knudsen, Gun Peggy; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

2017-08-01

Alcohol use disorder (AUD) and major depressive disorder (MDD) are often comorbid. It is not understood how genetic risk factors for these disorders relate to each other over time and to what degree they are stable. Age-dependent characteristics of the disorders indicate that different genetic factors could be relevant at different stages of life, and MDD may become increasingly correlated with AUD over time. DSM-IV diagnoses of AUD and MDD were assessed by interviews of 2,801 young adult twins between 1999 and 2004 (T1) and 2,284 of the same twins between 2010 and 2011 (T2). Stability, change, and covariation were investigated in longitudinal biometric models. New genetic factors explained 56.4% of the genetic variance in AUD at T2. For MDD, there was full overlap between genetic influences at T1 and T2. Genetic risk factors for MDD were related to AUD, but their association with AUD did not increase over time. Thus, genetic risk factors for AUD, but not MDD, vary with age, suggesting that AUD has age-dependent heritable etiologies. Molecular genetic studies of AUD may therefore benefit from stratifying by age. The new genetic factors in AUD were not related to MDD. Environmental influences on the 2 disorders were correlated in middle, but not in young adulthood. The environmental components for AUD correlated over time (r = .27), but not for MDD. Environmental influences on AUD can have long-lasting effects, and the effects of preventive efforts may be enduring. Environment influences seem to be largely transient. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Cortical thickness differences between bipolar depression and major depressive disorder.

PubMed

Lan, Martin J; Chhetry, Binod Thapa; Oquendo, Maria A; Sublette, M Elizabeth; Sullivan, Gregory; Mann, J John; Parsey, Ramin V

2014-06-01

Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to differentiate BD and MDD could help clinicians avoid risks of treating BD with antidepressants without mood stabilizers. Cortical thickness differences were assessed using magnetic resonance imaging in BD depressed patients (n = 18), MDD depressed patients (n = 56), and healthy volunteers (HVs) (n = 54). A general linear model identified clusters of cortical thickness difference between diagnostic groups. Compared to the HV group, the BD group had decreased cortical thickness in six regions, after controlling for age and sex, located within the frontal and parietal lobes, and the posterior cingulate cortex. Mean cortical thickness changes in clusters ranged from 7.6 to 9.6% (cluster-wise p-values from 1.0 e-4 to 0.037). When compared to MDD, three clusters of lower cortical thickness in BD were identified that overlapped with clusters that differentiated the BD and HV groups. Mean cortical thickness changes in the clusters ranged from 7.5 to 8.2% (cluster-wise p-values from 1.0 e-4 to 0.023). The difference in cortical thickness was more pronounced when the subgroup of subjects with bipolar I disorder (BD-I) was compared to the MDD group. Cortical thickness patterns were distinct between BD and MDD. These results are a step toward developing an imaging test to differentiate the two disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

SA45. Amotivation in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder: A Preliminary Comparison Study

PubMed Central

Zou, Ying-min; Ni, Ke; Wang, Yang-yu; Yu, En-qing; Lui, Simon S. Y.; Cheung, Eric F. C.; Chan, Raymond C. K.

2017-01-01

Abstract Background: Deficits in reward processing, such as approaching motivation, reward learning and effort-based decision-making, have been observed in patients with schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). However, little is known about the nature of reward-processing deficits in these 3 diagnostic groups. The present study aimed to compare and contrast amotivation in these 3 diagnostic groups using an effort-based decision-making task. Methods: Sixty patients (19 SCZ patients, 18 BD patients and 23 MDD patients) and 27 healthy controls (HC) were recruited for the present study. The Effort Expenditure for Reward Task (EEfRT) was administered to evaluate their effort allocation pattern. This task required participants to choose easy or hard tasks in response to different levels of reward magnitude and reward probability. Results: Results showed that SCZ, BD, and MDD patients chose fewer hard tasks compared to HC. As reward magnitude increased, MDD patients made the least effort to gain reward compared to the other groups. When reward probability was intermediate, MDD patients chose fewer hard tasks than SCZ patients, whereas BD patients and HC chose more hard tasks than MDD and SCZ patients. When the reward probability was high, all 3 groups of patients tried fewer hard tasks than HC. Moreover, SCZ and MDD patients were less likely to choose hard tasks than BD patients and HC in the intermediate estimated value conditions. However, in the highest estimated value condition, there was no group difference in hard task choices between these 3 clinical groups, and they were all less motivated than HC. Conclusion: SCZ, BD, and MDD patients shared common deficits in gaining reward if the reward probability and estimated value were high. SCZ and MDD patients showed less motivation than BD patients in gaining reward when the reward probability and estimated value was intermediate.

Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration.

PubMed

Lu, Yi; Shen, Zonglin; Cheng, Yuqi; Yang, Hui; He, Bo; Xie, Yue; Wen, Liang; Zhang, Zhenguang; Sun, Xuejin; Zhao, Wei; Xu, Xiufeng; Han, Dan

2017-01-01

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal-subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD.

Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration

PubMed Central

Lu, Yi; Shen, Zonglin; Cheng, Yuqi; Yang, Hui; He, Bo; Xie, Yue; Wen, Liang; Zhang, Zhenguang; Sun, Xuejin; Zhao, Wei; Xu, Xiufeng; Han, Dan

2017-01-01

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal–subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD. PMID:29118724

Antidepressant effectiveness of deep Transcranial Magnetic Stimulation (dTMS) in patients with Major Depressive Disorder (MDD) with or without Alcohol Use Disorders (AUDs): a 6-month, open label, follow-up study.

PubMed

Rapinesi, Chiara; Curto, Martina; Kotzalidis, Georgios D; Del Casale, Antonio; Serata, Daniele; Ferri, Vittoria Rachele; Di Pietro, Simone; Scatena, Paola; Bersani, Francesco Saverio; Raccah, Ruggero Nessim; Digiacomantonio, Vittorio; Ferracuti, Stefano; Bersani, Giuseppe; Zangen, Abraham; Angeletti, Gloria; Girardi, Paolo

2015-03-15

Co-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD. Twelve MDD patients and 11 with concomitant MDD and AUD (MDD+AUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDD+AUD, and functioning with the Global Assessment of Functioning (GAF). There were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDD+AUD, and 55.2% and 67.1% for MDD (p<0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD+AUD than in MDD LIMITATIONS: The small sample size and factors inherent to site and background treatment may have affected results. High frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluating the diagnostic utility of applying a machine learning algorithm to diffusion tensor MRI measures in individuals with major depressive disorder.

PubMed

Schnyer, David M; Clasen, Peter C; Gonzalez, Christopher; Beevers, Christopher G

2017-06-30

Using MRI to diagnose mental disorders has been a long-term goal. Despite this, the vast majority of prior neuroimaging work has been descriptive rather than predictive. The current study applies support vector machine (SVM) learning to MRI measures of brain white matter to classify adults with Major Depressive Disorder (MDD) and healthy controls. In a precisely matched group of individuals with MDD (n =25) and healthy controls (n =25), SVM learning accurately (74%) classified patients and controls across a brain map of white matter fractional anisotropy values (FA). The study revealed three main findings: 1) SVM applied to DTI derived FA maps can accurately classify MDD vs. healthy controls; 2) prediction is strongest when only right hemisphere white matter is examined; and 3) removing FA values from a region identified by univariate contrast as significantly different between MDD and healthy controls does not change the SVM accuracy. These results indicate that SVM learning applied to neuroimaging data can classify the presence versus absence of MDD and that predictive information is distributed across brain networks rather than being highly localized. Finally, MDD group differences revealed through typical univariate contrasts do not necessarily reveal patterns that provide accurate predictive information. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Smoking cue reactivity in adult smokers with and without depression: A pilot study

PubMed Central

Weinberger, Andrea H.; McKee, Sherry A.; George, Tony P.

2013-01-01

Little is known about the relationship between Major Depressive Disorder (MDD) and smoking-related behaviors such as cue-induced urges to smoke. The purpose of this pilot study was to examine: 1) differences in smoking cue reactivity by MDD history, and; 2) the association of a diagnosis of MDD, current depressive symptoms, and smoking variables to cue-induced urges to smoke. Participants (N=52) were n=31 smokers with no MDD history and n=21 smokers with past MDD. Participants completed a 2-hour laboratory session during which they were exposed to neutral (e.g., pencils) and smoking cues (e.g., cigarettes) after smoking one of their preferred brand cigarettes (Satiated Condition) and when it had been one hour since they smoked (Brief Deprivation Condition). Cue-induced urges increased with exposure to smoking cues and this increase did not significantly differ by diagnosis group. Current symptoms of depression, but not a diagnosis of MDD, were significantly and positively related to cue-induced cravings in satiated adult smokers. The association between depression symptoms and smoking urges was not significant in the Brief Deprivation Condition. Smoking cue reactivity may be a useful procedure for studying aspects of smoking behavior in adults with depression. PMID:22332857

A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up.

PubMed

Widom, Cathy Spatz; DuMont, Kimberly; Czaja, Sally J

2007-01-01

Few prospective longitudinal studies have examined the relationship between abuse or neglect in childhood and depression in adulthood. To determine whether abused and neglected children were at elevated risk of major depressive disorder (MDD) and psychiatric comorbidity, compared with matched control subjects, when followed up into young adulthood. Prospective cohort design study. Midwestern metropolitan county area. Children with substantiated cases of physical and sexual abuse and neglect (before the age of 11 years) from January 1, 1967, to December 31, 1971 (n = 676) were matched based on age, race, sex, and approximate family social class with a group of non-abused and non-neglected children (n = 520) and followed up into young adulthood (mean age, 28.7 years). Between October 20, 1989, and December 22, 1995, 2-hour in-person interviews were conducted, using the National Institute of Mental Health Diagnostic Interview Schedule, Version III Revised, to determine DSM-III-R MDD and other psychiatric diagnoses. Child abuse and neglect were associated with an increased risk for current MDD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.06-2.14; P< or=.05) in young adulthood. Children who were physically abused (OR, 1.59; 95% CI, 1.00-2.52; P< or =.05) or experienced multiple types of abuse (OR, 1.75; 95% CI, 1.01-3.02; P< or =.05) were at increased risk of lifetime MDD, whereas neglect increased risk for current MDD (OR, 1.59; 95% CI, 1.10-2.29; P<.01). Childhood sexual abuse was not associated with elevated risk of MDD. Kaplan-Meier age-of-onset curves (log-rank statistic, 4.03; df = 1; P=.04) showed earlier onset of MDD for abused and neglected children compared with controls. Among those with MDD, comorbidity was higher for abused and neglected individuals than for controls. These results support the need for clinicians to increase efforts to detect and treat depression in physically abused and neglected children.

Prevalence and correlates of major depressive disorder (MDD) among adolescent patients with epilepsy attending a Nigerian neuropsychiatric hospital.

PubMed

Fela-Thomas, Ayodele; Akinhanmi, Akinwande; Esan, Oluyomi

2016-01-01

A high prevalence of mood disorders exists in patients with epilepsy. In most cases, this is not detected and, consequently, not treated. This study aimed to determine the prevalence and correlates of major depressive disorder (MDD) among adolescents with epilepsy attending a child and adolescent clinic in Nigeria. We recruited 156 participants consecutively for the study. Adherence was assessed using the 8-item Morisky Medication Adherence Questionnaire, while the K-SADS was used to assess the presence of major depressive disorder. Seizure control was evaluated by the frequency of seizures within a year. Major depressive disorder (DSM-IV criteria) was diagnosed in 28.2% of the participants. The age of participants (p=0.013), seizure control (p=0.03), medication adherence (p=0.045), frequency of seizures in the preceding 4weeks (p<0.001), and duration of illness (p<0.001) were all significantly associated with the presence of MDD. Participants with seizures occurring more than once weekly in the preceding 4weeks were 16 times more likely to have a MDD compared with those with no seizures in the preceding 4weeks (p<0.001, 95% C.I. [4.13, 65.43]), while participants with a duration of illness more than 10years were more than four times likely to have MDD compared with those with an illness duration of 5-10years (p<0.01, 95% C.I. [0.07, 0.70]). The prevalence of MDD among patients with epilepsy was high. Poor seizure control, poor medication adherence, and long duration of illness were associated with the presence of MDD among such patients. Intervention should focus on ensuring good seizure control and optimal adherence in order to mitigate the impact of MDD in patients with epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Emotion Regulation in Current and Remitted Depression: A Systematic Review and Meta-Analysis

PubMed Central

Visted, Endre; Vøllestad, Jon; Nielsen, Morten Birkeland; Schanche, Elisabeth

2018-01-01

Background: Major Depressive Disorder (MDD) is a highly prevalent, recurrent, and potentially chronic disorder. Identifying risk factors and underlying mechanisms to inform preventive and therapeutic interventions is therefore imperative. Emotion regulation is a proposed factor in the development and maintenance of MDD. The aim of the present review was to summarize and synthesize research on self-reported emotion regulation strategy use and emotion regulation abilities in adults diagnosed with current and remitted MDD. Methods: Seventy-two eligible studies were retrieved from databases through a systematic literature search. Group differences between individuals with current MDD, remitted MDD, and healthy controls were calculated using meta-analytic procedures. Meta-regression analyses investigated potential moderator effects on emotion regulation difficulties. Results: Results indicated that individuals with current MDD report higher maladaptive emotion regulation strategy use for avoidance (Hedges' g = 1.3), rumination (g = 2.1), and suppression (g = 1.1) compared to healthy controls. Also, they reported lower adaptive emotion regulation strategy use for acceptance (g = −1.0), problem solving (g = −1.0), and reappraisal (g = −0.7). Individuals with current MDD reported limited general emotion regulation abilities, indicated by higher alexithymia (g = 1.45), lower emotional awareness (g = −0.95), emotional clarity (g = −1.50) and emotional tolerance (g = −1.89). Similar results were found in individuals with remitted MDD for avoidance (g = 1.0), rumination (g = 1.1), suppression (g = 0.6), and general emotion regulation abilities. However, no difference was found between individuals with remitted MDD and healthy controls for adaptive emotion regulation strategies. Meta-regression analyses suggest that age of illness onset, comorbid anxiety and duration of remission influence emotion regulation. Conclusion: The present review and meta-analysis indicates that individuals with current and remitted MDD have difficulties with emotion regulation compared to individuals who have never been depressed. Although depressive symptoms improve, emotion regulation difficulties may continue, and could be a contributing factor to relapse. Our findings inform future research on emotion regulation and psychotherapeutic interventions. PMID:29867700

Fate of thiamethoxam in mesocosms and response of the zooplankton community.

PubMed

Lobson, C; Luong, K; Seburn, D; White, M; Hann, B; Prosser, R S; Wong, C S; Hanson, M L

2018-05-14

Thiamethoxam is a neonicotinoid insecticide that can reach wetlands in agro-ecosystems through runoff. The fate and effects of thiamethoxam on non-target organisms in shallow wetland ecosystems have not been well characterized. To this end, a mesocosm study was conducted with a focus on characterizing zooplankton community responses. A single pulse application of thiamethoxam (0, 25, 50, 100, 250, and 500 μg/L; n = 3) was applied to experimental systems and monitored for 8 weeks. The mean half-life of thiamethoxam among the different treatments was 3.7 days in the water column with concentrations of <0.8 μg/L in the majority of mesocosms by 56 days. Principal response curve analysis did not show any significant concentration-dependent differences in the zooplankton community among treatments over the course of the study. The minimum detectable difference (MDD%) values for abundance of potentially sensitive arthropod taxa (nauplius larvae, cyclopoid copepods) allowed the detections from controls as low as 42 and 59% effect, respectively. The MDD% values for total abundance of zooplankton (including the potentially less sensitive taxonomic group of Rotifera) allowed the detection from controls as low as 41% effect. There were no statistically significant differences in zooplankton abundance or diversity between control and treated mesocosms at the end of the study. There were also no statistically significant differences for individual taxa that were sustained between sampling points, or manifested as a concentration-response. We conclude that acute exposure to thiamethoxam at environmentally relevant concentrations (typically ng/L) likely does not represent a significant adverse ecological risk to wetland zooplankton community abundance and structure. Copyright © 2018 Elsevier B.V. All rights reserved.

Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

PubMed

Al Shweiki, Mhd Rami; Oeckl, Patrick; Steinacker, Petra; Hengerer, Bastian; Schönfeldt-Lecuona, Carlos; Otto, Markus

2017-06-01

Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

The relationship between neuroticism, major depressive disorder and comorbid disorders in Chinese women

PubMed Central

Xia, Jing; He, Qiang; Li, Yihan; Xie, Dong; Zhu, Suoyu; Chen, Jing; Shen, Yuan; Zhang, Ning; Wei, Yan; Chen, Chunfeng; Shen, Jianhua; Zhang, Yan; Gao, Chengge; Li, Youhui; Ding, Jihong; Shen, Wenwu; Wang, Qian; Cao, Meiyue; Liu, Tiebang; Zhang, Jinbei; Duan, Huijun; Bao, Cheng; Ma, Ping; Zhou, Cong; Luo, Yanfang; Zhang, Fengzhi; Liu, Ying; Li, Yi; Jin, Guixing; Zhang, Yutang; Liang, Wei; Chen, Yunchun; Zhao, Changyin; Li, Haiyan; Chen, Yiping; Shi, Shenxun; Kendler, Kenneth S.; Flint, Jonathan; Wang, Xumei

2011-01-01

Objective The personality trait of neuroticism is a risk factor for major depressive disorder (MDD), but this relationship has not been demonstrated in clinical samples from Asia. Methods We examined a large-scale clinical study of Chinese Han women with recurrent major depression and community-acquired controls. Results Elevated levels of neuroticism increased the risk for lifetime MDD (with an odds ratio of 1.37 per SD), contributed to the comorbidity of MDD with anxiety disorders, and predicted the onset and severity of MDD. Our findings largely replicate those obtained in clinical populations in Europe and US but differ in two ways: we did not find a relationship between melancholia and neuroticism; we found lower mean scores for neuroticism (3.6 in our community control sample). Limitations Our findings do not apply to MDD in community-acquired samples and may be limited to Han Chinese women. It is not possible to determine whether the association between neuroticism and MDD reflects a causal relationship. Conclusions Neuroticism acts as a risk factor for MDD in Chinese women, as it does in the West and may particularly predispose to comorbidity with anxiety disorders. Cultural factors may have an important effect on its measurement. PMID:21824661

Emotional working memory in patients with major depressive disorder.

PubMed

Li, Mi; Feng, Lei; Liu, Xingwang; Zhang, Ming; Fu, Bingbing; Wang, Gang; Lu, Shengfu; Zhong, Ning; Hu, Bin

2018-05-01

Objective This study was performed to examine the working memory (WM) encoding and retrieval abilities in patients with major depressive disorder (MDD) and determine whether a mood-congruent memory effect is present. Methods The modified Sternberg WM paradigm with positive, negative, and neutral emotional pictures was used to investigate the WM abilities of 26 patients with MDD and 26 healthy controls (HCs). Results No significant difference in picture WM was found between the MDD and HC groups; however, the accuracy of picture position WM was significantly lower and the response time was significantly longer in the MDD than HC group, regardless of the picture or position WM. Additionally, in the MDD group, the accuracy of negative picture/position WM was significantly higher than that of positive picture/position WM. Conclusions These results suggest that in patients with MDD, spatial WM impairment was more severe than object WM. In addition, these patients' WM retrieval was impaired, resulting in a decrease in WM retrieval ability, which may be an important cause of the slow thought in patients with MDD. Moreover, patients with depression have a mood-congruent memory effect, which may be an important factor in the occurrence and maintenance of depression.

Detecting recurrent major depressive disorder within primary care rapidly and reliably using short questionnaire measures.

PubMed

Thapar, Ajay; Hammerton, Gemma; Collishaw, Stephan; Potter, Robert; Rice, Frances; Harold, Gordon; Craddock, Nicholas; Thapar, Anita; Smith, Daniel J

2014-01-01

Major depressive disorder (MDD) is often a chronic disorder with relapses usually detected and managed in primary care using a validated depression symptom questionnaire. However, for individuals with recurrent depression the choice of which questionnaire to use and whether a shorter measure could suffice is not established. To compare the nine-item Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory, and the Hospital Anxiety and Depression Scale against shorter PHQ-derived measures for detecting episodes of DSM-IV major depression in primary care patients with recurrent MDD. Diagnostic accuracy study of adults with recurrent depression in primary care predominantly from Wales Scores on each of the depression questionnaire measures were compared with the results of a semi-structured clinical diagnostic interview using Receiver Operating Characteristic curve analysis for 337 adults with recurrent MDD. Concurrent questionnaire and interview data were available for 272 participants. The one-month prevalence rate of depression was 22.2%. The area under the curve (AUC) and positive predictive value (PPV) at the derived optimal cut-off value for the three longer questionnaires were comparable (AUC = 0.86-0.90, PPV = 49.4-58.4%) but the AUC for the PHQ-9 was significantly greater than for the PHQ-2. However, by supplementing the PHQ-2 score with items on problems concentrating and feeling slowed down or restless, the AUC (0.91) and the PPV (55.3%) were comparable with those for the PHQ-9. A novel four-item PHQ-based questionnaire measure of depression performs equivalently to three longer depression questionnaires in identifying depression relapse in patients with recurrent MDD.

Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys.

PubMed

Kessler, R C; Sampson, N A; Berglund, P; Gruber, M J; Al-Hamzawi, A; Andrade, L; Bunting, B; Demyttenaere, K; Florescu, S; de Girolamo, G; Gureje, O; He, Y; Hu, C; Huang, Y; Karam, E; Kovess-Masfety, V; Lee, S; Levinson, D; Medina Mora, M E; Moskalewicz, J; Nakamura, Y; Navarro-Mateu, F; Browne, M A Oakley; Piazza, M; Posada-Villa, J; Slade, T; Ten Have, M; Torres, Y; Vilagut, G; Xavier, M; Zarkov, Z; Shahly, V; Wilcox, M A

2015-06-01

To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD). Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI). 45.7% of respondents with lifetime MDD (32.0-46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8-54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9-47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ 2 1 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ 2 1 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ 2 1 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ 2 1 = 11.7, p < 0.001). Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6-74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.

Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys

PubMed Central

Kessler, R.C.; Sampson, N.A.; Berglund, P.; Gruber, M.J.; Al-Hamzawi, A.; Andrade, L.; Bunting, B.; Demyttenaere, K.; Florescu, S.; de Girolamo, G.; Gureje, O.; He, Y.; Hu, C.; Huang, Y.; Karam, E.; Kovess-Masfety, V.; Lee, S; Levinson, D.; Mora, M.E. Medina; Moskalewicz, J.; Nakamura, Y.; Navarro-Mateu, F.; Oakley Browne, Mark A.; Piazza, M.; Posada-Villa, J.; Slade, T.; ten Have, M.; Torres, Y.; Vilagut, G.; Xavier, M.; Zarkov, Z.; Shahly, V.; Wilcox, M.A.

2016-01-01

AIMS To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD). METHODS Nationally or regionally representative epidemiological interviews were administered to 74,045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI). RESULTS 45.7% of respondents with lifetime MDD (32.0–46.5% inter-quartile range [IQR] across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8–54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9–47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset of their first anxiety disorder than their MDD, while 13.5% reported an earlier age-of-onset of MDD and the remaining 18.5% reported the same age-of-onset of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4% vs. 46.0%; χ21=187.0, p<.001) and suicide ideation (19.5% vs. 8.9%; χ21=71.6, p<.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high income countries (68.8% vs. 45.4%; χ21=108.8, p<.001) than low/middle income countries (30.3% vs. 20.6%; χ21=11.7, p<.001). CONCLUSIONS Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6–74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers versus causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence. PMID:25720357

Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder.

PubMed

Briceño, Emily M; Rapport, Lisa J; Kassel, Michelle T; Bieliauskas, Linas A; Zubieta, Jon-Kar; Weisenbach, Sara L; Langenecker, Scott A

2015-03-01

Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. Cross-sectional comparison of fMRI signal during performance of an emotion processing task. Outpatient university setting. One hundred adults recruited by MDD status, gender, and age. Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

PubMed Central

Middeldorp, C M; de Moor, M H M; McGrath, L M; Gordon, S D; Blackwood, D H; Costa, P T; Terracciano, A; Krueger, R F; de Geus, E J C; Nyholt, D R; Tanaka, T; Esko, T; Madden, P A F; Derringer, J; Amin, N; Willemsen, G; Hottenga, J-J; Distel, M A; Uda, M; Sanna, S; Spinhoven, P; Hartman, C A; Ripke, S; Sullivan, P F; Realo, A; Allik, J; Heath, A C; Pergadia, M L; Agrawal, A; Lin, P; Grucza, R A; Widen, E; Cousminer, D L; Eriksson, J G; Palotie, A; Barnett, J H; Lee, P H; Luciano, M; Tenesa, A; Davies, G; Lopez, L M; Hansell, N K; Medland, S E; Ferrucci, L; Schlessinger, D; Montgomery, G W; Wright, M J; Aulchenko, Y S; Janssens, A C J W; Oostra, B A; Metspalu, A; Abecasis, G R; Deary, I J; Räikkönen, K; Bierut, L J; Martin, N G; Wray, N R; van Duijn, C M; Smoller, J W; Penninx, B W J H; Boomsma, D I

2011-01-01

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13 835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case–Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other. PMID:22833196

Altered neural processing of reward and punishment in adolescents with Major Depressive Disorder.

PubMed

Landes, I; Bakos, S; Kohls, G; Bartling, J; Schulte-Körne, G; Greimel, E

2018-05-01

Altered reward and punishment function has been suggested as an important vulnerability factor for the development of Major Depressive Disorder (MDD). Prior ERP studies found evidence for neurophysiological dysfunctions in reinforcement processes in adults with MDD. To date, only few ERP studies have examined the neural underpinnings of reinforcement processing in adolescents diagnosed with MDD. The present event-related potential (ERP) study aimed to investigate neurophysiological mechanisms of anticipation and consumption of reward and punishment in adolescents with MDD in one comprehensive paradigm. During ERP recording, 25 adolescents with MDD and 29 healthy controls (12-17 years) completed a Monetary Incentive Delay Task comprising both a monetary reward and a monetary punishment condition. During anticipation, the cue-P3 signaling attentional allocation was recorded. During consumption, the feedback-P3 and Reward Positivity (RewP) were recorded to capture attentional allocation and outcome evaluation, respectively. Compared to controls, adolescents with MDD showed prolonged cue-P3 latencies to reward cues. Furthermore, unlike controls, adolescents with MDD displayed shorter feedback-P3 latencies in the reward versus punishment condition. RewPs did not differ between groups. It remains unanswered whether the observed alterations in adolescent MDD represent a state or trait. Delayed neural processing of reward cues corresponds to the clinical presentation of adolescent MDD with reduced motivational tendencies to obtain rewards. Relatively shorter feedback-P3 latencies in the reward versus punishment condition could indicate a high salience of performance-contingent reward. Frequent exposure of negatively biased adolescents with MDD to performance-contingent rewards might constitute a promising intervention approach. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of cigarette smoking on cortical thickness in major depressive disorder.

PubMed

Zorlu, Nabi; Cropley, Vanessa Louise; Zorlu, Pelin Kurtgoz; Delibas, Dursun Hakan; Adibelli, Zehra Hilal; Baskin, Emel Pasa; Esen, Özgür Sipahi; Bora, Emre; Pantelis, Christos

2017-01-01

Findings of surface-based morphometry studies in major depressive disorder (MDD) are still inconsistent. Given that cigarette smoking is highly prevalent in MDD and has documented negative effects on the brain, it is possible that some of the inconsistencies may be partly explained by cigarette use. The aim of the current study was to examine the influence of cigarette smoking on brain structure in MDD. 50 MDD patients (25 smokers and 25 non-smokers) and 22 age, education, gender and BMI matched non-smoker healthy controls underwent structural magnetic resonance imaging. Thickness and area of the cortex were measured using surface-based morphometry implemented with Freesurfer (v5.3.0). The non-smoker MDD patients had significantly increased cortical thickness, including in the left temporal cortex (p < 0.001), right insular cortex (p = 0.033) and left pre- and postcentral gyrus (p = 0.045), compared to healthy controls. We also found decreased cortical thickness in MDD patients who smoked compared to non-smoking patients in regions that overlapped with the regions found to be increased in non-smoking patients in comparison to controls. Non-smoker MDD patients had increased surface area in the right lateral occipital cortex (p = 0.009). We did not find any region where cortical thickness or surface area significantly differed between controls and either smoker MDD patients or all MDD patients. The findings of the current study suggest that cigarette smoking is associated with cortical thinning in regions found to be increased in patients with MDD. However, these results should be considered preliminary due to methodological limitations. Copyright © 2016 Elsevier Ltd. All rights reserved.

PTSD symptom severity and psychiatric comorbidity in recent motor vehicle accident victims: a latent class analysis.

PubMed

Hruska, Bryce; Irish, Leah A; Pacella, Maria L; Sledjeski, Eve M; Delahanty, Douglas L

2014-10-01

We conducted a latent class analysis (LCA) on 249 recent motor vehicle accident (MVA) victims to examine subgroups that differed in posttraumatic stress disorder (PTSD) symptom severity, current major depressive disorder and alcohol/other drug use disorders (MDD/AoDs), gender, and interpersonal trauma history 6-weeks post-MVA. A 4-class model best fit the data with a resilient class displaying asymptomatic PTSD symptom levels/low levels of comorbid disorders; a mild psychopathology class displaying mild PTSD symptom severity and current MDD; a moderate psychopathology class displaying severe PTSD symptom severity and current MDD/AoDs; and a severe psychopathology class displaying extreme PTSD symptom severity and current MDD. Classes also differed with respect to gender composition and history of interpersonal trauma experience. These findings may aid in the development of targeted interventions for recent MVA victims through the identification of subgroups distinguished by different patterns of psychiatric problems experienced 6-weeks post-MVA. Copyright © 2014 Elsevier Ltd. All rights reserved.

PTSD Symptom Severity and Psychiatric Comorbidity in Recent Motor Vehicle Accident Victims: A Latent Class Analysis

PubMed Central

Hruska, Bryce; Irish, Leah A.; Pacella, Maria L.; Sledjeski, Eve M.; Delahanty, Douglas L.

2014-01-01

We conducted a latent class analysis (LCA) on 249 recent motor vehicle accident (MVA) victims to examine subgroups that differed in posttraumatic stress disorder (PTSD) symptom severity, current major depressive disorder and alcohol/other drug use disorders (MDD/AoDs), gender, and interpersonal trauma history 6-weeks post-MVA. A 4-class model best fit the data with a resilient class displaying asymptomatic PTSD symptom levels/low levels of comorbid disorders; a mild psychopathology class displaying mild PTSD symptom severity and current MDD; a moderate psychopathology class displaying severe PTSD symptom severity and current MDD/AoDs; and a severe psychopathology class displaying extreme PTSD symptom severity and current MDD. Classes also differed with respect to gender composition and history of interpersonal trauma experience. These findings may aid in the development of targeted interventions for recent MVA victims through the identification of subgroups distinguished by different patterns of psychiatric problems experienced 6-weeks post-MVA. PMID:25124501

Brain Hypoactivation, Autonomic Nervous System Dysregulation, and Gonadal Hormones in Depression: A Preliminary Study

PubMed Central

Holsen, Laura M.; Lee, Jong-Hwan; Spaeth, Sarah B.; Ogden, Lauren A.; Klibanski, Anne; Whitfield-Gabrieli, Susan; Sloan, Richard P.; Goldstein, Jill M.

2012-01-01

The comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) is among the 10th leading cause of morbidity and mortality worldwide. Thus, understanding the co-occurrence of these disorders will have major public health significance. MDD is associated with an abnormal stress response, manifested in brain circuitry deficits, gonadal dysfunction, and autonomic nervous system (ANS) dysregulation. Contribution of the relationships between these systems to the pathophysiology of MDD is not well understood. The objective of this preliminary study was to investigate, in parallel, relationships between HPG-axis functioning, stress response circuitry activation, and parasympathetic reactivity in healthy controls and women with MDD. Using fMRI with pulse oximetry [from which we calculated the high frequency (HF) component of R-R interval variability (HF-RRV), a measure of parasympathetic modulation] and hormone data, we studied eight women with recurrent MDD in remission and six controls during a stress response paradigm. We demonstrated that hypoactivations of hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and subgenual ACC were associated with lower parasympathetic cardiac modulation in MDD women. Estradiol and progesterone attenuated group differences in the effect of HF-RRV on hypoactivation in the amygdala, hippocampus, ACC, and OFC in MDD women. Findings have implications for understanding the relationship between mood, arousal, heart regulation, and gonadal hormones, and may provide insights into MDD and CVD risk comorbidity. PMID:22395084

Epidemiology of Major Depressive Disorder in Iran: a Systematic Review and Meta-Analysis

PubMed Central

Sadeghirad, Behnam; Haghdoost, Ali-Akbar; Amin-Esmaeili, Masoumeh; Ananloo, Esmaeil Shahsavand; Ghaeli, Padideh; Rahimi-Movaghar, Afarin; Talebian, Elham; Pourkhandani, Ali; Noorbala, Ahmad Ali; Barooti, Esmat

2010-01-01

Objectives: There are a large number of primary researches on the prevalence of major depressive disorder (MDD) in Iran; however, their findings are varied considerably. A systematic review was performed in order to summarize the findings. Methods: Electronic and manual searches in international and Iranian journals were conducted to find relevant studies reporting MDD prevalence. To maximize the sensitivity of the search, the references of relevant papers were also explored. We explored the potential sources of heterogeneity such as diagnostic tools, gender and other characteristics using meta-regression model. The combined mean prevalence rates were calculated for genders, studies using each type of instruments and for each province using meta-analysis method. Results: From 44 articles included in the systematic review, 24 reported current prevalence and 20 reported lifetime prevalence of MDD. The overall estimation of current prevalence of MDD was 4.1% (95% CI: 3.1-5.1). Women were 1.95 (95% CI: 1.55-2.45) times more likely to have MDD. The current prevalence of MDD in urban inhabitants was not significantly different from rural inhabitants. The analysis identified the variations in diagnostic tools as an important source of heterogeneity. Conclusions: Although there is not adequate information on MDD prevalence in some areas of Iran, the overall current prevalence of MDD in the country is high and females are at the greater risk of disease. PMID:21566767

Cortical thickness and VBM in young women at risk for familial depression and their depressed mothers with positive family history.

PubMed

Ozalay, Ozgun; Aksoy, Burcu; Tunay, Sebnem; Simsek, Fatma; Chandhoki, Swati; Kitis, Omer; Eker, Cagdas; Gonul, Ali Saffet

2016-06-30

It has been demonstrated that compared to low-risk subjects, high-risk subjects for depression have structural and functional alterations in their brain scans even before the disease onset. However, it is not known if these alterations are related to vulnerability to depression or epiphenomena. One way to resolve this ambiguity is to detect the structural alterations in the high-risk subjects and determine if the same alterations are present in the probands. In this study, we recruited 24 women with the diagnosis of Major Depressive Disorder (MDD) with recurrent episodes and their healthy daughters (the high-risk for familial depression group; HRFD). We compared structural brain scans of the patients and HRFG group with those of 24 age-matched healthy mothers and their healthy daughters at similar ages to the HRFD group; respectively. Both cortical gray matter (GM) volume and thickness analyses revealed that HRFD daughters and their MDD mothers had similar GM differences in two regions: the right temporoparietal region and the dorsomedial prefrontal cortex. These results suggested that the observed alterations may be related to trait clinical and neurophysiological characteristics of MDD and may present before the onset of illness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Implicit and Explicit Self-Esteem in Current, Remitted, Recovered, and Comorbid Depression and Anxiety Disorders: The NESDA Study

PubMed Central

van Tuijl, Lonneke A.; Glashouwer, Klaske A.; Bockting, Claudi L. H.; Tendeiro, Jorge N.; Penninx, Brenda W. J. H.; de Jong, Peter J.

2016-01-01

Background Dual processing models of psychopathology emphasize the relevance of differentiating between deliberative self-evaluative processes (explicit self-esteem; ESE) and automatically-elicited affective self-associations (implicit self-esteem; ISE). It has been proposed that both low ESE and ISE would be involved in major depressive disorder (MDD) and anxiety disorders (AD). Further, it has been hypothesized that MDD and AD may result in a low ISE “scar” that may contribute to recurrence after remission. However, the available evidence provides no straightforward support for the relevance of low ISE in MDD/AD, and studies testing the relevance of discrepant SE even showed that especially high ISE combined with low ESE is predictive of the development of internalizing symptoms. However, these earlier findings have been limited by small sample sizes, poorly defined groups in terms of comorbidity and phase of the disorders, and by using inadequate indices of discrepant SE. Therefore, this study tested further the proposed role of ISE and discrepant SE in a large-scale study allowing for stricter differentiation between groups and phase of disorder. Method In the context of the Netherlands Study of Depression and Anxiety (NESDA), we selected participants with current MDD (n = 60), AD (n = 111), and comorbid MDD/AD (n = 71), remitted MDD (n = 41), AD (n = 29), and comorbid MDD/AD (n = 14), recovered MDD (n = 136) and AD (n = 98), and never MDD or AD controls (n = 382). The Implicit Association Test was used to index ISE and the Rosenberg Self-Esteem Scale indexed ESE. Results Controls reported higher ESE than all other groups, and current comorbid MDD/AD had lower ESE than all other clinical groups. ISE was only lower than controls in current comorbid AD/MDD. Discrepant self-esteem (difference between ISE and ESE) was not associated with disorder status once controlling for ESE. Limitations Cross-sectional design limits causal inferences. Conclusion Findings suggest a prominent role for ESE in MDD and AD, while in comorbid MDD/AD negative self-evaluations are also present at the implicit level. There was no evidence to support the view that AD and MDD would result in a low ISE “scar”. PMID:27846292

Response conflict and frontocingulate dysfunction in unmedicated participants with major depression.

PubMed

Holmes, Avram J; Pizzagalli, Diego A

2008-10-01

Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control.

Neighborhood Safety and Major Depressive Disorder in a National Sample of Black Youth; Gender by Ethnic Differences

PubMed Central

Assari, Shervin; Caldwell, Cleopatra Howard

2017-01-01

Adolescence is a developmental period marked by increased stress, especially among Black youth. In addition to stress related to their developmental transition, social factors such as a perceived unsafe neighborhood impose additional risks. We examined gender and ethnic differences in the association between perceived neighborhood safety and major depressive disorder (MDD) among a national sample of Black youth. We used data from the National Survey of American Life - Adolescents (NSAL-A), 2003–2004. In total, 1170 Black adolescents entered the study. This number was composed of 810 African American and 360 Caribbean Black youth (age 13 to 17). Demographic factors, perceived neighborhood safety, and MDD (Composite International Diagnostic Interview, CIDI) were measured. Logistic regressions were used to test the association between neighborhood safety and MDD in the pooled sample, as well as based on ethnicity by gender groups. In the pooled sample of Black youth, those who perceived their neighborhoods to be unsafe were at higher risk of MDD (Odds Ratio [OR] = 1.25; 95% Confidence Interval [CI] = 1.02-1.51). The perception that one’s neighborhood is unsafe was associated with a higher risk of MDD among African American males (OR=1.41; 95% CI = 1.03–1.93) but not African American females or Caribbean Black males and females. In conclusion, perceived neighborhood safety is not a universal psychological determinant of MDD across ethnic by gender groups of Black youth; however, policies and programs that enhance the sense of neighborhood safety may prevent MDD in male African American youth. PMID:28241490

Response conflict and frontocingulate dysfunction in unmedicated participants with Major Depression

PubMed Central

Holmes, Avram J.; Pizzagalli, Diego A.

2008-01-01

Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control. PMID:18577391

Proneness to decreased negative emotions in major depressive disorder when blaming others rather than oneself.

PubMed

Green, Sophie; Moll, Jorge; Deakin, John F William; Hulleman, Johan; Zahn, Roland

2013-01-01

One widespread view holds that vulnerability to major depressive disorder (MDD) is linked to overall increases in negative emotionality. In contrast, cognitive attribution theories emphasize the importance of blaming oneself rather than others for negative events. Thus far, the contrasting predictions of these models have not been directly compared. Following the attributional perspective, we tested the hypothesis that people with remitted MDD show no overall bias towards negative emotions, but a selective bias towards self-blaming emotions relative to those emotions associated with blaming others. We compared a remitted MDD and a control group on a novel experimental test that allowed us to directly compare proneness to specific emotions associated with different types of self-blame (guilt, shame, self-contempt/disgust) and blame of others (other-indignation/anger, other-contempt/disgust) whilst controlling for negative valence and medication status, and excluding comorbidity. In agreement with our hypothesis, individuals with remitted MDD exhibited an increased self-contempt bias (difference between contempt/disgust towards self and others) but no increased proneness to any other negative emotion or overall increases in perceived negative valence of stimuli. Moreover, the remitted MDD group exhibited reduced contempt/disgust towards others. Our results corroborate the prediction that vulnerability to MDD is associated with an imbalance of specific self- and other-blaming emotions rather than a general increase in negative emotions. Based on the composition of our sample, we speculate that self-contempt bias may be particularly characteristic of melancholic MDD subtypes and could be useful for stratification of depression in the future. Copyright © 2012 S. Karger AG, Basel.

Selective functional dysconnectivity of the dorsal-anterior subregion of the precuneus in drug-naive major depressive disorder.

PubMed

Zhu, Jiajia; Lin, Xiaodong; Lin, Chongguang; Zhuo, Chuanjun; Yu, Yongqiang

2018-01-01

Patients with major depressive disorder (MDD) have shown altered resting-state functional connectivity (rsFC) of the precuneus; however, it is unknown whether rsFC of the precuneus subregions is differentially affected in this disorder. In this study, we aimed to clarify this issue by comparing rsFC of each precuneus subregion between patients with MDD and healthy controls. Forty-seven drug-naive patients with MDD and 47 sex-, age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). The precuneus was divided into PCun-1 (dorsal-central portion; medial area 7), PCun-2 (dorsal-anterior portion; medial area 5), PCun-3 (dorsal-posterior portion; dorsomedial parietooccipital sulcus) and PCun-4 (ventral portion; area 31). The rsFC of each precuneus subregion was compared between the two groups. Compared with healthy controls, patients with MDD exhibited increased rsFC between the left PCun-2 and the right fusiform gyrus, lateral prefrontal cortex, sensorimotor cortex and supramarginal gyrus. No significant inter-group difference was observed in the rsFC of other precuneus subregions. In addition, there was no difference in gray matter volume of all the precuneus subregions between patients with MDD and healthy controls. Some of the patients had chronic MDD and relevant neuropsychological data were not collected. These findings suggest a selective functional dysconnectivity of the precuneus subregions in drug-naive MDD, characterized by the hyperconnnectivity between the dorsal-anterior subregion and regions involved in visual, executive control, sensorimotor and bottom-up attention functions. Copyright © 2017 Elsevier B.V. All rights reserved.

A Psychophysiological Investigation of Threat and Reward Sensitivity in Individuals With Panic Disorder and/or Major Depressive Disorder

PubMed Central

Shankman, Stewart A.; Nelson, Brady D.; Sarapas, Casey; Robison-Andrew, E. Jenna; Campbell, Miranda L.; Altman, Sarah E.; McGowan, Sarah Kate; Katz, Andrea C.; Gorka, Stephanie M.

2013-01-01

Heightened sensitivity to threat and reduced sensitivity to reward are potential mechanisms of dysfunction in anxiety and depressive disorders, respectively. However, few studies have simultaneously examined whether these mechanisms are unique or common to these disorders. In this study, sensitivity to predictable and unpredictable threat (measured by startle response during threat anticipation) and sensitivity to reward (measured by frontal electroencephalographic [EEG] asymmetry during reward anticipation) were assessed in 4 groups (N = 191): those with (1) panic disorder (PD) without a lifetime history of depression, (2) major depression (MDD) without a lifetime history of an anxiety disorder, (3) comorbid PD and MDD, and (4) controls. General distress/negative temperament (NT) was also assessed via self-report. Results indicated that PD (with or without comorbid MDD) was uniquely associated with heightened startle to predictable and unpredictable threat, and MDD (with or without comorbid PD) was uniquely associated with reduced frontal EEG asymmetry. Both psychophysiological measures of threat and reward sensitivity were stable on retest approximately 9 days later in a subsample of participants. Whereas the comorbid group did not respond differently on the tasks relative to the PD-only and MDD-only groups, they did report greater NT than these 2 groups (which did not differ from each other). Results suggest that heightened sensitivity to threat and reduced sensitivity to reward may be specific components of PD and MDD, respectively. In addition, relative to noncomorbid depression and PD, comorbid MDD and PD may be characterized by heightened NT, but not abnormal levels of these “specific” components. PMID:23148783

Early maladaptive schemas of emotional deprivation, social isolation, shame and abandonment are related to a history of suicide attempts among patients with major depressive disorders.

PubMed

Ahmadpanah, Mohammad; Astinsadaf, Sommayyeh; Akhondi, Amineh; Haghighi, Mohammad; Sadeghi Bahmani, Dena; Nazaribadie, Marzieh; Jahangard, Leila; Holsboer-Trachsler, Edith; Brand, Serge

2017-08-01

Patients with psychiatric disorders have an exceptionally high risk of completed or attempted suicide. This holds particularly true for patients with major depressive disorders. The aim of the present study was to explore whether patients with major depressive disorders (MDD) and a history of suicide attempts differed in their early maladaptive schemas from patients with MDD but without such a history or from healthy controls. Ninety participants took part in the study. Of these, 30 were patients with MDD who had made a recent suicide attempt; 30 were patients with MDD but no suicide attempts, and 30 were gender- and age-matched healthy controls. Participants completed questionnaires covering socio-demographic characteristics and the Young Schema Questionnaire (YSQ- RE2R) to assess early maladaptive schemas. Experts rated patients' MDD with the Montgomery-Asberg Depression Rating Scale. Patients did not differ in experts' ratings of symptoms of depression. Compared to healthy controls, patients with MDD recorded higher scores on maladaptive schemas such as recognition seeking, negativity/pessimism, and insufficient self-control. Compared to patients without suicide attempts and healthy controls, those who had made a suicide attempt had higher scores on dimensions such as failure, mistrust, emotional inhibition, social isolation, and abandonment/instability. Compared to healthy controls, patients with MDD had more pronounced maladaptive schemas, but this was more marked in patients with a history of suicide attempts. The results suggest that suicide attempts and poorer psychological functioning are related. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying latent profiles of posttraumatic stress and major depression symptoms in Canadian veterans: Exploring differences across profiles in health related functioning.

PubMed

Armour, Cherie; Contractor, Ateka; Elhai, Jon D; Stringer, Maurice; Lyle, Gary; Forbes, David; Richardson, J Don

2015-07-30

Posttraumatic stress disorder (PTSD) has been consistently reported as being highly comorbid with major depressive disorder (MDD) and as being associated with health related functional impairment (HRF). We used archival data from 283 previously war-zone deployed Canadian veterans. Latent profile analysis (LPA) was used to uncover patterns of PTSD and MDD comorbidity as measured via the PTSD Checklist-Military version (PCL-M) and the Patient Health Questionnaire-9 (PHQ-9). Individual membership of latent classes was used in a series of one-way ANOVAs to ascertain group differences related to HRF as measured via the Short-Form-36 Health Survey (SF-36). LPA resulted in three discrete patterns of PTSD and MDD comorbidity which were characterized by high symptoms of PTSD and MDD, moderate symptoms, and low symptoms. All ANOVAs comparing class membership on the SF-36 subscales were statistically significant demonstrating group differences across levels of HRF. The group with the highest symptoms reported the worst HRF followed by the medium and low symptom groups. These findings are clinically relevant as they demonstrate the need for continual assessment and targeted treatment of co-occurring PTSD and MDD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Temperament and character traits in major depressive disorder: influence of mood state and recurrence of episodes.

PubMed

Nery, Fabiano G; Hatch, John P; Nicoletti, Mark A; Monkul, E Serap; Najt, Pablo; Matsuo, Koji; Cloninger, C Robert; Soares, Jair C

2009-01-01

The objective of this study was to compare personality traits between major depressive disorder (MDD) patients and healthy comparison subjects (HC) and examine if personality traits in patients are associated with specific clinical characteristics of the disorder. Sixty MDD patients (45 depressed, 15 remitted) were compared to 60 HC using the Temperament and Character Inventory. Analysis of covariance, with age and gender as covariates, was used to compare the mean Temperament and Character Inventory scores among the subject groups. Depressed MDD patients scored significantly higher than HC on novelty seeking, harm avoidance, and self-transcendence and lower on reward dependence, self-directedness, and cooperativeness. Remitted MDD patients scored significantly lower than HC only on self-directedness. Comorbidity with anxiety disorder had a main effect only on harm avoidance. Harm avoidance was positively correlated with depression intensity and with number of episodes. Self-directedness had an inverse correlation with depression intensity. MDD patients present a different personality profile from HC, and these differences are influenced by mood state and comorbid anxiety disorders. When considering patients who have been in remission for some time, the differences pertain to few personality dimensions. Cumulated number of depressive episodes may result in increased harm avoidance. (c) 2009 Wiley-Liss, Inc.

Comparison of psychopathological dimensions between major depressive disorder and schizophrenia spectrum disorders focusing on language, affectivity and motor behavior.

PubMed

Steinau, Sarah; Stegmayer, Katharina; Lang, Fabian U; Jäger, Markus; Strik, Werner; Walther, Sebastian

2017-04-01

This study tested whether patients with major depressive disorder (MDD) and schizophrenia spectrum disorders would differ in three dimensions of psychopathology (language, affectivity and motor behavior) as assessed by the Bern Psychopathology Scale (BPS) in a cohort of 58 patients with MDD and 146 patients with schizophrenia spectrum disorders. The overall estimation of severity of each of the three dimensions was rated on a seven-point Likert scale from severely inhibited to severely disinhibited. Here, more than half of the patients endorsed ratings that showed normal or mildly (dis-)inhibited behavior. At group level more pronounced negative ratings of affect were seen in MDD. Group comparisons of the severity ratings on language or motor behavior yielded no differences between schizophrenia spectrum disorders and MDD. At the individuals' levels, extreme ratings in the language and motor dimensions were more frequent in schizophrenia spectrum disorders and in the affectivity dimension more frequent in MDD. Shared psychopathological features could be seen across diagnoses, supporting a dimensional approach to psychopathology in endogenous psychoses. However, the groups differ in the severity of affect ratings as well as in the distribution of language, affectivity and motor ratings with more variance among the group of schizophrenia spectrum disorders. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

The Everyday Emotional Experience of Adults with Major Depressive Disorder: Examining Emotional Instability, Inertia, and Reactivity

PubMed Central

Thompson, Renee J.; Mata, Jutta; Jaeggi, Susanne M.; Buschkuehl, Martin; Jonides, John; Gotlib, Ian H.

2013-01-01

Investigators have begun to examine the temporal dynamics of affect in individuals diagnosed with Major Depressive Disorder (MDD), focusing on instability, inertia, and reactivity of emotion. How these dynamics differ between individuals with MDD and healthy controls have not before been examined in a single study. In the present study, 53 adults with MDD and 53 healthy adults carried hand-held electronic devices for approximately seven days and were prompted randomly eight times per day to report their levels of current negative affect (NA), positive affect (PA), and the occurrence of significant events. In terms of NA, compared with healthy controls, depressed participants reported greater instability and greater reactivity to positive events, but comparable levels of inertia and reactivity to negative events. Neither average levels of NA nor NA reactivity to, frequency or intensity of, events accounted for the group difference in instability of NA. In terms of PA, the MDD and control groups did not differ significantly in their instability, inertia, or reactivity to positive or negative events. These findings highlight the importance of emotional instability in MDD, particularly with respect to NA, and contribute to a more nuanced understanding of the everyday emotional experiences of depressed individuals. PMID:22708886

Nonlinear analysis of EEGs of patients with major depression during different emotional states.

PubMed

Akdemir Akar, Saime; Kara, Sadık; Agambayev, Sümeyra; Bilgiç, Vedat

2015-12-01

Although patients with major depressive disorder (MDD) have dysfunctions in cognitive behaviors and the regulation of emotions, the underlying brain dynamics of the pathophysiology are unclear. Therefore, nonlinear techniques can be used to understand the dynamic behavior of the EEG signals of MDD patients. To investigate and clarify the dynamics of MDD patients׳ brains during different emotional states, EEG recordings were analyzed using nonlinear techniques. The purpose of the present study was to assess whether there are different EEG complexities that discriminate between MDD patients and healthy controls during emotional processing. Therefore, nonlinear parameters, such as Katz fractal dimension (KFD), Higuchi fractal dimension (HFD), Shannon entropy (ShEn), Lempel-Ziv complexity (LZC) and Kolmogorov complexity (KC), were computed from the EEG signals of two groups under different experimental states: noise (negative emotional content) and music (positive emotional content) periods. First, higher complexity values were generated by MDD patients relative to controls. Significant differences were obtained in the frontal and parietal scalp locations using KFD (p<0.001), HFD (p<0.05), and LZC (p=0.05). Second, lower complexities were observed only in the controls when they were subjected to music compared to the resting baseline state in the frontal (p<0.05) and parietal (p=0.005) regions. In contrast, the LZC and KFD values of patients increased in the music period compared to the resting state in the frontal region (p<0.05). Third, the patients׳ brains had higher complexities when they were exposed to noise stimulus than did the controls׳ brains. Moreover, MDD patients׳ negative emotional bias was demonstrated by their higher brain complexities during the noise period than the music stimulus. Additionally, we found that the KFD, HFD and LZC values were more sensitive in discriminating between patients and controls than the ShEn and KC measures, according to the results of ANOVA and ROC calculations. It can be concluded that the nonlinear analysis may be a useful and discriminative tool in investigating the neuro-dynamic properties of the brain in patients with MDD during emotional stimulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

An altered peripheral IL6 response in major depressive disorder.

PubMed

Money, Kelli M; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A; Shelton, Richard C; Mirnics, Karoly

2016-05-01

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

An altered peripheral IL6 response in major depressive disorder

PubMed Central

Money, Kelli M.; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A.; Shelton, Richard C.; Mirnics, Karoly

2016-01-01

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of antidepressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated proinflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients. PMID:26804030

Distinctive and common neural underpinnings of major depression, social anxiety, and their comorbidity

PubMed Central

Chen, Michael C.; Waugh, Christian E.; Joormann, Jutta; Gotlib, Ian H.

2015-01-01

Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural responding to criticism and praise that are specific to and common among major depressive disorder (MDD), social anxiety disorder (SAD) and comorbid MDD-SAD. Adult females who met formal diagnostic criteria for MDD, SAD or MDD-SAD and psychiatrically healthy participants underwent functional magnetic resonance imaging as they listened to statements directing praise or criticism at them or at another person. MDD groups showed reduced responding to praise across a distributed cortical network, an effect potentially mediated by thalamic nuclei undergirding arousal-mediated attention. SAD groups showed heightened anterior insula and decreased default-mode network response to criticism. The MDD-SAD group uniquely showed reduced responding to praise in the dorsal anterior cingulate cortex. Finally, all groups with psychopathology showed heightened response to criticism in a region of the superior frontal gyrus implicated in attentional gating. The present results suggest novel neural models of anhedonia in MDD, vigilance-withdrawal behaviors in SAD, and poorer outcome in MDD-SAD. Importantly, in identifying unique and common neural substrates of MDD and SAD, these results support a formulation in which common neural components represent general risk factors for psychopathology that, due to factors that are present at illness onset, lead to distinct forms of psychopathology with unique neural signatures. PMID:25038225

Clinical characteristics of patients with major depressive disorder with and without hypothyroidism: a comparative study.

PubMed

Mowla, Arash; Kalantarhormozi, Mohammad Reza; Khazraee, Samaneh

2011-01-01

Differentiating major depressive disorder (MDD) without hypothyroidism from MDD associated with hypothyroidism can be challenging. Therefore some authors have suggested that thyroid function should be tested in all depressed patients. This study compared the clinical characteristics of patients with MDD associated with hypothyroidism with those of patients with MDD without hypothyroidism. Thyroid function tests were administered to 75 patients (60 female and 15 male) who met DSM-IV criteria for MDD. The 15 patients with hypothyroidism (8 with subclinical hypothyroidism and 7 with overt hypothyroidism) were compared with the other 60 patients with regard to depressive characteristics. The primary measure of depressive signs and symptoms used to assess depression severity and symptoms was the Hamilton Rating Scale for Depression, first 17 items (Ham-D-17). Baseline demographic data, including age and sex, were also compared. The two groups did not differ significantly in severity of overall depression at baseline, as measured by total score on the Ham-D-17 (P=0.471, Z=0.970). Patients with MDD without hypothyroidism had worse scores on item 1 (depressed mood), item 2 (feelings of guilt), item 3 (suicidality), item 6 (late insomnia), and item 16 (loss of weight). In contrast, depressed patients with hypothyroidism had more severe anxiety symptoms and greater agitation (items 9, 10, and 11). Our results may help clinicians differentiate MDD associated with hypothyroidism from MDD without hypothyroidism. Depressed patients with hypothyroidism had more anxiety symptoms and greater agitation, but they had fewer severe core depressive symptoms and biological signs of MDD. (Journal of Psychiatric Practice. 2011;17:67-71).

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

PubMed

Rentería, M E; Schmaal, L; Hibar, D P; Couvy-Duchesne, B; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Gillespie, N A; Hatton, S N; Lagopoulos, J; Veltman, D J; van der Wee, N; van Erp, T G M; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Godlewska, B R; Cowen, P J; Penninx, B W J H; Jahanshad, N; Thompson, P M; Wright, M J; Martin, N G; Christensen, H; Hickie, I B

2017-05-02

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10 -3 ) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Predictors of remission from generalized anxiety disorder and major depressive disorder.

PubMed

Kelly, Kristen M; Mezuk, Briana

2017-01-15

The predictors of onset of major depressive disorder (MDD) and generalized anxiety disorder (GAD) are well-characterized. However the factors that predict remission from these conditions are less clear, and the study of this area is further complicated by differing definitions of remission. Data come from the National Comorbidity Survey - Replication, and analysis was limited to respondents with a lifetime history of GAD (n=621) or MDD (n=1299) assessed by the Composite International Diagnostic Interview. Predictors of remission included demographic factors, adverse childhood events, family history, and clinical characteristics. Multiple definitions of remission were explored to account for residual symptoms. Half (54.4%) of respondents with MDD and 41.1% of respondents with GAD experienced full remission. Older age and higher socioeconomic status were positively related to remission in a dose-response manner for both disorders. Adverse childhood experiences and family history of anxious/depressive symptoms were negatively associated with remission from MDD. Comorbid GAD was inversely associated with remission from MDD (Odds ratio (OR): 0.62, 95% Confidence interval (CI): 0.44-0.88), but comorbid MDD did not impact remission from GAD (OR: 0.93, 95% CI: 0.64-1.35). With the exception of the influence of comorbidity, these associations were robust across definitions of remission. Cross-sectional analysis and retrospective recall of onset of MDD/GAD. Many individuals with MDD or GAD will experience full remission. Some predictors appear to have a general association with remission from both disorders, while others are uniquely associated with remission from MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

Differentiating major depressive disorder in youths with attention deficit hyperactivity disorder.

PubMed

Diler, Rasim Somer; Daviss, W Burleson; Lopez, Adriana; Axelson, David; Iyengar, Satish; Birmaher, Boris

2007-09-01

Youths with attention deficit hyperactivity disorders (ADHD) frequently have comorbid major depressive disorders (MDD) sharing overlapping symptoms. Our objective was to examine which depressive symptoms best discriminate MDD among youths with ADHD. One-hundred-eleven youths with ADHD (5.2-17.8 years old) and their parents completed interviews with the K-SADS-PL and respective versions of the child or the parent Mood and Feelings Questionnaire (MFQ-C, MFQ-P). Controlling for group differences, logistic regression was used to calculate odds ratios reflecting the accuracy with which various depressive symptoms on the MFQ-C or MFQ-P discriminated MDD. Stepwise logistic regression then identified depressive symptoms that best discriminated the groups with and without MDD, using cross-validated misclassification rate as the criterion. Symptoms that discriminated youths with MDD (n=18) from those without MDD (n=93) were 4 of 6 mood/anhedonia symptoms, all 14 depressed cognition symptoms, and only 3 of 11 physical/vegetative symptoms. Mild irritability, miserable/unhappy moods, and symptoms related to sleep, appetite, energy levels and concentration did not discriminate MDD. A stepwise logistic regression correctly classified 89% of the comorbid MDD subjects, with only age, anhedonia at school, thoughts about killing self, thoughts that bad things would happen, and talking more slowly remaining in the final model. Results of this study may not generalize to community samples because subjects were drawn largely from a university-based outpatient psychiatric clinic. These findings stress the importance of social withdrawal, anhedonia, depressive cognitions, suicidal thoughts, and psychomotor retardation when trying to identify MDD among ADHD youths.

Cross-national differences in hypochondriasis symptoms between Korean and American outpatients with major depressive disorder.

PubMed

Chang, Kyung-Ah Judy; Kim, Kiwon; Fava, Maurizio; Mischoulon, David; Hong, Jin Pyo; Kim, Daniel J H; Heo, Jung-Yoon; Choi, Hong; Jeon, Hong Jin

2016-11-30

Hypochondriasis is defined as the tendency to worry excessively about having a serious illness. This study aimed to investigate cross-national differences in hypochondriasis symptoms between Korean and American patients with major depressive disorder (MDD). This study examined 1592 Korean and 3744 American MDD outpatients of age ≥18 years using the Hamilton Rating Scale for Depression (HAM-D) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). Korean MDD patients exhibited significantly higher scores for hypochondriasis than Americans after controlling for total HAM-D scores and demographic variables (p<0.0001), even though Americans had significantly higher total HAM-D scores (p<0.0001). Multivariate logistic regression analyses revealed that hypochondriasis was significantly associated with somatic and psychic anxiety, insomnia-middle, and suicide for both Korean and American MDD patients after adjusting for demographic covariates. Among all factors, somatic anxiety was the most strongly associated with hypochondriasis in both Korean (AOR=2.14, 95% CI 1.31-3.52) and American (AOR=1.98, 95% CI 1.69-2.31) MDD outpatients. Hypochondriasis symptoms are more prevalent among Korean than American MDD patients but appear to be associated with high levels of somatic anxiety regardless of culture. This suggests that cultural and personal factors play a shared role in the presentation of hypochondriasis symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transcranial Direct Current Stimulation (tDCS): A Promising Treatment for Major Depressive Disorder?

PubMed Central

Bennabi, Djamila; Haffen, Emmanuel

2018-01-01

Background: Transcranial direct current stimulation (tDCS) opens new perspectives in the treatment of major depressive disorder (MDD), because of its ability to modulate cortical excitability and induce long-lasting effects. The aim of this review is to summarize the current status of knowledge regarding tDCS application in MDD. Methods: In this review, we searched for articles published in PubMed/MEDLINE from the earliest available date to February 2018 that explored clinical and cognitive effects of tDCS in MDD. Results: Despite differences in design and stimulation parameters, the examined studies indicated beneficial effects of tDCS for MDD. These preliminary results, the non-invasiveness of tDCS, and its good tolerability support the need for further research on this technique. Conclusions: tDCS constitutes a promising therapeutic alternative for patients with MDD, but its place in the therapeutic armamentarium remains to be determined. PMID:29734768

A feasibility study for the application of seismic interferometry by multidimensional deconvolution for lithospheric-scale imaging

NASA Astrophysics Data System (ADS)

Ruigrok, Elmer; van der Neut, Joost; Djikpesse, Hugues; Chen, Chin-Wu; Wapenaar, Kees

2010-05-01

Active-source surveys are widely used for the delineation of hydrocarbon accumulations. Most source and receiver configurations are designed to illuminate the first 5 km of the earth. For a deep understanding of the evolution of the crust, much larger depths need to be illuminated. The use of large-scale active surveys is feasible, but rather costly. As an alternative, we use passive acquisition configurations, aiming at detecting responses from distant earthquakes, in combination with seismic interferometry (SI). SI refers to the principle of generating new seismic responses by combining seismic observations at different receiver locations. We apply SI to the earthquake responses to obtain responses as if there was a source at each receiver position in the receiver array. These responses are subsequently migrated to obtain an image of the lithosphere. Conventionally, SI is applied by a crosscorrelation of responses. Recently, an alternative implementation was proposed as SI by multidimensional deconvolution (MDD) (Wapenaar et al. 2008). SI by MDD compensates both for the source-sampling and the source wavelet irregularities. Another advantage is that the MDD relation also holds for media with severe anelastic losses. A severe restriction though for the implementation of MDD was the need to estimate responses without free-surface interaction, from the earthquake responses. To mitigate this restriction, Groenestijn en Verschuur (2009) proposed to introduce the incident wavefield as an additional unknown in the inversion process. As an alternative solution, van der Neut et al. (2010) showed that the required wavefield separation may be implemented after a crosscorrelation step. These last two approaches facilitate the application of MDD for lithospheric-scale imaging. In this work, we study the feasibility for the implementation of MDD when considering teleseismic wavefields. We address specific problems for teleseismic wavefields, such as long and complicated source wavelets, source-side reverberations and illumination gaps. We exemplify the feasibility of SI by MDD on synthetic data, based on field data from the Laramie and the POLARIS-MIT array. van Groenestijn, G.J.A. & Verschuur, D.J., 2009. Estimation of primaries by sparse inversion from passive seismic data, Expanded abstracts, 1597-1601, SEG. van der Neut, J.R, Ruigrok, E.N., Draganov, D.S., & Wapenaar, K., 2010. Retrieving the earth's reflection response by multi-dimensional deconvolution of ambient seismic noise, Extended abstracts, submitted, EAGE. Wapenaar, K., van der Neut, J., & Ruigrok, E.N., 2008. Passive seismic interferometry by multidimensional deconvolution, Geophysics, 75, A51-A56.

Differences in temperament and character dimensions of personality between patients with Hwa-byung, an anger syndrome, and patients with major depressive disorder.

PubMed

Lee, Jieun; Min, Sung Kil; Kim, Keung-Hyang; Kim, Borah; Cho, Sung Joon; Lee, Sang-Hyuk; Choi, Tae Kyou; Suh, Shin-Young

2012-04-01

This study examined differences in temperament and character dimensions of personality between patients with Hwa-byung (HB) and those with major depressive disorder (MDD). Of 144 participants, 96 completed the Korean version of the Temperament and Character Inventory-Revised Short (TCI-RS) and the Hwa-byung Scale. We diagnosed participants according to the DSM-IV and the Research Diagnostic Criteria for Hwa-byung. We compared TCI scores between the HB group (with or without MDD; N=55) and the MDD-only group (N=41) and correlated them with the total scores on six HB-specific symptoms (global HB severity) on the Hwa-byung Scale. Compared to patients with only MDD, patients with HB with or without MDD exhibited significantly higher scores on Impulsiveness; Harm Avoidance (HA) and its subscales of Anticipatory Worry; and Self-Transcendence (ST), with its subscale of Self-Forgetfulness. However, HB patients had lower scores on Self-Directedness, with its subscales of Responsibility, and Self-Acceptance; and Acceptance. Moreover, Global HB Severity had significant, positive correlations with ST, its subscale Self-Forgetfulness, and Anticipatory Worry but negative correlations with Attachment and Compassion. Our data are cross-sectional and self-reported, so they are subject to personal perceptual bias. The number of participants may be too low for us to generalize the results. These results suggest that HB is a different clinical entity from MDD in relation to personality traits, and that symptoms unique to HB are closely correlated with ST. Copyright © 2011 Elsevier B.V. All rights reserved.

Functional neuroimaging of sex differences in autobiographical memory recall in depression.

PubMed

Young, K D; Bodurka, J; Drevets, W C

2017-11-01

Females are more likely than males to develop major depressive disorder (MDD). The current study used fMRI to compare the neural correlates of autobiographical memory (AM) recall between males and females diagnosed with MDD. AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of which is correlated with depressive severity only in females. Delineating the neurobiological correlates of this deficit may elucidate the nature of sex-differences in the diathesis for developing MDD. Participants included unmedicated males and females diagnosed with MDD (n = 20/group), and an age and sex matched healthy control group. AM recall in response to positive, negative, and neutral cue words was compared with a semantic memory task. The behavioral properties of AMs did not differ between MDD males and females. In contrast, main effects of sex on cerebral hemodynamic activity were observed in left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of positive specific memories, and middle prefrontal cortex (mPFC), and precuneus during recall of negative specific memories. Moreover, main effects of diagnosis on regional hemodynamic activity were observed in left ventrolateral prefrontal cortex and mPFC during positive specific memory recall, and dorsal anterior cingulate cortex during negative specific memory recall. Sex × diagnosis interactions were evident in the dorsomedial prefrontal cortex, caudate, and precuneus during positive memory recall, and in the posterior cingulate cortex, insula, precuneus and thalamus during negative specific memory recall. The differential hemodynamic changes conceivably may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories.

Examination of the interrelations between the factors of PTSD, major depression, and generalized anxiety disorder in a heterogeneous trauma-exposed sample using DSM 5 criteria.

PubMed

Price, Matthew; van Stolk-Cooke, Katherine

2015-11-01

Exposure to traumatic events places individuals at high risk for multiple psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD). The high rates of comorbidity among these conditions merit evaluation in order to improve diagnosis and treatment approaches. The current study evaluated the association between PTSD, MDD, and GAD factors as presented in the DSM 5. 602 trauma-exposed individuals who experienced an event that met Criterion A for the DSM 5 PTSD diagnosis were recruited through Amazon.com, Inc.'s Mechanical Turk (MTurk) to complete an assessment of the impact of stressful events on their lives. High interrelations were detected among the 4 PTSD factors, 2 MDD factors that corresponded to somatic and affective symptoms, and the single GAD factor. The affective factor of MDD was most strongly related to the emotional numbing factor of PTSD, whereas the somatic factor of MDD was most strongly related to the hyperarousal factor of PTSD. The GAD factor was most strongly related to the hyperarousal factor of PTSD, relative to the other PTSD factors. The strength of the interrelations between factors of the three disorders is largely a function of the overlap in symptoms and calls into question the uniqueness of negative affective symptoms of PTSD, MDD and GAD. Results suggest that improved understanding of the trauma reaction requires a focus on the unique presentation of each individual and assessment of multiple disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controls.

PubMed

Halari, Rozmin; Simic, Mima; Pariante, Carmine M; Papadopoulos, Andrew; Cleare, Anthony; Brammer, Michael; Fombonne, Eric; Rubia, Katya

2009-03-01

There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naïve adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naïve adolescents with a first-episode of MDD aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.

Identify abnormalities in resting-state brain function between first-episode, drug-naive major depressive disorder and remitted individuals: a 3-year retrospective study.

PubMed

Yang, Chunxia; Zhang, Aixia; Jia, Aixiang; Ma, Jack X; Sun, Ning; Wang, Yanfang; Li, Xinrong; Liu, Zhifen; Liu, Sha; Xu, Yong; Zhang, Kerang

2018-06-15

This study aims to identify and characterize neurobiological markers for major depressive disorder (MDD) from resting-state brain functional MRI. We examined the abnormality in the regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) in first-episode, drug-naive major depressive disorder (fMDD), and remitted major depressive disorder (rMDD) and correlated these fluctuations with clinical markers of MDD. We conducted a retrospective study and reviewed the medical records of 43 patients with fMDD. Overall, 13 of the 43 patients who had at least 3 years of follow-up care and the 17-item Hamilton Depression rating scale less than 7 took no antidepressants for more than half a year at the end of the 3-year follow-up. We further chose a group of 14 healthy controls matched for age, sex and education level with patients with rMDD. Multiple comparison analysis was performed for ALFF and ReHo. The statistical significance level was set at P value of less than 0.05. We examined whether there were differences among the three groups in the whole-brain ALFF and ReHo during resting state. Compared with healthy controls, patients with fMDD showed significant decrease of ReHo in the right anterior lobe of cerebellum and significant increase of ReHo in the right inferior temporal gyrus, and significant decrease of ALFF in the left inferior parietal lobule and right caudate nucleus. Compared with patients with rMDD, those with fMDD showed significant increase of ReHo in the right fusiform gyrus and the left middle temporal gyrus, and significant increase of ALFF in the right superior temporal gyrus. Compared with healthy controls, patients with rMDD showed significant increase of ReHo in the right supramarginal and significant decrease of ReHo in the right precuneus, and significant decrease of ALFF in the right lingual gyrus and in the left superior frontal lobe. Only patients with fMDD showed the relatively robust increase in intrinsic activity of temporal gyrus. The temporal gyrus may play a critical role in depressive symptomatology. Abnormal right fusiform gyrus, left middle temporal gyrus, and right superior temporal gyrus alterations were present only in patients with rMDD but not in patients with fMDD, indicating that these alterations may be a therapeutic target for MDD. Abnormal right supramarginal, right precuneus, right lingual gyrus and left superior frontal lobe alterations were present only in patients with rMDD and not in healthy control, and thus may be used as a state marker of MDD.

Altered interaction with environmental reinforcers in major depressive disorder: Relationship to anhedonia.

PubMed

Szczepanik, Joanna E; Furey, Maura L; Nugent, Allison C; Henter, Ioline D; Zarate, Carlos A; Lejuez, Carl W

2017-10-01

Anhedonia-defined as loss of interest or pleasure-is one of two core symptoms of major depressive disorder (MDD). Anhedonia may involve decreased enjoyment of potentially rewarding activities and decreased motivation to engage in such activities. Increased engagement with reinforcers-activities with the potential to be positive experiences-is a frequent target of cognitive-behavioral therapies. Nevertheless, how environmental reinforcers are perceived, and how decisions to approach or avoid them are made by individuals with MDD, is largely unknown. We developed an experimental Behavioral Approach Motivation Paradigm to study how activities are evaluated and approached in MDD. Twenty-one MDD participants and 23 healthy controls performed an experimental task that rated activity words for their hedonic value, then engaged in an approach-avoidance joystick task with each individual's unique set of 'liked' and 'disliked' activity words. A negative correlation was observed between anhedonia and the number of 'liked' activities across participants. No significant difference between approach and avoidance behavior was found in direct comparisons between healthy controls and MDD participants; however, weaker avoidance and greater approach toward 'disliked' activities was found in MDD participants. This suggests negative bias in selecting environmental opportunities, potentially further compromising access to hedonic experiences in MDD. Copyright © 2017. Published by Elsevier Ltd.

Altered interaction with environmental reinforcers in major depressive disorder: Relationship to anhedonia

PubMed Central

Szczepanik, Joanna E.; Furey, Maura L.; Nugent, Allison C.; Henter, Ioline D.; Zarate, Carlos A.; Lejuez, Carl W.

2017-01-01

Anhedonia—defined as loss of interest or pleasure—is one of two core symptoms of major depressive disorder (MDD). Anhedonia may involve decreased enjoyment of potentially rewarding activities and decreased motivation to engage in such activities. Increased engagement with reinforcers—activities with the potential to be positive experiences—is a frequent target of cognitive-behavioral therapies. Nevertheless, how environmental reinforcers are perceived, and how decisions to approach or avoid them are made by individuals with MDD, is largely unknown. We developed an experimental Behavioral Approach Motivation Paradigm to study how activities are evaluated and approached in MDD. Twenty-one MDD participants and 23 healthy controls performed an experimental task that rated activity words for their hedonic value, then engaged in an approach-avoidance joystick task with each individual’s unique set of ‘liked’ and ‘disliked’ activity words. A negative correlation was observed between anhedonia and the number of ‘liked’ activities across participants. No significant difference between approach and avoidance behavior was found in direct comparisons between healthy controls and MDD participants; however, weaker avoidance and greater approach toward ‘disliked’ activities was found in MDD participants. This suggests negative bias in selecting environmental opportunities, potentially further compromising access to hedonic experiences in MDD. PMID:28806614

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.

PubMed

Zhu, Xi; Helpman, Liat; Papini, Santiago; Schneier, Franklin; Markowitz, John C; Van Meter, Page E; Lindquist, Martin A; Wager, Tor D; Neria, Yuval

2017-07-01

Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed. © 2016 Wiley Periodicals, Inc.

Beta-amyloid deposition in patients with major depressive disorder with differing levels of treatment resistance: a pilot study.

PubMed

Li, Peng; Hsiao, Ing-Tsung; Liu, Chia-Yih; Chen, Chia-Hsiang; Huang, She-Yao; Yen, Tzu-Chen; Wu, Kuan-Yi; Lin, Kun-Ju

2017-12-01

Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using 18 F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33).The standard uptake value ratio (SUVR) of each volume of interest was analysed, and voxel-wise comparisons were made between the MDD patients and HCs. Vascular risk factors, serum homocysteine level, and apolipoprotein E (ApoE) genotype were also determined. The MDD patients with moderate-to-severe treatment resistance had higher 18 F-florbetapir SUVRs than the HCs in the parietal region (P < 0.01). Voxel-wise comparisons further demonstrated elevated SUVRs in MDD patients with moderate-to-severe treatment resistance in the precuneus, parietal, temporal, and occipital regions. The MDD patients with mild treatment resistance were found to have increased 18 F-florbetapir uptake mainly in the left frontal and parietal regions as compared with the HCs. In addition, voxel-to-voxel correlation analysis showed that brain Aβ deposition was correlated positively with MSM score in the occipital region. 18 F-florbetapir SUVRs were correlated negatively with Mini Mental Status Examination (MMSE) score in the sample of all MDD patients (r = -0.355, P = 0.005). This study provided preliminary evidence that region-specific Aβ deposition was present in some (but not all) MDD patients, especially in those with moderate-to-severe treatment resistance, and their depressive symptoms may represent prodromal manifestations of Alzheimer's disease (AD). Depressive symptomatology in old age, particularly in subjects with a poor treatment response, may underscore early changes of AD-related pathophysiology.

Number needed to treat to harm for discontinuation due to adverse events in the treatment of bipolar depression, major depressive disorder, and generalized anxiety disorder with atypical antipsychotics.

PubMed

Gao, Keming; Kemp, David E; Fein, Elizabeth; Wang, Zuowei; Fang, Yiru; Ganocy, Stephen J; Calabrese, Joseph R

2011-08-01

To estimate the number needed to treat to harm (NNTH) for discontinuation due to adverse events with atypical antipsychotics relative to placebo during the treatment of bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). English-language literature published and cited in MEDLINE from January 1966 to May 2009 was searched with the terms antipsychotic, atypical antipsychotic, generic and brand names of atypical antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, sedation, weight gain, akathisia, or extrapyramidal side effect; and bipolar depression, major depressive disorder, or generalized anxiety disorder; and randomized, placebo-controlled clinical trial. This search was augmented with a manual search. Studies with a cumulative sample of ≥ 100 patients were included. The NNTHs for discontinuation due to adverse events, somnolence, sedation, ≥ 7% weight gain, and akathisia relative to placebo were estimated with 95% confidence intervals to reflect the magnitude of variance. Five studies in bipolar depression, 10 studies in MDD, and 4 studies in GAD were identified. Aripiprazole and olanzapine have been studied in bipolar depression and refractory MDD. Only quetiapine extended release (quetiapine-XR) has been studied in 3 psychiatric conditions with different fixed dosing schedules. For aripiprazole, the mean NNTH for discontinuation due to adverse events was 14 in bipolar depression, but was not significantly different from placebo in MDD. For olanzapine, the mean NNTHs were 24 in bipolar depression and 9 in MDD. The risk for discontinuation due to adverse events during quetiapine-XR treatment appeared to be associated with dose. For quetiapine-XR 300 mg/d, the NNTHs for discontinuation due to adverse events were 9 for bipolar depression, 8 for refractory MDD, 9 for MDD, and 5 for GAD. At the same dose of quetiapine-XR, patients with GAD appeared to have a lower tolerability than those with bipolar depression or MDD. Due to flexible dosing, the risk for discontinuation due to adverse events in the treatment of bipolar depression, MDD, or GAD with other atypical antipsychotics could not be compared. © Copyright 2011 Physicians Postgraduate Press, Inc.

Interaction of oxytocin level and past depression may predict postpartum depressive symptom severity

PubMed Central

Massey, Suena H.; Schuette, Stephanie A.; Pournajafi-Nazarloo, Hossein; Wisner, Katherine L.; Carter, C. Sue

2016-01-01

Purpose We examined plasma oxytocin concentration and postpartum depression (PPD) symptom severity in women who were not depressed during pregnancy, and whether this differed by major depressive disorder (MDD) history. Methods We assessed psychiatric history and plasma oxytocin in 66 healthy pregnant women in the third trimester (M = 35 ± 3 weeks) and depressive symptoms at 6 weeks postpartum (M = 5.9 ± 0.8 weeks). Linear regression analysis was used to examine oxytocin and PPD symptom severity, and moderation of oxytocin and PPD by past MDD. Results Women with (n = 13) and without (n = 53) past MDD differed in third trimester depressive symptom severity, but not oxytocin level, demographic factors or birth outcomes. Controlling for third trimester depressive symptoms, oxytocin level was unrelated to PPD symptom severity [B(SE) = −.019(.084); β = −.025; t = −.227; p = .821]. However, oxytocin level interacted with past MDD to predict PPD symptom severity [(B(SE) = 7.489(2.429); β = .328; t = 3.084; p = .003]. Higher oxytocin predicted greater PPD symptom severity in women with past MDD (p = .019), but not in women without (p = .216). Conclusions Replication in a larger sample and methodologic challenges are discussed. PMID:26957508

Gender differences in major depressive disorder: results from the Netherlands study of depression and anxiety.

PubMed

Schuch, Jérôme J J; Roest, Annelieke M; Nolen, Willem A; Penninx, Brenda W J H; de Jonge, Peter

2014-03-01

Although an overall gender difference in prevalence of major depressive disorder (MDD) has been well established, several questions concerning gender differences in the clinical manifestation of depression remain. This study aims to identify gender differences in psychopathology, treatment, and public health consequences in patients with MDD. Baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were used, including 1115 participants (364 men, 751 women, mean age 41 years) with a DSM-IV diagnosis of current MDD. Characteristics studied included symptom profiles, comorbidity, treatment, and public health consequences. Women reported a younger age of onset of single (27.8 years vs. 31.6 years; p=0.001) and recurrent MDD (24.8 years vs. 27.6 years; p=0.014), a higher comorbidity of panic disorder with agoraphobia (24.9% vs. 17.3%; p=0.006) and life-time overall anxiety disorder (77.6% vs. 71.4%; p=0.029) than men. More men than women suffered from comorbid alcohol dependence or abuse (48.1% vs. 24.5%; p<0.001). An increased prevalence of atypical depression in women (24.6% vs. 17.3%; p=0.009) was found. Women were treated more frequently by an alternative caretaker (20.6% vs. 14.8%; p=0.025), men more often in mental health care organizations (61.0% vs. 53.7%; p=0.025). No gender differences in frequency of medication use or counseling were found. Cross sectional design. Main gender differences in the clinical presentation of MDD concerned a younger age of onset, higher anxiety and lower alcohol use comorbidity and higher prevalence of atypical depression in women. These differences were accompanied by differences in health care use. Copyright © 2013 Elsevier B.V. All rights reserved.

Gender differences in demographic and clinical features and prescribing patterns of psychotropic medications in patients with major depressive disorder in China.

PubMed

Xiang, Yu-Tao; Wang, Gang; Guo, Tong; Hu, Chen; Ungvari, Gabor S; Kilbourne, Amy M; Lai, Kelly Y C; Wong, Samuel Y S; Si, Tian-Mei; Zheng, Qi-Wen; Chen, Da-Fang; Fang, Yi-Ru; Lu, Zheng; Yang, Hai-Chen; Hu, Jian; Chen, Zhi-Yu; Huang, Yi; Sun, Jing; Wang, Xiao-Ping; Li, Hui-Chun; Zhang, Jin-Bei; Chiu, Helen F K

2013-11-01

Little is known about gender differences associated with major depressive disorder (MDD) in China. This study examined gender differences associated with other demographic and clinical characteristics and psychotropic drug treatment in Chinese patients with MDD. A total of 1178 patients with MDD from 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide were enrolled. Cross-sectional data including patients' demographic and clinical characteristics and prescriptions of psychotropic medications were recorded using a standardized protocol and data collection procedure. The sample consisted of 793 female and 385 male patients. Univariate analyses revealed that male patients were younger than female patients, had a younger age of onset of depression, had less lifetime depressive episodes and had more bipolar features (i.e. patients who screened positive for hypomanic symptoms on the 32-item Hypomania Checklist, but did not meet the diagnostic criteria for DSM-IV bipolar disorders as measured by the Mini International Neuropsychiatric Interview). Also, men were more likely to be employed than women and less likely to have depressive episodes following stressful life events. In multivariate analyses, being employed, having bipolar features and not having depressive episodes following stressful life events were independently associated with being a male patient with major depressive disorder. There was no difference in use of psychotropic medications by gender. Most gender differences in MDD patients in this study are not consistent with findings of Western studies suggesting that gender differences in MDD may be determined by both biological and sociocultural differences among ethnically different patient populations. Copyright © 2013 Elsevier Inc. All rights reserved.

Plasma Testosterone and the Course of Major Depressive Disorder in Older Men and Women.

PubMed

Giltay, Erik J; van der Mast, Roos C; Lauwen, Esther; Heijboer, Annemieke C; de Waal, Margot W M; Comijs, Hannie C

2017-04-01

To investigate associations between testosterone levels and major depressive disorder (MDD) in older men and women. In a cross-sectional, 2-year prospective analyses within the Netherlands Study on Depression in Older persons cohort study, 469 participants comprised 350 patients with MDD and 119 nondepressed participants in the comparison group (mean age 70.5 ± 7.3 years; 166 [35.4%] men). MDD was assessed by the Composite International Diagnostic Interview. Baseline plasma total testosterone and sex hormone binding globulin (SHBG) were assessed to calculate free testosterone. The Inventory of Depressive Symptomatology was assessed every 6 months. Whereas SHBG levels did not differ between the depressed/nondepressed groups (F(1,149) = 0.075, p = 0.78), men with MDD had lower mean total and free testosterone levels than the comparison group in the multivariate adjusted analyses (F(1,150) = 7.249, p = 0.008, Cohen's d = 0.51; and F(1,149) = 8.548, p = 0.004 Cohen's d = 0.55, respectively). This could be ascribed to lower testosterone in men with "pure" MDD and not in men with MDD and comorbid anxiety. Nine men (5.4%) had a total testosterone level < 8 nmol/L, of whom 8 suffered from MDD. In women, hormone levels showed no significant difference between the groups. In men (using all five measurement points during follow-up) baseline free testosterone was inversely associated with depression severity in the adjusted analyses (β = -0.15, t(151) = -2.15, p = 0.03). Testosterone levels were lower in men with MDD compared with healthy men after adjustment for confounders, such as body mass index. No significant associations were found in women. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder.

PubMed

Sacchet, Matthew D; Ho, Tiffany C; Connolly, Colm G; Tymofiyeva, Olga; Lewinn, Kaja Z; Han, Laura Km; Blom, Eva H; Tapert, Susan F; Max, Jeffrey E; Frank, Guido Kw; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T

2016-11-01

Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.

Patterns of co-occurring addictions, posttraumatic stress disorder, and major depressive disorder in detoxification treatment seekers: Implications for improving detoxification treatment outcomes.

PubMed

Anderson, RaeAnn E; Hruska, Bryce; Boros, Alec P; Richardson, Christopher J; Delahanty, Douglas L

2018-03-01

Poly-substance use and psychiatric comorbidity are common among individuals receiving substance detoxification services. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are the most common co-occurring psychiatric disorders with substance use disorder (SUD). Current treatment favors a one-size-fits-all approach to treating addiction focusing on one substance or one comorbidity. Research examining patterns of substance use and comorbidities can inform efforts to effectively identify and differentially treat individuals with co-occurring conditions. Using latent class analysis, the current study identified four patterns of PTSD, MDD, and substance use among 375 addiction treatment seekers receiving medically supervised detoxification. The four identified classes were: 1) a PTSD-MDD-Poly SUD class characterized by PTSD and MDD occurring in the context of opioid, cannabis, and tobacco use disorders; 2) an MDD-Poly SUD class characterized by MDD and alcohol, opioid, tobacco, and cannabis use disorders; 3) an alcohol-tobacco class characterized by alcohol and tobacco use disorders; and 4) an opioid-tobacco use disorder class characterized by opioid and tobacco use disorders. The observed classes differed on gender and clinical characteristics including addiction severity, trauma history, and PTSD/MDD symptom severity. The observed classes likely require differing treatment approaches. For example, people in the PTSD-MDD-Poly SUD class would likely benefit from treatment approaches targeting anxiety sensitivity and distress tolerance, while the opioid-tobacco class would benefit from treatments that incorporate motivational interviewing. Appropriate matching of treatment to class could optimize treatment outcomes for polysubstance and comorbid psychiatric treatment seekers. These findings also underscore the importance of well-developed referral networks to optimize outpatient psychotherapy for detoxification treatment-seekers to enhance long-term recovery, particularly those that include transdiagnostic treatment components. Copyright © 2017. Published by Elsevier Inc.

Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder

PubMed Central

Sacchet, Matthew D; Ho, Tiffany C; Connolly, Colm G; Tymofiyeva, Olga; Lewinn, Kaja Z; Han, Laura KM; Blom, Eva H; Tapert, Susan F; Max, Jeffrey E; Frank, Guido KW; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T

2016-01-01

Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period. PMID:27238621

Emotional availability in mothers with borderline personality disorder and mothers with remitted major depression is differently associated with psychopathology among school-aged children.

PubMed

Kluczniok, Dorothea; Boedeker, Katja; Hindi Attar, Catherine; Jaite, Charlotte; Bierbaum, Anna-Lena; Fuehrer, Daniel; Paetz, Luisa; Dittrich, Katja; Herpertz, Sabine C; Brunner, Romuald; Winter, Sibylle; Heinz, Andreas; Roepke, Stefan; Heim, Christine; Bermpohl, Felix

2018-04-15

Both, maternal borderline personality disorder (BPD) and maternal major depressive disorder (MDD) are often associated with adverse consequences for children, including increased risk for child behavior problems. Reduced maternal emotional availability might play a critical role in transmitting maternal psychopathology on the child. Our aim was to investigate the association between emotional availability and maternal BPD and MDD in remission (rMDD), and if this interrelatedness mediates the association between maternal mental disorders and child behavior problems. The interaction of 178 mother-child dyads was assessed during a play situation using the Emotional Availability Scales. Children were between 5 and 12 years old. Regression analyses were used to investigate the impact of maternal BPD and maternal rMDD on emotional availability. Ordinary least squares regression analyses using bootstrapping were conducted to investigate the mediating effect of emotional availability on the association between maternal mental disorders and child behavior problems. Mothers with BPD showed increased hostility during mother-child interaction, whereas history of MDD was associated with reduced sensitivity. Maternal hostility was a mediator between maternal BPD and number of child psychiatric disorders, as well as externalizing and internalizing behavior. Maternal sensitivity mediated the association between maternal rMDD and number of child psychiatric disorders, as well as internalizing child behavior. Our data suggest that mothers with BPD show a qualitatively different pattern of emotional availability compared to mothers with rMDD. These patterns might reflect two separate pathways of transgenerational transmission of aspects of maternal mental disorders, where intervention and training programs could start: maternal rMDD impacts on child behavior problems via reduced sensitivity, and maternal BPD via increased hostility, which could both be addressed with specific therapeutic interventions. Copyright © 2018 Elsevier B.V. All rights reserved.

PATIENT-REPORTED OUTCOMES OF QUALITY OF LIFE, FUNCTIONING, AND DEPRESSIVE SYMPTOM SEVERITY IN MAJOR DEPRESSIVE DISORDER COMORBID WITH PANIC DISORDER BEFORE AND AFTER SSRI TREATMENT IN THE STAR*D TRIAL

PubMed Central

IsHak, Waguih William; Mirocha, James; Christensen, Scott; Wu, Fan; Kwock, Richard; Behjat, Joseph; Pi, Sarah; Akopyan, A.; Peselow, Eric D.; Cohen, Robert M.; Elashoff, David

2014-01-01

Background Panic disorder (PD) is highly comorbid with major depressive disorder (MDD) with potential impact on patient-reported outcomes of quality of life (QOL), functioning, and depressive symptom severity Methods Using data from the sequenced treatment alternatives to relieve depression (STAR*D) trial, we compared entry and post-SSRI-treatment QOL, functioning, and depressive symptom severity scores in MDD patients with comorbid PD (MDD+PD) to MDD patients without PD (MDDnoPD). We also compared pre- and posttreatment proportions of patients with severe impairments in quality of life and functioning. Results MDD+PD patients experienced significantly lower QOL and functioning and more severe depressive symptoms than MDDnoPD patients at entry. Following treatment with citalopram, both groups showed significant improvements, however, nearly 30–60% of patients still suffered from severe quality of life and functioning impairments. MDD+PD patients exited with lower QOL and functioning than MDDnoPD patients, a difference that became statistically insignificant after adjusting for baseline measures of depressive symptom severity, functioning, and QOL, comorbid anxiety disorders (PTSD, GAD, social, and specific phobias), age, and college education. Conclusions Functional outcomes using QOL and functioning measures should be utilized in treating and researching MDD so that shortfalls in traditional treatment can be identified and additional interventions can be designed to address severe baseline QOL and functioning deficits in MDD comorbid with PD. PMID:23861180

The role of comorbid major depressive disorder in the clinical presentation of adult ADHD.

PubMed

Fischer, Aline G; Bau, Claiton H D; Grevet, Eugenio H; Salgado, Carlos A I; Victor, Marcelo M; Kalil, Katiane L S; Sousa, Nyvia O; Garcia, Christiane R; Belmonte-de-Abreu, Paulo

2007-12-01

Most adults with attention-deficit/hyperactivity disorder (ADHD) are not recognized and remain untreated, although a large fraction of these individuals are diagnosed and treated for other comorbid mental disorders, such as major depressive disorder (MDD). The fact that MDD is one of the most commonly occurring mental disorders with high comorbidity with adult ADHD raises the question whether such comorbidity is associated with differences in the clinical picture of ADHD. Three hundred and twenty adult ADHD outpatients were evaluated. Diagnoses followed DSM-IV criteria. Interviews to evaluate ADHD and oppositional defiant disorder (ODD) were performed based on the Portuguese version of K-SADS-E. Psychiatric comorbidities were investigated using SCID-IV and MINI. Regression models were applied to test MDD association with clinical and demographic outcomes. Subjects presenting ADHD and MDD had a higher frequency of generalized anxiety disorder and social phobia and a lower frequency of substance dependence, grade repetition and school suspensions, when compared to subjects with ADHD without MDD. Furthermore, adults presenting ADHD and MDD reported higher demand for psychotherapy and pharmacological treatment prior to enrollment in the study when compared to ADHD subjects free of MDD. However, contrary to what could be expected based on these data, the presence of MDD was not associated with an earlier ADHD diagnosis. These results point to the need for research and medical education into an earlier and more efficient ADHD diagnosis in patients who search for mental health care.

Elevated amygdala activity to sad facial expressions: a state marker of bipolar but not unipolar depression.

PubMed

Almeida, Jorge R C; Versace, Amelia; Hassel, Stefanie; Kupfer, David J; Phillips, Mary L

2010-03-01

Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Telomere length is inversely correlated with urinary stress hormone levels in healthy controls but not in un-medicated depressed individuals-preliminary findings.

PubMed

Fair, Brittany; Mellon, Synthia H; Epel, Elissa S; Lin, Jue; Révész, Dóra; Verhoeven, Josine E; Penninx, Brenda W; Reus, Victor I; Rosser, Rebecca; Hough, Christina M; Mahan, Laura; Burke, Heather M; Blackburn, Elizabeth H; Wolkowitz, Owen M

2017-08-01

Leukocyte telomere length (LTL) is a biomarker of cellular aging affected by chronic stress. The relationship of LTL to the stress hormones, cortisol and catecholamines, is unclear, as are possible differences between healthy controls (HC) and individuals with Major Depressive Disorder (MDD). This small pilot study is the first to examine the relationship between cortisol, catecholamines and LTL specifically in un-medicated MDD in comparison with HC. Participants included 16 un-medicated MDD subjects and 15 HC for assay of LTL, 12-hour overnight urinary free cortisol and catecholamine levels. LTL, cortisol and catecholamine levels did not significantly differ between groups. In HC, a hierarchical regression analysis indicated that higher levels of cortisol were correlated with shorter LTL (p=0.003) above and beyond age and sex. Higher catecholamine levels were nearly-significant with shorter LTL (p=0.055). Neither hormone was correlated with shorter LTL in MDD (p's>0.28). To assess a possible cumulative effect of stress hormone activation, a summary score was calculated for each subject based on the number of stress hormone levels above the median for that group (HC or MDD). A significant inverse graded relationship was observed between LTL and the number of activated systems in HC (p=0.001), but not in MDD (p=0.96). This pilot study provides preliminary evidence that stress hormone levels, especially cortisol, are inversely related to LTL in HC, but not in un-medicated MDD. Clarification of these relationships in larger samples could aid in understanding differential mechanisms underlying stress-related cellular aging in healthy and depressed populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered inhibition of negative emotions in subjects at family risk of major depressive disorder.

PubMed

Lisiecka, Danuta M; Carballedo, Angela; Fagan, Andrew J; Connolly, Gerald; Meaney, James; Frodl, Thomas

2012-02-01

Unaffected 1st degree relatives of patients with major depressive disorder (MDD) are more likely to develop MDD than healthy controls. The aim of our study was to establish neuronal correlates of familial susceptibility in the process of inhibition of emotional information. Unaffected 1st degree relatives of patients with MDD (N = 21) and matched healthy controls (N = 25) underwent a functional magnetic resonance imaging procedure with an inhibition task. Blood oxygenated level dependent signal was evaluated for the two groups during inhibition of positive, negative and neutral information. In a 2 × 3 ANOVA unaffected relatives of patients with MDD were compared to healthy controls, jointly and separately for all three levels of emotional valence of the information. The interaction between group and emotional valence of the inhibited information was significant, indicating "a negative neural drift" in unaffected relatives of patients with MDD. The unaffected relatives of patients with MDD displayed an increased activation during inhibiting of negative material in the right middle cingulate cortex and the left caudate nucleus (p < 0.05, family wise error corrected). There was no difference between the two groups in terms of inhibiting positive or neutral stimuli. Our findings provide the first evidence that unaffected relatives of patients with MDD differ from the standard population in terms of neural correlates of inhibition of negative emotional information. Overactivation of cingulate cortex and caudate nucleus may indicate a learnt strategy aimed at coping with increased susceptibility to negative information schemata and may have future consequences for therapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder.

PubMed

Wan, Yunqiang; Liu, Yuanhui; Wang, Xiaobin; Wu, Jiali; Liu, Kezhi; Zhou, Jun; Liu, Li; Zhang, Chunxiang

2015-01-01

Major depression is a debilitating disease. To date, the development of biomarkers of major depressive disorder (MDD) remains a challenge. Recently, alterations in the expression of microRNAs (miRNAs) from post-mortem brain tissue and peripheral blood have been linked to MDD. The goals of this study were to detect the differential miRNAs in cerebrospinal fluid (CSF) and serum of MDD patients. First, the relative expression levels of 179 miRNAs (relative high levels in serum) were analyzed by miRNA PCR Panel in the CSF of MDD patients. Then, the differentially altered miRNAs from CSF were further assessed by qRT-PCR in the serum of the same patients. Finally, the serum differentially altered miRNAs were further validated by qRT-PCR in the serum of another MDD patients. The CSF-results indicated that 11 miRNAs in MDD patients were significantly higher than these in control subjects, and 5 miRNAs were significantly lower than these in control subjects. The serum-results from the same patients showed that 3 miRNAs (miR-221-3p, miR-34a-5p, and let-7d-3p) of the 11 miRNAs were significantly higher than these in control subjects, and 1 miRNA (miR-451a) of 5 miRNAs was significantly lower than these in control subjects. The up-regulation of miR-221-3p, miR-34a-5p, let-7d-3p and down-regulation of miR-451a was further validated in another 32 MDD patients. ROC analysis showed that the area under curve of let-7d-3p, miR-34a-5p, miR-221-3p and miR-451a was 0.94, 0.98, 0.97 and 0.94, with specificity of 90.48%, 95.24%, 90.48% and 90.48%, and sensitivity of 93.75%, 96.88%, 90.63% and 84.85%, respectively. In addition, target gene prediction found that the altered miRNAs are involved in affecting some important genes and pathway related to MDD. Our results suggested that differentially altered miRNAs in CSF might be involved in MDD, and serum miR-221-3p, miR-34a-5p, let-7d-3p, and miR-451a might be able to serve as biomarkers for MDD.

Differential neural correlates of autobiographical memory recall in bipolar and unipolar depression.

PubMed

Young, Kymberly D; Bodurka, Jerzy; Drevets, Wayne C

2016-11-01

Autobiographical memory (AM) recall is impaired in both bipolar depression (BD) and major depressive disorder (MDD). The current study used functional magnetic resonance imaging (fMRI) to investigate differences between healthy controls (HCs) and depressed participants with either BD or MDD as they recalled AMs that varied in emotional valence. Unmedicated adults in a current major depressive episode who met criteria for either MDD or BD and HCs (n=16/group) underwent fMRI while recalling AMs in response to emotionally valenced cue words. Control tasks involved generating examples from a given category and counting the number of risers in a letter string. Both participants with BD and those with MDD recalled fewer specific and more categorical memories than HC participants. During specific AM recall of positive memories, participants with BD showed increased hemodynamic activity in the ventrolateral prefrontal cortex, posterior cingulate cortex, anterior insula, middle temporal gyrus, parahippocampus, and amygdala relative to MDD and HC participants, as well as decreased dorsolateral prefrontal (DLPFC) activity relative to MDD participants. During specific AM recall of negative memories, participants with BD manifested decreased activity in the precuneus, amygdala, anterior cingulate, and DLPFC along with increased activity in the dorsomedial PFC relative to MDD participants. While depressed participants with BD and MDD exhibited similar depression ratings and memory deficits, the brain regions underlying successful AM recall significantly differentiated these patient groups. Differential amygdala activity during emotional memory recall (particularly increased activity in participants with BD for positive AMs) may prove useful in the differentiation of individuals with MDD and BD experiencing a depressive episode. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gray matter volume and rapid decision-making in major depressive disorder.

PubMed

Nakano, Masayuki; Matsuo, Koji; Nakashima, Mami; Matsubara, Toshio; Harada, Kenichiro; Egashira, Kazuteru; Masaki, Hiroaki; Takahashi, Kanji; Watanabe, Yoshifumi

2014-01-03

Reduced motivation and blunted decision-making are key features of major depressive disorder (MDD). Patients with MDD show abnormal decision-making when given negative feedback regarding a reward. The brain mechanisms underpinning this behavior remain unclear. In the present study, we examined the association between rapid decision-making with negative feedback and brain volume in MDD. Thirty-six patients with MDD and 54 age-, sex- and IQ-matched healthy subjects were studied. Subjects performed a rapid decision-making monetary task in which participants could make high- or low-risk choices. We compared between the 2 groups the probability that a high-risk choice followed negative feedback. In addition, we used voxel-based morphometry (VBM) to compare between group differences in gray matter volume, and the correlation between the probability for high-risk choices and brain volume. Compared to the healthy group, the MDD group showed significantly lower probabilities for high-risk choices following negative feedback. VBM analysis revealed that the MDD group had less gray matter volume in the right medial prefrontal cortex and orbitofrontal cortex (OFC) compared to the healthy group. The right OFC volume was negatively correlated with the probability that a high-risk choice followed negative feedback in patients with MDD. We did not observe these trends in healthy subjects. Patients with MDD show reduced motivation for monetary incentives when they were required to make rapid decisions following negative feedback. We observed a correlation between this reduced motivation and gray matter volume in the medial and ventral prefrontal cortex, which suggests that these brain regions are likely involved in the pathophysiology of aberrant decision-making in MDD. © 2013.

Blunted neural responses to reward in remitted major depression: A high-density event-related potential study

PubMed Central

Whitton, Alexis E.; Kakani, Pragya; Foti, Dan; Van’t Veer, Ashlee; Haile, Anja; Crowley, David J.; Pizzagalli, Diego A.

2015-01-01

Background Major depressive disorder (MDD) is a highly recurrent condition, and improving our understanding of the abnormalities that persist in remitted MDD (rMDD) may provide insight into mechanisms that contribute to relapse. MDD has been characterized by reward learning deficits linked to dysfunction in frontostriatal regions. Although initial behavioral evidence of reward learning deficits in rMDD has recently emerged, it is unclear whether these reflect impairments in neural reward processing that persist into remission. Methods We examined behavioral reward learning and 128-channel event-related potentials (ERP) during a well-validated probabilistic reward task in 26 rMDD individuals and 34 never-depressed controls. Temporo-spatial principal components analysis (PCA) was used to separate overlapping ERP components, and group differences in neural activity in a priori regions were examined using low-resolution electromagnetic tomography (LORETA). Results Individuals with rMDD displayed reduced behavioral reward learning, as well as blunted ERP amplitude to reward feedback. Importantly, the reduction in ERP amplitude occurred at a PCA factor that peaked during the time at which phasic reward feedback-related signaling – hypothesized to originate in the striatum and project to the anterior cingulate cortex (ACC) – are thought to modulate scalp-recorded activity. Consistent with this, LORETA analyses revealed reduced activity in the ACC in the rMDD group, and this blunting correlated with poorer reward learning. Conclusion These findings suggest that the reward learning impairment observed in acute MDD persists into full remission and that these impairments may be attributable to abnormalities in the neural processes that support reward feedback monitoring, particularly within the ACC. PMID:26858994

Prevalence of major depressive disorder in the general population of South Korea.

PubMed

Ohayon, Maurice M; Hong, Seung-Chul

2006-02-01

Previous epidemiological studies have reported a high prevalence of major depressive disorder (MDD) in North America and Western Europe. However, little information exists on MDD in Asian countries. This study investigates the prevalence of MDD and its characteristics in the general population of South Korea. A representative sample of the South Korean general population composed of 3719 non-institutionalized individuals aged 15 years or older was interviewed by telephone using the Sleep-EVAL system. The participation rate was 91.4%. The interviews covered sociodemographic characteristics, health care utilization, physical illnesses and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) psychiatric disorders. A depressive mood, i.e., feeling sad, downcast, having the blues or having lost interest in things formerly pleasant was reported by 20.9% of the sample without significant difference between men and women and among age groups. DSM-IV MDD was found in 3.6% (95% CI: 3.0-4.2%) of the sample. The prevalence of MDD was comparable among age groups. Shift workers were more likely to have MDD than daytime workers. Factor significantly associated with MDD were: being a woman, being a light or heavy smoker, perceiving one's health as being average or poor, doing physical activities at least three times per week in the evening, having a BMI below 18.5 kg/m2 and perceiving one's life as being moderately or highly stressful. Prevalence of MDD in Korea is higher than what it was previously estimated to be two decades ago. The number of individuals seeking help for depression was very low, and only a small number of MDD subjects received appropriate treatment for their condition.

Prevalence of major depressive disorder among spouses of men who use alcohol in a rural community in Central Sri Lanka.

PubMed

Ariyasinghe, Dewasmika; Abeysinghe, Ranil; Siriwardhana, Prabhash; Dassanayake, Tharaka

2015-05-01

To estimate the prevalence of major depressive disorder (MDD) among spouses of men who use alcohol in two rural areas in Sri Lanka, and to examine whether the severity of alcohol-related problems (ARPs) in men and presence of alcohol-related domestic violence are associated with MDD among these women. In a cross-sectional study, ARPs among men were assessed using Alcohol Use Disorders Identification Test (AUDIT) questionnaire filled in by men, and domestic violence and husbands' drinking pattern data obtained from the women. MDD among the women was ascertained using the Structured Clinical Interview for DSM-IV Disorders for major depression. Using logistic regression we examined whether age, past history of depression, different indices of ARPs and domestic violence were associated with current MDD among the women. Point prevalence of MDD in the sample was 33.3% (95% CI: 25.93, 40.73%). Once adjusted for other factors, morning drinking of the spouse (odds ratio = 4.11, 95% CI: 1.25, 13.47; P = 0.019) and increasing age (odds ratio = 1.05, 95% CI: 1.01, 1.09; P = 0.003) significantly increased the odds of MDD. Being subjected to domestic violence/arguments also had a trend to be associated with MDD among women, but was not significant (odds ratio = 2.29, 95% CI: 0.95, 5.48; P = 0.062). The prevalence of MDD among spouses of men who use alcohol is markedly higher than that has been observed among Sri Lankan women in previous studies. The prevalence of MDD in women seems to increase when their husbands are morning drinkers, and with increasing age. © The Author 2015. Medical Council on Alcohol and Oxford University Press.

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group

PubMed Central

Rentería, M E; Schmaal, L; Hibar, D P; Couvy-Duchesne, B; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Gillespie, N A; Hatton, S N; Lagopoulos, J; Veltman, D J; van der Wee, N; van Erp, T G M; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Godlewska, B R; Cowen, P J; Penninx, B W J H; Jahanshad, N; Thompson, P M; Wright, M J; Martin, N G; Christensen, H; Hickie, I B

2017-01-01

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10−3) or a 2.87% smaller volume compared with controls (Cohen’s d=−0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28–0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments. PMID:28463239

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression.

PubMed

Kochunov, Peter; Glahn, David C; Rowland, Laura M; Olvera, Rene L; Winkler, Anderson; Yang, Yi-Hong; Sampath, Hemalatha; Carpenter, Will T; Duggirala, Ravindranath; Curran, Joanne; Blangero, John; Hong, L Elliot

2013-03-01

Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort. Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

PubMed Central

Kochunov, P.; Glahn, D.C.; Rowland, L.M.; Olvera, R.L.; Winkler, A; Yang, Y.H.; Sampath, H.; Carpenter, W.T.; Dugarrila, R.; Curran, J.; Blangero, J.; Hong, L.E.

2012-01-01

Introduction Elevated rate of aging-related biological and functional decline, termed accelerated aging, is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging (DTI) derived fractional anisotropy (FA) as biomarkers of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. Methods The SCZ cohort was composed of 58/60 SCZ patients/controls (age=20–60years). MDD cohort was composed of 136/351 MDD patients/controls (age=20–79years). Main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from twelve major WM tracts. Results Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p=0.04) but not in MDD cohort (p=0.80). Diagnosis-by-age interaction was nominally significant (p<0.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of- peak myelination and the rates of age-related decline obtained from normative sample (r=−0.61 and −0.80, p<0.05, respectively). No such trends existed for MDD cohort. Conclusion Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: white matter tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. PMID:23200529

Distinctive and common neural underpinnings of major depression, social anxiety, and their comorbidity.

PubMed

Hamilton, J Paul; Chen, Michael C; Waugh, Christian E; Joormann, Jutta; Gotlib, Ian H

2015-04-01

Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural responding to criticism and praise that are specific to and common among major depressive disorder (MDD), social anxiety disorder (SAD) and comorbid MDD-SAD. Adult females who met formal diagnostic criteria for MDD, SAD or MDD-SAD and psychiatrically healthy participants underwent functional magnetic resonance imaging as they listened to statements directing praise or criticism at them or at another person. MDD groups showed reduced responding to praise across a distributed cortical network, an effect potentially mediated by thalamic nuclei undergirding arousal-mediated attention. SAD groups showed heightened anterior insula and decreased default-mode network response to criticism. The MDD-SAD group uniquely showed reduced responding to praise in the dorsal anterior cingulate cortex. Finally, all groups with psychopathology showed heightened response to criticism in a region of the superior frontal gyrus implicated in attentional gating. The present results suggest novel neural models of anhedonia in MDD, vigilance-withdrawal behaviors in SAD, and poorer outcome in MDD-SAD. Importantly, in identifying unique and common neural substrates of MDD and SAD, these results support a formulation in which common neural components represent general risk factors for psychopathology that, due to factors that are present at illness onset, lead to distinct forms of psychopathology with unique neural signatures. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

White matter correlates of impaired attention control in major depressive disorder and healthy volunteers.

PubMed

Rizk, Mina M; Rubin-Falcone, Harry; Keilp, John; Miller, Jeffrey M; Sublette, M Elizabeth; Burke, Ainsley; Oquendo, Maria A; Kamal, Ahmed M; Abdelhameed, Mohamed A; Mann, J John

2017-11-01

Major depressive disorder (MDD) is associated with impaired attention control and alterations in frontal-subcortical connectivity. We hypothesized that attention control as assessed by Stroop task interference depends on white matter integrity in fronto-cingulate regions and assessed this relationship using diffusion tensor imaging (DTI) in MDD and healthy volunteers (HV). DTI images and Stroop task were acquired in 29 unmedicated MDD patients and 16 HVs, aged 18-65 years. The relationship between Stroop interference and fractional anisotropy (FA) was examined using region-of-interest (ROI) and tract-based spatial statistics (TBSS) analyses. ROI analysis revealed that Stroop interference correlated positively with FA in left caudal anterior cingulate cortex (cACC) in HVs (r = 0.62, p = 0.01), but not in MDD (r = -0.05, p= 0.79) even after controlling for depression severity. The left cACC was among 4 ROIs in fronto-cingulate network where FA was lower in MDD relative to HVs (F (1,41) = 8.87, p = 0.005). Additionally, TBSS showed the same group interaction of differences and correlations, although only at a statistical trend level. The modest sample size limits the generalizability of the findings. Structural connectivity of white matter network of cACC correlated with magnitude of Stroop interference in HVs, but not MDD. The cACC-frontal network, sub-serving attention control, may be disrupted in MDD. Less cognitive control may include enhanced effects of salience in HVs, or less effective response inhibition in MDD. Further studies of salience and inhibition components of executive function may better elucidate the relationship between brain white matter changes and executive dysfunction in MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

The Link between Mastery and Depression among Black Adolescents; Ethnic and Gender Differences

PubMed Central

Assari, Shervin; Caldwell, Cleopatra Howard

2017-01-01

Purpose: Although the link between depression and lower levels of mastery is well established, limited information exists on ethnic and gender differences in the association between the two. The current study investigated ethnic, gender, and ethnic by gender differences in the link between major depressive disorder (MDD) and low mastery in the United States. Methods: We used data from the National Survey of American Life-Adolescent supplement (NSAL-A), 2003–2004. In total, 1170 Black adolescents entered the study. This number was composed of 810 African-American and 360 Caribbean Black youth (age 13 to 17). Demographic factors, socioeconomic status (family income), mastery (sense of control over life), and MDD (Composite International Diagnostic Interview, CIDI) were measured. Logistic regressions were used to test the association between mastery and MDD in the pooled sample, as well as based on ethnicity and gender. Results: In the pooled sample, a higher sense of mastery was associated with a lower risk of MDD. This association, however, was significant for African Americans but not Caribbean Blacks. Similarly, among African American males and females, higher mastery was associated with lower risk of MDD. Such association could not be found for Caribbean Black males or females. Conclusion: Findings indicate ethnic rather than gender differences in the association between depression and mastery among Black youth. Further research is needed to understand how cultural values and life experiences may alter the link between depression and mastery among ethnically diverse Black youth. PMID:28498355

Are there temperament differences between major depression and dysthymic disorder in adolescent clinical outpatients?

PubMed

Dinya, Elek; Csorba, Janos; Grósz, Zsofia

2012-05-01

The aim of the study was to explore possible differences in temperament and character dimensions between 2 monodiagnostic adolescent groups of depression, namely, one with a present episode of major depression and subjects with the other being their dysthymic peers. From a multisite Western Hungarian sample of consecutively referred 14- to 18-year-old new psychiatric adolescent outpatients, 2 groups were compared: group I, n = 56 (9 males, 47 females), with major depressive disorder (MDD) and group II, n = 27 (6 males, 21 females), with a diagnosis of dysthymic disorder (DD). All other comorbid diagnoses including bipolar and double depression (MDD + DD) cases were excluded. Present suicide events, if the attempter had an underlying diagnosis of depression, were not causes for exclusion. Assessment methods used were the adapted Hungarian versions of the Mini International Neuropsychiatric Interview and the Junior Temperament (Cloninger) Character Inventory. The only difference between the major depressive and dysthymic adolescents was harm avoidance, adolescents with major depression having a higher level practice of harm avoidance, whereas the temperament type of MDD vs DD seems to differ only in the aspect of avoiding painful stress. Expectations regarding a worse degree of self-directedness and lower levels of persistence and cooperativeness in the MDD sample were not proved. No essential temperament differences were found between the 2 adolescent depressive groups. Scarce differences between temperament qualities of MDD and DD may support Akiskal's continuum theory of depressive disorders. More research and the use of closer clinical personality typologies are warranted to explore possible personality trait differences (if they exist) between clinical diagnostic groups of adolescent patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

PubMed

Witt, S H; Streit, F; Jungkunz, M; Frank, J; Awasthi, S; Reinbold, C S; Treutlein, J; Degenhardt, F; Forstner, A J; Heilmann-Heimbach, S; Dietl, L; Schwarze, C E; Schendel, D; Strohmaier, J; Abdellaoui, A; Adolfsson, R; Air, T M; Akil, H; Alda, M; Alliey-Rodriguez, N; Andreassen, O A; Babadjanova, G; Bass, N J; Bauer, M; Baune, B T; Bellivier, F; Bergen, S; Bethell, A; Biernacka, J M; Blackwood, D H R; Boks, M P; Boomsma, D I; Børglum, A D; Borrmann-Hassenbach, M; Brennan, P; Budde, M; Buttenschøn, H N; Byrne, E M; Cervantes, P; Clarke, T-K; Craddock, N; Cruceanu, C; Curtis, D; Czerski, P M; Dannlowski, U; Davis, T; de Geus, E J C; Di Florio, A; Djurovic, S; Domenici, E; Edenberg, H J; Etain, B; Fischer, S B; Forty, L; Fraser, C; Frye, M A; Fullerton, J M; Gade, K; Gershon, E S; Giegling, I; Gordon, S D; Gordon-Smith, K; Grabe, H J; Green, E K; Greenwood, T A; Grigoroiu-Serbanescu, M; Guzman-Parra, J; Hall, L S; Hamshere, M; Hauser, J; Hautzinger, M; Heilbronner, U; Herms, S; Hitturlingappa, S; Hoffmann, P; Holmans, P; Hottenga, J-J; Jamain, S; Jones, I; Jones, L A; Juréus, A; Kahn, R S; Kammerer-Ciernioch, J; Kirov, G; Kittel-Schneider, S; Kloiber, S; Knott, S V; Kogevinas, M; Landén, M; Leber, M; Leboyer, M; Li, Q S; Lissowska, J; Lucae, S; Martin, N G; Mayoral-Cleries, F; McElroy, S L; McIntosh, A M; McKay, J D; McQuillin, A; Medland, S E; Middeldorp, C M; Milaneschi, Y; Mitchell, P B; Montgomery, G W; Morken, G; Mors, O; Mühleisen, T W; Müller-Myhsok, B; Myers, R M; Nievergelt, C M; Nurnberger, J I; O'Donovan, M C; Loohuis, L M O; Ophoff, R; Oruc, L; Owen, M J; Paciga, S A; Penninx, B W J H; Perry, A; Pfennig, A; Potash, J B; Preisig, M; Reif, A; Rivas, F; Rouleau, G A; Schofield, P R; Schulze, T G; Schwarz, M; Scott, L; Sinnamon, G C B; Stahl, E A; Strauss, J; Turecki, G; Van der Auwera, S; Vedder, H; Vincent, J B; Willemsen, G; Witt, C C; Wray, N R; Xi, H S; Tadic, A; Dahmen, N; Schott, B H; Cichon, S; Nöthen, M M; Ripke, S; Mobascher, A; Rujescu, D; Lieb, K; Roepke, S; Schmahl, C; Bohus, M; Rietschel, M

2017-06-20

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10 -7 ) and PKP4 (P=8.67 × 10 -7 ); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P FDR =0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r g =0.28 [P=2.99 × 10 -3 ]), SCZ (r g =0.34 [P=4.37 × 10 -5 ]) and MDD (r g =0.57 [P=1.04 × 10 -3 ]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Minimum Detectable Dose as a Measure of Bioassay Programme Capability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carbaugh, Eugene H.

2003-01-01

This paper suggests that minimum detectable dose (MDD) be used to describe the capability of bioassay programs for which intakes are expected to be rare. This allows expression of the capability in units that correspond directly to primary dose limits. The concept uses the well-established analytical statistic minimum detectable amount (MDA) as the starting point and assumes MDA detection at a prescribed time post intake. The resulting dose can then be used as an indication of the adequacy or capability of the program for demonstrating compliance with the performance criteria. MDDs can be readily tabulated or plotted to demonstrate themore » effectiveness of different types of monitoring programs. The inclusion of cost factors for bioassay measurements can allow optimisation.« less

Minimum detectable dose as a measure of bioassay programme capability.

PubMed

Carbaugh, E H

2003-01-01

This paper suggests that minimum detectable dose (MDD) be used to describe the capability of bioassay programmes for which intakes are expected to be rare. This allows expression of the capability in units that correspond directly to primary dose limits. The concept uses the well established analytical statistic minimum detectable amount (MDA) as the starting point, and assumes MDA detection at a prescribed time post-intake. The resulting dose can then be used as an indication of the adequacy or capability of the programme for demonstrating compliance with the performance criteria. MDDs can be readily tabulated or plotted to demonstrate the effectiveness of different types of monitoring programmes. The inclusion of cost factors for bioassay measurements can allow optimisation.

The neural basis of social risky decision making in females with major depressive disorder.

PubMed

Shao, Robin; Zhang, Hui-jun; Lee, Tatia M C

2015-01-01

Recent evidence indicates that Major Depressive Disorder (MDD) may be associated with reduced tendency of committing noncompliant actions during social decision-making even when the risk of being punished is low. The neural underpinnings of this behavioral pattern are unknown, although it likely relates to compromised functioning of the lateral prefrontal-striatal/limbic networks implicated in executive control, emotion regulation and risk/value-based instrumental behaviors. We employed a modified trust game (TG) that provided explicit information on the risk levels of cheating behaviors being detected and punished. Behavioral and neuro-image data were acquired and analyzed from 14 first-episode female MDD patients and 15 age- and gender-matched controls performing the role of trustee in the TG. Relative to controls, MDD patients exhibited less behavioral switching to making cheating choices under low risk, and reduced activity in the dorsal putamen, anterior insula and dorsolateral prefrontal cortex (DLPFC) during making low-risk cheating versus benevolent choices, with limited evidence indicating abnormal bilateral inferior frontal gyrus activities of patients when making high-risk cheating versus benevolent choices. Patients' left dorsal putamen/anterior insular signals correlated positively with their frequency of low-risk cheating. MDD patients' symptom severity correlated positively with their signals in the lateral prefrontal networks during decision-making. A psycho-physiological interaction analysis provided tentative evidence for the recruitment of IFG-striatal/limbic circuitry among the control participants, but greater frontopolar-striatal/limbic connectivity among the MDD patients, during low-risk decision-making. We propose that making risky social decisions based on the balancing of self-gain and other's welfare relies on the functioning of the integrated lateral prefrontal-striatal/limbic networks, which are less efficient and dysregulated among MDD patients compared with controls, impacting negatively on the patients' social capacity and highlighting a key therapeutic target for MDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neural activity during interoceptive awareness and its associations with alexithymia—An fMRI study in major depressive disorder and non-psychiatric controls

PubMed Central

Wiebking, Christine; Northoff, Georg

2015-01-01

Objective: Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. Methods: A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD. PMID:26074827

Depression, comorbid anxiety disorders, and heart rate variability in physically healthy, unmedicated patients: implications for cardiovascular risk.

PubMed

Kemp, Andrew H; Quintana, Daniel S; Felmingham, Kim L; Matthews, Slade; Jelinek, Herbert F

2012-01-01

There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction. To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal). A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use. HRV was calculated from electrocardiography under a standardized short-term resting state condition. HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size. Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.

Impact of early and recent stress on white matter microstructure in major depressive disorder.

PubMed

Poletti, Sara; Aggio, Veronica; Brioschi, Silvia; Bollettini, Irene; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

2018-01-01

Major Depressive Disorder (MDD) is a worldwide-spread pathology, characterized by lifetime-recurrent episodes. Adverse childhood experiences (ACE) increase the lifetime risk of developing depression and affect the structure of the brain. Recent stressful events (RSE) can trigger the onset of depressive episodes, and affect grey matter volume. The aim of our study is to analyse the effect of both early and recent stress events on white matter microstructure in MDD patients and healthy volunteers. Sixty-five MDD inpatients and fifty-nine healthy controls underwent MRI acquisition of diffusion tensor images with a 3.0T scanner. Severity of ACE and RSE was rated, respectively, on the Risky Families Questionnaire and on the Social Readjustment Rating Scale. A significant effect of diagnosis was observed, with MDD subjects showing reduced fractional anisotropy (FA) and axial diffusivity (AD) compared to healthy controls in all the major association, projection and commissural tracts. In patients with MDD, but not in healthy controls, both ACE and RSE correlated with measures of WM microstructure: ACE correlated negatively with AD and MD, whereas RSE correlated negatively with FA. The two diagnostic groups differed for age and education, previous and current medications, and treatment periods. Exposure to both early and recent stress exerts a widespread effect on WM microstructure of MDD patients, with a different impact possibly depending from the developmental period in which the stress has occurred. Copyright © 2017 Elsevier B.V. All rights reserved.

Regional homogeneity and functional connectivity patterns in major depressive disorder, cognitive vulnerability to depression and healthy subjects.

PubMed

Sun, Hui; Luo, Lizhu; Yuan, Xinru; Zhang, Lu; He, Yini; Yao, Shuqiao; Wang, Jiaojian; Xiao, Jing

2018-08-01

Cognitive vulnerability to depression (CVD) is a high risk for depressive disorder. Recent studies focus on individuals with CVD to determine the neural basis of major depressive disorder (MDD) neuropathology. However, whether CVD showed specific or similar brain functional activity and connectivity patterns, compared to MDD, remain largely unknown. Here, using resting-state functional magnetic resonance imaging in subjects with CVD, healthy controls (HC) and MDD, regional homogeneity (ReHo) and resting-state functional connectivity (R-FC) analyses were conducted to assess local synchronization and changes in functional connectivity patterns. Significant ReHo differences were found in right posterior lobe of cerebellum (PLC), left lingual gyrus (LG) and precuneus. Compared to HC, CVD subjects showed increased ReHo in the PLC, which was similar to the difference found between MDD and HC. Compared to MDD patients, CVD subjects showed decreased ReHo in PLC, LG, and precuneus. R-FC analyses found increased functional connections between LG and left inferior parietal lobule, posterior cingulate cortex, and dorsolateral prefrontal cortex in CVD compared to both HC and MDD. Moreover, Regional mean ReHo values were positively correlated with Center for Epidemiologic Studies Depression Scale scores. These analyses revealed that PLC and functional connections between LG and left inferior parietal lobule, posterior cingulate cortex, and dorsolateral prefrontal cortex may be a potential marker for CVD. Copyright © 2018 Elsevier B.V. All rights reserved.

Long noncoding RNA expression in peripheral blood mononuclear cells and suicide risk in Chinese patients with major depressive disorder.

PubMed

Cui, Xuelian; Niu, Wei; Kong, Lingming; He, Mingjun; Jiang, Kunhong; Chen, Shengdong; Zhong, Aifang; Li, Wanshuai; Lu, Jim; Zhang, Liyi

2017-06-01

WHO stated that nearly one million people commit suicide every year worldly, and 40% of the suicide completer suffered from depression. The primary aim of this study was to explore the association between long noncoding RNAs (lncRNAs) expression in peripheral blood mononuclear cells (PBMCs) and suicide risk of patients with major depressive disorder (MDD). Using Human LncRNA 3.0 microarray profiling which includes 30,586 human lncRNAs and RT-PCR, six down-regulated lncRNAs were identified differentially expressed in MDD patients. According to suicidal ideation and suicidal attempt, the suicide risk of MDD patients was classified into suicidal ideation versus no suicidal ideation groups, and past attempt versus no past attempt groups, respectively. The expression of six lncRNAs in MDD patients and controls were examined by RT-PCR. The expression of six lncRNAs had significant differences between no suicidal ideation, suicidal ideation, and controls; corresponding lncRNAs associated with suicidal attempt had remarkable differences between no past attempt, past attempt, and controls. Additionally, only the expression of lncRNAs in suicidal ideation group and past attempt group markedly declined compared with controls. This study indicated that the expression of six down-regulated lncRNAs had a negative association with suicide risk in MDD patients, and the expression of lncRNAs in PBMCs could have the potential to help clinician judge the suicide risk of MDD patients to provide timely treatment and prevent suicide.

Can lncRNAs be indicators for the diagnosis of early onset or acute schizophrenia and distinguish major depressive disorder and generalized anxiety disorder?-A cross validation analysis.

PubMed

Cui, Xuelian; Niu, Wei; Kong, Lingming; He, Mingjun; Jiang, Kunhong; Chen, Shengdong; Zhong, Aifang; Li, Wanshuai; Lu, Jim; Zhang, Liyi

2017-06-01

Depression and anxiety are apparent symptoms in the early onset or acute phase of schizophrenia (SZ), which complicate timely diagnosis and treatment. It is imperative to seek an indicator to distinguish schizophrenia from depressive and anxiety disorders. Using lncRNA microarray profiling and RT-PCR, three up-regulated lncRNAs in SZ, six down-regulated lncRNAs in major depressive disorder (MDD), and three up-regulated lncRNAs in generalized anxiety disorder (GAD) had been identified as potential biomarkers. All the lncRNAs were, then, cross-validated in 40 SZ patients, 40 MDD patients, 40 GAD patients, and 40 normal controls. Compared with controls, three up-regulated SZ lncRNAs had a significantly down-regulated expression in GAD, and no remarkable differences existed between MDD and the controls. Additionally, the six down-regulated MDD lncRNAs were expressed in an opposite fashion in SZ, and the expression of the three up-regulated GAD lncRNAs were significantly different between SZ and GAD. These results indicate that the expression patterns of the three up-regulated SZ lncRNAs could not be completely replicated in MDD and GAD, and vice versa. Thus, these three SZ lncRNAs seem to be established as potential indicators for diagnosis of schizophrenia and distinguishing it from MDD and GAD. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Neural correlates of working memory in first episode and recurrent depression: An fMRI study.

PubMed

Yüksel, Dilara; Dietsche, Bruno; Konrad, Carsten; Dannlowski, Udo; Kircher, Tilo; Krug, Axel

2018-06-08

Patients suffering from major depressive disorder (MDD) show deficits in working memory (WM) performance accompanied by bilateral fronto-parietal BOLD signal changes. It is unclear whether patients with a first depressive episode (FDE) exhibit the same signal changes as patients with recurrent depressive episodes (RDE). We investigated seventy-four MDD inpatients (48 RDE, 26 FDE) and 74 healthy control (HC) subjects performing an n-back WM task (0-back, 2-back, 3-back condition) in a 3T-fMRI. FMRI analyses revealed deviating BOLD signal in MDD in the thalamus (0-back vs. 2-back), the angular gyrus (0-back vs. 3-back), and the superior frontal gyrus (2-back vs. 3-back). Further effects were observed between RDE vs. FDE. Thus, RDE displayed differing neural activation in the middle frontal gyrus (2-back vs. 3-back), the inferior frontal gyrus, and the precentral gyrus (0-back vs. 2-back). In addition, both HC and FDE indicated a linear activation trend depending on task complexity. Although we failed to find behavioral differences between the groups, results suggest differing BOLD signal in fronto-parietal brain regions in MDD vs. HC, and in RDE vs. FDE. Moreover, both HC and FDE show similar trends in activation shapes. This indicates a link between levels of complexity-dependent activation in fronto-parietal brain regions and the stage of MDD. We therefore assume that load-dependent BOLD signal during WM is impaired in MDD, and that it is particularly affected in RDE. We also suspect neurobiological compensatory mechanisms of the reported brain regions in (working) memory functioning. Copyright © 2018 Elsevier Inc. All rights reserved.

Neural Activation During Cognitive Emotion Regulation in Previously Depressed Compared to Healthy Children: Evidence of Specific Alterations

PubMed Central

Belden, Andy C.; Pagliaccio, David; Murphy, Eric R.; Luby, Joan L.; Barch, Deanna M.

2015-01-01

Objective Impairments in cognitive emotion regulation (CER) have been linked to functional neural abnormalities and the pathogenesis of major depressive disorder (MDD). Few functional magnetic resonance imaging (fMRI) studies have investigated the neural underpinnings of CER in samples with depression. As CER develops in childhood, understanding dysfunctional CER-related alterations in brain function during this period could advance knowledge of the developmental psychopathology of MDD. Method This study tested whether neural activity in brain regions known to support cognitive reappraisal differed between healthy 7- to 15-year-old children and same-age peers with a history of MDD (MDD-ever). A total of 64 children participated in this event-related fMRI study, which used a developmentally appropriate and validated fMRI reappraisal task. Children were instructed to passively view sad or neutral images and to decrease negative emotions using cognitive reappraisal. Results MDD-ever and healthy children showed similar patterns of cortical activation during reappraisal, but with a significant difference found in 1 key CER region, the left inferior frontal gyrus (IFG). In addition, individual differences in CER were associated with left IFG activity during reappraisal. Conclusion Alterations in the neurocircuitry of reappraisal are evident in children with a depression history compared to healthy controls. The finding that MDD-ever children showed reappraisal-related neural responses in many regions similar to healthy controls has clinical implications. Findings suggest that identification of alterations in reappraisal in children with remitted depression, for whom much, although not all, of the neural circuitry remains intact, may be an important window of opportunity for intervention. PMID:26299299

Familiality of major depressive disorder and patterns of lifetime comorbidity. The NEMESIS and GenMood studies. A comparison of three samples.

PubMed

Verhagen, Maaike; van der Meij, Annemarie; Franke, Barbara; Vollebergh, Wilma A M; de Graaf, Ron; Buitelaar, Jan K; Janzing, Joost G E

2008-12-01

Major depressive disorder (MDD) aggregates in families and is associated with high rates of lifetime axis-I comorbidity. This study examined whether familiality of MDD is associated with the presence of specific comorbid disorders, which might be an important factor to be taken into account in MDD treatment and research into MDD etiology. A population sample was divided into subjects with familial (f-MDD; n=432) and nonfamilial MDD (nf-MDD; n=454). Since, more comorbidity was expected in clinical cases, a clinical sample with f-MDD (n=120) was also studied. Subjects were assessed with the Composite International Diagnostic Interview and family history methods. Binary logistic regression analyses were carried out to examine the influence of familiality of MDD on comorbidity. Analyses were adjusted for potential confounders, including MDD characteristics such as severity and age of onset. Dysthymia, anxiety disorders, and alcohol use disorders were significantly more prevalent in subjects with f-MDD than in subjects with nf-MDD. Clinical f-MDD was associated with more anxiety disorders and fewer alcohol use disorders than population f-MDD. After adjustment for MDD characteristics including age at onset, severity, and disease course, comorbid disorders remained more prevalent in f-MDD than in nf-MDD. The instruments used in the population and the clinical samples were not identical, however, they were comparable to a substantial degree. F-MDD, especially in clinical cases, appears to increase the risk of development of comorbid disorders, regardless of MDD characteristics. The link between familiality and comorbidity is important because it will aid a better understanding of the MDD phenotype, and it contributes to planning of effective treatment and to molecular genetic studies.

Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials.

PubMed

Bridge, Jeffrey A; Iyengar, Satish; Salary, Cheryl B; Barbe, Rémy P; Birmaher, Boris; Pincus, Harold Alan; Ren, Lulu; Brent, David A

2007-04-18

The US Food and Drug Administration (FDA) has issued warnings that use of antidepressant medications poses a small but significantly increased risk of suicidal ideation/suicide attempt for children and adolescents. To assess the efficacy and risk of reported suicidal ideation/suicide attempt of antidepressants for treatment of pediatric major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders. PubMed (1988 to July 2006), relevant US and British regulatory agency reports, published abstracts of important scientific meetings (1998-2006), clinical trial registries, and information from authors. Studies were published and unpublished randomized, placebo-controlled, parallel-group trials of second-generation antidepressants (selective serotonin reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine) in participants younger than 19 years with MDD, OCD, or non-OCD anxiety disorders. Information was extracted on study characteristics, efficacy outcomes, and spontaneously reported suicidal ideation/suicide attempt. Twenty-seven trials of pediatric MDD (n = 15), OCD (n = 6), and non-OCD anxiety disorders (n = 6) were selected, and risk differences for response and for suicidal ideation/suicide attempt estimated by random-effects methods. Pooled risk differences in rates of primary study-defined measures of responder status significantly favored antidepressants for MDD (11.0%; [95% confidence interval {CI}, 7.1% to 14.9%]), OCD (19.8% [95% CI, 13.0% to 26.6%), and non-OCD anxiety disorders (37.1% [22.5% to 51.7%]), corresponding to a number needed to treat (NNT) of 10 (95% CI, 7 to 15), 6 (4 to 8), and 3 (2 to 5), respectively. While there was increased risk difference of suicidal ideation/suicide attempt across all trials and indications for drug vs placebo (0.7%; 95% CI, 0.1% to 1.3%) (number needed to harm, 143 [95% CI, 77 to 1000]), the pooled risk differences within each indication were not statistically significant: 0.9% (95% CI, -0.1% to 1.9%) for MDD, 0.5% (-1.2% to 2.2%) for OCD, and 0.7% (-0.4% to 1.8%) for non-OCD anxiety disorders. There were no completed suicides. Age-stratified analyses showed that for children younger than 12 years with MDD, only fluoxetine showed benefit over placebo. In MDD trials, efficacy was moderated by age, duration of depression, and number of sites in the treatment trial. Relative to placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD anxiety disorders, although the effects are strongest in non-OCD anxiety disorders, intermediate in OCD, and more modest in MDD. Benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempt across indications, although comparison of benefit to risk varies as a function of indication, age, chronicity, and study conditions.

Using thermographic cameras to investigate eye temperature and clinical severity in depression

NASA Astrophysics Data System (ADS)

Maller, Jerome J.; George, Shefin Sam; Viswanathan, Rekha Puzhavakkathumadom; Fitzgerald, Paul B.; Junor, Paul

2016-02-01

Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but the association between major depressive disorder (MDD) and corneal temperature has yet to be assessed. The aim of this study is to investigate whether eye temperature is different among MDD patients than among healthy individuals. We used a thermographic camera to measure and compare the temperature profile across the corneas of 16 patients with MDD and 16 age- and sex-matched healthy subjects. We found that the average corneal temperature between the two groups did not differ statistically, although clinical severity correlated positively with right corneal temperature. Corneal temperature may be an indicator of clinical severity in psychiatric disorders, including depression.

Serum Brain-derived neurotrophic factor (BDNF): the severity and symptomatic dimensions of depression.

PubMed

Jevtović, Saša; Karlović, Dalibor; Mihaljević-Peleš, Alma; Šerić, Vesna; Vrkić, Nada; Jakšić, Nenad

2011-12-01

The aim of this study was to compare the concentration of serum Brain-derived neurotrophic factor (BDNF) in patients suffering from major depressive disorder (MDD) considering the severity of MDD episode defined by the Hamilton rating scale for depression (HAMD-17). The other aim was to research the connection between serum BDNF and the symptomatic dimensions of MDD. The study includes 139 participants with major depressive disorder (MDD). Diagnosis of MDD was set by DSM-IV-TR criteria. The severity of MDD was estimated with HAM-D-17 in the manner that mild episode was diagnosed if the score on HAMD-17 was up to 18, moderately severe 18-25 and severe over 25. Concentration of BDNF was determined by the ELISA method. This research could not find a difference in BDNF concentration considering the severity of the depressive disorder in groups suffering from mild, moderately severe and severe episodes of MDD (F=1.816; p=0.169). Factor analysis of HAMD-17 extracted four dimensions of depressive symptoms. None of the symptomatic dimensions was significantly related to BDNF concentration. Results of this study indicate that serum BDNF levels are not related to the severity of depression and its specific symptomatic dimensions. These findings support the idea of a complex relationship between BDNF concentration at the periphery and in the CNS.

Cognitive Styles in Mood Disorders: Discriminative Ability of Unipolar and Bipolar Cognitive Profiles

PubMed Central

Shapero, Benjamin G.; Stange, Jonathan P.; Goldstein, Kim E.; Black, Chelsea L.; Molz, Ashleigh R.; Hamlat, Elissa J.; Black, Shimrit K.; Boccia, Angelo S.; Abramson, Lyn Y.; Alloy, Lauren B.

2015-01-01

Although previous research has identified cognitive styles that distinguish individuals with bipolar disorder (BD), individuals with major depressive disorder (MDD), and individuals without mood disorders from one another, findings have been inconsistent. The current study included 381 participants classified into a BD group, a MDD group, and a no mood disorder group. To differentiate between these groups, this study evaluated cognitive styles with a battery of traditional and more recently-developed measures. Receiver operating characteristics (ROC) analyses were used to determine the discriminate ability of variables with significant between group differences. Results supported that BD and MDD may be characterized by distinct cognitive styles. Given work showing that interventions for MDD may not be effective at treating BD, it is important to directly compare individuals with these disorders. By clarifying the overlapping and divergent cognitive styles characterizing BD and MDD, research can not only improve diagnostic validity, but also provide more efficacious and effective interventions. PMID:25893033

Reduced anterior cingulate glutamate in pediatric major depression: a magnetic resonance spectroscopy study.

PubMed

Rosenberg, David R; Macmaster, Frank P; Mirza, Yousha; Smith, Janet M; Easter, Phillip C; Banerjee, S Preeya; Bhandari, Rashmi; Boyd, Courtney; Lynch, Michelle; Rose, Michelle; Ivey, Jennifer; Villafuerte, Rosemond A; Moore, Gregory J; Renshaw, Perry

2005-11-01

Anterior cingulate cortex has been implicated in the pathogenesis of major depressive disorder (MDD). With single voxel proton magnetic resonance spectroscopy, we reported reductions in anterior cingulate glutamatergic concentrations (grouped value of glutamate and glutamine) in 14 pediatric MDD patients versus 14 case-matched healthy control subjects. These changes might reflect a change in glutamate, glutamine, or their combination. Fitting to individually quantify anterior cingulate glutamate and glutamine was performed in these subjects with a new basis set created from data acquired on a 1.5 Tesla General Electric Signa (GE Healthcare, Waukesha, Wisconsin) magnetic resonance imaging scanner with LCModel (Version 6.1-0; Max-Planck-Institute, Gottingen, Germany). Reduced anterior cingulate glutamate was observed in MDD patients versus control subjects (8.79 +/- 1.68 vs. 11.46 +/- 1.55, respectively, p = .0002; 23% decrease). Anterior cingulate glutamine did not differ significantly between patients with MDD and control subjects. These findings provide confirmatory evidence of anterior cingulate glutamate alterations in pediatric MDD.

Gender effect on pre-attentive change detection in major depressive disorder patients revealed by auditory MMN.

PubMed

Qiao, Zhengxue; Yang, Aiying; Qiu, Xiaohui; Yang, Xiuxian; Zhang, Congpei; Zhu, Xiongzhao; He, Jincai; Wang, Lin; Bai, Bing; Sun, Hailian; Zhao, Lun; Yang, Yanjie

2015-10-30

Gender differences in rates of major depressive disorder (MDD) are well established, but gender differences in cognitive function have been little studied. Auditory mismatch negativity (MMN) was used to investigate gender differences in pre-attentive information processing in first episode MDD. In the deviant-standard reverse oddball paradigm, duration auditory MMN was obtained in 30 patients (15 males) and 30 age-/education-matched controls. Over frontal-central areas, mean amplitude of increment MMN (to a 150-ms deviant tone) was smaller in female than male patients; there was no sex difference in decrement MMN (to a 50-ms deviant tone). Neither increment nor decrement MMN differed between female and male patients over temporal areas. Frontal-central MMN and temporal MMN did not differ between male and female controls in any condition. Over frontal-central areas, mean amplitude of increment MMN was smaller in female patients than female controls; there was no difference in decrement MMN. Neither increment nor decrement MMN differed between female patients and female controls over temporal areas. Frontal-central MMN and temporal MMN did not differ between male patients and male controls. Mean amplitude of increment MMN in female patients did not correlate with symptoms, suggesting this sex-specific deficit is a trait- not a state-dependent phenomenon. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Do anxiety symptoms predict major depressive disorder in midlife women? The Study of Women’s Health Across the Nation (SWAN) Mental Health Study (MHS)

PubMed Central

Kravitz, H. M.; Schott, L. L.; Joffe, H.; Cyranowski, J.M.; Bromberger, J. T.

2014-01-01

Background In women, anxiety symptoms are common and increase during midlife, but little is known about whether these symptoms predict onsets of major depressive disorder (MDD) episodes. We examined whether anxiety symptoms are associated with subsequent episodes of MDD in midlife African-American and Caucasian women, and whether they confer a different risk for first versus recurrent MDD episodes. Method A longitudinal analysis was conducted using 12 years of data from the Study of Women’s Health Across the Nation (SWAN) Mental Health Study (MHS). The baseline sample comprised 425 Caucasian (n=278) and African American (n=147) community-dwelling women, aged 46.1±2.5 years. Anxiety symptoms measured annually using a self-report questionnaire were examined in relation to MDD episodes in the subsequent year, assessed with the SCID. Multivariable models were estimated with random effects logistic regression. Results Higher anxiety symptoms scores were associated with a significantly higher adjusted odds of developing an episode of MDD at the subsequent annual visit [odds ratio (OR) 1.47, p=0.01], specifically for a recurrent episode (OR 1.49, p=0.03) but non-significant for a first episode (OR 1.32, p=0.27). There were no significant racial effects in the association between anxiety symptoms and subsequent MDD episodes. Conclusions Anxiety symptoms often precede MDD and may increase the vulnerability of midlife women to depressive episodes, particularly recurrences. Women with anxiety symptoms should be monitored clinically during the ensuing year for the development of an MDD episode. PMID:24467997

Local functional connectivity alterations in schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Wei, Yange; Chang, Miao; Womer, Fay Y; Zhou, Qian; Yin, Zhiyang; Wei, Shengnan; Zhou, Yifang; Jiang, Xiaowei; Yao, Xudong; Duan, Jia; Xu, Ke; Zuo, Xi-Nian; Tang, Yanqing; Wang, Fei

2018-08-15

Local functional connectivity (FC) indicates local or short-distance functional interactions and may serve as a neuroimaging marker to investigate the human brain connectome. Local FC alterations suggest a disrupted balance in the local functionality of the whole brain network and are increasingly implicated in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We aim to examine the similarities and differences in the local FC across SZ, BD, and MDD. In total, 537 participants (SZ, 126; BD, 97; MDD, 126; and healthy controls, 188) completed resting-state functional magnetic resonance imaging at a single site. The local FC at resting state was calculated and compared across SZ, BD, and MDD. The local FC increased across SZ, BD, and MDD within the bilateral orbital frontal cortex (OFC) and additional region in the left OFC extending to putamen and decreased in the primary visual, auditory, and motor cortices, right supplemental motor area, and bilateral thalami. There was a gradient in the extent of alterations such that SZ > BD > MDD. This cross-sectional study cannot consider medications and other clinical variables. These findings indicate a disrupted balance between network integration and segregation in SZ, BD, and MDD, including over-integration via increased local FC in the OFC and diminished segregation of neural processing with the weakening of the local FC in the primary sensory cortices and thalamus. The shared local FC abnormalities across SZ, BD, and MDD may shed new light on the potential biological mechanisms underlying these disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Binge eating, trauma, and suicide attempt in community adults with major depressive disorder.

PubMed

Baek, Ji Hyun; Kim, Kiwon; Hong, Jin Pyo; Cho, Maeng Je; Fava, Maurizio; Mischoulon, David; Chang, Sung Man; Kim, Ji Yeon; Cho, Hana; Jeon, Hong Jin

2018-01-01

Eating disorders comorbid with depression are an established risk factor for suicide. In this study, we aimed to determine the effects of binge eating (BE) symptoms on suicidality and related clinical characteristics in major depressive disorder (MDD). A total of 817 community participants with MDD were included. We compared two groups (with and without lifetime BE symptoms). The MDD with BE group was subdivided into a frequent BE (FBE) subgroup (BE symptoms greater than twice weekly) and any BE (ABE) subgroup (BE symptoms greater than twice weekly). The MDD with BE group comprised 142 (17.38%) patients. The FBE and ABE subgroups comprised 75 (9.18%) and 67 (8.20%) patients, respectively. Comorbid alcohol use disorder, anxiety disorder, post-traumatic stress disorder (PTSD) and history of suicide attempt were significantly more frequent in the MDD with BE group than MDD without BE group. Sexual trauma was also reported more frequently in MDD with BE group. No significant differences were observed between the ABE and FBE subgroups. Multivariate logistic regression revealed an association of suicide attempt with BE symptoms and sexual trauma. Structural equation modeling showed that sexual trauma increased BE (β = 0.337, P <0.001) together with alcohol use (β = 0.185, P <0.001) and anxiety (β = 0.299, p<0.001), which in turn increased suicide attempt (β = 0.087, p = 0.011). BE symptoms were associated with suicide attempt in MDD after adjusting for other factors associated with suicidality. BE symptoms also moderated an association between suicide attempt and sexual trauma.

A review of the relationship between proinflammatory cytokines and major depressive disorder.

PubMed

Young, Juan Joseph; Bruno, Davide; Pomara, Nunzio

2014-12-01

Determining etiological factors and reviewing advances in diagnostic modalities sensitive and specific to Major Depressive Disorder (MDD) is of importance in its evaluation and treatment. The inflammatory hypothesis is one of the most prevalent topics concerning MDD and may provide insight into the pathogenesis of depression, development of biomarkers, and ultimately production of more effective depression therapies. We reviewed several studies to evaluate contemporary concepts concerning proinflammatory cytokines and their relationship to various depressive disorders, the use of anti-inflammatory therapies in MDD treatment, and the application of neuroimaging in conjunction with cytokine profiles from both plasma and CSF as possible diagnostic tools. Proinflammatory cytokines in both plasma and CSF have been found to influence the progression and severity of depressive disorders in different populations. Studies have shown elevated serum levels of IL-1, IL-6, TNF-α, CRP, and MCP-1 in depressed patients, but have presented mixed results with IL-8 serum levels, and with IL-6 and MCP-1 CSF levels. Anti-inflammatory treatment of MDD may have adjuvant properties with current depression medications. MRI and NIRS neuroimaging confirm neurological abnormalities in the presence of elevated proinflammatory cytokines in depressed or stressed patients. Heterogeneity of MDD and limited CSF cytokine research complicate the study of MDD pathogenesis. There is significant evidence that inflammatory processes influence the development and progression of MDD. Future studies with larger arrays of cytokine profiles aided by neuroimaging may provide more sensitive and specific modes of diagnostics in determining MDD etiology and provide guidance in individual therapies. Copyright © 2014 Elsevier B.V. All rights reserved.

Glutamatergic stimulation of the left dentate gyrus abolishes depressive-like behaviors in a rat learned helplessness paradigm.

PubMed

Seo, Jeho; Cho, Hojin; Kim, Gun Tae; Kim, Chul Hoon; Kim, Dong Goo

2017-10-01

Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors). We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity. After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies. Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Disrupted topology of hippocampal connectivity is associated with short-term antidepressant response in major depressive disorder.

PubMed

Gong, Liang; Hou, Zhenghua; Wang, Zan; He, Cancan; Yin, Yingying; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

2018-01-01

Graph theoretical analyses have identified disrupted functional topological organization across the brain in patients with major depressive disorder (MDD). However, the relationship between brain topology and short-term treatment responses in patients with MDD remains unknown. Sixty-eight patients with MDD and 63 cognitively normal (CN) subjects were recruited at baseline and underwent resting-state functional magnetic resonance imaging scans. Graph theory analysis was used to examine group differences in the whole-brain functional topological properties. The association between altered brain topology and the early antidepressant response was examined. Patients with MDD showed lower normalized clustering coefficients, lower small-worldness scalars and increased nodal efficiencies in the default mode network and decreased nodal efficiencies in basal ganglia and hippocampal networks. In addition, the decreased nodal efficiency in left hippocampus was negatively correlated with depressive severity at baseline and positively correlated with changes in the depressive scores after two weeks of antidepressant treatment. The patients in the present study received different medications. These findings indicated that the altered brain functional topological organization in patients with MDD is associated with the treatment response in the early phase of medication. Therefore, brain topology assessments might be considered a useful and convenient predictor of short-term antidepressant responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Suicide Attempts in Juvenile Bipolar Versus Major Depressive Disorders: Systematic Review and Meta-Analysis.

PubMed

De Crescenzo, Franco; Serra, Giulia; Maisto, Francesco; Uchida, Mai; Woodworth, Hilary; Casini, Maria Pia; Baldessarini, Ross J; Vicari, Stefano

2017-10-01

Suicide attempts are prevalent in association with major mood disorders, and risk is greater with bipolar disorder (BD) than major depressive disorder (MDD) in adults. There may be similar relationships in juvenile mood disorders, but the evidence has not been compiled systematically and quantitatively. We searched for reports of studies comparing rates of suicide attempts in children or adolescents diagnosed with BD or MDD, and applied random-effects meta-analysis. In 6 reports from 1995 to 2017, with 2,303 participants diagnosed with mood disorder from the United States and South Korea, aged 3 to 18 years, rates of suicide attempts differed significantly by diagnosis: BD (31.5%) > MDD (20.5%) > hypomania or mania-only (8.49%). Risk of suicide attempts differed (BD > MDD) highly significantly by meta-analysis (odds ratio [OR] = 1.71, CI = 1.33-2.20, p < .0001), and was very similar if a study with attempts and suicidal ideation was excluded (OR = 1.64, CI = 1.26-2.15, p < .0001). Risk of suicide attempts in juvenile mood disorder patients ranked: BD > MDD > hypomania or mania-only > juvenile general population. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Quality of Life in Major Depressive Disorder Before/After Multiple Steps of Treatment and One-year Follow-up

PubMed Central

IsHak, Waguih William; Mirocha, James; James, David; Tobia, Gabriel; Vilhauer, Jennice; Fakhry, Hala; Pi, Sarah; Hanson, Eric; Nashawati, Rama; Peselow, Eric D.; Cohen, Robert M.

2014-01-01

Objective This study examines the impact of Major Depressive Disorder (MDD) and its treatment on Quality of Life (QOL). Method From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2,280 adult MDD outpatients at entry/exit of each level of antidepressant treatments and after 12-months of entry to follow-up. QOL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The proportions of patients scoring ‘within-normal’ QOL (within 10% of Q-LES-Q community-norms) and those with ‘severely-impaired’ QOL (>2SD below Q-LES-Q community-norms) were analyzed. Results Before treatment, no more than 3% of MDD patients experienced ‘within-normal’ QOL. Following treatment, statistically significant improvements were detected, however the proportion of patients achieving ‘within-normal’ QOL did not exceed 30%, with>50% of patients experiencing ‘severely-impaired’ QOL. Although remitted-patients had greater improvements compared to non-remitters, 32%-60% continued to experience reduced QOL. 12-month follow-up data revealed that the proportion of patients experiencing ‘within-normal’ QOL show a statistically significant decrease in non-remitters. Conclusion Symptom-focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD. PMID:24954156

A pilot study on predictors of brainstem raphe abnormality in patients with major depressive disorder.

PubMed

Kostić, Milutin; Munjiza, Ana; Pesic, Danilo; Peljto, Amir; Novakovic, Ivana; Dobricic, Valerija; Tosevski, Dusica Lecic; Mijajlovic, Milija

2017-02-01

Hypo/anechogenicity of the brainstem raphe (BR) structures has been suggested as a possible transcranial parenchymal sonography (TCS) marker associated with depression. The aim of this study was to analyze possible association of the abnormal BR echogenicity in patients with major depression when compared to healthy controls, and to evaluate its clinical and genetic correlates. TCS was performed in 53 patients diagnosed as major depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched controls. The TCS detected BR abnormalities were significantly more frequent in MDD patients (35 out of 53; 66%) in comparison to matched controls (5 out of 56; 9%). The prevalence of short allele (s) homozygocity in the length polymorphism of the promoter region of the serotonin transporter gene (5-HTTLPR) was significantly higher in MDD patients relative to those with normal BR echogenicity. A stepwise statistical discriminant analysis revealed statistically significant separation between MDD patients with and without BR abnormalities groups based on the four predictors combined: the Hamilton Anxiety Rating Scale item 5 ("difficulty in concentration, poor memory"), presence of social phobia, s allele homozygocity of the 5-HTTLPR polymorphism, and presence of generalized anxiety disorder. Cross-sectional design and heterogenous treatment of depressed patients. Reduced BR echogenicity in at least a subgroup of MDD patients may reflect a particular phenotype, characterized by more prevalent comorbid anxiety disorders, associated with particular genetic polymorphisms and neurotransmitter(s) deficits, most probably altered serotonergic mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Major depressive disorder in a family study of obsessive-compulsive disorder with pediatric probands.

PubMed

Hanna, Gregory L; Himle, Joseph A; Hanna, Barbara S; Gold, Katherine J; Gillespie, Brenda W

2011-06-01

This study examined the comorbidity of obsessive-compulsive disorder (OCD) with major depressive disorder (MDD) in a family study of OCD with pediatric probands. This study assessed the lifetime prevalence of MDD in 141 first-degree relatives (FDR) and 452 second-degree relatives (SDR) of pediatric probands with OCD and healthy controls, and identified variables associated with MDD in case FDR. All available FDR were directly interviewed blind to proband status; parents were also interviewed to assess the family psychiatric history of FDR and SDR. Best-estimate diagnoses were made using all sources of information. Data were analyzed with logistic regression and robust Cox regression models. Lifetime MDD prevalence was significantly higher in case than in control FDR (30.4 versus 15.4%). Lifetime MDD prevalence was significantly higher in FDR of case probands with MDD than in FDR of case probands without MDD or control FDR (46.3 versus 19.7 versus 15.4%, respectively). MDD in case FDR was significantly associated with MDD in case probands and with age and OCD in those relatives. Lifetime MDD prevalence was similar in case and control SDR. However, lifetime MDD prevalence was significantly higher in SDR of case probands with MDD than in SDR of case probands without MDD or control SDR (31.9 versus 16.8 versus 15.4%, respectively). MDD prevalence was significantly higher in both FDR and SDR of case probands with MDD than in relatives of case probands without MDD or control relatives, suggesting that pediatric OCD comorbid with MDD is a complex familial syndrome. © 2011 Wiley-Liss, Inc.

Interoception in insula subregions as a possible state marker for depression—an exploratory fMRI study investigating healthy, depressed and remitted participants

PubMed Central

Wiebking, Christine; de Greck, Moritz; Duncan, Niall W.; Tempelmann, Claus; Bajbouj, Malek; Northoff, Georg

2015-01-01

Background: Interoceptive awareness (iA), the awareness of stimuli originating inside the body, plays an important role in human emotions and psychopathology. The insula is particularly involved in neural processes underlying iA. However, iA-related neural activity in the insula during the acute state of major depressive disorder (MDD) and in remission from depression has not been explored. Methods: A well-established fMRI paradigm for studying (iA; heartbeat counting) and exteroceptive awareness (eA; tone counting) was used. Study participants formed three independent groups: patients suffering from MDD, patients in remission from MDD or healthy controls. Task-induced neural activity in three functional subdivisions of the insula was compared between these groups. Results: Depressed participants showed neural hypo-responses during iA in anterior insula regions, as compared to both healthy and remitted participants. The right dorsal anterior insula showed the strongest response to iA across all participant groups. In depressed participants there was no differentiation between different stimuli types in this region (i.e., between iA, eA and noTask). Healthy and remitted participants in contrast showed clear activity differences. Conclusions: This is the first study comparing iA and eA-related activity in the insula in depressed participants to that in healthy and remitted individuals. The preliminary results suggest that these groups differ in there being hypo-responses across insula regions in the depressed participants, whilst non-psychiatric participants and patients in remission from MDD show the same neural activity during iA in insula subregions implying a possible state marker for MDD. The lack of activity differences between different stimulus types in the depressed group may account for their symptoms of altered external and internal focus. PMID:25914633

Interoception in insula subregions as a possible state marker for depression-an exploratory fMRI study investigating healthy, depressed and remitted participants.

PubMed

Wiebking, Christine; de Greck, Moritz; Duncan, Niall W; Tempelmann, Claus; Bajbouj, Malek; Northoff, Georg

2015-01-01

Interoceptive awareness (iA), the awareness of stimuli originating inside the body, plays an important role in human emotions and psychopathology. The insula is particularly involved in neural processes underlying iA. However, iA-related neural activity in the insula during the acute state of major depressive disorder (MDD) and in remission from depression has not been explored. A well-established fMRI paradigm for studying (iA; heartbeat counting) and exteroceptive awareness (eA; tone counting) was used. Study participants formed three independent groups: patients suffering from MDD, patients in remission from MDD or healthy controls. Task-induced neural activity in three functional subdivisions of the insula was compared between these groups. Depressed participants showed neural hypo-responses during iA in anterior insula regions, as compared to both healthy and remitted participants. The right dorsal anterior insula showed the strongest response to iA across all participant groups. In depressed participants there was no differentiation between different stimuli types in this region (i.e., between iA, eA and noTask). Healthy and remitted participants in contrast showed clear activity differences. This is the first study comparing iA and eA-related activity in the insula in depressed participants to that in healthy and remitted individuals. The preliminary results suggest that these groups differ in there being hypo-responses across insula regions in the depressed participants, whilst non-psychiatric participants and patients in remission from MDD show the same neural activity during iA in insula subregions implying a possible state marker for MDD. The lack of activity differences between different stimulus types in the depressed group may account for their symptoms of altered external and internal focus.

The prevalence and impact of major depressive disorder among Chinese, Malays and Indians in an Asian multi-racial population.

PubMed

Chong, Siow Ann; Vaingankar, Janhavi; Abdin, Edimansyah; Subramaniam, Mythily

2012-04-01

Reports of rates of depression among different Asian ethnic groups within the same country using standardized assessments are rare in the extant literature. This was a household survey of 6616 adult residents of Singapore which constituted a national representative sample. Face to face interviews were conducted with the English, Chinese and Malay versions of the World Mental Health Composite International Diagnostic Interview. The response rate was 75.9%. The lifetime and 12-month prevalence estimates for MDD were 5.8% and 2.2%, respectively. MDD was significantly higher among the females, Indians, those who were divorced/separated, or widowed. The median age of onset of MDD was 26 years with the highest risk of onset in those aged 18-34 years while the age group of 65 years and above had the lowest risk of onset. Chronic physical conditions were present in approximately half of the respondents with MDD. MDD was also associated with considerable disability in terms of days of role impairment. More than half (59.6%) of those with lifetime MDD had not ever sought professional help. This was a cross-sectional household survey that excluded those who were institutionalized. Responses were self-reported and therefore subjected to recall bias. Our findings add to the body of knowledge on the differential rates of depression among different ethnic groups; the association with disability, comorbid physical conditions and the considerable proportion of untreated cases also have important clinical and policy implications. Copyright © 2011 Elsevier B.V. All rights reserved.

Differing antidepressant maintenance methodologies.

PubMed

Safer, Daniel J

2017-10-01

The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

Differential performance on tasks of affective processing and decision-making in patients with Panic Disorder and Panic Disorder with comorbid Major Depressive Disorder.

PubMed

Kaplan, Johanna S; Erickson, Kristine; Luckenbaugh, David A; Weiland-Fiedler, Petra; Geraci, Marilla; Sahakian, Barbara J; Charney, Dennis; Drevets, Wayne C; Neumeister, Alexander

2006-10-01

Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. The sample size was limited, however, all patients were drug-free at the time of testing. The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes.

Enhanced subgenual cingulate response to altruistic decisions in remitted major depressive disorder

PubMed Central

Pulcu, Erdem; Zahn, Roland; Moll, Jorge; Trotter, Paula D.; Thomas, Emma J.; Juhasz, Gabriella; Deakin, J.F.William; Anderson, Ian M.; Sahakian, Barbara J.; Elliott, Rebecca

2014-01-01

Background Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown. Methods Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD. Results Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture. Conclusions We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called “warm glow” of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies. PMID:24936421

Modeling the Dynamics of Disease States in Depression

PubMed Central

Demic, Selver; Cheng, Sen

2014-01-01

Major depressive disorder (MDD) is a common and costly disorder associated with considerable morbidity, disability, and risk for suicide. The disorder is clinically and etiologically heterogeneous. Despite intense research efforts, the response rates of antidepressant treatments are relatively low and the etiology and progression of MDD remain poorly understood. Here we use computational modeling to advance our understanding of MDD. First, we propose a systematic and comprehensive definition of disease states, which is based on a type of mathematical model called a finite-state machine. Second, we propose a dynamical systems model for the progression, or dynamics, of MDD. The model is abstract and combines several major factors (mechanisms) that influence the dynamics of MDD. We study under what conditions the model can account for the occurrence and recurrence of depressive episodes and how we can model the effects of antidepressant treatments and cognitive behavioral therapy within the same dynamical systems model through changing a small subset of parameters. Our computational modeling suggests several predictions about MDD. Patients who suffer from depression can be divided into two sub-populations: a high-risk sub-population that has a high risk of developing chronic depression and a low-risk sub-population, in which patients develop depression stochastically with low probability. The success of antidepressant treatment is stochastic, leading to widely different times-to-remission in otherwise identical patients. While the specific details of our model might be subjected to criticism and revisions, our approach shows the potential power of computationally modeling depression and the need for different type of quantitative data for understanding depression. PMID:25330102

Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses

PubMed Central

Lee, Jiyeong; Joo, Eun-Jeong; Lim, Hee-Joung; Park, Jong-Moon; Lee, Kyu Young; Park, Arum; Seok, AeEun

2015-01-01

Objective Currently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum. Methods Blood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed. Results The quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together. Conclusion This is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation. PMID:25866527

Identifying current and remitted major depressive disorder with the Hurst exponent: a comparative study on two automated anatomical labeling atlases

PubMed Central

Yan, Huagang; Dong, Jianxin; Mo, Xiao; Li, Dan; Liu, Chunhong; Li, Haiyun

2017-01-01

Major depressive disorder (MDD) is a leading world-wide psychiatric disorder with high recurrence rate, therefore, it is desirable to identify current MDD (cMDD) and remitted MDD (rMDD) for their appropriate therapeutic interventions. In the study, 19 cMDD, 19 rMDD and 19 well-matched healthy controls (HC) were enrolled and scanned with the resting-state functional magnetic resonance imaging (rs-fMRI). The Hurst exponent (HE) of rs-fMRI in AAL-90 and AAL-1024 atlases were calculated and compared between groups. Then, a radial basis function (RBF) based support vector machine was proposed to identify every pair of the cMDD, rMDD and HC groups using the abnormal HE features, and a leave-one-out cross-validation was used to evaluate the classification performance. Applying the proposed method with AAL-1024 and AAL-90 atlas respectively, 87% and 84% subjects were correctly identified between cMDD and HC, 84% and 71% between rMDD and HC, and 89% and 74% between cMDD and rMDD. Our results indicated that the HE was an effective feature to distinguish cMDD and rMDD from HC, and the recognition performances with AAL-1024 parcellation were better than that with the conventional AAL-90 parcellation. PMID:29163844

Zinc transporters protein level in postmortem brain of depressed subjects and suicide victims.

PubMed

Rafalo-Ulinska, Anna; Piotrowska, Joanna; Kryczyk, Agata; Opoka, Włodzimierz; Sowa-Kucma, Magdalena; Misztak, Paulina; Rajkowska, Grazyna; Stockmeier, Craig A; Datka, Wojciech; Nowak, Gabriel; Szewczyk, Bernadeta

2016-12-01

Major depressive disorder (MDD) is a serious psychiatric illness, associated with an increasing rate of suicide. The pathogenesis of depression may be associated with the disruption of zinc (Zn) homeostasis. In the brain, several proteins that regulate Zn homeostasis are present, including Zn transporters (ZnTs) which remove Zn from the cytosol. The present study was designed to investigate whether depression and suicide are associated with alterations in the expression of the ZnTs protein. Protein levels of ZnT1, ZnT3, ZnT4, ZnT5 and ZnT6 were measured in postmortem brain tissue from two different cohorts. Cohort A contained 10 subjects diagnosed with MDD (7 were suicide victims) and 10 psychiatrically-normal control subjects and cohort B contained 11 non-diagnosed suicide victims and 8 sudden-death control subjects. Moreover, in cohort A we measured protein level of NMDA (GluN2A subunit), AMPA (GluA1 subunit) and 5-HT1A receptors and PSD-95. Proteins were measured in the prefrontal cortex (PFC) using Western blotting. In addition, Zn concentration was measured using a voltammetric method. There was a significant increase in protein levels of ZnT1, ZnT4, ZnT5 in the PFC in MDD, relative to control subjects, while ZnT3 protein level was decreased in MDD. There was no significant difference in the Zn concentration in the PFC between control and MDD subjects. Similarly, in the PFC of suicide victims (non-diagnosed), an increase in protein levels of ZnT1, ZnT4, ZnT5 and ZnT6 was observed. Conversely, protein levels of ZnT3 were decreased in both suicide victims and subjects with MDD, in comparison with control subjects. There was also a significant decrease in the protein level of GluA1, GluN2A, PSD-95 and 5-HT1A in MDD. Our studies suggest that alterations in Zn transport proteins are associated with the pathophysiology of MDD and suicide. Copyright © 2016 Elsevier Ltd. All rights reserved.

Similarities of biochemical abnormalities between major depressive disorder and bipolar depression: a proton magnetic resonance spectroscopy study.

PubMed

Zhong, Shuming; Wang, Ying; Zhao, Guoxiang; Xiang, Qi; Ling, Xueying; Liu, Sirun; Huang, Li; Jia, Yanbin

2014-10-01

Depression in the context of bipolar disorder (BD) is often misdiagnosed as major depressive disorder (MDD), leading to mistreatments and poor clinical outcomes for many bipolar patients. Previous neuroimaging studies found mixed results on brain structure, and biochemical metabolism of the two disorders. To eliminate the compounding effects of medication, and aging, this study sought to investigate the brain biochemical changes of treatment-naïve, non-late-life patients with MDD and BD in white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC) and hippocampus by using proton magnetic resonance spectroscopy ((1)H-MRS). Three groups of participants were recruited: 26 MDD patients, 20 depressed BD patients, and 13 healthy controls. The multi-voxel (1)H-MRS [repetition time (TR)=1000ms; echo-time (TE)=144ms] was used for the measurement of N-acetylaspartate(NAA), choline containg compounds (Cho), and creatine (Cr) in three brain locations: white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC), and hippocampus. Two ratios of NAA/Cr and Cho/Cr as a measure of brain biochemical changes were compared among three experimental groups. On the comparison of brain biochemical changes, both MDD patients and BD patients showed many similarities compared to the controls. They both had a significantly lower NAA/Cr ratio in the left WMP lobe. There were no significant differences among three experimental groups for Cho/Cr ratio in the WMP lobe, and for the ratios of NAA/Cr and Cho/Cr in the bilateral ACC and hippocampus. The only difference between MDD and BD patients existed for the NAA/Cr ratio in the right WMP lobe. While MDD patients had a significantly lower NAA/Cr ratio than controls, BD patients showed no such differences. On the comparison of correlation of medical variables and brain biochemical changes, all participants demonstrated no significant correlations. Reduced NAA/Cr ratio at the left WMP lobe indicated the dysfunction of neuronal viability in deep white matter, in both MDD and BD patients who shared similarities of brain biochemical abnormalities, which might imply an overlap in neuropathology of depression. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy.

PubMed

Barton, David A; Esler, Murray D; Dawood, Tye; Lambert, Elisabeth A; Haikerwal, Deepak; Brenchley, Celia; Socratous, Florentia; Hastings, Jacqueline; Guo, Ling; Wiesner, Glen; Kaye, David M; Bayles, Richard; Schlaich, Markus P; Lambert, Gavin W

2008-01-01

The biological basis for the development of major depressive disorder (MDD) remains incompletely understood. To quantify brain serotonin (5-hydroxytryptamine [5-HT]) turnover in patients with MDD. Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI) in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. Studies were performed in 21 patients fulfilling the DSM-IV and International Statistical Classification of Diseases, 10th Revision diagnostic criteria for MDD and in 40 healthy volunteers. Treatment for patients consisted of SSRI administration for approximately 12 weeks. Brain serotonin turnover before and after SSRI therapy. Brain serotonin turnover was significantly elevated in unmedicated patients with MDD compared with healthy subjects (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 4.4 [4.3] vs 1.6 [2.4] nmol/L, respectively; P = .003). Analysis of the influence of the 5-HTT genotype in MDD indicated that carriage of the s allele compared with the l allele was associated with greater than a 2-fold increase in brain serotonin turnover (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.5 [4.7] vs 2.7 [2.9] nmol/L, respectively; P = .04). Following SSRI therapy, brain serotonin turnover was substantially reduced (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.0 [4.0] nmol/L prior to treatment vs 2.0 [3.3] nmol/L following therapy; P = .008). Brain serotonin turnover is elevated in unmedicated patients with MDD and is influenced by the 5-HTT genotype. The marked reduction in serotonin turnover following SSRI treatment and the accompanying improvement in symptoms suggest that high brain serotonin turnover may be a biological substrate of MDD.

Personality traits in the differentiation of major depressive disorder and bipolar disorder during a depressive episode.

PubMed

Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos

2016-02-28

The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Depression and eating disorders: treatment and course.

PubMed

Mischoulon, David; Eddy, Kamryn T; Keshaviah, Aparna; Dinescu, Diana; Ross, Stephanie L; Kass, Andrea E; Franko, Debra L; Herzog, David B

2011-05-01

We examined the course of major depressive disorder (MDD) and predictors of MDD recovery and relapse in a longitudinal sample of women with eating disorders (ED). 246 Boston-area women with DSM-IV anorexia nervosa-restricting (ANR; n=51), AN-binge/purge (ANBP; n=85), and bulimia nervosa (BN; n=110) were recruited between 1987 and 1991 and interviewed using the Eating Disorders Longitudinal Interval Follow-up Evaluation (LIFE-EAT-II) every 6-12 months for up to 12 years. 100 participants had MDD at study intake and 45 developed MDD during the study. Psychological functioning and treatment were assessed. Times to MDD onset (1 week-4.3 years), recovery (8 weeks-8.7 years), and relapse (1 week-5.2 years) varied. 70% recovered from MDD, but 65% subsequently relapsed. ANR patients were significantly less likely to recover from MDD than ANBP patients (p=0.029). Better psychological functioning and history of MDD were associated with higher chance of MDD recovery. Higher baseline depressive severity and full recovery from ED were associated with greater likelihood of MDD relapse; increased weight loss was somewhat protective. Adequate antidepressant treatment was given to 72% of patients with MDD and generally continued after MDD recovery. Time on antidepressants did not predict MDD recovery (p=0.27) or relapse (p=0.26). Small ED diagnostic subgroups; lack of non-ED control group. The course of MDD in EDs is protracted; MDD recovery may depend on ED type. Antidepressants did not impact likelihood of MDD recovery, nor protect against relapse, which may impact on treatment strategies for comorbid MDD and EDs. Copyright © 2010 Elsevier B.V. All rights reserved.

Prefrontal cortex activation is associated with a discrepancy between self- and observer-rated depression severities of major depressive disorder: a multichannel near-infrared spectroscopy study.

PubMed

Akashi, Hiroyuki; Tsujii, Noa; Mikawa, Wakako; Adachi, Toru; Kirime, Eiji; Shirakawa, Osamu

2015-03-15

Studies on major depressive disorder (MDD) show that the degree of correlation between the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) varies widely. We aimed to determine whether this discrepancy reflects specific functional abnormalities in the frontotemporal cortex. Mildly depressed or euthymic patients with MDD (n=52), including 21 patients with MDD with the discrepancy, i.e., those with low HAMD17 scores (≤13) but high BDI-II scores (>28), and 31 patients without the discrepancy, i.e., those with low HAMD17 scores and low BDI-II scores (≤28), participated in the study along with 48 control subjects. Regional changes of oxygenated hemoglobin (oxy-Hb) levels during a verbal fluency task (VFT) were monitored using a 52-channel near-infrared spectroscopy (NIRS) device. In the frontotemporal regions, mean oxy-Hb changes induced by the VFT were significantly smaller in patients with MDD than in control subjects. In 5 channels within frontal regions, the increase in mean oxy-Hb levels was significantly greater in MDD patients with the BDI-HAMD discrepancy than in those without the discrepancy. In 6 channels within the frontal region of the patients with MDD, significant positive correlations were observed between mean oxy-Hb changes and BDI total scores (ρ=0.38-0.59; P<0.05, false discovery rate corrected). Our findings required replication in severely depressed patients, particularly those with melancholia. The distinct pattern of activation of the prefrontal cortex suggests that MDD with the BDI-HAMD discrepancy is pathophysiologically different from MDD without the discrepancy. Copyright © 2014 Elsevier B.V. All rights reserved.

Distinguishing medication-free subjects with unipolar disorder from subjects with bipolar disorder: state matters.

PubMed

Rive, Maria M; Redlich, Ronny; Schmaal, Lianne; Marquand, André F; Dannlowski, Udo; Grotegerd, Dominik; Veltman, Dick J; Schene, Aart H; Ruhé, Henricus G

2016-11-01

Recent studies have indicated that pattern recognition techniques of functional magnetic resonance imaging (fMRI) data for individual classification may be valuable for distinguishing between major depressive disorder (MDD) and bipolar disorder (BD). Importantly, medication may have affected previous classification results as subjects with MDD and BD use different classes of medication. Furthermore, almost all studies have investigated only depressed subjects. Therefore, we focused on medication-free subjects. We additionally investigated whether classification would be mood state independent by including depressed and remitted subjects alike. We applied Gaussian process classifiers to investigate the discriminatory power of structural MRI (gray matter volumes of emotion regulation areas) and resting-state fMRI (resting-state networks implicated in mood disorders: default mode network [DMN], salience network [SN], and lateralized frontoparietal networks [FPNs]) in depressed (n=42) and remitted (n=49) medication-free subjects with MDD and BD. Depressed subjects with MDD and BD could be classified based on the gray matter volumes of emotion regulation areas as well as DMN functional connectivity with 69.1% prediction accuracy. Prediction accuracy using the FPNs and SN did not exceed chance level. It was not possible to discriminate between remitted subjects with MDD and BD. For the first time, we showed that medication-free subjects with MDD and BD can be differentiated based on structural MRI as well as resting-state functional connectivity. Importantly, the results indicated that research concerning diagnostic neuroimaging tools distinguishing between MDD and BD should consider mood state as only depressed subjects with MDD and BD could be correctly classified. Future studies, in larger samples are needed to investigate whether the results can be generalized to medication-naïve or first-episode subjects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blood-Based Gene Expression Profiles Models for Classification of Subsyndromal Symptomatic Depression and Major Depressive Disorder

PubMed Central

Yu, Shunying; Yuan, Chengmei; Hong, Wu; Wang, Zuowei; Cui, Jian; Shi, Tieliu; Fang, Yiru

2012-01-01

Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD). Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P< = 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell–derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls. PMID:22348066

Synchrony of Physiological Activity during Mother-Child Interaction: Moderation by Maternal History of Major Depressive Disorder

PubMed Central

Woody, Mary L.; Feurer, Cope; Sosoo, Effua E.; Hastings, Paul D.; Gibb, Brandon E.

2017-01-01

Background The family environment plays an important role in the intergenerational transmission of MDD, but less is known about how day-to-day mother-child interactions may be disrupted in families with a history of MDD. Disruptions in mother-child synchrony, the dynamic and convergent exchange of physiological and behavioral cues during interactions, may be one important risk factor. Although maternal MDD is associated with a lack of mother-child synchrony at the behavioral level, no studies have examined the impact of maternal MDD on physiological synchrony. Therefore, the current study examined whether maternal history of MDD moderates mother-child physiological synchrony (measured via RSA) during positive and negative discussions. Method Children ages 7–11 and mothers with either a history of MDD during the child’s lifetime (n=44) or no lifetime diagnosis of any mood disorder (n=50) completed positive and negative discussion tasks while RSA was continuously recorded for both child and mother. Results Results indicated significant between-dyad and within-dyad group differences in physiological synchrony during positive and negative discussions. Between-dyad analyses revealed evidence of synchrony only among never depressed dyads, among whom higher average mother RSA during both discussions was associated with higher average child RSA. Within-dyad analyses revealed that never depressed dyads displayed positive synchrony (RSA concordance) whereas dyads with a history of maternal MDD displayed negative synchrony (RSA discordance) during the negative discussion and that the degree of negative synchrony exhibited during the negative discussion was associated with mothers’ and children’s levels of sadness. Conclusions These results provide preliminary evidence that physiological synchrony is disrupted in families with a history of maternal MDD and may be a potential risk factor for the intergenerational transmission of depression. PMID:27090774

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

PubMed

Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Partially distinct combinations of psychological, metabolic and inflammatory risk factors are prospectively associated with the onset of the subtypes of Major Depressive Disorder in midlife.

PubMed

Rudaz, Dominique A; Vandeleur, Caroline L; Gebreab, Sirak Z; Gholam-Rezaee, Mehdi; Strippoli, Marie-Pierre F; Lasserre, Aurélie M; Glaus, Jennifer; Castelao, Enrique; Pistis, Giorgio; von Känel, Roland; Marques-Vidal, Pedro; Waeber, Gérard; Vollenweider, Peter; Preisig, Martin

2017-11-01

Given the well known heterogeneity of Major Depressive Disorder (MDD), dividing this complex disorder into subtypes is likely to be a more promising approach to identify its determinants than to study it as a whole. In a prospective population-based cohort study (CoLaus|PsyCoLaus) with 5.5 years of follow-up, 1524 participants without MDD at baseline, aged 35-66 years (mean age 51.4 years, 43.4% females), participated in the physical and psychiatric baseline and the psychiatric follow-up evaluations. The incidence of both atypical and melancholic MDD during the follow-up period were predicted by female sex, a lifetime history of minor depressive disorders and higher neuroticism scores. Higher baseline body mass index was associated with the onset of atypical MDD, whereas the absence of hypertension and younger age were associated with the development of melancholic MDD. Unspecified MDD was predicted by younger age, low concentrations of tumor necrosis factor-α and elevated life-event impact scores. The age range of our cohort restricts the identification of risk factors to MDD with onset in midlife and the recruitment in an urban area limits the generalizability of the findings. Our data suggest that MDD subtypes are predicted by partially distinct combinations of baseline characteristics suggesting that these subtypes not only differ in their clinical manifestations but also in factors that contribute to their development. Subjects with minor depressive episodes, especially in combination with particular personality features, deserve close clinical attention to prevent the subsequent onset of atypical and melancholic major depression. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of obesity measures in the development and persistence of major depressive disorder.

PubMed

Gibson-Smith, Deborah; Bot, Mariska; Paans, Nadine Pg; Visser, Marjolein; Brouwer, Ingeborg; Penninx, Brenda Wjh

2016-07-01

The role of obesity with the development of major depressive disorder (MDD) requires conformation and whether obesity contributes to more chronic depression in persons with established (MDD) is unknown. This study examined the longitudinal relationship of body mass index (BMI) and waist circumference with the incidence and persistence of MDD over 2-year and 6-year periods. Data were sourced from the Netherlands Study of Depression and Anxiety. MDD was established with Composite International Diagnostic Interviews. The relationship of BMI and waist circumference with the development of depression two and six years later were estimated in the subsample with no current psychopathology at baseline. Associations with the persistence of depression was estimated in the subsample with current MDD. Higher BMI at baseline, but not waist circumference, slightly increased the odds of the development of MDD after two years (odds ratio (OR) per standard deviation increase: 1.11; p=0.03), This relationship was not significant after adjustment for health and lifestyle variables. Conversely, over a 6-year period both BMI and waist circumference moderately increased the odds of developing MDD even after adjustment (OR:1.17; p=0.05, OR:1.20; p=0.05). Persistence of MDD in currently depressed subjects, is not related with BMI or waist circumference (adjusted OR:0.93; p=0.2, OR:0.91; p=0.15). Development of depression may differ in participants lost to follow-up. Over a 6 year period, patients with higher BMI show a slightly increased risk of development of depression. However, in depressed patients there is no relationship between BMI and the persistence of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Pre-adult versus adult onset major depressive disorder in a naturalistic patient sample: the Leiden Routine Outcome Monitoring Study.

PubMed

van Noorden, M S; Minkenberg, S E; Giltay, E J; den Hollander-Gijsman, M E; van Rood, Y R; van der Wee, N J; Zitman, F G

2011-07-01

Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients. Altogether, 1552 out-patients, mean age 39.2 ± 11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20-40/40-65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender. Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV - Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97-5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26-2.60) in patients with pre-adult versus adult onset MDD. Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Negative emotions towards others are diminished in remitted major depression.

PubMed

Zahn, R; Lythe, K E; Gethin, J A; Green, S; Deakin, J F W; Workman, C; Moll, J

2015-06-01

One influential view is that vulnerability to major depressive disorder (MDD) is associated with a proneness to experience negative emotions in general. In contrast, blame attribution theories emphasise the importance of blaming oneself rather than others for negative events. Our previous exploratory study provided support for the attributional hypothesis that patients with remitted MDD show no overall bias towards negative emotions, but a selective bias towards emotions entailing self-blame relative to emotions that entail blaming others. More specifically, we found a decreased proneness for contempt/disgust towards others relative to oneself (i.e. self-contempt bias). Here, we report a definitive test of the competing general negative versus specific attributional bias theories of MDD. We compared a medication-free remitted MDD (n=101) and a control group (n=70) with no family or personal history of MDD on a previously validated experimental test of moral emotions. The task measures proneness to specific emotions associated with different types of self-blame (guilt, shame, self-contempt/disgust, self-indignation/anger) and blame of others (other-indignation/anger, other-contempt/disgust) whilst controlling for the intensity of unpleasantness. We confirmed the hypothesis that patients with MDD exhibit an increased self-contempt bias with a reduction in contempt/disgust towards others. Furthermore, they also showed a decreased proneness for indignation/anger towards others. This corroborates the prediction that vulnerability to MDD is associated with an imbalance of specific self- and other-blaming emotions rather than a general increase in negative emotions. This has important implications for neurocognitive models and calls for novel focussed interventions to rebalance blame in MDD. Crown Copyright © 2015. Published by Elsevier Masson SAS. All rights reserved.

A cross-sectional survey to investigate the prevalence of pain in Japanese patients with major depressive disorder and schizophrenia.

PubMed

Kishi, Taro; Matsuda, Yuki; Mukai, Tomohiko; Matsunaga, Shinji; Yasue, Ichiro; Fujita, Kiyoshi; Okochi, Tomo; Hirano, Shigeki; Kajio, Yusuke; Funahashi, Toshihiko; Akamatsu, Kaku; Ino, Kei; Okuda, Momoko; Tabuse, Hideaki; Iwata, Nakao

2015-05-01

We conducted a cross-sectional survey to assess the prevalence of physical pain in Japanese major depressive disorder (MDD) and schizophrenia (SZ) patients as well as in healthy controls (HCs). We also examined the association between their psychopathology and characteristics of pain according to a face-to-face survey by an experienced psychiatrist and psychologist. We analyzed 233 HCs, 94 MDD patients, and 75 SZ patients using the McGill Pain Questionnaire (MPQ) and SF-8 (all participants), the Hamilton Depression Rating Scale 21 items (MDD patients), and the Positive and Negative Symptom Scale (SZ patients). Although MDD patients experienced more pain than HCs, there was no difference in the prevalence of pain between SZ patients and HCs. Moreover, HCs with pain did not have higher SF-8 total scores than those without pain, whereas both MDD and SZ patients with pain had higher SF-8 total scores than those without pain. The severity of psychopathology in MDD and SZ patients was also positively associated with both the prevalence of pain and MPQ scores. MPQ scores were also associated with positive symptoms in SZ patients. Considering these results, physicians need to query MDD patients about physical pain during examination if they are to ensure a favorable and quick response to treatment. The severity of positive symptoms (i.e., clinical status) in SZ patients might also be associated with pain sensitivity, and warrants further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Insular subdivisions functional connectivity dysfunction within major depressive disorder.

PubMed

Peng, Xiaolong; Lin, Pan; Wu, Xiaoping; Gong, Ruxue; Yang, Rui; Wang, Jue

2018-02-01

Major depressive disorder (MDD) is a mental disorder characterized by cognitive and affective deficits. Previous studies suggested that insula is a crucial node of the salience network for initiating network switching, and dysfunctional connection to this region may be related to the mechanism of MDD. In this study, we systematically investigated and quantified the altered functional connectivity (FC) of the specific insular subdivisions and its relationship to psychopathology of MDD. Resting-state FC of insular subdivisions, including bilateral ventral/dorsal anterior insula and posterior insula, were estimated in 19 MDD patients and 19 healthy controls. Abnormal FC was quantified between groups. Additionally, we investigated the relationships between insular connectivity and depressive symptom severity. MDD patients demonstrated aberrant FC for insular subdivisions to superior temporal sulcus, inferior prefrontal gyrus, amygdala and posterior parietal cortex. Moreover, depression symptoms (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scorers) were associated with the FC values of insular subdivisions. First, the sample size of our current study is relatively small, which may affect the statistic power. Second, using standardized insular subdivision seeds for FC analyses may neglect subtle natural differences in size and location of functional area across individuals and may thus affect connectivity maps. Abnormal FC of insular subdivisions to default network and central executive network may represent impaired intrinsic networks switching which may affect the underlying emotional and sensory disturbances in MDD. And our findings can help to understand the pathophysiology and underlying neural mechanisms of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

IS GENERALIZED ANXIETY DISORDER AN ANXIETY OR MOOD DISORDER? CONSIDERING MULTIPLE FACTORS AS WE PONDER THE FATE OF GAD

PubMed Central

Mennin, Douglas S.; Heimberg, Richard G.; Fresco, David M.; Ritter, Michael R.

2016-01-01

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) demonstrate a strong relationship to each other at both genotypic and phenotypic levels, and both demonstrate substantial loadings on a higher-order negative affectivity factor. On the basis of these findings, there have been a number of calls to reclassify GAD in the same category as MDD (the “distress disorders”). However, any consideration of the reclassification of GAD should also take into account a number of other factors not only related to GAD and MDD but also to the overlap of these disorders with other anxiety and mood disorders. First, GAD has established reliability and validity in its own right, and specific features (e.g., worry) may become obscured by attempts at reclassification. Second, examination of the nature of the overlap of GAD and MDD with each other and with other disorders suggests a more complex pattern of differences between these conditions than has been suggested (e.g., MDD has strong relationships with other anxiety disorders, and GAD may be more strongly related to fear than it may first appear). Third, although findings suggest that GAD and MDD may have overlapping heritable characteristics, other evidence suggests that the two disorders may be distinguished by both environmental factors and temporal presentations. Finally, although overlap between GAD and MDD is reflected in their relationships to negative affectivity, temporal relationships between these disorders may be demonstrated by functional changes in emotional responsivity. PMID:18412056

A pattern of cerebral perfusion anomalies between Major Depressive Disorder and Hashimoto Thyroiditis

PubMed Central

2011-01-01

Background This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion. Methods Design: Analysis of data derived from two separate data banks. Sample: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25). Assessment: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by 99 mTc-ECD SPECT. Statistical analysis was done through logistic regression. Results MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group. Conclusion In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD. PMID:21910915

Experiential avoidance in the vulnerability to depression among adolescent females.

PubMed

Mellick, William; Vanwoerden, Salome; Sharp, Carla

2017-01-15

Although various mechanisms in the maternal transmission of Major Depressive Disorder (MDD) have been investigated, it is unknown whether experiential avoidance (EA) is a vulnerability factor in the development of depression or a consequence of the illness. The present study utilized a high-risk design to determine if EA indeed poses vulnerability to adolescent MDD. Secondly, we examined the means by which adolescent EA may come to pose vulnerability, namely that it explains the relation between maternal EA and adolescent depressive symptoms. One-hundred and forty-six biological mother/adolescent daughter dyads comprised three diagnostic groups: mothers with a history of MDD and their depressed daughters (MDD; n=21), mothers with a history of MDD and their never-depressed daughters (high-risk, HR; n=69), and healthy controls (HCs; n=56). Groups differed on daughter EA such that the MDD group reported greater EA than the HR group, which in turn reported greater EA than HCs. Daughter EA mediated the relation between maternal EA and daughter depressive symptoms after controlling for maternal depressive symptoms. Strengths aside, this study included a relatively small group of depressed mother-daughter dyads and relied on cross-sectional self-report data. EA appears to serve as a vulnerability factor for adolescent MDD, and the mechanistic role of daughter EA highlights the significance of intergenerational EA in the maternal transmission of depression. Therapeutic approaches may therefore consider reducing the transmission of EA from mothers to daughters. Copyright © 2016 Elsevier B.V. All rights reserved.

Posttraumatic Stress Disorder Increases Sensitivity to Long Term Losses among Patients with Major Depressive Disorder

PubMed Central

Vaughan, Christopher; Paulus, Martin P.; Dunlop, Boadie W.

2013-01-01

Background Decisions under risk and with outcomes that are delayed in time are ubiquitous in real life and can have a significant impact on the health and wealth of the decision-maker. Despite its potential relevance for real-world choices, the degree of aberrant risky and intertemporal decision-making in patients suffering from major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) has received little attention to date. Method We used a case-control design to compare decision-making in healthy control subjects (N=16) versus untreated depressed subjects in a current major depressive episode (N=20). In order to examine how major depressive disorder (MDD) may impact decision-making, subjects made decisions over (1) risky outcomes and (2) delayed outcomes in the domain of gains and losses using choice paradigms from neuroeconomics. In a pre-planned analysis, depressed subjects were subdivided into those with primary PTSD along with comorbid MDD (MDD+PTSD) versus those with primary MDD without PTSD (MDD-only). Choice behavior was modeled via a standard econometric model of intertemporal choice, a quasi-hyperbolic temporal discounting function, which was estimated for each subject group separately. Results Under conditions of potential gain, depressed subjects demonstrated greater discounting for gains across all time frames compared to controls. In the realm of losses, both subgroups of depressed subjects discounted more steeply than controls for short time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD subjects showed shallower discounting rates relative to MDD-only subjects, who continued to discount future losses steeply. Risk attitudes did not contribute to differences in intertemporal choice. Conclusions Depressed patients make choices that minimize current pain and maximize current reward, despite severe later consequences or lost opportunities. Anxiety associated with PTSD may serve as a partially protective factor in decision-making about long-term potential losses compared to MDD patients without PTSD. PMID:24116235

Prevalence of major depressive disorder and socio-demographic correlates: Results of a representative household epidemiological survey in Beijing, China.

PubMed

Liu, Jing; Yan, Fang; Ma, Xin; Guo, Hong-Li; Tang, Yi-Lang; Rakofsky, Jeffrey J; Wu, Xiao-Mei; Li, Xiao-Qiang; Zhu, Hong; Guo, Xiao-Bing; Yang, Yang; Li, Peng; Cao, Xin-Dong; Li, Hai-Ying; Li, Zhen-Bo; Wang, Ping; Xu, Qiu-Yue

2015-07-01

Major depressive disorder (MDD) is the most prevalent mental disorder in the general population and has been associated with socioeconomic factors. Beijing has undergone significant socioeconomic changes in last decade, however no large-scale community epidemiological surveys of MDD have been conducted in Beijing since 2003. To determine the prevalence of MDD and its socio-demographic correlates in a representative household sample of the general population in Beijing, China. Data were collected from the 2010 representative household epidemiological survey of mental disorders in Beijing. The multistage cluster random sampling method was used to select qualified subjects in 18 districts and counties, and then face-to-face interviews were administered using the Chinese version of Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) during November 1, 2010 to December 31, 2010. 19,874 registered permanent residents were randomly identified and 16,032 (response rate=80.7%) completed face-to-face interviews. The time-point and life-time prevalence rates of MDD were estimated to be 1.10% (95% CI: 0.94-1.26%) and 3.56% (95% CI: 3.27-3.85%) respectively. Significant differences were found in sex, age, location of residence, marital status, education, employment status, personal/family monthly income, perception of family environment and relationship with others, when comparing residents with MDD to those without MDD. Those who were female, aged 45 or above, reported low family income, or reported an "average" or "poor" family environment were associated with a higher risk of MDD. The prevalence of MDD reported in this survey is relatively lower than that in other western countries. Female sex, age older than 45, low family income, and poor family environment appear to be independent risk factors for MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

Posttraumatic stress disorder increases sensitivity to long term losses among patients with major depressive disorder.

PubMed

Engelmann, Jan B; Maciuba, Britta; Vaughan, Christopher; Paulus, Martin P; Dunlop, Boadie W

2013-01-01

Decisions under risk and with outcomes that are delayed in time are ubiquitous in real life and can have a significant impact on the health and wealth of the decision-maker. Despite its potential relevance for real-world choices, the degree of aberrant risky and intertemporal decision-making in patients suffering from major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) has received little attention to date. We used a case-control design to compare decision-making in healthy control subjects (N=16) versus untreated depressed subjects in a current major depressive episode (N=20). In order to examine how major depressive disorder (MDD) may impact decision-making, subjects made decisions over (1) risky outcomes and (2) delayed outcomes in the domain of gains and losses using choice paradigms from neuroeconomics. In a pre-planned analysis, depressed subjects were subdivided into those with primary PTSD along with comorbid MDD (MDD+PTSD) versus those with primary MDD without PTSD (MDD-only). Choice behavior was modeled via a standard econometric model of intertemporal choice, a quasi-hyperbolic temporal discounting function, which was estimated for each subject group separately. Under conditions of potential gain, depressed subjects demonstrated greater discounting for gains across all time frames compared to controls. In the realm of losses, both subgroups of depressed subjects discounted more steeply than controls for short time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD subjects showed shallower discounting rates relative to MDD-only subjects, who continued to discount future losses steeply. Risk attitudes did not contribute to differences in intertemporal choice. Depressed patients make choices that minimize current pain and maximize current reward, despite severe later consequences or lost opportunities. Anxiety associated with PTSD may serve as a partially protective factor in decision-making about long-term potential losses compared to MDD patients without PTSD.

Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder.

PubMed

Green, Sophie; Lambon Ralph, Matthew A; Moll, Jorge; Deakin, John F W; Zahn, Roland

2012-10-01

Proneness to overgeneralization of self-blame is a core part of cognitive vulnerability to major depressive disorder (MDD) and remains dormant after remission of symptoms. Current neuroanatomical models of MDD, however, assume general increases of negative emotions and are unable to explain biases toward emotions entailing self-blame (eg, guilt) relative to those associated with blaming others (eg, indignation). Recent functional magnetic resonance imaging (fMRI) studies in healthy participants have shown that moral feelings such as guilt activate representations of social meaning within the right superior anterior temporal lobe (ATL). Furthermore, this area was selectively coupled with the subgenual cingulate cortex and adjacent septal region (SCSR) during the experience of guilt compared with indignation. Despite its psychopathological importance, the functional neuroanatomy of guilt in MDD is unknown. To use fMRI to test the hypothesis that, in comparison with control individuals, participants with remitted MDD exhibit guilt-selective SCSR-ATL decoupling as a marker of deficient functional integration. Case-control study from May 1, 2008, to June 1, 2010. Clinical research facility. Twenty-five patients with remitted MDD (no medication in 16 patients) with no current comorbid Axis I disorders and 22 controls with no personal or family history of MDD. Between-group difference of ATL coupling with a priori SCSR region of interest for guilt vs indignation. We corroborated the prediction of a guilt-selective reduction in ATL-SCSR coupling in MDD vs controls (familywise error-corrected P=.001 over the region of interest) and revealed additional medial frontopolar, right hippocampal, and lateral hypothalamic areas of decoupling while controlling for medication status and intensity of negative emotions. Lower levels of ATL-SCSR coupling were associated with higher scores on a validated measure of overgeneralized self-blame (67-item Interpersonal Guilt Questionnaire). Vulnerability to MDD is associated with temporofrontolimbic decoupling that is selective for self-blaming feelings. This provides the first neural mechanism ofMDD vulnerability that accounts for self-blaming biases.

Biological Sex Differences in Depression: A Systematic Review.

PubMed

Labaka, Ainitze; Goñi-Balentziaga, Olatz; Lebeña, Andrea; Pérez-Tejada, Joana

2018-07-01

Depression is the leading cause of disability worldwide, and its prevalence is 2 times higher in women than in men. There is, however, a lack of data on sex-specific pathophysiology of this disorder. The purpose of this systematic review is to identify the biological sex differences found in major depressive disorder (MDD) in studies published in the last 10 years. We conducted a literature search using the Medline, PsycInfo, PubMed, and Web of Science databases, selecting English-language studies that included physiological measures compared by sex in addition to MDD. We identified 20 relevant studies, which consisted primarily of mixed methodology and samples. The reported physiological measures comprised a variety of serum biomarkers, gene mRNA expression, and brain activity. Findings suggest different biological patterns in those with MDD depending on sex. Specifically, women presented higher levels of inflammatory, neurotrophic, and serotonergic markers and a stronger correlation between levels of some inflammatory and neurotrophic factors and the severity of symptoms. This review provides information about possible different biological patterns for women and men with depressive disorder and may have important implications for treatment. Future research should include homogeneous samples; make comparisons based on sex, control sex hormone fluctuations and pharmacological treatment; and use consistent criteria for evaluating psychobiological changes in MDD.

Problem-solving ability and comorbid personality disorders in depressed outpatients.

PubMed

Harley, Rebecca; Petersen, Timothy; Scalia, Margaret; Papakostas, George I; Farabaugh, Amy; Fava, Maurizio

2006-01-01

Major depressive disorder (MDD) is associated with poor problem-solving abilities. In addition, certain personality disorders (PDs) that are common among patients with MDD are also associated with limited problem-solving skills. Attempts to understand the relationship between PDs and problem solving can be complicated by the presence of acute MDD. Our objective in this study was to investigate the relationships between PDs, problem-solving skills, and response to treatment among outpatients with MDD. We enrolled 312 outpatients with MDD in an open, fixed-dose, 8-week fluoxetine trial. PD diagnoses were ascertained via structured clinical interview before and after fluoxetine treatment. Subjects completed the Problem-Solving Inventory (PSI) at both time points. We used analyses of covariance (ANCOVAs) to assess relationships between PD diagnoses and PSI scores prior to treatment. Subjects were divided into three groups: those with PD diagnoses that remained stable after fluoxetine treatment (N=91), those who no longer met PD criteria after fluoxetine treatment (N=119), and those who did not meet criteria for a PD at any time point in the study (N=95). We used multiple chi(2) analyses to compare rates of MDD response and remission between the three PD groups. ANCOVA was also used to compare posttreatment PSI scores between PD groups. Prior to fluoxetine treatment, patients with avoidant, dependent, narcissistic, and borderline PDs reported significantly worse problem-solving ability than did patients without any PDs. Only subjects with dependent PD remained associated with poorer baseline problem-solving reports after the effects of baseline depression severity were controlled. Patients with stable PD diagnoses had significantly lower rates of MDD remission. Across PD groups, problem solving improved as MDD improved. No significant differences in posttreatment problem-solving were found between PD groups after controlling for baseline depression severity, baseline PSI score, and response to treatment. Treatment with fluoxetine is less likely to lead to remission of MDD in patients with stable PDs. More study is needed to investigate causal links between PDs, problem solving, and MDD treatment response. Published 2006 Wiley-Liss, Inc.

Exercise therapy improves aerobic capacity of inpatients with major depressive disorder.

PubMed

Kerling, Arno; von Bohlen, Anne; Kück, Momme; Tegtbur, Uwe; Grams, Lena; Haufe, Sven; Gützlaff, Elke; Kahl, Kai G

2016-06-01

Unipolar depression is one of the most common diseases worldwide and is associated with a higher cardiovascular risk partly due to reduced aerobic capacity. Therefore, the aim of our study was to examine whether a structured aerobic training program can improve aerobic capacity in inpatients with MDD (major depressive disorder). Overall, 25 patients (13 women, 12 men) diagnosed with MDD were included in the study. Parameters of aerobic capacity, such as maximum performance, maximum oxygen consumption, and VAT (ventilatory anaerobic threshold), were assessed on a bicycle ergometer before and 6 weeks after a training period (three times per week for 45 min on two endurance machines). In addition, a constant load test was carried out at 50% of the maximum performance prior to and after the training period. The performance data were compared with 25 healthy controls matched for sex, age, and body mass index before and after the training period. Compared to controls, patients with MDD had significantly lower aerobic capacity. After training, there was a significant improvement in their performance data. A significant difference remained only for VAT between patients with MDD and healthy controls. With regard to the coincidence of MDD with cardiovascular and cardiometabolic disorders, a structured supervised exercise program carried out during hospitalization is a useful supplement for patients with MDD.

Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.

PubMed

Zheng, P; Zeng, B; Zhou, C; Liu, M; Fang, Z; Xu, X; Zeng, L; Chen, J; Fan, S; Du, X; Zhang, X; Yang, D; Yang, Y; Meng, H; Li, W; Melgiri, N D; Licinio, J; Wei, H; Xie, P

2016-06-01

Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.

Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain.

PubMed

Strigo, Irina A; Simmons, Alan N; Matthews, Scott C; Craig, Arthur D Bud; Paulus, Martin P

2008-11-01

Chronic pain and depression are highly comorbid conditions, yet little is known about the neurobiological basis of pain processing in major depressive disorder (MDD). To examine the neural substrates underlying anticipation and processing of heat pain in a group of unmedicated young adults with current MDD. Functional magnetic resonance neuroimaging data were collected during an event-related factorial experimental pain paradigm. Painful and nonpainful heat stimuli were applied to the left volar forearm while different color shapes explicitly signaled the intensity of the upcoming stimulus. University brain imaging center. Patients Fifteen (12 female) young adults with current MDD and 15 (10 female) healthy subjects with no history of MDD were recruited and matched for age and level of education. The Structured Clinical Interview for DSM-IV was administered to all participants by a board-certified psychiatrist. Main Outcome Measure Between-group differences in blood oxygen level-dependent functional magnetic resonance neuroimaging signal change to anticipation and processing of painful vs nonpainful temperature stimuli. Subjects with MDD compared with healthy controls showed (1) increased activation in the right anterior insular region, dorsal anterior cingulate, and right amygdala during anticipation of painful relative to nonpainful stimuli, (2) increased activation in the right amygdala and decreased activation in periaqueductal gray matter and the rostral anterior cingulate and prefrontal cortices during painful stimulation relative to nonpainful stimulation, and (3) greater activation in the right amygdala during anticipation of pain, which was associated with greater levels of perceived helplessness. These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in MDD. Future studies should examine the degree to which altered functional brain response during anticipatory processing affects the ability to modulate negative affective states in MDD, which is a core characteristic of this disorder.

Factors Associated with Depression in Obsessive-Compulsive Disorder: A Cross-Sectional Study

PubMed Central

ALTINTAŞ, Ebru; TAŞKINTUNA, Nilgün

2015-01-01

Introduction Major depressive disorder (MDD) is the most frequent comorbid psychiatric condition associated with obsessive-compulsive disorder (OCD). This study aimed to evaluate the prevalence of current depression in OCD, differences in socio-demographic and clinical characteristics, and obsessive-compulsive symptoms between OCD patients with and without depression. Additionally, factors associated with comorbid depression were investigated in our study. Methods In total, 140 OCD patients, of which 63 were OCD patients with MDD (OCD+MDD, n=63) and 77 were OCD patients without depression (OCD−MDD, n=77) were included in the study. All patients were diagnosed with OCD using the Structured Clinical Interview for DSM-IV. The Yale–Brown Obsessive-Compulsive Scale, Beck Anxiety Scale, and Beck Depression Scale were administered to all patients. After the socio-demographic and clinical variables and scales were accomplished, the OCD patients divided into two groups as OCD with or without depression and we compared their mean scores of the variables and scales. Univariate analyses were followed by logistic regression. Results There were no significant differences in age, gender, marital status, period without treatment, profession, medical and family history, and social support between the two groups. Anxiety, depression, and obsession and compulsion scores were significantly higher in the OCD+MDD group. The avoidance, insight, instability, and retardation scores of the OCD+MDD group were also significantly higher than those of the OCD−MDD group. Conclusion Our study suggests that many factors are strongly associated with depression in OCD. Positive correlations between poor insight, severity of obsession and compulsion, and stressful life events during the last six months increased the risk of depression in OCD. Our study suggests that high level of avoidance, instability and retardation, history of suicidal attempt, and delayed treatment are other notable factors associated with the development of depression in OCD. PMID:28360738

Interactions between the vascular endothelial growth factor gene polymorphism and life events in susceptibility to major depressive disorder in a Chinese population.

PubMed

Han, Dong; Qiao, Zhengxue; Chen, Lu; Qiu, Xiaohui; Fang, Deyu; Yang, Xiuxian; Ma, Jingsong; Chen, Mingqi; Yang, Jiarun; Wang, Lin; Zhu, Xiongzhao; Zhang, Congpei; Yang, Yanjie; Pan, Hui

2017-08-01

Recent studies suggest that vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder. The aim of this study is to investigate the interaction between vascular endothelial growth factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the pathogenesis of major depressive disorder (MDD). DNA genotyping was performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and sex-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A logistics method was employed to assess the gene-environment interaction (G×E). Differences in rs2010963 genotype distributions were observed between MDD patients and controls. Significant G×E interactions between allelic variation of rs2010963 and negative life events were observed. Individuals carrying the C alleles were susceptible to MDD only when exposed to high-negative life events. These results indicate that interactions between the VEGF rs2010963 polymorphism and environment increases the risk of developing MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Linking Goal-Oriented Requirements and Model-Driven Development

NASA Astrophysics Data System (ADS)

Pastor, Oscar; Giachetti, Giovanni

In the context of Goal-Oriented Requirement Engineering (GORE) there are interesting modeling approaches for the analysis of complex scenarios that are oriented to obtain and represent the relevant requirements for the development of software products. However, the way to use these GORE models in an automated Model-Driven Development (MDD) process is not clear, and, in general terms, the translation of these models into the final software products is still manually performed. Therefore, in this chapter, we show an approach to automatically link GORE models and MDD processes, which has been elaborated by considering the experience obtained from linking the i * framework with an industrially applied MDD approach. The linking approach proposed is formulated by means of a generic process that is based on current modeling standards and technologies in order to facilitate its application for different MDD and GORE approaches. Special attention is paid to how this process generates appropriate model transformation mechanisms to automatically obtain MDD conceptual models from GORE models, and how it can be used to specify validation mechanisms to assure the correct model transformations.

"I won, but I’m not getting my hopes up": Depression Moderates the Relationship Outcomes and Reward Anticipation

PubMed Central

Olino, Thomas M.; McMakin, Dana L.; Dahl, Ronald E.; Ryan, Neal D.; Silk, Jennifer S.; Birmaher, Boris; Axelson, David A.; Forbes, Erika E.

2011-01-01

Major Depressive Disorder (MDD) in adolescents is characterized by alterations in positive emotions and reward processing. Recent investigations using functional magnetic resonance imaging (fMRI) find depression-related differences in reward anticipation. However, it is unknown whether feedback influences subsequent reward anticipation, which may highlight the context of reward processing. Ten youth with MDD and sixteen youth with no history of MDD completed an fMRI assessment using a reward task. Reward anticipation was indexed by blood oxygen level dependent signal change in the striatum following winning; losing; non-winning; and non-losing outcomes. A significant interaction between diagnostic status and outcome condition predicted reward anticipation in the caudate. Decomposition of the interaction indicated that following winning outcomes, depressed youth demonstrated reduced reward anticipation relative to healthy youth. However, no significant differences between depressed and healthy youth were found after other outcomes. Reward anticipation is altered following winning outcomes. This finding has implications for understanding the developmental pathophysiology of MDD and suggests specific contexts where altered motivational system functioning may play a role in maintaining depression. PMID:22079656

Disorder-specific versus transdiagnostic and clinician-guided versus self-guided treatment for major depressive disorder and comorbid anxiety disorders: A randomized controlled trial.

PubMed

Titov, N; Dear, B F; Staples, L G; Terides, M D; Karin, E; Sheehan, J; Johnston, L; Gandy, M; Fogliati, V J; Wootton, B M; McEvoy, P M

2015-10-01

Disorder-specific cognitive behavior therapy (DS-CBT) is effective at treating major depressive disorder (MDD) while transdiagnostic CBT (TD-CBT) addresses both principal and comorbid disorders by targeting underlying and common symptoms. The relative benefits of these two models of therapy have not been determined. Participants with MDD (n=290) were randomly allocated to receive an internet delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided (CG-CBT) or self-guided (SG-CBT) formats. Large reductions in symptoms of MDD (Cohen's d≥1.44; avg. reduction≥45%) and moderate-to-large reductions in symptoms of comorbid generalised anxiety disorder (Cohen's d≥1.08; avg. reduction≥43%), social anxiety disorder (Cohen's d≥0.65; avg. reduction≥29%) and panic disorder (Cohen's d≥0.45; avg. reduction≥31%) were found. No marked or consistent differences were observed across the four conditions, highlighting the efficacy of different forms of CBT at treating MDD and comorbid disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

POSTPARTUM GAD IS A RISK FACTOR FOR POSTPARTUM MDD: THE COURSE AND LONGITUDINAL RELATIONSHIPS OF POSTPARTUM GAD AND MDD

PubMed Central

Prenoveau, Jason; Craske, Michelle; Counsell, Nicholas; West, Valerie; Davies, Beverley; Cooper, Peter; Rapa, Elizabeth; Stein, Alan

2013-01-01

Background The objective was to examine the course and longitudinal associations of generalized anxiety disorder (GAD) and major depressive disorder (MDD) in mothers over the postpartum 2 years. Method Using a prospective naturalistic design, 296 mothers recruited from a large community pool were assessed for GAD and MDD at 3, 6, 10, 14, and 24 months postpartum. Structured clinical interviews were used for diagnoses, and symptoms were assessed using self-report questionnaires. Logistic regression analyses were used to examine diagnostic stability and longitudinal relations, and latent variable modeling was employed to examine change in symptoms. Results MDD without co-occurring GAD, GAD without co-occurring MDD, and co-occurring GAD and MDD, displayed significant stability during the postpartum period. Whereas MDD did not predict subsequent GAD, GAD predicted subsequent MDD (in the form of GAD + MDD). Those with GAD + MDD at 3 months postpartum were significantly less likely to be diagnosis free during the follow-up period than those in other diagnostic categories. At the symptom level, symptoms of GAD were more trait-like than those of depression. Conclusions Postpartum GAD and MDD are relatively stable conditions, and GAD is a risk factor for MDD but not vice versa. Given the tendency of MDD and GAD to be persistent, especially when comorbid, and the increased risk for MDD in mothers with GAD, as well as the potential negative effects of cumulative exposure to maternal depression and anxiety on child development, the present findings clearly highlight the need for screening and treatment of GAD in addition to MDD during the postpartum period. PMID:23288653

Functional Connectivity of the Amygdala in Early Childhood Onset Depression

PubMed Central

Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

2011-01-01

Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

Differences in smoking expectancies in smokers with and without a history of major depression.

PubMed

Weinberger, Andrea H; George, Tony P; McKee, Sherry A

2011-04-01

Adults with depression evidence higher rates of smoking and lower quit rates than adults without depression. Little is known about the relationship between depression and smoking beliefs which are associated with both smoking and smoking cessation behavior. The primary aim of this study was to examine whether adult smokers with and without a history of major depressive disorder (MDD) differ in their endorsement of smoking expectancies. The secondary aim of the study was to examine whether there were interactions of depression and gender on the endorsement of expectancies. Adult cigarette smokers participating in a clinical trial of Selegiline hydrochloride for smoking cessation were classified as having a history of depression (MDD+, n=26) or no history of depression (MDD-, n=75). History of depression and smoking expectancies were assessed prior to randomization into the clinical trial. There was a main effect of depression on 7 out of 10 of the assessed beliefs. MDD+ smokers, compared to MDD- smokers, more strongly endorsed beliefs that smoking reduces negative affect, boredom, and cravings; smoking increases stimulation and social facilitation; smoking helps to manage cravings and weight; and that the taste is enjoyable. The main effect of gender and the interactive effect of depression and gender were not significant. Incorporating expectancies into cognitive-behavioral treatments for smoking cessation may be useful for smokers with a history of depression. Copyright © 2010 Elsevier Ltd. All rights reserved.

Racial and Ethnic Disparity in Major Depressive Disorder.

PubMed

Shao, Zhili; Richie, William D; Bailey, Rahn Kennedy

2016-12-01

Major depressive disorder (MDD) is one of the most common and disabling psychiatric disorders in the USA. Early diagnosis and appropriate treatment are extremely important to prevent disability and improve quality of life. Recent studies have demonstrated racial and ethnic disparities in the diagnosis and treatment of MDD. African Americans (AA), Hispanics, and Asian Americans were significantly less likely to receive a depression diagnosis from a health-care provider than were non-Hispanic whites. The underdiagnosis of MDD in minority groups may be due to differences in socioeconomic status (SES), care affordability, cultural beliefs about depression, help-seeking patterns, access to culturally and linguistically appropriate care, patient-physician relationship, clinical presentation of depression, etc. Meanwhile, the likelihood of both having access to and receiving adequate care for depression was significantly low for AA, Hispanics, and Asian Americans, in contrast to whites. Similar disparities also exist in treatment outcomes. Besides the reasons for MDD underdiagnosis, additional contributing factors include access barriers to preferred mode of treatment, cultural concerns about antidepressants and different metabolism of antidepressants, etc. There are many ways to address these disparities and improve MDD care in minority populations, including universal depression screening, public financial incentives to ensure access to care in low-income and minority neighborhoods, quality improvement programs, cultural competency of mental health professionals, collaborative care management, community engagement and planning, and enhanced participation of minorities in clinical research.

Increased neural and pupillary reactivity to emotional faces in adolescents with current and remitted major depressive disorder.

PubMed

Burkhouse, Katie L; Owens, Max; Feurer, Cope; Sosoo, Effua; Kudinova, Anastacia; Gibb, Brandon E

2017-05-01

This study combined multiple levels of analysis to examine whether disrupted neural and pupillary reactivity to emotional faces serves as a state- or trait-like marker of adolescent major depressive disorder (MDD). The study examined differences in pupil dilation and the event-related potential (ERP) late positive potential (LPP) component to emotional faces before and after a negative mood induction between 71 adolescents (age 11-18 years) with (i) a current diagnosis of MDD, (ii) a past episode of MDD currently in full remission and (iii) no lifetime history of any Axis I disorder. Relative to healthy control (HC) youth, adolescents with current or remitted MDD exhibited an enhanced LPP and pupillary response to all emotional facial expressions (fearful, happy and sad). This difference in reactivity between remitted depressed and HC adolescents persisted following the negative mood induction. Results also revealed that LPP and pupillary responses to emotional faces were significantly related, but only among the currently depressed adolescents. This study suggests that increased physiological and neural activation in response to social-emotional stimuli may not only characterize currently depressed adolescents, but also remains following MDD remission, potentially serving as a mechanism of risk for future depression relapse. © The Author (2017). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in female patients with major depressive disorder.

PubMed

Kim, Bora; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Soskin, David; Yu, Bum-Hee; Lee, Dongsoo; Lee, Dong-Yun; Park, Hyung-Doo; Jeon, Hong Jin

2013-12-30

Current suicidal ideation and attempts are more commonly found in female patients with major depressive disorder (MDD) than in males. However, little is known about the relationship between activity of female reproductive hormones and suicide. The study population consisted of 490 female MDD patients of age ≥18. They were assessed by the Mini-International Neuropsychiatric Interview. At the same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH), cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant difference among female MDD patients with suicide attempt, those with ideation, and those without within the previous month. Post-hoc analysis also showed that FSH was significantly lower in MDD patients with suicide attempt and ideation than those without, whereas other hormones showed no differences between those with and without attempt. FSH was negatively associated with current suicidality scores after adjustment for age and education years in all age groups. FSH was significantly lower in those with current suicide ideation or attempt than those without in age 45 years or under, but not in other age groups. In conclusion, blood FSH is significantly lower in female MDD patients with current suicide attempt or ideation than those without, especially in age 45 years or under. © 2013 Elsevier Ireland Ltd. All rights reserved.

Prescribing patterns of psychotropic medications and clinical features in patients with major depressive disorder with and without comorbid dysthymia in China.

PubMed

Feng, Yuan; Sha, Sha; Hu, Chen; Wang, Gang; Ungvari, Gabor S; Chiu, Helen F K; Ng, Chee H; Si, Tian-Mei; Chen, Da-Fang; Fang, Yi-Ru; Lu, Zheng; Yang, Hai-Chen; Hu, Jian; Chen, Zhi-Yu; Huang, Yi; Sun, Jing; Wang, Xiao-Ping; Li, Hui-Chun; Zhang, Jin-Bei; Xiang, Yu-Tao

2017-03-01

Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs. Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers. One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups. There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions. © 2016 John Wiley & Sons Australia, Ltd.

Immediate or deferred adjustment of drug regimens in multidose drug dispensing systems.

PubMed

Mertens, Bram J; Kwint, Henk-Frans; van Marum, Rob J; Bouvy, Marcel L

2018-05-18

Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system. The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments. This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist. Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p < 0.001). This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated. Copyright © 2018. Published by Elsevier Inc.

Single versus recurrent depression history: differentiating risk factors among current US smokers.

PubMed

Strong, David R; Cameron, Amy; Feuer, Shelley; Cohn, Amy; Abrantes, Ana M; Brown, Richard A

2010-06-01

The strong relationship between persistent tobacco use and Major Depressive Disorder (MDD) has motivated clinical trials of specialized treatments targeting smokers with a history of MDD. Meta-analyses suggest positive responses to specialized treatments have been observed consistently among smokers with history of recurrent rather than a single episode of MDD. Approximately 15% of current US smokers have a history of recurrent MDD. Little is known about the risk factors that contribute to persistent smoking and differentiate these at-risk smokers, US. The National Comorbidity Survey - Replication (NCS-R) included a survey of 1560 smokers participants aged 18 and older in the United States. Lifetime history of MDD was categorized according to chronicity: no history (No MDD), single episode (MDD-S) and recurrent depression (MDD-R). The relationship between the chronicity of MDD, smoking characteristics, cessation history, nicotine dependence, comorbidity with psychiatric disorders, and current functional impairments were examined. MDD-R smokers reported fewer lifetime cessation efforts, smoked more cigarettes, had higher levels of nicotine dependence, had higher rates of comorbid psychiatric disorders and greater functional impairment than smokers with No MDD. MDD-S smokers were not consistently distinguished from No MDD smokers on cessation attempts, level of daily smoking, nicotine dependence or functional impairment indices. The study highlights the importance of chronicity when characterizing depression-related risk of persistent smoking behavior. Although, clinical trials suggest MDD-R smokers specifically benefit from specialized behavioral treatments, these services are not widely available and more efforts are needed to engage MDD-R smokers in efficacious treatments. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Altered expression of γ-secretase components in animal model of major depressive disorder induced by reserpine administration.

PubMed

Lee, Hye-Ryun; Hwang, In-Sik; Kim, Ji-Eun; Choi, Sun-Il; Lee, Young-Ju; Goo, Jun-Seo; Lee, Eon-Pil; Choi, Hae-Wook; Kim, Hong-Sung; Lee, Jae-Ho; Jung, Young-Jin; Hwang, Dae-Youn

2012-06-01

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of γ-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of γ-secretase components decreased (P<0.03). Among the three components of the γ-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

Altered tryptophan catabolite concentrations in major depressive disorder and associated changes in hippocampal subfield volumes.

PubMed

Doolin, Kelly; Allers, Kelly A; Pleiner, Sina; Liesener, Andre; Farrell, Chloe; Tozzi, Leonardo; O'Hanlon, Erik; Roddy, Darren; Frodl, Thomas; Harkin, Andrew; O'Keane, Veronica

2018-05-19

Tryptophan depletion is a well-replicated biological finding in Major Depressive Disorder (MDD). The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme, indolamine 2,3 dioxygenase (IDO), have been implicated in the pathogenesis of depression. IDO expression is driven by inflammatory cytokines, providing a putative link between inflammation and neuropathology. This study examined circulating concentrations of C-reactive protein (CRP), plasma tryptophan, kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) and whole blood mRNA expression of IDO in patients with major depressive disorder (MDD) compared with healthy controls (HC). A diagnosis of major depression was made according to DSM-IV. Depression severity was assessed using the Hamilton depression (HAM-D) rating scale. 74 MDD patients, 39 with a first presentation of MDD (fpMDD) and 35 with chronic or recurrent episodes (rMDD), and 37 HC were recruited to the study. Whole blood and plasma samples were collected. Expression of markers in whole blood were measured by PCR, circulating CRP by ELISA and KP metabolites by LC-MS/MS. Hippocampal cornu ammonis (CA) and subiculum volumes were determined by MRI and calculated using FreeSurfer. Tryptophan concentrations were significantly reduced in MDD compared to HC. There was a positive correlation between QUIN and both CRP concentrations and whole blood IDO1 in MDD. KYNA concentrations were reduced in MDD patients presenting with a first episode (fpMDD) compared to those presenting with recurrent depression (rMDD) and HC. By contrast QUIN concentrations were elevated in rMDD compared to fpMDD and HC. KYNA/QUIN was reduced in MDD and rMDD but not fpMDD compared to HC. Hippocampal subfield volumes were smaller in MDD patients than HC for CA1 (left only), CA2/3 (left and right) and CA4 (right only). CRP and CA1 volumes were negatively correlated bilaterally in MDD patients. KYNA and subiculum volume were positively correlated bilaterally. This study found evidence of KP metabolism imbalance in MDD patients in addition to tryptophan reduction and mild immune activation. Relationships between CRP and KYNA with some hippocampal subfield volumes in MDD patients suggest that this inflammatory signature may be associated with reduced hippocampal subfield volumes in depression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls.

PubMed

Silarova, Barbora; Giltay, Erik J; Van Reedt Dortland, Arianne; Van Rossum, Elisabeth F C; Hoencamp, Erik; Penninx, Brenda W J H; Spijker, Annet T

2015-04-01

We aimed to investigate the prevalence of the metabolic syndrome (MetS) and its individual components in subjects with bipolar disorder (BD) compared to those with major depressive disorder (MDD) and non-psychiatric controls. We examined 2431 participants (mean age 44.3±13.0, 66.1% female), of whom 241 had BD; 1648 had MDD; and 542 were non-psychiatric controls. The MetS was ascertained according to NCEP ATP III criteria. Multivariable analyses were adjusted for age, sex, ethnicity, level of education, smoking status and severity of depressive symptoms, and in the case of BD subjects, also for psychotropic medication use. Subjects with BD had a significantly higher prevalence of MetS when compared to subjects with MDD and non-psychiatric controls (28.4% vs. 20.2% and 16.5%, respectively, p<0.001), also when adjusted for sociodemographic and lifestyle factors (OR 1.52, 95% CI: 1.09-2.12, p=0.02 compared to MDD; OR 1.79, 95% CI: 1.20-2.67, p=0.005 compared to non-psychiatric controls). The differences between BD subjects with controls could partly be ascribed to a higher mean waist circumference (91.0 cm vs. 88.8, respectively, p=0.03). In stratified analysis, the differences in the prevalence of MetS between patients with BD and MDD were found in symptomatic but not in asymptomatic cases. This study confirms a higher prevalence of MetS in patients with BD compared to both MDD patients and controls. Specifically at risk are patients with a higher depression score and abdominal obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

[Dysfunctional resting-state connectivity of default mode network in adolescent patients with first-episode drug-naive major depressive disorder].

PubMed

Li, S Y; Zhu, Y; Wang, Y L; Lü, P P; Zuo, W B; Li, F Y

2017-12-05

Objective: To study resting-state functional connectivity (FC) of default mode network (DMN) in adolescent patients with first-episode drug-naive major depressive disorder (MDD). Methods: We enrolled thirty first-episode and drug-naive adolescent MDD patients and twenty-nine adolescent healthy control (HC) participants in the First Affiliated Hospital of Zhengzhou University. There were no differences in age, sex, and education between the MDD and HC group. Resting-state functional magnetic resonance images (fMRI) was performed. We selected posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) of DMN as regions of interests (ROI). The differences of these regions from the whole brain functional connectivity were analyzed. The relations between abnormalities in FCs of DMN and clinical variables were further investigated. Results: Compared to the HCs, the MDD patients had congruently reduced FCs between the PCC and cerebellum, temporal cortices, occipital cortices, fusiform, dorsolateral prefrontal cortex. MPFC not only had reduced FCs with fusiform, temporal cortices, anterior cingulate cortex, but also had enhanced FCs with occipital cortices, parietal cortices, and precentral gyrus. In addition, the increased FC between the right MPFC and right precentral gyrus was positive correlated with Hamilton Rating Scale for Depression (HAMD) scores ( r =0.38, P =0.04). The reduced FC between the left middle temporal gyrus and left PCC as well as the enhanced FC between the right middle cingulum and right MPFC were positive correlated with the duration of depression since onset ( r =0.39, P =0.03; r =0.38, P =0.04). Conclusions: These findings show dysfunctional DMN connectivity of adolescent MDD patients. Neurodevelopmental abnormalities in DMN may present in adolescent MDD.

Dependency and self-criticism: relationship with major depressive disorder, severity of depression, and clinical presentation.

PubMed

Luyten, Patrick; Sabbe, Bernard; Blatt, Sidney J; Meganck, Sieglinde; Jansen, Bart; De Grave, Carmen; Maes, Frank; Corveleyn, Jozef

2007-01-01

Dependency and self-criticism have been proposed as personality dimensions that confer vulnerability to depression. In this study we set out to investigate the diagnostic specificity of these personality dimensions and their relationship with gender differences, severity of depression, and specific depressive symptoms. Levels of dependency and self-criticism as measured by the Depressive Experiences Questionnaire (DEQ) were compared among patients with major depressive disorder (MDD; n=93), mixed psychiatric patients (n=43), university students (n=501), and community adults (n=253). Associations with severity of depression and specific depressive symptoms were also explored. Results showed that dependency was more specifically associated with MDD, whereas self-criticism did not differ between depressed and mixed psychiatric patients. In line with the gender incongruence hypothesis, women with MDD and other psychiatric disorders had higher levels of self-criticism compared to men, whereas men with MDD had higher levels of dependency compared to women. Severity of depression was more clearly linked to self-criticism than to dependency, particularly in patients with MDD. Finally, both dependency and self-criticism were related to theoretically predicted clusters of depressive symptoms, especially after we controlled for shared variance between self-critical and dependent symptoms, respectively. Limitations of this study include the cross-sectional design, which limited the ability to draw causal conclusions. In addition, this study relied exclusively on self-reported personality and mood. Overall, findings of this study suggest that both dependency and self-criticism are associated with MDD, severity of depression, and specific depressive symptoms, and that gender-incongruent personality traits may be associated with increased risk for depression and other disorders.

Differences in major depressive disorder and generalised anxiety disorder symptomatology between prostate cancer patients receiving hormone therapy and those who are not.

PubMed

Sharpley, Christopher F; Bitsika, Vicki; Wootten, Addie C; Christie, David R H

2014-12-01

The aim of this study is to explore the associations between hormone treatment variables and depression, and the nature of depression in prostate cancer (PCa) patients by comparing the severity and symptom profile of anxiety and depression in men who were currently receiving hormone therapy (HT) versus those who were not. Self-reports of anxiety and depression on standardized scales of GAD and major depressive disorder (MDD) were collected from 156 PCa patients across two recruitment sites in Australia. Patients who were currently receiving HT were compared with patients not receiving HT for their severity and symptom profiles on GAD and MDD. Participants receiving HT had significantly higher GAD and MDD total scores than patients who were not receiving HT. In addition, the symptom profiles of these two HT subgroups were differentiated by significantly higher scores on the key criteria for GAD and MDD plus fatigue and sleeping difficulties but not the remaining symptoms of GAD and MDD. However, there were no significant differences between HT subgroups for the degree of functional impairment experienced by these symptoms. Although these data confirm the association between HT and anxiety/depression, the range of GAD and MDD symptoms influenced is relatively restricted. Moreover, functional ability does not appear to be impaired by HT. These findings clarify the ways in which HT affects PCa patients and suggests that a simple total scale score for anxiety and depression may not be as helpful in designing treatment as consideration of the symptomatic profiles of PCa patients receiving HT. Copyright © 2014 John Wiley & Sons, Ltd.

A personality-based latent class typology of outpatients with major depressive disorder: association with symptomatology, prescription pattern and social function.

PubMed

Hori, Hiroaki; Teraishi, Toshiya; Nagashima, Anna; Koga, Norie; Ota, Miho; Hattori, Kotaro; Kim, Yoshiharu; Higuchi, Teruhiko; Kunugi, Hiroshi

2017-08-01

While major depressive disorder (MDD) is considered to be a heterogeneous disorder, the nature of the heterogeneity remains unclear. Studies have attempted to classify patients with MDD using latent variable techniques, yet the empirical approaches to symptom-based subtyping of MDD have not provided conclusive evidence. Here we aimed to identify homogeneous classes of MDD based on personality traits, using a latent profile analysis. We studied 238 outpatients with DSM-IV MDD recruited from our specialized depression outpatient clinic and assessed their dimensional personality traits with the Temperament and Character Inventory. Latent profile analysis was conducted with 7 dimensions of the Temperament and Character Inventory as indicators. Relationships of the identified classes with symptomatology, prescription pattern, and social function were then examined. The latent profile analysis indicated that a 3-class solution best fit the data. Of the sample, 46.2% was classified into a "neurotic" group characterized by high harm avoidance and low self-directedness; 30.3% into an "adaptive" group characterized by high self-directedness and cooperativeness; and 23.5% into a "socially-detached" group characterized by low reward dependence and cooperativeness and high self-transcendence. The 2 maladaptive groups, namely neurotic and socially-detached groups, demonstrated unique patterns of symptom expression, different classes of psychotropic medication use, and lower social functioning. Generalizability of the findings was limited since our patients were recruited from the specialized depression outpatient clinic. Our personality-based latent profile analysis identified clinically meaningful 3 MDD groups that were markedly different in their personality profiles associated with distinct symptomatology and functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

PubMed

Brakowski, Janis; Spinelli, Simona; Dörig, Nadja; Bosch, Oliver Gero; Manoliu, Andrei; Holtforth, Martin Grosse; Seifritz, Erich

2017-09-01

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alterations in regional homogeneity of resting-state brain activity in patients with major depressive disorder screening positive on the 32-item hypomania checklist (HCL-32).

PubMed

Yang, Haichen; Li, Linling; Peng, Hongjun; Liu, Tiebang; Young, Allan H; Angst, Jules; Ye, Rong; Rong, Han; Ji, Erni; Qiu, Yunhai; Li, Lingjiang

2016-10-01

Bipolar disorder (BD) is difficult to diagnose in the early stages of the illness, with the most frequent misdiagnosis being major depressive disorder (MDD). We aimed to use a regional homogeneity (ReHo) approach with resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the features of spontaneous brain activity in MDD patients screening positive on the 32-item Hypomania Checklist (HCL-32). Nineteen MDD patients screening positive (HCL-32(+); 9 males; 24.9±5.7 years) and 18 patients screening negative (HCL-32(-); 9 males; 27.1±6.7 years), together with 24 healthy controls (HC; 11 males; 26.4±3.9 years) were studied. ReHo maps were compared and an receiver operating characteristic (ROC) analysis was conducted to confirm the utility of the identified ReHo differences in classifying the patients. The MDD versus HC showed different ReHo in many brain areas, especially in the frontal and parietal cortex. The HCL-32(+) versus HCL-32(-) showed significant increase of ReHo in the right medial superior frontal cortex, left inferior parietal cortex and middle/inferior temporal cortex, and decrease of ReHo in the left postcentral cortex and cerebellum. ROC analysis showed good sensitivity and specificity for distinguishing these two subgroups of MDD. Recruited patients were all on antidepressants and standard mania rating scales were not performed to assess their hypomanic symptoms. The rs-fMRI measurement of ReHo in distributed brain regions may be putative biomarkers which could differentiate subthreshold BD from MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

[Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

PubMed

Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

2015-12-01

To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

Translational Shifts in Preclinical Models of Depression: Implications for Biomarkers for Improved Treatments.

PubMed

Slaney, Chloe; Hinchcliffe, Justyna K; Robinson, Emma S J

2018-04-26

Understanding the neurobiology of major depressive disorder (MDD) remains one of the major challenges in neuroscience. The disease is heterogeneous in nature, and patients present with a varied symptom profile. Studies seeking to identify biomarkers for MDD diagnosis and treatment have not yet found any one candidate which achieves sufficient sensitivity and specificity. In this article, we consider whether neuropsychological impairments, specifically affective biases, could provide a behavioural biomarker. Affective biases are observed when emotional states influence cognitive function. These biases have been shown to influence a number of different cognitive domains with some specific deficits observed in MDD. It has also been possible to use these neuropsychological tests to inform the development of translational tasks for non-human species. The results from studies in rodents suggest that quantification of affective biases is feasible and may provide a reliable method to predict antidepressant efficacy as well as pro-depressant risk. Animal studies suggest that affective state-induced biases in learning and memory operate over a different time course to biases influencing decision-making. The implications for these differences in terms of task validity and future ideas relating to affective biases and MDD are discussed. We also describe our most recent studies which have shown that depression-like phenotypes share a common deficit in reward-related learning and memory which we refer to as a reward-induced positive bias. This deficit is dissociable from more typical measures of hedonic behaviour and motivation for reward and may represent an important and distinct form of reward deficit linked to MDD.

Neural Processing of Emotional Musical and Nonmusical Stimuli in Depression

PubMed Central

Atchley, Ruth Ann; Chrysikou, Evangelia; Martin, Laura E.; Clair, Alicia A.; Ingram, Rick E.; Simmons, W. Kyle; Savage, Cary R.

2016-01-01

Background Anterior cingulate cortex (ACC) and striatum are part of the emotional neural circuitry implicated in major depressive disorder (MDD). Music is often used for emotion regulation, and pleasurable music listening activates the dopaminergic system in the brain, including the ACC. The present study uses functional MRI (fMRI) and an emotional nonmusical and musical stimuli paradigm to examine how neural processing of emotionally provocative auditory stimuli is altered within the ACC and striatum in depression. Method Nineteen MDD and 20 never-depressed (ND) control participants listened to standardized positive and negative emotional musical and nonmusical stimuli during fMRI scanning and gave subjective ratings of valence and arousal following scanning. Results ND participants exhibited greater activation to positive versus negative stimuli in ventral ACC. When compared with ND participants, MDD participants showed a different pattern of activation in ACC. In the rostral part of the ACC, ND participants showed greater activation for positive information, while MDD participants showed greater activation to negative information. In dorsal ACC, the pattern of activation distinguished between the types of stimuli, with ND participants showing greater activation to music compared to nonmusical stimuli, while MDD participants showed greater activation to nonmusical stimuli, with the greatest response to negative nonmusical stimuli. No group differences were found in striatum. Conclusions These results suggest that people with depression may process emotional auditory stimuli differently based on both the type of stimulation and the emotional content of that stimulation. This raises the possibility that music may be useful in retraining ACC function, potentially leading to more effective and targeted treatments. PMID:27284693

A Korean validation study of the Clinically Useful Anxiety Outcome Scale: Comorbidity and differentiation of anxiety and depressive disorders

PubMed Central

Jeon, Sang Won; Ko, Young-Hoon; Yoon, Seoyoung; Pae, Chi-Un; Choi, Joonho; Kim, Jae-Min; Yoon, Ho-Kyoung; Lee, Hoseon; Patkar, Ashwin A.; Zimmerman, Mark

2017-01-01

Background This study aimed to evaluate the psychometric properties of the Korean version of the Clinically Useful Anxiety Outcome Scale (CUXOS) and to examine the current diagnostic comorbidity and differential severity of anxiety symptoms between major depressive disorder (MDD) and anxiety disorders. Methodology In total, 838 psychiatric outpatients were analyzed at their intake appointment. Diagnostic characteristics were examined using the structured clinical interview from the DSM-IV because the DSM5 was not available at the start of the study. The CUXOS score was measured and compared with that of 3 clinician rating scales and 4 self-report scales. Principal findings The CUXOS showed excellent results for internal consistency (Cronbach’s α = 0.90), test–retest reliability (r = 0.74), and discriminant and convergent validity. The CUXOS significantly discriminated between different levels of anxiety severity, and the measure was sensitive to change after treatment. Approximately 45% of patients with MDD were additionally diagnosed with anxiety disorders while 55% of patients with anxiety disorders additionally reported an MDD. There was a significant difference in CUXOS scores between diagnostic categories (MDD only, anxiety only, both disorders, and no MDD or anxiety disorder). The CUXOS scores differed significantly between all categories of depression (major, minor, and non-depression) except for the comparison between minor depression and non-depression groups. Conclusions The Korean version of the CUXOS is a reliable and valid measure of the severity of anxiety symptoms. The use of the CUXOS could broaden the understanding of coexisting and differentiating characteristics of anxiety and depression. PMID:28604808

Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. I. Classification, burden and principles of management.

PubMed

Patten, Scott B; Kennedy, Sidney H; Lam, Raymond W; O'Donovan, Claire; Filteau, Marie J; Parikh, Sagar V; Ravindran, Arun V

2009-10-01

Major depressive disorder (MDD) is one of the most burdensome illnesses in Canada. The purpose of this introductory section of the 2009 revised CANMAT guidelines is to provide definitions of the depressive disorders (with an emphasis on MDD), summarize Canadian data concerning their epidemiology and describe overarching principles of managing these conditions. This section on "Classification, Burden and Principles of Management" is one of 5 guideline articles in the 2009 CANMAT guidelines. The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to the Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support. Epidemiologic data indicate that MDD afflicts 11% of Canadians at some time in their lives, and approximately 4% during any given year. MDD has a detrimental impact on overall health, role functioning and quality of life. Detection of MDD, accurate diagnosis and provision of evidence-based treatment are challenging tasks for both clinicians and for the health systems in which they work. Epidemiologic and clinical data cannot be seamlessly linked due to heterogeneity of syndromes within the population. In the eight years since the last CANMAT Guidelines for Treatment of Depressive Disorders were published, progress has been made in understanding the epidemiology and treatment of these disorders. Evidence supporting specific therapeutic interventions is summarized and evaluated in subsequent sections.

Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression.

PubMed

Wang, Wei; Guo, Hua; Zhang, Shu-Xiao; Li, Juan; Cheng, Ke; Bai, Shun-Jie; Yang, De-Yu; Wang, Hai-Yang; Liang, Zi-Hong; Liao, Li; Sun, Lin; Xie, Peng

2016-10-07

Major depressive disorder (MDD) is a severe psychiatric disease that has critically affected life quality for millions of people. Chronic stress is gradually recognized as a primary pathogenesis risk factor of MDD. Despite the remarkable progress in mechanism research, the pathogenesis mechanism of MDD is still not well understood. Therefore, we conducted a liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of 25 major metabolites of tryptophanic, GABAergic, and catecholaminergic pathways in the prefontal cortex (PFC) of mice in chronic social defeat stress (CSDS). The depressed mice exhibit significant reduction of glutamate in the GABAergic pathway and an increase of L-DOPA and vanillylmandelic acid in catecholaminergic pathways. The data of real-time-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis revealed an altered level of glutamatergic circuitry. The metabolomic and molecular data reveal that the glutamatergic disorder in mice shed lights to reveal a mechanism on depression-like and stress resilient phenotype.

Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder

PubMed Central

Janes, Amy C; Pedrelli, Paola; Whitton, Alexis E; Pechtel, Pia; Douglas, Samuel; Martinson, Max A; Huz, Ilana; Fava, Maurizio; Pizzagalli, Diego A; Evins, A Eden

2015-01-01

Major depressive disorder (MDD) and nicotine dependence are highly comorbid, with studies showing that ~50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evidence indicates that individuals with rMDD show blunted responses to reward as measured by a probabilistic reward task (PRT), which assesses the ability to modify behavior as a function of reward history. Given nicotine's ability to enhance reward responsiveness, individuals with rMDD might smoke to address this persistent reward deficit. However, it is unclear whether smokers with rMDD show enhanced reward responsiveness relative to rMDD individuals who do not smoke. To test this hypothesis, we evaluated reward responsiveness on the PRT in four groups (N=198): individuals with and without rMDD who were or were not nicotine dependent. As hypothesized, rMDD nonsmokers had lower reward responsiveness relative to both control nonsmokers and rMDD smokers; conversely, smokers with rMDD showed behavioral patterns comparable to those without a history of depression. Given nicotine's ability to enhance reward sensitivity, it is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD. Therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD. PMID:25662839

Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression

PubMed Central

Mocking, Roel J T; van Wingen, Guido; Martens, Suzanne; Ruhé, Henricus G; Schene, Aart H

2017-01-01

Abstract Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = −0.21, P = 0.046) and rumination (r = −0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission. PMID:28981917

Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression.

PubMed

Figueroa, Caroline A; Mocking, Roel J T; van Wingen, Guido; Martens, Suzanne; Ruhé, Henricus G; Schene, Aart H

2017-11-01

Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = -0.21, P = 0.046) and rumination (r = -0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission. © The Author (2017). Published by Oxford University Press.

Multifamily psychoeducation groups (MFPG) for families of children with bipolar disorder.

PubMed

Fristad, Mary A; Goldberg-Arnold, Jill S; Gavazzi, Stephen M

2002-08-01

Multi-family psychoeducation groups (MFPG) have been developed and tested for adults, but not for children with bipolar disorder (BPD). We present data from a pilot study of our manual-driven MFPG treatment for families of children with mood disorders and address two questions: Do families of children with BPD and families of children with major depressive disorder/dysthymic disorder (MDD/DD): 1) differ at treatment entry?; 2) benefit equally from intervention? A total of 35 children (n=16, BPD; n=19, MDD/DD) aged 8-11 years and their parents were randomized into immediate MFPG plus treatment as usual (TAU) or wait-list + TAU and assessed periodically. At baseline, there was a trend toward parents in BPD families being more knowledgeable about mood symptoms than parents in MDD/DD families (p < 0.04). Additionally at baseline, children with BPD evidenced greater mood severity historically and a trend toward more hospitalizations, day treatment, outpatient treatment, medication trials, and placement in special education classrooms than children with MDD/DD. Immediately following and 4 months post-treatment, both BPD and MDD/DD families described having gained knowledge, skills, support, and positive attitudes during treatment. MDD/DD families increased their knowledge of symptoms to the same level as BPD families. While BPD families enter treatment with more impaired children and more extensive treatment histories, both BPD and MDD/DD families benefit from intervention. The clinical issues concerning combining families of children with bipolar and depressive spectrum illnesses in groups are discussed. Clinical impressions suggest that such combinations are clinically feasible and potentially beneficial.

Disrupted reward and cognitive control networks contribute to anhedonia in depression.

PubMed

Gong, Liang; He, Cancan; Zhang, Haisan; Zhang, Hongxing; Zhang, Zhijun; Xie, Chunming

2018-08-01

Neuroimaging studies have identified that anhedonia, a core feature of major depressive disorder (MDD), is associated with dysfunction in reward and cognitive control processing. However, it is still not clear how the reward network (β-network) and the cognitive control network (δ-network) are linked to biased anhedonia in MDD patients. Sixty-eight MDD patients and 64 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. A 2*2 ANCOVA analysis was used to explore the differences in the nucleus accumbens-based, voxelwise functional connectivity (FC) between the groups. Then, the β- and δ-networks were constructed, and the FC intensities were compared within and between theβ- and δ-networks across all subjects. Multiple linear regression analyses were also employed to investigate the relationships between the neural features of the β- and δ-networks and anhedonia in MDD patients. Compared to the CN subjects, the MDD patients showed synergistic functional decoupling in both the β- and δ-networks, as well as decreased FC intensities in the intra- and inter- β- and δ-networks. In addition, the FC in both the β- and δ-networks was significantly correlated with anhedonia severity in the MDD patients. Importantly, the integrated neural features of the β- and δ-networks could more precisely predict anhedonic symptoms. These findings initially demonstrated that the imbalance between β- and δ-network activity successfully predicted anhedonia severity and suggested that the neural features of both the β- and δ-networks could represent a fundamental mechanism that underlies anhedonia in MDD patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stress reactivity and its effects on subsequent food intake in depressed and healthy women with and without adverse childhood experiences.

PubMed

Wingenfeld, Katja; Kuehl, Linn K; Boeker, Anita; Schultebraucks, Katharina; Ritter, Kristin; Hellmann-Regen, Julian; Otte, Christian; Spitzer, Carsten

2017-06-01

Adverse childhood experiences (ACE) increase the risk to develop major depressive disorder (MDD) and obesity or metabolic syndrome in adulthood. In addition, ACE may be associated with an exaggerated endocrine response to stress, which, in turn, may lead to enhanced food intake resulting in obesity and metabolic problems. We systematically examined the stress response and consecutive food intake in 32 women with MDD and ACE as determined by a clinical interview (Early Trauma Inventory), 52 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. All participants underwent a psychosocial stress test (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST) before they were offered a buffet of snacks. Participants were not aware that the primary outcome variable was the amount of consumed kilocalories (kcal). The four groups did not differ in demographic variables. Stress resulted in higher cortisol release and higher blood pressure compared to the control condition. Patients with MDD without ACE had a significantly lower cortisol response to stress compared to controls. Across groups, we found higher kcal intake after stress compared to the control condition. Comparing high and low cortisol responders to stress, higher kcal intake after stress was only seen in those with low cortisol release. This study provides evidence that blunted rather than enhanced cortisol release to stress might lead to increased food intake, independent from MDD and ACE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dissociation in Rating Negative Facial Emotions between Behavioral Variant Frontotemporal Dementia and Major Depressive Disorder.

PubMed

Chiu, Isabelle; Piguet, Olivier; Diehl-Schmid, Janine; Riedl, Lina; Beck, Johannes; Leyhe, Thomas; Holsboer-Trachsler, Edith; Berres, Manfred; Monsch, Andreas U; Sollberger, Marc

2016-11-01

Features of behavioral variant frontotemporal dementia (bvFTD) such as executive dysfunction, apathy, and impaired empathic abilities are also observed in major depressive disorder (MDD). This may contribute to the reason why early stage bvFTD is often misdiagnosed as MDD. New assessment tools are thus needed to improve early diagnosis of bvFTD. Although emotion processing is affected in bvFTD and MDD, growing evidence indicates that the pattern of emotion processing deficits varies between the two disorders. As such, emotion processing paradigms have substantial potentials to distinguish bvFTD from MDD. The current study compared 25 patients with bvFTD, 21 patients with MDD, 21 patients with Alzheimer disease (AD) dementia, and 31 healthy participants on a novel facial emotion intensity rating task. Stimuli comprised morphed faces from the Ekman and Friesen stimulus set containing faces of each sex with two different degrees of emotion intensity for each of the six basic emotions. Analyses of covariance uncovered a significant dissociation between bvFTD and MDD patients in rating the intensity of negative emotions overall (i.e., bvFTD patients underrated negative emotions overall, whereas MDD patients overrated negative emotions overall compared with healthy participants). In contrast, AD dementia patients rated negative emotions similarly to healthy participants, suggesting no impact of cognitive deficits on rating facial emotions. By strongly differentiating bvFTD and MDDpatients through negative facial emotions, this sensitive and short rating task might help improve the early diagnosis of bvFTD. Copyright © 2016 American Association for Geriatric Psychiatry. All rights reserved.

The impact of educational status on the clinical features of major depressive disorder among Chinese women.

PubMed

Gan, Zhaoyu; Li, Yihan; Xie, Dong; Shao, Chunhong; Yang, Fuzhong; Shen, Yuan; Zhang, Ning; Zhang, Guanghua; Tian, Tian; Yin, Aihua; Chen, Ce; Liu, Jun; Tang, Chunling; Zhang, Zhuoqiu; Liu, Jia; Sang, Wenhua; Wang, Xumei; Liu, Tiebang; Wei, Qinling; Xu, Yong; Sun, Ling; Wang, Sisi; Li, Chang; Hu, Chunmei; Cui, Yanping; Liu, Ying; Li, Ying; Zhao, Xiaochuan; Zhang, Lan; Sun, Lixin; Chen, Yunchun; Zhang, Yueying; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S; Flint, Jonathan; Zhang, Jinbei

2012-02-01

Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting. Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD. Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide. Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample. The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD. Copyright © 2011 Elsevier B.V. All rights reserved.

The impact of educational status on the clinical features of major depressive disorder among Chinese women

PubMed Central

Gan, Zhaoyu; Li, Yihan; Xie, Dong; Shao, Chunhong; Yang, Fuzhong; Shen, Yuan; Zhang, Ning; Zhang, Guanghua; Tian, Tian; Yin, Aihua; Chen, Ce; Liu, Jun; Tang, Chunling; Zhang, Zhuoqiu; Liu, Jia; Sang, Wenhua; Wang, Xumei; Liu, Tiebang; Wei, Qinling; Xu, Yong; Sun, Ling; Wang, Sisi; Li, Chang; Hu, Chunmei; Cui, Yanping; Liu, Ying; Li, Ying; Zhao, Xiaochuan; Zhang, Lan; Sun, Lixin; Chen, Yunchun; Zhang, Yueying; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S.; Flint, Jonathan; Zhang, Jinbei

2012-01-01

Background Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting. Methods Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD. Results Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide. Limitations Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample. Conclusions The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD. PMID:21824664

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barta, Michael L.; Skaff, D. Andrew; McWhorter, William J.

The polyisoprenoid compound undecaprenyl phosphate is required for biosynthesis of cell wall peptidoglycans in Gram-positive bacteria, including pathogenic Enterococcus, Streptococcus, and Staphylococcus spp. In these organisms, the mevalonate pathway is used to produce the precursor isoprenoid, isopentenyl 5-diphosphate. Mevalonate diphosphate decarboxylase (MDD) catalyzes formation of isopentenyl 5-diphosphate in an ATP-dependent irreversible reaction and is therefore an attractive target for inhibitor development that could lead to new antimicrobial agents. To facilitate exploration of this possibility, we report the crystal structure of Staphylococcus epidermidis MDD (1.85 {angstrom} resolution) and, to the best of our knowledge, the first structures of liganded MDD. Thesemore » structures include MDD bound to the mevalonate 5-diphosphate analogs diphosphoglycolyl proline (2.05 {angstrom} resolution) and 6-fluoromevalonate diphosphate (FMVAPP; 2.2 {angstrom} resolution). Comparison of these structures provides a physical basis for the significant differences in K{sub i} values observed for these inhibitors. Inspection of enzyme/inhibitor structures identified the side chain of invariant Ser{sup 192} as making potential contributions to catalysis. Significantly, Ser {yields} Ala substitution of this side chain decreases k{sub cat} by {approx}10{sup 3}-fold, even though binding interactions between FMVAPP and this mutant are similar to those observed with wild type MDD, as judged by the 2.1 {angstrom} cocrystal structure of S192A with FMVAPP. Comparison of microbial MDD structures with those of mammalian counterparts reveals potential targets at the active site periphery that may be exploited to selectively target the microbial enzymes. These studies provide a structural basis for previous observations regarding the MDD mechanism and inform future work toward rational inhibitor design.« less

Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence

PubMed Central

Adam, Emma K.; Doane, Leah D.; Zinbarg, Richard E.; Mineka, Susan; Craske, Michelle G.; Griffith, James W.

2010-01-01

Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30-40 minutes after waking, an effect known as the cortisol awakening response (CAR). There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR, and the CAR has been found to be altered in the presence of stress-related diseases, including Major Depressive Disorder (MDD). To date, no prospective longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD. In a sample of 230 late adolescents, clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered one year earlier, including: waking cortisol levels, bedtime cortisol levels, the size of the CAR, average cortisol, and the slope of the diurnal cortisol rhythm across the waking day. Age and gender, health and health behaviors, baseline neuroticism, exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates, to help ensure effects are attributable to the CAR rather than related variables. A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up, even when excluding individuals with baseline MDD. No other baseline cortisol measures were significant prospective predictors of MDD. In summary, the CAR is a significant prospective risk factor for the development of MDD in young adults, providing some support for the possibility that a heightened CAR may play a role in the etiology of Major Depressive Disorder. PMID:20079576

Complicated grief among individuals with major depression: prevalence, comorbidity, and associated features.

PubMed

Sung, Sharon C; Dryman, M Taylor; Marks, Elizabeth; Shear, M Katherine; Ghesquiere, Angela; Fava, Maurizio; Simon, Naomi M

2011-11-01

Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders. The present study examined rates of bereavement and threshold CG symptoms (defined as a score ≥ 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD+CG) to those without (MDD-CG). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support. Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Among those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder. Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability. We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG. Copyright © 2011 Elsevier B.V. All rights reserved.

An fMRI study of emotional face processing in adolescent major depression.

PubMed

Hall, Leah M J; Klimes-Dougan, Bonnie; Hunt, Ruskin H; Thomas, Kathleen M; Houri, Alaa; Noack, Emily; Mueller, Bryon A; Lim, Kelvin O; Cullen, Kathryn R

2014-10-01

Major depressive disorder (MDD) often begins during adolescence when the brain is still maturing. To better understand the neurobiological underpinnings of MDD early in development, this study examined brain function in response to emotional faces in adolescents with MDD and healthy (HC) adolescents using functional magnetic resonance imaging (fMRI). Thirty-two unmedicated adolescents with MDD and 23 healthy age- and gender-matched controls completed an fMRI task viewing happy and fearful faces. Fronto-limbic regions of interest (ROI; bilateral amygdala, insula, subgenual and rostral anterior cingulate cortices) and whole-brain analyses were conducted to examine between-group differences in brain function. ROI analyses revealed that patients had greater bilateral amygdala activity than HC in response to viewing fearful versus happy faces, which remained significant when controlling for comorbid anxiety. Whole-brain analyses revealed that adolescents with MDD had lower activation compared to HC in a right hemisphere cluster comprised of the insula, superior/middle temporal gyrus, and Heschl׳s gyrus when viewing fearful faces. Brain activity in the subgenual anterior cingulate cortex was inversely correlated with depression severity. Limitations include a cross-sectional design with a modest sample size and use of a limited range of emotional stimuli. Results replicate previous studies that suggest emotion processing in adolescent MDD is associated with abnormalities within fronto-limbic brain regions. Findings implicate elevated amygdalar arousal to negative stimuli in adolescents with depression and provide new evidence for a deficit in functioning of the saliency network, which may be a future target for early intervention and MDD treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Complicated grief among individuals with major depression: Prevalence, comorbidity, and associated features

PubMed Central

Sung, Sharon C.; Dryman, M. Taylor; Marks, Elizabeth; Shear, M. Katherine; Ghesquiere, Angela; Fava, Maurizio; Simon, Naomi M.

2011-01-01

Background Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders. Methods The present study examined rates of bereavement and threshold CG symptoms (defined as a score ≥ 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD + CG) to those without (MDD – CG). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support. Results Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Amongst those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder. Limitations Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability. Conclusions We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG. PMID:21621849

History of childhood trauma as risk factors to suicide risk in major depression.

PubMed

Dias de Mattos Souza, Luciano; Lopez Molina, Mariane; Azevedo da Silva, Ricardo; Jansen, Karen

2016-12-30

The aim of this study was to compare childhood trauma scores domains between Major Depressive Disorder (MDD) patients with and without suicide risk. This is cross-sectional study including a clinical sample of adults (18-60 years) diagnosed with MDD through the Mini International Neuropsychiatric Interview Plus version (MINI Plus). The Childhood Trauma Questionnaire (CTQ) was also used to verify types of trauma scores: abuse (emotional, physical, and sexual) and neglect (emotional and physical). Adjusted analysis was performed by linear regression. The sample was composed to 473 patients, suicide risk was observed in 16.3% of them. Suicide risk was independently associated with emotional abuse and neglect and sexual abuse, but not with physical abuse and neglect. Different domains of childhood trauma are associated with suicide risk in MDD population and emotional trauma should be considered a risk factor for suicide risk in MDD patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neonatal testosterone partially organizes sex differences in stress-induced emotionality in mice.

PubMed

Seney, Marianne L; Walsh, Christopher; Stolakis, Ryan; Sibille, Etienne

2012-05-01

Major depressive disorder (MDD) is a debilitating disorder of altered mood regulation. Despite well established sex differences in MDD prevalence, the mechanism underlying the increased female vulnerability remains unknown. Although evidence suggests an influence of adult circulating hormone levels on mood (i.e. activational effects of hormones), MDD prevalence is consistently higher in women across life stages (and therefore hormonal states), suggesting that additional underlying structural or biological differences place women at higher risk. Studies in human subjects and in rodent models suggest a developmental origin for mood disorders, and interestingly, a developmental process also establishes sex differences in the brain. Hence, based on these parallel developmental trajectories, we hypothesized that a proportion of the female higher vulnerability to MDD may originate from the differential organization of mood regulatory neural networks early in life (i.e. organizational effects of hormones). To test this hypothesis in a rodent system, we took advantage of a well-established technique used in the field of sexual differentiation (neonatal injection with testosterone) to masculinize sexually dimorphic brain regions in female mice. We then investigated adult behavioral consequences relating to emotionality by comparing neonatal testosterone-treated females to normal males and females. Under baseline/trait conditions, neonatal testosterone treatment of female mice did not influence adult emotionality, but masculinized adult locomotor activity, as revealed by the activational actions of hormones. Conversely, the increased vulnerability of female mice to develop high emotionality following unpredictable chronic mild stress (UCMS) was partially masculinized by neonatal testosterone exposure, with no effect on post-UCMS locomotion. The elevated female UCMS-induced vulnerability did not differ between adult hormone treated groups. These results demonstrate that sex differences in adult emotionality in mice are partially caused by the organizational effects of sex hormones during development, hence supporting a developmental hypothesis of the human adult female prevalence of MDD. Copyright © 2012 Elsevier Inc. All rights reserved.

Neonatal testosterone partially organizes sex differences in stress-induced emotionality in mice

PubMed Central

Seney, Marianne L.; Walsh, Christopher; Stolakis, Ryan; Sibille, Etienne

2012-01-01

Major depressive disorder (MDD) is a debilitating disorder of altered mood regulation. Despite well established sex differences in MDD prevalence, the mechanism underlying the increased female vulnerability remains unknown. Although evidence suggests an influence of adult circulating hormone levels on mood (i.e. activational effects of hormones), MDD prevalence is consistently higher in women across life stages (and therefore hormonal states), suggesting that additional underlying structural or biological differences place women at higher risk. Studies in human subjects and in rodent models suggest a developmental origin for mood disorders, and interestingly, a developmental process also establishes sex differences in the brain. Hence, based on these parallel developmental trajectories, we hypothesized that a proportion of the female higher vulnerability to MDD may originate from the differential organization of mood regulatory neural networks early in life (i.e. organizational effects of hormones). To test this hypothesis in a rodent system, we took advantage of a well-established technique used in the field of sexual differentiation (neonatal injection with testosterone) to masculinize sexually dimorphic brain regions in female mice. We then investigated adult behavioral consequences relating to emotionality by comparing neonatal testosterone-treated females to normal males and females. Under baseline/trait conditions, neonatal testosterone treatment of female mice did not influence adult emotionality, but masculinized adult locomotor activity, as revealed by the activational actions of hormones. Conversely, the increased vulnerability of female mice to develop high emotionality following unpredictable chronic mild stress (UCMS) was partially masculinized by neonatal testosterone exposure, with no effect on post-UCMS locomotion. The elevated female UCMS-induced vulnerability did not differ between adult hormone treated groups. These results demonstrate that sex differences in adult emotionality in mice are partially caused by the organizational effects of sex hormones during development, hence supporting a developmental hypothesis of the human adult female prevalence of MDD. PMID:22394611

Are multidose drug dispensing systems initiated for the appropriate patients?

PubMed

Mertens, Bram J; Kwint, H F; van Marum, Rob J; Bouvy, Marcel L

2018-05-16

It is unknown if multidose drug dispensing (MDD) systems are initiated for the appropriate patients. Therefore, the objective of this study was to compare the medication management problems of patients who were about to start with a MDD system (MDD patients) and patients who continued manually dispensed medication (non-MDD users) in order to identify if the appropriate patients receive a MDD system. Patient interviews (semi-structured) were conducted by 44 community pharmacists at the patient's home. Patients over 65 years of age, home dwelling and using at least five chronic drugs, were eligible for the study. An assessment tool was developed including 22 potential medication management problems, covering four domains: functional (7), organizational (7), medication adherence (6), and medication knowledge (2). Median scores were calculated with the interquartile range. Additionally, cognitive function was assessed with the Mini-Cog and frailty using the Groningen Frailty Indicator. One hundred eighty-eight MDD users and 230 non-MDD users were interviewed. MDD users were older, more often female, and using more drugs. Forty-two percent of the MDD users were possibly cognitively impaired and 63% were assessed as frail compared to 20 and 27% respectively of the non-MDD users. MDD users had more potential organizational problems (3 vs. 1; p < 0.01), functional problems (2 vs. 1; p < 0.01), medication adherence problems (1 vs. 0; p < 0.01), and medication knowledge problems (1 vs. 0; p < 0.01) compared to non-MDD users. Seventy percent of the MDD users scored six or more potential medication management problems while this was 22% among non-MDD users. The majority of MDD systems were initiated for patients who experienced multiple potential medication management problems suggesting a decreased medication management capacity.

Gene expression in blood of children and adolescents: Mediation between childhood maltreatment and major depressive disorder.

PubMed

Spindola, Leticia Maria; Pan, Pedro Mario; Moretti, Patricia Natalia; Ota, Vanessa Kiyomi; Santoro, Marcos Leite; Cogo-Moreira, Hugo; Gadelha, Ary; Salum, Giovanni; Manfro, Gisele Gus; Mari, Jair Jesus; Brentani, Helena; Grassi-Oliveira, Rodrigo; Brietzke, Elisa; Miguel, Euripedes Constantino; Rohde, Luis Augusto; Sato, João Ricardo; Bressan, Rodrigo Affonseca; Belangero, Sintia Iole

2017-09-01

Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group). The differentially expressed genes were inserted in a mediation model in which CM, MDD, and gene expression were, respectively, the independent variable, outcome, and intermediary variable. NR3C1, TNF, TNFR1 and IL1B were expressed at significantly lower levels in the MDD group than in the other groups. CM history did not exert a significant direct effect on MDD. However, an indirect effect of the aggregate expression of the 4 genes mediated the relationship between CM and MDD. In the largest study investigating gene expression in children with MDD, we demonstrated that NR3C1, TNF, TNFR1 and IL1B expression levels are related to MDD and conjunctly mediate the effect of CM history on the risk of developing MDD. This supports a role of glucocorticoids and inflammation as potential effectors of environmental stress in MDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

MDD diagnosis based on partial-brain functional connection network

NASA Astrophysics Data System (ADS)

Yan, Gaoliang; Hu, Hailong; Zhao, Xiang; Zhang, Lin; Qu, Zehui; Li, Yantao

2018-04-01

Artificial intelligence (AI) is a hotspot in computer science research nowadays. To apply AI technology in all industries has been the developing direction for researchers. Major depressive disorder (MDD) is a common disease of serious mental disorders. The World Health Organization (WHO) reports that MDD is projected to become the second most common cause of death and disability by 2020. At present, the way of MDD diagnosis is single. Applying AI technology to MDD diagnosis and pathophysiological research will speed up the MDD research and improve the efficiency of MDD diagnosis. In this study, we select the higher degree of brain network functional connectivity by statistical methods. And our experiments show that the average accuracy of Logistic Regression (LR) classifier using feature filtering reaches 88.48%. Compared with other classification methods, both the efficiency and accuracy of this method are improved, which will greatly improve the process of MDD diagnose. In these experiments, we also define the brain regions associated with MDD, which plays a vital role in MDD pathophysiological research.

Prospective inter-relationships between late adolescent personality and major depressive disorder in early adulthood.

PubMed

Wilson, S; DiRago, A C; Iacono, W G

2014-02-01

A well-established body of literature demonstrates concurrent associations between personality traits and major depressive disorder (MDD), but there have been relatively few investigations of their dynamic interplay over time. Prospective inter-relationships between late-adolescent personality and MDD in early adulthood were examined in a community sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252). Participants were classified into naturally occurring MDD groups based on the timing (adolescent versus adult onset) and course (chronic/recurrent versus remitting) of MDD. MDD diagnoses were assessed at ages 17, 20, 24 and 29 years, and personality traits [negative emotionality (NEM), positive emotionality (PEM) and constraint (CON)] were assessed at ages 17, 24 and 29 years. Multilevel modeling (MLM) analyses indicated that higher age-17 NEM was associated with the subsequent development of MDD, and any MDD, regardless of onset or course, was associated with higher NEM up to age 29. Moreover, the chronic/recurrent MDD groups failed to show the normative decrease in NEM from late adolescence to early adulthood. Lower age-17 PEM was also associated with the subsequent development of MDD but only among the chronic/recurrent MDD groups. Finally, the adolescent-onset MDD groups reported lower age-17 CON relative to the never-depressed and adult-onset MDD groups. Taken together, the results speak to the role of personality traits for conferring risk for the onset of MDD in late adolescence and early adulthood, in addition to the pernicious implications of chronic/recurrent MDD, particularly when it onsets during adolescence, for adaptive personality development.

Heritability of major depressive and comorbid anxiety disorders in multi-generational families at high risk for depression.

PubMed

Guffanti, Guia; Gameroff, Marc J; Warner, Virginia; Talati, Ardesheer; Glatt, Charles E; Wickramaratne, Priya; Weissman, Myrna M

2016-12-01

Family studies have shown that MDD is highly transmittable but have not studied its heritability. Twin studies show heritability of about 40% and do not include anxiety disorders. We assessed heritability of MDD and comorbid anxiety disorders in a multigenerational study of family members at high risk for MDD. In addition, we tested the hypothesis that examined clinical subtypes of MDD defined by early and late age of onset would be under relatively stronger genetic control than broadly defined DSM-IV MDD. The first generation with moderate to severe MDD was recruited from an ambulatory psychiatric treatment setting, and their descendants in the second, third, and fourth generation, were interviewed by clinicians up to six times during a 30-year period. Lifetime rates of MDD and anxiety disorders were collected for 545 participants from 65 multigenerational families. The heritability (h 2 ) of MDD in this high risk sample was estimated at 67%. Anxiety and sequential comorbidity of anxiety disorders and MDD revealed h 2 of 49% and 53%, respectively, and strong positive genetic correlation (rho g  = 0.92, P = 7.3 × 10 -7 ). Early onset MDD did not appear to be under greater genetic control than broadly defined DSM-IV MDD. Individuals who are direct descendants of subjects ascertained for moderate to severe MDD have strong genetic vulnerability to develop anxiety or MDD. Our findings support family based studies as appropriate and useful design to understand the heritability of common disorders such as MDD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Time course for memory dysfunction in early-life and late-life major depression: a longitudinal study from the Juntendo University Mood Disorder Project.

PubMed

Maeshima, Hitoshi; Baba, Hajime; Nakano, Yoshiyuki; Satomura, Emi; Namekawa, Yuki; Takebayashi, Naoko; Nomoto, Hiroshi; Suzuki, Toshihito; Mimura, Masaru; Arai, Heii

2013-10-01

Previous studies have demonstrated that patients with depression also have memory dysfunctions during depressive episodes. These dysfunctions partially remain immediately after remission from a depressive state; however, it is unclear whether these residual memory dysfunctions may disappear through long-term remission from depression. The present study compared patients during early-life (age<60) and late-life (age ≥ 60) depression while in their remitted stage with healthy controls to elucidate the impact of a long-term course on memory. Logical memory from the Wechsler Memory Scale-Revised was administered to 67 patients with major depressive disorder (MDD) (47 patients with early-life depression and residual 20 patients with late-life depression) and 50 healthy controls. MDD patients received memory assessments at the time of their initial remission and at a follow-up three years after remission. At the time of initial remission, scores for logical memory were significantly lower in both patient groups compared to matched controls. At follow-up, memory dysfunction for early-life MDD patients disappeared, whereas scores in the late-life MDD group remained significantly lower than those of matched controls. All patients in the present study were on antidepressant medications. Our findings suggested that the progress of memory performance in late-life MDD patients may be different from early-life MDD patients. © 2013 Elsevier B.V. All rights reserved.

Stroop performance in major depression: selective attention impairment or psychomotor slowness?

PubMed

Kertzman, Semion; Reznik, Ilya; Hornik-Lurie, Tzipi; Weizman, Abraham; Kotler, Moshe; Amital, Daniela

2010-04-01

Numerous neuropsychological studies reported impaired Stroop performance in major depressive disorder (MDD) patients. The present study attempted to identify possible neuropsychological mechanisms involved in this impairment in untreated MDD outpatients (n=75) as compared to healthy subjects (n=83). Inspection Time, Finger Tapping, Simple and Choice Reaction Time were considered as measures of perceptual, motor, psychomotor speed, and response selection, respectively. MDD patients performed significantly slower than healthy controls in the neutral and the congruent conditions, but not in the incongruent ones. In order to identify predictors of Stroop performance, linear hierarchical regressions analyses were performed. Age, motor and psychomotor speed were predictors of response time and accuracy on Stroop performance. Significant correlations between response time and the number of errors in all three Stroop conditions were found in MDD patients, while such a correlation was obtained in the healthy controls only in the incongruent condition. Although education was included as a covariate in our analyses, suggesting that the observed effects could not be ascribed to education differences, further testing with education-matched samples is warranted. Our study shows that the Stroop task performance is affected by both aging and MDD. Impairment in the Stroop performance can be predicted by psychomotor slowness and by vigilance level in MDD outpatients, but not by impairment of selective attention per se. Copyright 2009 Elsevier B.V. All rights reserved.

Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in depression and response to antidepressants

PubMed Central

Duclot, Florian; Kabbaj, Mohamed

2015-01-01

Major depressive disorder (MDD) is a devastating neuropsychiatric disorder encompassing a wide range of cognitive and emotional dysfunctions. The prevalence of MDD is expected to continue its growth to become the second leading cause of disease burden (after HIV) by 2030. Despite an extensive research effort, the exact etiology of MDD remains elusive and the diagnostics uncertain. Moreover, a marked inter-individual variability is observed in the vulnerability to develop depression, as well as in response to antidepressant treatment, for nearly 50% of patients. Although a genetic component accounts for some cases of MDD, it is now clearly established that MDD results from strong gene and environment interactions. Such interactions could be mediated by epigenetic mechanisms, defined as chromatin and DNA modifications that alter gene expression without changing the DNA structure itself. Some epigenetic mechanisms have recently emerged as particularly relevant molecular substrates, promoting vulnerability or resilience to the development of depressive-like symptoms. Although the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of MDD remains unclear, its modulation of the efficacy of antidepressants is clearly established. Therefore, in this review, we focus on the epigenetic mechanisms regulating the expression of BDNF in humans and in animal models of depression, and discuss their role in individual differences in vulnerability to depression and response to antidepressant drugs. PMID:25568448

A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression.

PubMed

Diener, Carsten; Kuehner, Christine; Brusniak, Wencke; Ubl, Bettina; Wessa, Michèle; Flor, Herta

2012-07-02

Major depressive disorder (MDD) is characterized by altered emotional and cognitive functioning. We performed a voxel-based whole-brain meta-analysis of functional neuroimaging data on altered emotion and cognition in MDD. Forty peer-reviewed studies in English-language published between 1998 and 2010 were included, which used functional neuroimaging during cognitive-emotional challenge in adult individuals with MDD and healthy controls. All studies reported between-groups differences for whole-brain analyses in standardized neuroanatomical space and were subjected to Activation Likelihood Estimation (ALE) of brain cluster showing altered responsivity in MDD. ALE resulted in thresholded and false discovery rate corrected hypo- and hyperactive brain regions. Against the background of a complex neural activation pattern, studies converged in predominantly hypoactive cluster in the anterior insular and rostral anterior cingulate cortex linked to affectively biased information processing and poor cognitive control. Frontal areas showed not only similar under- but also over-activation during cognitive-emotional challenge. On the subcortical level, we identified activation alterations in the thalamus and striatum which were involved in biased valence processing of emotional stimuli in MDD. These results for active conditions extend findings from ALE meta-analyses of resting state and antidepressant treatment studies and emphasize the key role of the anterior insular and rostral anterior cingulate cortex for altered emotion and cognition in MDD. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression.

PubMed

Sohn, Hoyoung; Kwon, Min-Soo; Lee, Sun-Woo; Oh, Jongsoo; Kim, Min-Kyoung; Lee, Sang-Hyuk; Lee, Kang Soo; Kim, Borah

2018-06-07

Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD. A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses. Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM. The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia.

PubMed

Duprat, Romain; Wu, Guo-Rong; De Raedt, Rudi; Baeken, Chris

2017-08-09

Accelerated intermittent theta-burst stimulation (aiTBS) anti-depressive working mechanisms are still unclear. Because aiTBS may work through modulating the reward system and the level of anhedonia may influence this modulation, we investigated the effect of aiTBS on reward responsiveness in high and low anhedonic MDD patients. In this registered RCT (NCT01832805), 50 MDD patients were randomised to a sham-controlled cross-over aiTBS treatment protocol over the left dorsolateral prefrontal cortex (DLPFC). Patients performed a probabilistic learning task in fMRI before and after each week of stimulation. Task performance analyses did not show any significant effects of aiTBS on reward responsiveness, nor differences between both groups of MDD patients. However, at baseline, low anhedonic patients displayed higher neural activity in the caudate and putamen. After the first week of aiTBS treatment, in low anhedonic patients we found a decreased neural activity within the reward system, in contrast to an increased activity observed in high anhedonic patients. No changes were observed in reward related neural regions after the first week of sham stimulation. Although both MDD groups showed no differences in task performance, our brain imaging findings suggest that left DLPFC aiTBS treatment modulates the reward system differently according to anhedonia severity.

Internet-delivered cognitive behaviour therapy for depression in people with diabetes: study protocol for a randomised controlled trial.

PubMed

Robins, Lisa; Newby, Jill; Wilhelm, Kay; Smith, Jessica; Fletcher, Therese; Ma, Trevor; Finch, Adam; Campbell, Lesley; Andrews, Gavin

2015-01-01

Depression substantially contributes to the personal burden and healthcare costs of living with diabetes mellitus (DM). Comorbid depression and DM are associated with poorer quality of life, poorer self-management and glycemic control, increased risk for DM complications and higher mortality rates, and higher health service utilization. Depression remains under-recognized and undertreated in people with DM, which may, in part, result from barriers associated with accessing face-to-face treatment. This study will examine the efficacy of an internet-based cognitive behaviour therapy programme for major depressive disorder (iCBT-MDD) in people with DM. A CONSORT 2010 compliant, registered randomised controlled trial of the intervention (iCBT-MDD) versus a treatment as usual control group will be conducted. The study will include 100 adults aged 18 years and over with a diagnosis of type 1 or type 2 DM and self-reported symptoms that satisfy MDD which will enable us to detect a statistically significant difference with a group effect size of 0.6 at a power of 80% and significance level of p=0.05. Participants will be randomised to receive the iCBT-MDD programme immediately, or to wait 10 weeks before accessing the programme. Primary outcomes will be self-reported depression severity, DM-related distress, and glycemic control (glycosylated hemoglobin). Secondary outcomes will be general distress and disability, generalized anxiety, lifestyle behaviours, somatization, eating habits, alcohol use, and acceptability of the iCBT programme to participants, and practicality for clinicians. Data will be analyzed with linear mixed models for each outcome measure. The Human Research Ethics Committee of St Vincent's Hospital Australia have given ethics approval (HREC/13/SVH/291). Results will be disseminated via peer-reviewed publication and social media channels of Australian Diabetes Consumer Representative Bodies. The trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12613001198718).

Internet-delivered cognitive behaviour therapy for depression in people with diabetes: study protocol for a randomised controlled trial

PubMed Central

Robins, Lisa; Newby, Jill; Wilhelm, Kay; Smith, Jessica; Fletcher, Therese; Ma, Trevor; Finch, Adam; Campbell, Lesley; Andrews, Gavin

2015-01-01

Introduction Depression substantially contributes to the personal burden and healthcare costs of living with diabetes mellitus (DM). Comorbid depression and DM are associated with poorer quality of life, poorer self-management and glycemic control, increased risk for DM complications and higher mortality rates, and higher health service utilization. Depression remains under-recognized and undertreated in people with DM, which may, in part, result from barriers associated with accessing face-to-face treatment. This study will examine the efficacy of an internet-based cognitive behaviour therapy programme for major depressive disorder (iCBT-MDD) in people with DM. Methods and analysis A CONSORT 2010 compliant, registered randomised controlled trial of the intervention (iCBT-MDD) versus a treatment as usual control group will be conducted. The study will include 100 adults aged 18 years and over with a diagnosis of type 1 or type 2 DM and self-reported symptoms that satisfy MDD which will enable us to detect a statistically significant difference with a group effect size of 0.6 at a power of 80% and significance level of p=0.05. Participants will be randomised to receive the iCBT-MDD programme immediately, or to wait 10 weeks before accessing the programme. Primary outcomes will be self-reported depression severity, DM-related distress, and glycemic control (glycosylated hemoglobin). Secondary outcomes will be general distress and disability, generalized anxiety, lifestyle behaviours, somatization, eating habits, alcohol use, and acceptability of the iCBT programme to participants, and practicality for clinicians. Data will be analyzed with linear mixed models for each outcome measure. Ethics and dissemination The Human Research Ethics Committee of St Vincent's Hospital Australia have given ethics approval (HREC/13/SVH/291). Results will be disseminated via peer-reviewed publication and social media channels of Australian Diabetes Consumer Representative Bodies. Trial registration number The trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12613001198718). PMID:26688735

Incidence and Persistence of Major Depressive Disorder Among People Living with HIV in Uganda.

PubMed

Kinyanda, Eugene; Weiss, Helen A; Levin, Jonathan; Nakasujja, Noeline; Birabwa, Harriet; Nakku, Juliet; Mpango, Richard; Grosskurth, Heiner; Seedat, Soraya; Araya, Ricardo; Patel, Vikram

2017-06-01

Data on the course of major depressive disorder (MDD) among people living with HIV (PLWH) are needed to inform refinement of screening and interventions for MDD. This paper describes the incidence and persistence rate of MDD in PLWH in Uganda. 1099 ART-naïve PLWH attending HIV clinics in Uganda were followed up for 12 months. MDD was assessed using the DSM IV based Mini-International Neuropsychiatric Interview with a prevalence for MDD at baseline of 14.0 % (95 % CI 11.7-16.3 %) reported. Multivariable logistic regression was used to determine predictors of incident and persistent MDD. Cumulative incidence of MDD was 6.1 per 100 person-years (95 % CI 4.6-7.8) with significant independent predictors of study site, higher baseline depression scores and increased stress. Persistence of MDD was 24.6 % (95 % CI 17.9-32.5 %) with independent significant predictors of study site, higher baseline depression scores, and increased weight. Risks of incident and persistent MDD observed in this study were high. Potentially modifiable factors of elevated baseline depressive scores and stress (only for incident MDD) were important predictors of incident and persistent MDD.

Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder: A Danish National Register-Based Study.

PubMed

Musliner, Katherine L; Munk-Olsen, Trine; Laursen, Thomas M; Eaton, William W; Zandi, Peter P; Mortensen, Preben B

2016-04-01

Evidence suggests that long-term trajectories of major depressive disorder (MDD) are heterogeneous. The Danish Psychiatric Central Research Register (DPCRR) provides a rare opportunity to examine patterns and correlates of long-term trajectories in a large sample of patients with moderate to severe MDD. To characterize patterns and correlates of 10-year course trajectories of MDD in the DPCRR. A cohort containing 11 640 individuals born in Denmark in 1955 or later with their first recorded MDD diagnosis in the DPCRR between 1995 and 2002 was established. Patients were followed for 10 years from the date of their initial MDD diagnosis. Data were obtained from Danish civil and psychiatric national registers in June 2013 and were analyzed from April 4, 2014, to December 17, 2015. Correlates of trajectory class membership were sex, characteristics of the first recorded MDD episode (ie, age, severity, inpatient treatment, and record of suicide attempt or self-harm), and psychiatric diagnoses in parents (ie, depression, bipolar disorder, schizophrenia-spectrum disorders, substance abuse, and anxiety or somatoform disorders). The outcome variable was past-year contact at a psychiatric hospital with a main diagnosis of MDD during each of the 10 years following the initial MDD diagnosis. Trajectories were modeled using latent class growth analysis. The sample included 11 640 individuals (7493 [64.4%] women) aged 18 to 48 years (mean [SD], 31.4 [7.3]) at their first recorded MDD diagnosis. Four trajectory classes were identified: brief contact (77.0%) (characterized by low probability of contact after 2 years); prolonged initial contact (12.8%) (characterized by high decreasing probability of contact during the first 5 years); later reentry (7.1%) (characterized by moderate probability of contact during the second 5 years); and persistent contact (3.1%) (characterized by high or moderate probability of contact throughout). Female sex (odds ratio [OR] range, 1.82-2.22), inpatient treatment (OR range, 1.40-1.50), and severity at first recorded MDD episode (OR range: moderate, 1.61-1.84; severe, 1.93-2.23; and psychotic, 2.73-3.07) were associated with more severe trajectories. Parental anxiety (OR, 1.34 [95% CI, 1.10-1.63]) and depression (OR, 1.63 [95% CI, 1.28-2.09]) were associated with the prolonged initial contact and later reentry classes, respectively. Parental schizophrenia was associated with the persistent contact class (OR range, 2.55-3.04). Most people treated for moderate to severe MDD in Danish psychiatric hospitals do not receive additional MDD treatment after 2 years; however, a minority receive specialty treatment for up to a decade. Observable heterogeneity in the course may be indicative of underlying etiologic differences.

Course of major depressive disorder and labor market outcome disruption.

PubMed

Luo, Zhehui; Cowell, Alexander J; Musuda, Yuta J; Novak, Scott P; Johnson, Eric O

2010-09-01

Major depressive disorder (MDD) has been found to be negatively associated with labor market outcomes. However, MDD has many different courses that are chronic or persistent, relapsing and remitting, or limited to a single lifetime episode. Such heterogeneity has been ignored in most past analyses. We examine the impact of heterogeneity in course of MDD on labor market outcomes. Wave I (2001-2002) respondents of the National Epidemiological Survey on Alcohol and Related Conditions - a nationally representative panel survey - were interviewed on average 3 years later (2004-2005). We categorized changes in MDD before and after wave I and before wave II into six courses: incident, recent remission, persistent remission, relapse, persistent depression, and no history of MDD. Odds ratios (ORs) and marginal effects of MDD transitions in multivariable multinomial regressions of labor market outcomes (being out of the labor force, being unemployed, working part-time, and working full-time -- the reference outcome) are reported. Men and women who exhibited persistent remission (2 to 3 years) were equally likely to be in the labor force, employed, and working full-time, compared to those with no history of MDD (reference group). For men, recently remitted MDD (less than 1 year), compared to the reference group, increased the likelihood of being unemployed (3.2% higher probability of being unemployed conditional on being in the labor force; OR = 1.97, 95% confidence interval [CI] = 1.13--3.44) and working part-time (5.8% higher probability of working part-time conditional on being employed; OR = 1.75, 95% CI = 1.10-2.80). For women, no statistically significant effect for recent remission was found. The negative effects of incident onset, relapse, and persistence of MDD were found on some labor market outcomes for men and, to a lesser extent, for women. Clinical treatment for depression should be coordinated and/or integrated with work-related interventions that help individuals who are recovering from depression to maintain their jobs. Such coordination will add to the value of clinical treatment for depression. The impact of MDD on labor market outcomes varies by course of illness. Past studies may have underestimated lost earnings due to mental illness because they did not distinguish between recent and persistent remission and thus did not account for lost earnings due to recent remission. Further research is needed to understand why there are differential impacts for men and women and to make causal inferences on the relationships between MDD and labor market outcomes.

Antecedents of New-Onset Major Depressive Disorder in Children and Adolescents at High Familial Risk.

PubMed

Rice, Frances; Sellers, Ruth; Hammerton, Gemma; Eyre, Olga; Bevan-Jones, Rhys; Thapar, Ajay K; Collishaw, Stephan; Harold, Gordon T; Thapar, Anita

2017-02-01

Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational outcomes. To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents. This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean [SD] age of 12.4 [2.0] years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up. The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score. On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (β = 0.12, P = .03) and fear and/or anxiety (β = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (β = -0.08, P = .14) and low mood (β = -0.03, P = .65) were not. The results were similar for the DSM-IV symptom count at follow-up. All the measured familial/genetic and social risk indicators directly influenced risk for new-onset MDD rather than indirectly through acting on dimensional clinical antecedents. There are multiple pathways to first-onset adolescent depression in individuals at familial risk. Irritability and fear/anxiety may be additional clinical phenomena to be included as targets in primary preventive interventions focusing on the child. In addition to targeting these phenomena in parents and children, depression prevention methods in high-risk groups may need to take into consideration social risks, such as poverty and psychosocial adversity.

Self-blame-Selective Hyperconnectivity Between Anterior Temporal and Subgenual Cortices and Prediction of Recurrent Depressive Episodes.

PubMed

Lythe, Karen E; Moll, Jorge; Gethin, Jennifer A; Workman, Clifford I; Green, Sophie; Lambon Ralph, Matthew A; Deakin, John F W; Zahn, Roland

2015-11-01

Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional magnetic resonance imaging connectivity (fMRI) between the right superior anterior temporal lobe (RSATL) and the subgenual cingulate cortex and adjacent septal region (SCSR) when experiencing self-blaming emotions relative to emotions related to blaming others (eg, "indignation or anger toward others"). This finding provided the first neural signature of biases toward overgeneralized self-blaming emotions (eg, "feeling guilty for everything"), known to have a key role in cognitive vulnerability to MDD. It is unknown whether this neural signature predicts risk of recurrence, a crucial step in establishing its potential as a prognostic biomarker, which is urgently needed for stratification into pathophysiologically more homogeneous subgroups and for novel treatments. To use fMRI in remitted MDD at baseline to test the hypothesis that RSATL-SCSR connectivity for self-blaming relative to other-blaming emotions predicts subsequent recurrence of depressive episodes. A prospective cohort study from June 16, 2011, to October 10, 2014, in a clinical research facility completed by 75 psychotropic medication-free patients with remitted MDD and no relevant comorbidity. In total, 31 remained in stable remission, and 25 developed a recurring episode over the 14 months of clinical follow-up and were included in the primary analysis. Thirty-nine control participants with no personal or family history of MDD were recruited for further comparison. Between-group difference (recurring vs stable MDD) in RSATL connectivity, with an a priori SCSR region of interest for self-blaming vs other-blaming emotions. We corroborated our hypothesis that during the experience of self-blaming vs other-blaming emotions, RSATL-SCSR connectivity predicted risk of subsequent recurrence. The recurring MDD group showed higher connectivity than the stable MDD group (familywise error-corrected P < .05 over the a priori SCSR region of interest) and the control group. In addition, the recurring MDD group also exhibited RSATL hyperconnectivity with the right ventral putamen and claustrum and the temporoparietal junction. Together, these regions predicted recurrence with 75% accuracy. To our knowledge, this study is the first to provide a robust demonstration of an fMRI signature of recurrence risk in remitted MDD. Additional studies are needed for its further optimization and validation as a prognostic biomarker.

Disrupted reinforcement learning and maladaptive behavior in women with a history of childhood sexual abuse: a high-density event-related potential study.

PubMed

Pechtel, Pia; Pizzagalli, Diego A

2013-05-01

Childhood sexual abuse (CSA) has been associated with psychopathology, particularly major depressive disorder (MDD), and high-risk behaviors. Despite the epidemiological data available, the mechanisms underlying these maladaptive outcomes remain poorly understood. We examined whether a history of CSA, particularly in conjunction with a past episode of MDD, is associated with behavioral and neural dysfunction in reinforcement learning, and whether such dysfunction is linked to maladaptive behavior. Participants completed a clinical evaluation and a probabilistic reinforcement task while 128-channel event-related potentials were recorded. Academic setting; participants recruited from the community. Fifteen women with a history of CSA and remitted MDD (CSA + rMDD), 16 women with remitted MDD with no history of CSA (rMDD), and 18 healthy women (controls). Three or more episodes of coerced sexual contact (mean [SD] duration, 3.00 [2.20] years) between the ages of 7 and 12 years by at least 1 male perpetrator. Participants' preference for choosing the most rewarded stimulus and avoiding the most punished stimulus was evaluated. The feedback-related negativity and error-related negativity-hypothesized to reflect activation in the anterior cingulate cortex-were used as electrophysiological indices of reinforcement learning. No group differences emerged in the acquisition of reinforcement contingencies. In trials requiring participants to rely partially or exclusively on previously rewarded information, the CSA + rMDD group showed (1) lower accuracy (relative to both controls and the rMDD group), (2) blunted electrophysiological differentiation between correct and incorrect responses (relative to controls), and (3) increased activation in the subgenual anterior cingulate cortex (relative to the rMDD group). A history of CSA was not associated with impairments in avoiding the most punished stimulus. Self-harm and suicidal behaviors correlated with poorer performance of previously rewarded, but not previously punished, trials. Irrespective of past MDD episodes, women with a history of CSA showed neural and behavioral deficits in utilizing previous reinforcement to optimize decision making in the absence of feedback (blunted "Go learning"). Although our study provides initial evidence for reward-specific deficits associated with CSA, future research is warranted to determine if disrupted positive reinforcement learning predicts high-risk behavior following CSA.

A Combined Study of SLC6A15 Gene Polymorphism and the Resting-State Functional Magnetic Resonance Imaging in First-Episode Drug-Naive Major Depressive Disorder.

PubMed

Wang, Lijuan; Liu, Zhifen; Cao, Xiaohua; Li, Jianying; Zhang, Aixia; Sun, Ning; Yang, Chunxia; Zhang, Kerang

2017-09-01

The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). However, the mechanism underlying the effects of how the SLC6A15 gene affects functional brain activity of patients with MDD remains unknown. In the present study, we investigated the effect of the SLC6A15 gene polymorphism, rs1545843, on resting-state brain function in MDD with the imaging genomic technology and the regional homogeneity (ReHo) method. Sixty-seven MDD patients and 44 healthy controls underwent functional magnetic resonance imaging scans and genotyping. The differences in ReHo between genotypes were initially tested using the student's t test. We then performed a 2 × 2 (genotypes × disease status) analysis of variance to identify the main effects of genotypes, disease status, and their interactions in MDD. MDD patients with A+ genotypes showed decreased ReHo in the medial cingulum compared with MDD patients with the GG genotype. This was in contrast to normal controls with A+ genotypes who showed increased ReHo in the posterior cingulum and the frontal, temporal, and parietal lobes and decreased ReHo in the left corpus callosum, compared with controls with the GG genotypes. The main effect of disease was found in the frontal, parietal, and temporal lobes. The main effect of genotypes was found in the left corpus callosum and the frontal lobe. There was no interaction between rs1545843 genotypes and disease status. We found that the left corpus callosum ReHo was positively correlated with total scores of the Hamilton Depression Scale (HAMD) (p = 0.021), so as was the left inferior parietal gyrus ReHo with cognitive disorder (p = 0.02). In addition, the right middle temporal gyrus had a negative correlation with retardation (p = 0.049). We observed an association between the SLC6A15 rs1545843 and resting-state brain function of the corpus callosum, cingulum and the frontal, parietal, and temporal lobes in MDD patients, which may be involved in the pathogenesis of MDD.

Altered anatomical patterns of depression in relation to antidepressant treatment: Evidence from a pattern recognition analysis on the topological organization of brain networks.

PubMed

Qin, Jiaolong; Wei, Maobin; Liu, Haiyan; Chen, Jianhuai; Yan, Rui; Yao, Zhijian; Lu, Qing

2015-07-15

Accumulated evidence has illuminated the topological infrastructure of major depressive disorder (MDD). However, the changes of topological properties of anatomical brain networks in remitted major depressive disorder patients (rMDD) remain an open question. The present study provides an exploratory examination of pattern changes among current major depressive disorder patients (cMDD), rMDD patients and healthy controls (HC) by means of a pattern recognition analysis. Twenty-eight cMDD patients (age range: 22-54, mean age: 39.57), 15 rMDD patients (age range: 23-53, mean age: 38.40) and 30 HC (23-54, mean age: 35.57) were enrolled. For each subject, we computed five kinds of weighted white matter (WM) networks via employing five physiological parameters (i.e. fractional anisotropy, mean diffusivity, λ1, λ2 and λ3) and then calculated three network measures of these weighted networks. We treated these measures as features and fed into a feature selection mechanism to choose the most discriminative features for linear support vector machine (SVM) classifiers. Linear SVM could excellently distinguish the three groups with the 100% classification accuracy of recognizing cMDD/rMDD from HC, and 97.67% classification accuracy of recognizing cMDD from rMDD. The further pattern analysis found two types of discriminative patterns among cMDD, rMDD and HC. (i) Compared with HC, both cMDD and rMDD exhibited the similar deficit patterns of node strength primarily involving the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). (ii) Compared with cMDD and rMDD showed the altered pattern of intra-communicability within DMN and inter-communicability between DMN and the other sub-networks including the visual recognition network (VRN) and SN. The present study had a limited sample size and a lack of larger independent data set to validate the methods and confirm the findings. These findings implied that the impairment of MDD was closely associated with the alterations of connections within SN, DMN and FPN, whereas the remission of MDD was benefitted from the network compensatory of intra-communication within DMN and inter-communication between DMN and the other sub-networks (i.e., VRN and SN). Copyright © 2015 Elsevier B.V. All rights reserved.

The role of controlled attention on recall in major depression

PubMed Central

Ellis, Alissa J.; Wells, Tony T.; Vanderlind, W. Michael; Beevers, Christopher G.

2013-01-01

Information processing biases are hallmark features of major depressive disorder (MDD). Depressed individuals display biased memory and attention for negative material. Given that memory is highly dependent on attention for initial encoding, understanding the interplay of these processes may provide important insight into mechanisms that produce memory biases in depression. In particular, attentional control—the ability to selectively attend to task-relevant information by both inhibiting the processing of irrelevant information and disengaging attention from irrelevant material—may be one area of impairment in MDD. In the current study, clinically depressed (MDD: n = 15) and never depressed (non- MDD: n = 22) participants’ line of visual gaze was assessed while participants viewed positive and negative word pairs. For each word pair, participants were instructed to attend to one word (target) and ignore one word (distracter). Free recall of study stimuli was then assessed. Depressed individuals displayed greater recall of negatively valenced target words following the task. Although there were no group differences in attentional control in the context of negative words, attention to negative targets mediated the relationship between depression status and recall of negative words. Results suggest a stronger link between attention and memory for negative material in MDD. PMID:24006889

The role of controlled attention on recall in major depression.

PubMed

Ellis, Alissa J; Wells, Tony T; Vanderlind, W Michael; Beevers, Christopher G

2014-04-01

Information processing biases are hallmark features of major depressive disorder (MDD). Depressed individuals display biased memory and attention for negative material. Given that memory is highly dependent on attention for initial encoding, understanding the interplay of these processes may provide important insight into mechanisms that produce memory biases in depression. In particular, attentional control-the ability to selectively attend to task-relevant information by both inhibiting the processing of irrelevant information and disengaging attention from irrelevant material-may be one area of impairment in MDD. In the current study, clinically depressed (MDD: n = 15) and never depressed (non-MDD: n = 22) participants' line of visual gaze was assessed while participants viewed positive and negative word pairs. For each word pair, participants were instructed to attend to one word (target) and ignore one word (distracter). Free recall of study stimuli was then assessed. Depressed individuals displayed greater recall of negatively valenced target words following the task. Although there were no group differences in attentional control in the context of negative words, attention to negative targets mediated the relationship between depression status and recall of negative words. Results suggest a stronger link between attention and memory for negative material in MDD.

Intrinsic disruption of white matter microarchitecture in first-episode, drug-naive major depressive disorder: A voxel-based meta-analysis of diffusion tensor imaging.

PubMed

Chen, Guangxiang; Guo, Yi; Zhu, Hongyan; Kuang, Weihong; Bi, Feng; Ai, Hua; Gu, Zhongwei; Huang, Xiaoqi; Lui, Su; Gong, Qiyong

2017-06-02

Previous studies have demonstrated the influences of episodes and antidepressant drugs on white matter (WM) in patients with major depressive disorder (MDD). However, most diffusion tensor imaging (DTI) studies included highly heterogeneous individuals with different numbers of depressive episodes or medication status. To exclude the confounding effects of multiple episodes or medication, we conducted a quantitative voxel-based meta-analysis of fractional anisotropy (FA) in patients with first-episode, drug-naive MDD to identify the intrinsic WM alterations involved in the pathogenesis of MDD. The pooled meta-analysis revealed significant FA reductions in the body of the corpus callosum (CC), bilateral anterior limb of the internal capsule (ALIC), right inferior temporal gyrus (ITG) and right superior frontal gyrus (SFG) in MDD patients relative to healthy controls. Meta-regression analyses revealed that FA reduction in the right ALIC and right SFG was negatively correlated with symptom severity and duration of depression, respectively. Our findings provide robust evidence that the WM impairments in the interhemispheric connections and frontal-subcortical neuronal circuits may play an important role in MDD pathogenesis. Copyright © 2017. Published by Elsevier Inc.

Association between Perceived Stressfulness of Stressful Life Events and the Suicidal Risk in Chinese Patients with Major Depressive Disorder.

PubMed

Lin, Jing-Yu; Huang, Yu; Su, Yun-Ai; Yu, Xin; Lyu, Xiao-Zhen; Liu, Qi; Si, Tian-Mei

2018-04-20

Patients with major depressive disorder (MDD) usually have high risk of suicidality. Few studies have investigated the effects of stressful life events (SLEs) on the risk of suicide in Chinese patients who have developed MDD. This study aimed to investigate the impact of SLEs on suicidal risk in Chinese patients with MDD. In total, 1029 patients with MDD were included from nine psychiatric hospitals to evaluate the impact of SLEs on suicidal risk. Patients fulfilling the Mini-International Neuropsychiatric Interview (MINI) criteria for MDD were included in the study. Patients were excluded if they had lifetime or current diagnoses of psychotic disorder, bipolar disorder, and alcohol or substance dependence. Depressive symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17). The suicidal risk of MDD patients was determined by the suicide risk module of MINI. SLEs were assessed by the Life Events Scale. No gender difference was found for suicidal risk in MDD patients. Patients with suicidal risk had younger ages, lower education levels, more drinking behavior, and lower marriage rate, and fewer people had child and more severe depressive symptoms than nonsuicidal risk group. High-level perceived stressfulness (HPS) and number of SLEs that patients were exposed to were significantly greater in patients with suicidal risk than patients without. In multivariate logistic analysis, HPS of SLEs (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.16-2.05, P = 0.003) and depressive symptoms (OR = 1.08, 95% CI: 1.05-1.11, P < 0.001) were associated with suicidal risk even after adjustment of gender, age, marriage, drinking behavior, and childless. HPS of SLEs is associated with suicide risk in Chinese patients with MDD. Further suicide prevention programs targeting this risk factor are needed. ClinicalTrials.gov: NCT02023567; https://clinicaltrials.gov/ct2/show/NCT02023567?term=NCT02023567&rank=1.

Synchrony of physiological activity during mother-child interaction: moderation by maternal history of major depressive disorder.

PubMed

Woody, Mary L; Feurer, Cope; Sosoo, Effua E; Hastings, Paul D; Gibb, Brandon E

2016-07-01

Family environment plays an important role in the intergenerational transmission of major depressive disorder (MDD), but less is known about how day-to-day mother-child interactions may be disrupted in families with a history of MDD. Disruptions in mother-child synchrony, the dynamic and convergent exchange of physiological and behavioral cues during interactions, may be one important risk factor. Although maternal MDD is associated with a lack of mother-child synchrony at the behavioral level, no studies have examined the impact of maternal MDD on physiological synchrony. Therefore, this study examined whether maternal history of MDD moderates mother-child physiological synchrony [measured via respiratory sinus arrhythmia (RSA)] during positive and negative discussions. Children aged 7-11 years and mothers with either a history of MDD during the child's lifetime (n = 44) or no lifetime diagnosis of any mood disorder (n = 50) completed positive and negative discussion tasks while RSA was continuously recorded for both child and mother. Results indicated significant between-dyad and within-dyad group differences in physiological synchrony during positive and negative discussions. Between-dyad analyses revealed evidence of synchrony only among never depressed dyads, among whom higher average mother RSA during both discussions was associated with higher average child RSA. Within-dyad analyses revealed that never depressed dyads displayed positive synchrony (RSA concordance), whereas dyads with a history of maternal MDD displayed negative synchrony (RSA discordance) during the negative discussion and that the degree of negative synchrony exhibited during the negative discussion was associated with mothers' and children's levels of sadness. These results provide preliminary evidence that physiological synchrony is disrupted in families with a history of maternal MDD and may be a potential risk factor for the intergenerational transmission of depression. © 2016 Association for Child and Adolescent Mental Health.

Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

PubMed

Sharp, Carla; Kim, Sohye; Herman, Levi; Pane, Heather; Reuter, Tyson; Strathearn, Lane

2014-05-01

Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a potential endophenotype for the development of depression.

Disrupted Reinforcement Learning and Maladaptive Behavior in Women with a History of Childhood Sexual Abuse: A High-Density Event-Related Potential Study

PubMed Central

Pechtel, Pia; Pizzagalli, Diego A.

2013-01-01

Context Childhood sexual abuse (CSA) has been associated with psychopathology, particularly major depressive disorder (MDD), and high-risk behaviors. Despite grave epidemiological data, the mechanisms underlying these maladaptive outcomes remain poorly understood. Objective We examined whether CSA history, particularly in conjunction with past MDD, is associated with behavioral and neural dysfunction in reinforcement learning, and whether such dysfunction is linked to maladaptive behavior. Design Participants completed a clinical evaluation and a probabilistic reinforcement task while 128-channel event-related potentials were recorded. Setting Academic setting; participants recruited from the community. Participants Fifteen remitted depressed females with CSA history (CSA+rMDD), 16 remitted depressed females without CSA history (rMDD), and 18 healthy females. Main Outcome Measures Participants’ preference for choosing the most rewarded stimulus and avoiding the most punished stimulus was evaluated. The feedback-related negativity (FRN) and error-related negativity (ERN)–hypothesized to reflect activation in the anterior cingulate cortex–were used as electrophysiological indices of reinforcement learning. Results No group differences emerged in the acquisition of reinforcement contingencies. In trials requiring to rely partially or exclusively on previously rewarded information, the CSA+rMDD group showed (1) lower accuracy (relative to both controls and rMDD), (2) blunted electrophysiological differentiation between correct and incorrect responses (relative to controls), and (3) increased activation in the subgenual anterior cingulate cortex (relative to rMDD). CSA history was not associated with impairments in avoiding the most punished stimulus. Self-harm and suicidal behaviors correlated with poorer performance of previously rewarded–but not previously punished–trials. Conclusions Irrespective of past MDD, women with CSA histories showed neural and behavioral deficits in utilizing previous reinforcement to optimize decision-making in the absence of feedback (blunted “Go learning”). While the current study provides initial evidence for reward-specific deficits associated with CSA, future research is warranted to determine if disrupted positive reinforcement learning predicts high-risk behavior following CSA. PMID:23487253

Differential gene expression in patients with subsyndromal symptomatic depression and major depressive disorder.

PubMed

Yang, Chengqing; Hu, Guoqin; Li, Zezhi; Wang, Qingzhong; Wang, Xuemei; Yuan, Chengmei; Wang, Zuowei; Hong, Wu; Lu, Weihong; Cao, Lan; Chen, Jun; Wang, Yong; Yu, Shunying; Zhou, Yimin; Yi, Zhenghui; Fang, Yiru

2017-01-01

Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and can lead to significant psychosocial functional impairment. Although the pathogenesis of major depressive disorder (MDD) and SSD still remains poorly understood, a set of studies have found that many same genetic factors play important roles in the etiology of these two disorders. Nowadays, the differential gene expression between MDD and SSD is still unknown. In our previous study, we compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD and matched healthy controls (8 subjects in each group), and finally determined 48 gene expression signatures. Based on these findings, we further clarify whether these genes mRNA was different expressed in peripheral blood in patients with SSD, MDD and healthy controls (60 subjects respectively). With the help of the quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), we gained gene relative expression levels among the three groups. We found that there are three of the forty eight co-regulated genes had differential expression in peripheral blood among the three groups, which are CD84, STRN, CTNS gene (F = 3.528, p = 0.034; F = 3.382, p = 0.039; F = 3.801, p = 0.026, respectively) while there were no significant differences for other genes. CD84, STRN, CTNS gene may have significant value for performing diagnostic functions and classifying SSD, MDD and healthy controls.

Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study.

PubMed

Ou, Jian-Jun; Xun, Guang-Lei; Wu, Ren-Rong; Li, Le-Hua; Fang, Mao-Sheng; Zhang, Hong-Geng; Xie, Shi-Ping; Shi, Jian-Guo; Du, Bo; Yuan, Xue-Qin; Zhao, Jing-Ping

2011-02-01

S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD). The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients. In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10-20 mg/d) or citalopram (20-40 mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator. Two hundred and three (85%) patients completed the trial. The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study. The study suggests that escitalopram 10-20 mg/d are as effective and safe as citalopram 20-40 mg/d in the short-term treatment for Chinese MDD patients.

Prevalence of depression and its correlates among undergraduates in Sri Lanka.

PubMed

Amarasuriya, Santushi Devini; Jorm, Anthony Francis; Reavley, Nicola Jane

2015-06-01

There is a dearth of mental health research on undergraduates in Sri Lanka. This study examines the prevalence of depression in a sample of Sri Lankan undergraduates, their exposure to threatening life events and the predictors of their depression. Responses of 4304 undergraduates were obtained on the Patient Health Questionnaire-9 and a measure of exposure to threatening life events, with binary logistic regression models used to identify the demographic and life event correlates of screening positive for Major Depressive Disorder (MDD). PHQ-9 diagnoses of 'Major' and 'Other' depression were obtained by 9.3% and 13.5% of undergraduates, respectively. A higher likelihood of MDD was seen among those who were older and those living in hostels (compared to home), although no differences were seen between genders or those studying in different faculties. Likelihood of MDD was higher in undergraduates exposed to multiple threatening life events as well as those exposed to physical threat; family deaths; romantic break-ups; a problem with a close associate; educational difficulties; unemployment and domestic violence, and among male undergraduates harassed by another student. MDD is prevalent in these undergraduates and universities need to develop services to assist them. Such services may also need to focus on supporting those who have experienced threatening life events, particularly those that arise as a result of being an undergraduate, as these may increase the risk of MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

Orbitofrontal cortex volumes in medication naïve children with major depressive disorder: a magnetic resonance imaging study.

PubMed

Chen, Hua-Hsuan; Rosenberg, David R; MacMaster, Frank P; Easter, Philip C; Caetano, Sheila C; Nicoletti, Mark; Hatch, John P; Nery, Fabiano G; Soares, Jair C

2008-12-01

Adults with major depressive disorder (MDD) are reported to have reduced orbitofrontal cortex (OFC) volumes, which could be related to decreased neuronal density. We conducted a study on medication naïve children with MDD to determine whether abnormalities of OFC are present early in the illness course. Twenty seven medication naïve pediatric Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) MDD patients (mean age +/- SD = 14.4 +/- 2.2 years; 10 males) and 26 healthy controls (mean age +/- SD = 14.4 +/- 2.4 years; 12 males) underwent a 1.5T magnetic resonance imaging (MRI) with 3D spoiled gradient recalled acquisition. The OFC volumes were compared using analysis of covariance with age, gender, and total brain volume as covariates. There was no significant difference in either total OFC volume or total gray matter OFC volume between MDD patients and healthy controls. Exploratory analysis revealed that patients had unexpectedly larger total right lateral (F = 4.2, df = 1, 48, p = 0.05) and right lateral gray matter (F = 4.6, df = 1, 48, p = 0.04) OFC volumes compared to healthy controls, but this finding was not significant following statistical correction for multiple comparisons. No other OFC subregions showed a significant difference. The lack of OFC volume abnormalities in pediatric MDD patients suggests the abnormalities previously reported for adults may develop later in life as a result of neural cell loss.

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

PubMed

Zeng, Yanni; Navarro, Pau; Xia, Charley; Amador, Carmen; Fernandez-Pujals, Ana M; Thomson, Pippa A; Campbell, Archie; Nagy, Reka; Clarke, Toni-Kim; Hafferty, Jonathan D; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2016-12-01

Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated genetic effect and non-genetic effects associated with common environments were estimated in a linear mixed model (LMM). Both MDD and SDD had significant contributions from components representing the effect from common genetic variants, the additional genetic effect associated with the pedigree and the common environmental effect shared by couples. The estimate of correlation between SDD and MDD was high (r=1.00, se=0.20) for common-variant-associated genetic effect and lower for the additional genetic effect from the pedigree (r=0.57, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22). Both genetics and couple-shared environmental effects were major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

C-reactive protein: A differential biomarker for major depressive disorder and bipolar II disorder.

PubMed

Chang, Hui Hua; Wang, Tzu-Yun; Lee, I Hui; Lee, Sheng-Yu; Chen, Kao Chin; Huang, San-Yuan; Yang, Yen Kuang; Lu, Ru-Band; Chen, Po See

2017-02-01

Objectives We aimed to examine whether the C-reactive protein (CRP) level could be used to differentiate between major depressive disorder (MDD) and bipolar II disorder (BD II). Methods Ninety-six healthy controls, 88 BD II and 72 MDD drug-naïve patients in their major depressive episodes were enrolled. The fasting plasma level of high-sensitivity CRP was assessed at baseline and after treatment. Results The BD II patients presented significantly higher 17-item Hamilton Depression Rating Scale (HDRS) scores and CRP levels at baseline when adjustment for age, gender, and body mass index (P <  0.001 and P <  0.001, respectively). After treatment the CRP levels remained significantly different (P <  0.001), although the HDRS score was not significantly different between the BD II and MDD patients. A receiver-operating characteristic analysis showed that a baseline CRP level of 621.6 ng/mL could discriminate between BD II and MDD, with an area under the curve of 0.816 and a sensitivity and specificity of 0.699 and 0.882, respectively. Furthermore, the baseline CRP level greater than 621.6 ng/ml had 28.2 higher odds of a diagnosis of BD II (P <  0.001, 95% confidence interval: 10.96-72.35). Conclusions The level of CRP plays a role of biomarker to differentiate between MDD and BD II depression in both their depressed and euthymic state.

Attitudes toward Substance Abuse Clients: An Empirical Study of Clinical Psychology Trainees.

PubMed

Mundon, Chandra R; Anderson, Melissa L; Najavits, Lisa M

2015-01-01

Despite the high prevalence of substance use disorder (SUD) and its frequent comorbidity with mental illness, individuals with SUD are less likely to receive effective SUD treatment from mental health practitioners than SUD counselors. Limited competence and interest in treating this clinical population are likely influenced by a lack of formal training in SUD treatment. Using a factorial survey-vignette design that included three clinical vignettes and a supplementary survey instrument, we investigated whether clinical psychology doctoral students differ in their level of negative emotional reactions toward clients with SUD versus major depressive disorder (MDD); whether they differ in their attributions for SUD versus MDD; and how their negative emotional reactions and attributions impact their interest in pursuing SUD clinical work. Participants were 155 clinical psychology graduate-level doctoral students (72% female). Participants endorsed more negative emotional reactions toward clients with SUD than toward clients with MDD. They were also more likely to identify poor willpower as the cause for SUD than for MDD. More than a third reported interest in working with SUD populations. Highest levels of interest were associated with prior professional and personal experience with SUD, four to six years of clinical experience, and postmodern theoretical orientation.

Predicting the Naturalistic Course of Major Depressive Disorder Using Clinical and Multimodal Neuroimaging Information: A Multivariate Pattern Recognition Study.

PubMed

Schmaal, Lianne; Marquand, Andre F; Rhebergen, Didi; van Tol, Marie-José; Ruhé, Henricus G; van der Wee, Nic J A; Veltman, Dick J; Penninx, Brenda W J H

2015-08-15

A chronic course of major depressive disorder (MDD) is associated with profound alterations in brain volumes and emotional and cognitive processing. However, no neurobiological markers have been identified that prospectively predict MDD course trajectories. This study evaluated the prognostic value of different neuroimaging modalities, clinical characteristics, and their combination to classify MDD course trajectories. One hundred eighteen MDD patients underwent structural and functional magnetic resonance imaging (MRI) (emotional facial expressions and executive functioning) and were clinically followed-up at 2 years. Three MDD trajectories (chronic n = 23, gradual improving n = 36, and fast remission n = 59) were identified based on Life Chart Interview measuring the presence of symptoms each month. Gaussian process classifiers were employed to evaluate prognostic value of neuroimaging data and clinical characteristics (including baseline severity, duration, and comorbidity). Chronic patients could be discriminated from patients with more favorable trajectories from neural responses to various emotional faces (up to 73% accuracy) but not from structural MRI and functional MRI related to executive functioning. Chronic patients could also be discriminated from remitted patients based on clinical characteristics (accuracy 69%) but not when age differences between the groups were taken into account. Combining different task contrasts or data sources increased prediction accuracies in some but not all cases. Our findings provide evidence that the prediction of naturalistic course of depression over 2 years is improved by considering neuroimaging data especially derived from neural responses to emotional facial expressions. Neural responses to emotional salient faces more accurately predicted outcome than clinical data. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Is there Progress? An Overview of Selecting Biomarker Candidates for Major Depressive Disorder

PubMed Central

Young, Juan Joseph; Silber, Tim; Bruno, Davide; Galatzer-Levy, Isaac Robert; Pomara, Nunzio; Marmar, Charles Raymond

2016-01-01

Major depressive disorder (MDD) contributes to a significant worldwide disease burden, expected to be second only to heart disease by 2050. However, accurate diagnosis has been a historical weakness in clinical psychiatry. As a result, there is a demand for diagnostic modalities with greater objectivity that could improve on current psychiatric practice that relies mainly on self-reporting of symptoms and clinical interviews. Over the past two decades, literature on a growing number of putative biomarkers for MDD increasingly suggests that MDD patients have significantly different biological profiles compared to healthy controls. However, difficulty in elucidating their exact relationships within depression pathology renders individual markers inconsistent diagnostic tools. Consequently, further biomarker research could potentially improve our understanding of MDD pathophysiology as well as aid in interpreting response to treatment, narrow differential diagnoses, and help refine current MDD criteria. Representative of this, multiplex assays using multiple sources of biomarkers are reported to be more accurate options in comparison to individual markers that exhibit lower specificity and sensitivity, and are more prone to confounding factors. In the future, more sophisticated multiplex assays may hold promise for use in screening and diagnosing depression and determining clinical severity as an advance over relying solely on current subjective diagnostic criteria. A pervasive limitation in existing research is heterogeneity inherent in MDD studies, which impacts the validity of biomarker data. Additionally, small sample sizes of most studies limit statistical power. Yet, as the RDoC project evolves to decrease these limitations, and stronger studies with more generalizable data are developed, significant advances in the next decade are expected to yield important information in the development of MDD biomarkers for use in clinical settings. PMID:27199779

The association of minor and major depression with health problem-solving and diabetes self-care activities in a clinic-based population of adults with type 2 diabetes mellitus.

PubMed

Shin, Na; Hill-Briggs, Felicia; Langan, Susan; Payne, Jennifer L; Lyketsos, Constantine; Golden, Sherita Hill

2017-05-01

We examined whether problem-solving and diabetes self-management behaviors differ by depression diagnosis - major depressive disorder (MDD) and minor depressive disorder (MinDD) - in adults with Type 2 diabetes (T2DM). We screened a clinical sample of 702 adults with T2DM for depression, identified 52 positive and a sample of 51 negative individuals, and performed a structured diagnostic psychiatric interview. MDD (n=24), MinDD (n=17), and no depression (n=62) were diagnosed using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria. Health Problem-Solving Scale (HPSS) and Summary of Diabetes Self-Care Activities (SDSCA) questionnaires determined problem-solving and T2DM self-management skills, respectively. We compared HPSS and SDSCA scores by depression diagnosis, adjusting for age, sex, race, and diabetes duration, using linear regression. Total HPSS scores for MDD (β=-4.38; p<0.001) and MinDD (β=-2.77; p<0.01) were lower than no depression. Total SDSCA score for MDD (β=-10.1; p<0.01) was lower than for no depression, and was partially explained by total HPSS. MinDD and MDD individuals with T2DM have impaired problem-solving ability. MDD individuals had impaired diabetes self-management, partially explained by impaired problem-solving. Future studies should assess problem-solving therapy to treat T2DM and MinDD and integrated problem-solving with diabetes self-management for those with T2DM and MDD. Copyright © 2017 Elsevier Inc. All rights reserved.

Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

PubMed

Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

2016-05-24

Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.

Efficacy of escitalopram monotherapy in the treatment of major depressive disorder

PubMed Central

Li, Guanjun; Shen, Yifeng; Luo, Jianfeng; Li, Huafang

2017-01-01

Abstract This study aimed to evaluate the efficacy of escitalopram monotherapy in the treatment of major depressive disorder (MDD) on the basis of pooled data analysis of 4 Chinese clinical trials. A total of 649 outpatients with MDD score of ≥18 at the 17-item Hamilton Depression Rating Scale (HAMD17) were included across 4 eligible studies. Patients were treated with 10 mg/day escitalopram for 2 weeks, and then 20 mg/day escitalopram was administered if the clinical response was poor. The change in total HAMD17 score was significantly greater in moderate MDD group than in other subgroups (P < .001), but the proportion of responders and remission rate in moderate MDD group were markedly lower than in mild MDD group. As compared to patients with concomitant anxiety, anxiety free patients showed significant improvement in total HAMD17 score at days 14 and 28 (P < .05). However, there was no significant difference in the change of total HAMD17 score at day 7 and the end of study. According to clinical global impression (CGI) score, the total response rate (very much improved and much improved) was 86.7%. There were 479 adverse events (AEs), but serious AEs were not observed. A total of 3.39% (22/649) of patients withdrew from these studies due to AEs. The most common (incidence ≥2.0%) AEs were nausea, dry mouth, somnolence, dizziness, fatigue, dyspepsia, liver dysfunction, and loss of appetite. Escitalopram monotherapy is effective and safe in the treatment of MDD in Chinese patients, and therapeutic efficacy is dependent on the severity of MDD. Further study is needed to identify better predictors of therapeutic responses. PMID:28953649

Are there common familial influences for major depressive disorder and an overeating-binge eating dimension in both European American and African American female twins?

PubMed

Munn-Chernoff, Melissa A; Grant, Julia D; Agrawal, Arpana; Koren, Rachel; Glowinski, Anne L; Bucholz, Kathleen K; Madden, Pamela A F; Heath, Andrew C; Duncan, Alexis E

2015-05-01

Although prior studies have demonstrated that depression is associated with an overeating-binge eating dimension (OE-BE) phenotypically, little research has investigated whether familial factors contribute to the co-occurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups. Participants included 3,226 European American (EA) and 550 African American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age. The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg  = .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re  = .26 [.09, .42]). Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD and OE-BE across these groups. © 2014 Wiley Periodicals, Inc.

Are There Common Familial Influences for Major Depressive Disorder and an Overeating-Binge Eating Dimension in both European-American and African-American Female Twins?

PubMed Central

Munn-Chernoff, Melissa A.; Grant, Julia D.; Agrawal, Arpana; Koren, Rachel; Glowinski, Anne L.; Bucholz, Kathleen K.; Madden, Pamela A. F.; Heath, Andrew C.; Duncan, Alexis E.

2014-01-01

Objective Although prior studies have demonstrated that depression is associated with an overeating-binge eating dimension (OE-BE), phenotypically, little research has investigated whether familial factors contribute to the co-occurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups Method Participants included 3226 European-American (EA) and 550 African-American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age. Results The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg = .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re = .26 [.09, .42]) Discussion Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD and OE-BE across these groups. PMID:24659561

Diagnostic performance of major depression disorder case-finding instruments used among mothers of young children in the United States: A systematic review.

PubMed

Owora, Arthur H; Carabin, Hélène; Reese, Jessica; Garwe, Tabitha

2016-09-01

Growing recognition of the interrelated negative outcomes associated with major depression disorder (MDD) among mothers and their children has led to renewed public health interest in the early identification and treatment of maternal MDD. Healthcare providers, however, remain unsure of the validity of existing case-finding instruments. We conducted a systematic review to identify the most valid maternal MDD case-finding instrument used in the United States. We identified articles reporting the sensitivity and specificity of MDD case-finding instruments based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) by systematically searching through three electronic bibliographic databases, PubMed, PsycINFO, and EMBASE, from 1994 to 2014. Study eligibility and quality were evaluated using the Standards for the Reporting of Diagnostic Accuracy studies and Quality Assessment of Diagnostic Accuracy Studies guidelines respectively. Overall, we retrieved 996 unduplicated articles and selected 74 for full-text review. Of these, 14 articles examining 21 different instruments were included in the systematic review. The 10 item Edinburgh Postnatal Depression Scale and Postpartum Depression Screening Scale had the most stable (lowest variation) and highest diagnostic performance during the antepartum and postpartum periods (sensitivity range: 0.63-0.94 and 0.67-0.95; specificity range: 0.83-0.98 and 0.68-0.97 respectively). Greater variation in diagnostic performance was observed among studies with higher MDD prevalence. Factors that explain greater variation in instrument diagnostic performance in study populations with higher MDD prevalence were not examined. Findings suggest that the diagnostic performance of maternal MDD case-finding instruments is peripartum period-specific. Published by Elsevier B.V.

Long Non-Coding RNA: Potential Diagnostic and Therapeutic Biomarker for Major Depressive Disorder.

PubMed

Cui, Xuelian; Sun, Xinyang; Niu, Wei; Kong, Lingming; He, Mingjun; Zhong, Aifang; Chen, Shengdong; Jiang, Kunhong; Zhang, Liyi; Cheng, Zaohuo

2016-12-31

BACKGROUND The criteria for diagnosing depression are based on behavioral observation and self-reporting of symptoms by the patients or guardians without any biological validation of the disease. This study aimed to identify long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) as robust and predictive biomarkers for diagnosis and therapy response in major depressive disorder (MDD). MATERIAL AND METHODS We used human lncRNA 3.0 microarray profiling (which covers 30,586 human lncRNAs), using PBMCs from five MDD patients and five controls. Differentially expressed lncRNAs in the PBMCs of MDD patients were identified, of which 10 candidate lncRNAs were selected for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 138 MDD patients and 63 healthy controls. Then among the 138 MDD patients who received standard antidepressant treatment, 30 were randomly selected for lncRNAs expression retesting and symptomatology assessments after three-weeks and six-weeks of antidepressant treatment. RESULTS Six lncRNAs (TCONS_00019174, ENST00000566208, NONHSAG045500, ENST00000517573, NONHSAT034045, and NONHSAT142707) were significantly downregulated in MDD patients compared to control patients, and the area under the receiver operator curve (ROC) of these six lncRNAs cases, combined, was 0.719 (95% confidence interval (CI): 0.617-0.821). There was no difference in the expression of these six lncRNAs based on gender (p>0.05) or age (p>0.05). CONCLUSIONS These results suggest that the combined expression of six lncRNAs in PBMCs may serve as a potential biomarker for diagnosis and therapy response of MDD in the clinical setting.

Affective traits and history of depression are related to ventral striatum connectivity.

PubMed

DelDonno, Sophie R; Jenkins, Lisanne M; Crane, Natania A; Nusslock, Robin; Ryan, Kelly A; Shankman, Stewart A; Phan, K Luan; Langenecker, Scott A

2017-10-15

Studying remitted Major Depressive Disorder (rMDD) facilitates a better understanding of neural mechanisms for risk, given that confounding effects of active symptoms are removed. Disrupted functional connectivity has been reported in multiple networks in MDD. However, no study to date of rMDD has specifically examined connectivity of the ventral striatum (VS), a region highly implicated in reward and motivation. We investigated functional connectivity of the VS in individuals with and without a history of MDD, and in relation to affective personality traits. Forty-two individuals with rMDD and 28 healthy controls across two sites completed resting-state fMRI and the Behavioral Inhibition System/Behavioral Activation System Scale. Voxel-wise, whole-brain comparisons were conducted across and between groups for four seeds: left and right inferior VS (VSi), left and right superior VS (VSs). VSs connectivity to temporal and subcortical regions including the putamen and amygdala was positive and greater in HCs compared to rMDD individuals. Across groups, VSi connectivity was positively correlated with trait reward-responsiveness in somatomotor regions. Across groups, VSs connectivity was positively correlated with trait drive, particularly in the putamen, parahippocampal, and inferior temporal gyrus, and was negatively associated with trait behavioral inhibition in the anterior cingulate, frontal gyri, and insula. Limitations include scanning at two sites and using multiple comparisons. Group connectivity differences emerged from the VSs rather than VSi. VSs showed associations with trait drive and behavioral inhibition, whereas VSi corrrelated with reward-responsiveness. Depression history and affective traits contribute meaningful and specific information about VS connectivity in understanding risk for MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Stressful Life Events in a Clinical Sample of Depressed Children in Hungary

PubMed Central

Mayer, László; Lopez-Duran, Nestor L.; Kovacs, Maria; George, Charles; Baji, Ildikó; Kapornai, Krisztina; Kiss, Enikő; Vetró, Ágnes

2009-01-01

Background There is limited information on the characteristics of stressful life events in depressed pediatric clinical populations and the extent to which sex, age, and their interactions may influence the relations of life events and depression. Using a very large clinical sample of children and adolescents with major depressive disorder (MDD), we therefore examined life events in various ways as well as their relations to age and sex. Method The study included a clinic-based sample of 434 children (ages 7–14) with a DSM-IV diagnosis of MDD and their mothers, and a school-based comparison sample of 724 children and their mothers. Life event information was obtained from the mothers. Results Children with MDD had twice the number of lifetime stressful events than did the comparison group, with very high levels of stressors by the age of 7–9 that stabilized across adolescence. In contrast, the comparison sample experienced a gradual increase in stressful life events as a function of age up to mid-adolescence. Parental health events, death of close relatives, and intra-familial events were significantly associated with MDD diagnosis. There were significantly stronger associations between parental health- as well as death-event clusters and MDD diagnosis among younger children than adolescents. Limitations Geographical differences between the clinical and comparison samples, as well as possible parental reporting biases may affect the generalizability of these findings. Conclusion The association between some stressful life events and MDD seems to be moderated by age, underscoring the need to examine specific events, as well as clusters of events. Better understanding of such interactions may facilitate early identification of possible risk factors for pediatric MDD. PMID:18845343

Stressful life events in a clinical sample of depressed children in Hungary.

PubMed

Mayer, László; Lopez-Duran, Nestor L; Kovacs, Maria; George, Charles J; Baji, Ildikó; Kapornai, Krisztina; Kiss, Eniko; Vetró, Agnes

2009-05-01

There is limited information on the characteristics of stressful life events in depressed pediatric clinical populations and the extent to which sex, age, and their interactions may influence the relations of life events and depression. Using a very large clinical sample of children and adolescents with major depressive disorder (MDD), we therefore examined life events in various ways, as well as their relations to age and sex. The study included a clinic-based sample of 434 children (ages 7-14) with a DSM-IV diagnosis of MDD and their mothers, and a school-based comparison sample of 724 children and their mothers. Life event information was obtained from the mothers. Children with MDD had twice the number of lifetime stressful events than did the comparison group, with very high levels of stressors by the age of 7-9 that stabilized across adolescence. In contrast, the comparison sample experienced a gradual increase in stressful life events as a function of age up to mid-adolescence. Parental health events, death of close relatives, and intrafamilial events were significantly associated with MDD diagnosis. There were significantly stronger associations between parental health- as well as death-event clusters and MDD diagnosis among younger children than adolescents. Geographical differences between the clinical and comparison samples, as well as possible parental reporting biases may affect the generalizability of these findings. The association between some stressful life events and MDD seems to be moderated by age, underscoring the need to examine specific events, as well as clusters of events. Better understanding of such interactions may facilitate early identification of possible risk factors for pediatric MDD.

Differential urinary metabolites related with the severity of major depressive disorder.

PubMed

Chen, Jian-Jun; Zhou, Chan-Juan; Zheng, Peng; Cheng, Ke; Wang, Hai-Yang; Li, Juan; Zeng, Li; Xie, Peng

2017-08-14

Major depressive disorder (MDD) is a common mental disorder that affects a person's general health. However, there is still no objective laboratory test for diagnosing MDD. Here, an integrated analysis of data from our previous studies was performed to identify the differential metabolites in the urine of moderate and severe MDD patients. A dual platform approach (NMR spectroscopy and GC-MS) was used. Consequently, 14 and 22 differential metabolites responsible for separating moderate and severe MDD patients, respectively, from their respective healthy controls (HCs) were identified. Meanwhile, the moderate MDD-specific panel (N-Methylnicotinamide, Acetone, Choline, Citrate, vanillic acid and azelaic acid) and severe MDD-specific panel (indoxyl sulphate, Taurine, Citrate, 3-hydroxyphenylacetic acid, palmitic acid and Lactate) could discriminate moderate and severe MDD patients, respectively, from their respective HCs with high accuracy. Moreover, the differential metabolites in severe MDD were significantly involved in three metabolic pathways and some biofunctions. These results showed that there were divergent urinary metabolic phenotypes in moderate and severe MDD patients, and the identified potential urinary biomarkers might be useful for future developing objective diagnostic tests for MDD diagnosis. Our results could also be helpful for researchers to study the pathogenesis of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Unique and related predictors of major depressive disorder, posttraumatic stress disorder, and their comorbidity after Hurricane Katrina.

PubMed

Nillni, Yael I; Nosen, Elizabeth; Williams, Patrick A; Tracy, Melissa; Coffey, Scott F; Galea, Sandro

2013-10-01

The current study examined demographic and psychosocial factors that predict major depressive disorder (MDD) and comorbid MDD/posttraumatic stress disorder (MDD/PTSD) diagnostic status after Hurricane Katrina, one of the deadliest and costliest hurricanes in the history of the United States. This study expanded on the findings published in the article by Galea, Tracy, Norris, and Coffey (J Trauma Stress 21:357-368, 2008), which examined the same predictors for PTSD, to better understand related and unique predictors of MDD, PTSD, and MDD/PTSD comorbidity. A total of 810 individuals representative of adult residents living in the 23 southernmost counties of Mississippi before Hurricane Katrina were interviewed. Ongoing hurricane-related stressors, low social support, and hurricane-related financial loss were common predictors of MDD, PTSD, and MDD/PTSD, whereas educational and marital status emerged as unique predictors of MDD. Implications for postdisaster relief efforts that address the risk for both MDD and PTSD are discussed.

Epidemiology of Major Depressive Disorder Disability in the US Military: FY 2007-2012.

PubMed

Packnett, Elizabeth R; Elmasry, Hoda; Toolin, Christine F; Cowan, David N; Boivin, Michael R

2017-09-01

This study assesses the incidence of major depressive disorder (MDD) disability discharge and retirement in the Army, Navy, Marine Corps and Air Force and describes MDD comorbidity. Service members with a disability discharge for either MDD (n = 2,882) or any nonpsychiatric disability (n = 56,145), between fiscal years 2007 and 2012, were included in the study population. Those with MDD disability at first evaluation but not at last evaluation were excluded. The incidence of MDD disability discharge increased significantly in the Army and Air Force between fiscal years 2007 and 2012. MDD disability retirement significantly increased in the Army, Navy, and Air Force. Females, and those who experienced at least one deployment, had higher incidence rates of MDD disability discharge. All services included spinal diseases and posttraumatic stress disorder in their top five comorbid categories. Given the association between trauma and MDD, further research into the role of both combat exposure and injury on MDD is merited.

The effects of co-morbidity in defining major depression subtypes associated with long-term course and severity.

PubMed

Wardenaar, K J; van Loo, H M; Cai, T; Fava, M; Gruber, M J; Li, J; de Jonge, P; Nierenberg, A A; Petukhova, M V; Rose, S; Sampson, N A; Schoevers, R A; Wilcox, M A; Alonso, J; Bromet, E J; Bunting, B; Florescu, S E; Fukao, A; Gureje, O; Hu, C; Huang, Y Q; Karam, A N; Levinson, D; Medina Mora, M E; Posada-Villa, J; Scott, K M; Taib, N I; Viana, M C; Xavier, M; Zarkov, Z; Kessler, R C

2014-11-01

Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question. Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes. Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6-72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors. Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion.

What does the electroencephalogram tell us about the mechanisms of action of ECT in major depressive disorders?

PubMed

Farzan, Faranak; Boutros, Nash N; Blumberger, Daniel M; Daskalakis, Zafiris J

2014-06-01

Electroconvulsive therapy (ECT) remains to be one of the most effective treatment options in treatment-resistant major depressive disorder (MDD). From the early days, researchers have embarked on extracting information from electroencephalography (EEG) recordings before, during, and after ECT to identify neurophysiological targets of ECT and discover EEG predictors of response to ECT in patients with MDD. In this article, we provide an overview of visually detected and quantitative EEG features that could help in furthering our understanding of the mechanisms of action of ECT in MDD. We further discuss the EEG findings in the context of postulated hypotheses of ECT therapeutic pathways. We introduce an alternative and unifying hypothesis suggesting that ECT may exert its therapeutic efficacy through resetting the aberrant functional connectivity and promoting the generation of new and healthy connections in brain regions implicated in MDD pathophysiology, a mechanism that may be in part mediated by the ECT-induced activation of inhibitory and neuroplasticity mechanisms. We further discuss the added value of EEG markers in the larger context of ECT research and as complementary to neuroimaging and genetic markers. We conclude by drawing attention to the need for longitudinal studies in large cohort of patients and the need for standardization and validation of EEG algorithms of functional connectivity across studies to facilitate the translation of EEG correlates of ECT response in routine clinical practice.

Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression

PubMed Central

Posner, Jonathan; Cha, Jiook; Wang, Zhishun; Talati, Ardesheer; Warner, Virginia; Gerber, Andrew; Peterson, Bradley S; Weissman, Myrna

2016-01-01

Research into the pathophysiology of major depressive disorder (MDD) has focused largely on individuals already affected by MDD. Studies have thus been limited in their ability to disentangle effects that arise as a result of MDD from precursors of the disorder. By studying individuals at high familial risk for MDD, we aimed to identify potential biomarkers indexing risk for developing MDD, a critical step toward advancing prevention and early intervention. Using resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 111 individuals, aged 11–60 years, at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Based on rs-fcMRI, individuals at high vs low familial risk for depression showed increased DMN connectivity, as well as decreased DMN-CEN-negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMN-CEN-negative connectivity. Path analyses indicated that decreased DMN-CEN-negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Our findings suggest that DMN and DMN-CEN connectivity differ in those at high vs low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD. PMID:26593265

Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression.

PubMed

Posner, Jonathan; Cha, Jiook; Wang, Zhishun; Talati, Ardesheer; Warner, Virginia; Gerber, Andrew; Peterson, Bradley S; Weissman, Myrna

2016-06-01

Research into the pathophysiology of major depressive disorder (MDD) has focused largely on individuals already affected by MDD. Studies have thus been limited in their ability to disentangle effects that arise as a result of MDD from precursors of the disorder. By studying individuals at high familial risk for MDD, we aimed to identify potential biomarkers indexing risk for developing MDD, a critical step toward advancing prevention and early intervention. Using resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 111 individuals, aged 11-60 years, at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Based on rs-fcMRI, individuals at high vs low familial risk for depression showed increased DMN connectivity, as well as decreased DMN-CEN-negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMN-CEN-negative connectivity. Path analyses indicated that decreased DMN-CEN-negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Our findings suggest that DMN and DMN-CEN connectivity differ in those at high vs low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD.

Clinical features and risk factors for post-partum depression in a large cohort of Chinese women with recurrent major depressive disorder

PubMed Central

Tian, Tian; Li, Yihan; Xie, Dong; Shen, Yifeng; Ren, Jianer; Wu, Wenyuan; Guan, Chengbin; Zhang, Zhen; Zhang, Danning; Gao, Chengge; Zhang, Xiaoming; Wu, Jinbo; Deng, Hong; Wang, Gang; Zhang, Yunshu; Shao, Yun; Rong, Han; Gan, Zhaoyu; Sun, Yan; Hu, Bin; Pan, Jiyang; Li, Yi; Sun, Shufan; Song, Libo; Fan, Xuesheng; Li, Yi; Zhao, Xiaochuan; Yang, Bin; Lv, Luxian; Chen, Yunchun; Wang, Xiaoli; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S.; Flint, Jonathan; Tian, Hongjun

2012-01-01

Background Post partum depression (PPD) is relatively common in China but its clinical characteristics and risk factors have not been studied. We set out to investigate whether known risk factors for PPD could be found in Chinese women. Methods A case control design was used to determine the impact of known risk factors for PPD in a cohort of 1970 Chinese women with recurrent DSM-IV major depressive disorder (MDD). In a within-case design we examined the risk factors for PPD in patients with recurrent MDD. We compared the clinical features of MDD in cases with PPD to those without MDD. Odds ratios were calculated using logistic and ordinal regression. Results Lower occupational and educational statuses increased the risk of PPD, as did a history of pre-menstrual symptoms, stressful life events and elevated levels of the personality trait of neuroticism. Patients with PPD and MDD were more likely to experience a comorbid anxiety disorder, had a younger age of onset of MDD, have higher levels of neuroticism and dysthymia. Limitations Results obtained in this clinical sample may not be applicable to PPD within the community. Data were obtained retrospectively and we do not know whether the correlations we observe have the same causes as those operating in other populations. Conclusions Our results are consistent with the hypothesis that the despite cultural differences between Chinese and Western women, the phenomenology and risk factors for PPD are very similar. PMID:21824665

A history of major depressive disorder and the response to stress.

PubMed

Ilgen, Mark A; Hutchison, Kent E

2005-06-01

The occurrence of Major Depressive Disorder (MDD) has been linked to an increased vulnerability to stress. However, the specific behavioral and affective aspects that may underlie this vulnerability to stress have not been well studied. This study examined sensitivity to a stress manipulation in 62 participants, 30 with and 32 without a previous episode of MDD. Comparisons were made between those with a history of depression and those without, randomized to either the high or low stress conditions on self-report measures of affect and behavior measures of performance. A significant interaction was found between depression history and level of stress on measures of self-report tension and behavioral performance on the experimental task. Specifically, those with a history of MDD in the high stress condition reported significantly more tension than other participants. Additionally, participants in the high stress condition without a history of MDD responded to uncontrollable stress by responding at a significantly higher rate on the task while those individuals with a history of MDD responded to uncontrollable stress by maintaining a relatively low level of responding. No differences in self-report depressed affect were found. The study utilized a laboratory stressor in a sample composed primarily of college students. A history of MDD appears to be associated with an increased sensitivity to uncontrollable stress. This vulnerability may manifest itself in the subjective state of individuals (i.e., tension) or in their behavioral responses to stress.

Hippocampal shape deformation in female patients with unremitting major depressive disorder.

PubMed

Tae, W S; Kim, S S; Lee, K U; Nam, E C; Choi, J W; Park, J I

2011-04-01

The hippocampal atrophy of MDD has been known, but the region shape contractions of the hippocampus in MDD were inconsistent. Spheric harmonic shape analysis was applied to the hippocampus in female patients with unremitting MDD to evaluate morphometric changes of the hippocampus. Shape analysis was performed by using T1-weighted MR imaging in 21 female patients with MDD and 21 age- and sex-matched healthy controls. Manually segmented hippocampi were parameterized, and the point-to-point-based group difference was compared by using the Hotelling T-squared test. The partial correlation analyses were tested between clinical variables and shape changes. Both hippocampal volumes were small in patients with MDD compared with healthy controls, and the right hippocampal volume was negatively correlated with the number of episodes at marginal significance. Regional shape contractions were found in the ambient gyrus, basal hippocampal head, posterior subiculum, and dorsal hippocampus of the left hemisphere. The right hippocampus showed a similar pattern but was less atrophic compared with the left hippocampus. A negative correlation was found between the HDRS and shape deformation in the CA3, ambient gyrus, posterior subiculum, and gyrus fasciolaris of the left hippocampus. We showed atrophy and regional shape contractions in the hippocampi of patients with MDD, which were more dominant on the left side. The causes of hippocampal damage could be the hypersecretion of glucocorticoids contributing to neuronal death or the failing of adult neurogenesis in the dentate gyrus.

Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions

PubMed Central

Moreno, Carmen; Hasin, Deborah S.; Arango, Celso; Oquendo, Maria A.; Vieta, Eduard; Liu, Shangmin; Grant, Bridget F.; Blanco, Carlos

2012-01-01

Objectives To compare the clinical features and course of major depressive episodes (MDE) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Methods Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001–2002), a nationally representative face-to-face survey of more than 43,000 adults in the United States, including 5,695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Results Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent—and number of depressive symptoms per MDE were higher—among subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDE, had the worst quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about 10 years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Conclusions Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications. PMID:22548900

Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder.

PubMed

Kim, Yong-Ku; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

2014-04-01

Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk. Copyright © 2014 Elsevier B.V. All rights reserved.

Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

PubMed

Moreno, Carmen; Hasin, Deborah S; Arango, Celso; Oquendo, Maria A; Vieta, Eduard; Liu, Shangmin; Grant, Bridget F; Blanco, Carlos

2012-05-01

To compare the clinical features and course of major depressive episodes (MDEs) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002), a nationally representative face-to-face survey of more than 43000 adults in the USA, including 5695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent-and number of depressive symptoms per MDE was higher-among subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDEs, had a poorer quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about ten years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications. © 2012 John Wiley and Sons A/S.

Italian neurologists' perception on cognitive symptoms in major depressive disorder.

PubMed

Neri, G; Serrati, C; Zolo, P; Cataldo, N; Ripellino, C

2016-09-01

The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians' perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists' perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists' socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients' functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists' perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.

Symptoms of major depressive disorder subsequent to child maltreatment: Examining change across multiple levels of analysis to identify transdiagnostic risk pathways.

PubMed

Shenk, Chad E; Griffin, Amanda M; O'Donnell, Kieran J

2015-11-01

Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: neuroendocrine, autonomic, affective, and emotion regulation. Female adolescents (N = 110; age range = 14-19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed 18 months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed.

Childhood depressive disorders.

PubMed

Wesselhöft, Rikke Thaarup

2016-10-01

Major depressive disorder (MDD) is a frequent and painful mental disorder considered among the five leading causes of disability in Western countries by the World Health Organization. MDD occurs at all ages, but childhood onset MDD has a more severe course with longer depressive episodes, more suicidality, and more frequent hospitalization, than later onset MDD. Childhood seems to be a window of opportunity for prevention of mental disorders, and subsequently prevention of MDD onset in childhood is recommended. Feasible prevention targets either individuals who present early signs of a given disorder but have not reached diagnostic threshold (indicated prevention) or individuals who are at increased risk for a disorder due to risk factor exposure (selective prevention). Indicated prevention is rational also for depressive disorders, because subthreshold depression (SD) in adults is found to be a precursor to MDD. The purpose of this thesis was to provide information necessary for the prevention of MDD onset in childhood. First, we examined whether the literature supports that SD is a MDD precursor also in children (systematic review). Second, we explored the risk that gender might constitute for pre-pubertal and post-pubertal onset MDD (register study). Third, we estimated the prevalence of SD and MDD in a large-scale pre-pubertal sample, and compared the clinical features of SD and MDD and potential risk factors (population-based study). The systematic review of the literature showed that SD in children and adolescents presents analogous comorbidity and symptom patterns (including self-harm symptoms). It also supports that SD is a precursor to MDD in children and adolescents causing poor outcomes like psychopathology, functional impairment and high use of health service. In the register study of Danish children and adolescents, we found a higher incidence of clinical MDD for girls after puberty compared to boys. Before puberty however, we demonstrated that boys had higher MDD incidence rates than girls. The population-based study including 3,421 8-10-year-old children from the Danish National Birth Cohort (DNBC) showed point prevalence estimates of 0.5% for MDD and 1.0% for SD. Children with SD by definition hold fewer depressive symptoms, but the ranking and frequency of these individual depressive symptoms was almost similar. Only irritability, anhedonia and worthlessness/guilt were more common in children with MDD. DNBC children with SD and MDD had comorbid anxiety or conduct/oppositional disorders just as frequently, and the degree of functional impairment was the same. When examining potential risk factors for SD and MDD, we found that poor general health, more than two stressful life events (SLE) within the past year, and a high level of maternal depressive symptoms were correlated to both SD and MDD. In addition we found epilepsy/convulsions, one SLE within the past year and parental divorce/separation to be correlated to MDD. In conclusion, the findings reported in this thesis underline that SD in childhood and adolescence is a significant condition calling for attention, due to the early onset, the risk for progression into MDD and the poor outcome. Indicated prevention aimed at MDD in childhood should target SD children who are characterised by fewer depressive symptoms but the same symptom pattern, the same level of impairment, and the same amount of comorbid anxiety and conduct/oppositional disorders, as presented by children with MDD. Selective preventive interventions could effectively target children who suffer from chronic physical illness and children whose mothers present depressive symptoms, also below clinical threshold. In addition, boys might have an increased risk for developing pre-pubertal MDD, but this has to be explored further in non-clinical samples. We recommend that more attention is paid to children and adolescents with subthreshold depressive symptoms who also pre-sent significant functional impairment. Emphasis must be put on the risk for SD transforming into MDD, especially in those exposed to the potential risk factors identified in this thesis.

Psychiatric comorbidities in patients with major depressive disorder.

PubMed

Thaipisuttikul, Papan; Ittasakul, Pichai; Waleeprakhon, Punjaporn; Wisajun, Pattarabhorn; Jullagate, Sudawan

2014-01-01

Psychiatric comorbidities are common in major depressive disorder (MDD). They may worsen outcome and cause economic burden. The primary objective was to examine the prevalence of psychiatric comorbidities in MDD. The secondary objectives were to compare the presence of comorbidities between currently active and past MDD, and between patients with and without suicidal risk. This was a cross-sectional study. A total of 250 patients with lifetime MDD and age ≥18 years were enrolled. The Mini International Neuropsychiatric Interview (MINI), Thai version, was used to confirm MDD diagnosis and classify comorbidities. MDD diagnosis was confirmed in 190, and 60 patients were excluded due to diagnosis of bipolar disorder. Of the 190 MDD patients, 25.8% had current MDD and 74.2% had past MDD. Eighty percent were women. The mean age at enrollment was 50 years, and at MDD onset was 41 years. Most patients were married (53.2%), employed (54.8%), and had ≥12 years of education (66.9%). There were 67 patients (35.3%) with one or more psychiatric comorbidities. Comorbidities included dysthymia (19.5%), any anxiety disorders (21.1%) (panic disorder [6.8%], agoraphobia [5.8%], social phobia [3.7%], obsessive-compulsive disorder [OCD] [4.7%], generalized anxiety disorder [5.3%], and post-traumatic stress disorder [4.2%]), alcohol dependence (0.5%), psychotic disorder (1.6%), antisocial personality (1.1%), and eating disorders (0%). Compared with past MDD, the current MDD group had significantly higher OCD (P<0.001), psychotic disorder (P=0.048), past panic disorder (P=0.017), and suicidal risk (P<0.001). Suicidal risk was found in 32.1% of patients. Patients with suicidal risk had more comorbid anxiety disorder of any type (P=0.019) and psychotic disorder (P=0.032). Several comorbidities were associated with MDD. Patients with active MDD had higher comorbid OCD, psychotic disorder, past panic disorder, and suicidal risk. Patients with suicide risk had higher comorbid anxiety and psychotic disorders.

Symptoms of major depression in people with spinal cord injury: implications for screening.

PubMed

Bombardier, Charles H; Richards, J Scott; Krause, James S; Tulsky, David; Tate, Denise G

2004-11-01

To provide psychometric data on a self-report measure of major depressive disorder (MDD) and to determine whether somatic symptoms are nonspecific or count toward the diagnosis. Survey. Data from the National Spinal Cord Injury Statistical Center representing 16 Model Spinal Cord Injury Systems. Eight hundred forty-nine people with spinal cord injury who completed a standardized follow-up evaluation 1 year after injury. Not applicable. The Patient Health Questionnaire-9 (PHQ-9), a measure of MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition . We computed descriptive statistics on rates of depressive symptoms and probable MDD, evaluated internal consistency and construct validity, and analyzed the accuracy of individual items as predictors of MDD. Exactly 11.4% of participants met criteria for probable MDD. Probable MDD was associated with poorer subjective health, lower satisfaction with life, and more difficulty in daily role functioning. Probable MDD was not related to most demographic or injury-related variables. Both somatic and psychologic symptoms predicted probable MDD. The PHQ-9 has promise as a tool with which to identify probable MDD in people with SCI. Somatic symptoms should be counted toward the diagnosis and should alert health care providers to the likelihood of MDD. More efficient screening is only one of the quality improvement efforts needed to enhance management of MDD.

Major depressive disorder symptoms in male and female young adults.

PubMed

Lopez Molina, Mariane Acosta; Jansen, Karen; Drews, Cláudio; Pinheiro, Ricardo; Silva, Ricardo; Souza, Luciano

2014-01-01

This research aimed to compare the prevalence rates of major depressive disorder (MDD) and to differentiate the presence and severity of depressive symptoms between women and men aged 18-24 years. In this population-based, cross-sectional study (n = 1560), young adults were screened with the Mini International Neuropsychiatric Interview for MDD (n = 137). Participants then completed a self-report questionnaire to gather sociodemographic data, and the presence of each symptom of depression was assessed with the Beck Depression Inventory. The proportion of women (12.2%) with MDD was higher than that of men (5.3%). The symptoms of depression found to be significantly more prevalent in women were sadness, crying, difficulty making decisions, and lack of energy, as well as self-criticism, irritability, changes in self-image, work difficulty, and loss of interest in sex. Sadness and self-criticism were significantly more severe in women than in men. The presentation of depressive symptoms in young adults with MDD differed between men and women.

Depression and cardiovascular disease: Epidemiological evidence on their linking mechanisms.

PubMed

Penninx, Brenda W J H

2017-03-01

Depression's burden of disease goes beyond functioning and quality of life and extends to somatic health. Results from longitudinal cohort studies converge in illustrating that major depressive disorder (MDD) subsequently increases the risk of cardiovascular morbidity and mortality with about 80%. The impact of MDD on cardiovascular health may be partly explained by mediating mechanisms such as unhealthy lifestyle (smoking, excessive alcohol use, physical inactivity, unhealthy diet, therapy non-compliance) and unfavorable pathophysiological disturbances (autonomic, HPA-axis, metabolic and immuno-inflammatory dysregulations). A summary of the literature findings as well as relevant results from the large-scale Netherlands Study of Depression and Anxiety (N=2981) are presented. Persons with MDD have significantly worse lifestyles as well as more pathophysiological disturbances as compared to healthy controls. Some of these differences seem to be specific for (typical versus 'atypical', or antidepressant treated versus drug-naive) subgroups of MDD patients. Alternative explanations are also present, namely undetected confounding, iatrogenic effects or 'third factors' such as genetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Negative Affect Instability among Individuals with Comorbid Borderline Personality Disorder and Posttraumatic Stress Disorder

PubMed Central

Scheiderer, Emily M.; Wang, Ting; Tomko, Rachel L.; Wood, Phillip K.; Trull, Timothy J.

2015-01-01

Ecological momentary assessment (EMA; Stone & Shiffman, 1994) was utilized to examine affective instability (AI) in the daily lives of outpatients with borderline personality disorder (BPD; n=78) with and without posttraumatic stress disorder (PTSD). A psychiatric control group (n=50) composed of outpatients with major depressive disorder/dysthymia (MDD/DYS) was employed to compare across subgroups: BPD-only, BPD+PTSD, MDD/DYS-only, and MDD/DYS+PTSD. Compared to the BPD-only group, the BPD+PTSD group had significantly greater instability of fear and sadness, but did not significantly differ in instability of hostility or aggregate negative affect. This pattern of elevated instability of fear and sadness was not present—and, in fact, was reversed—in the MDD/DYS group. Results emphasize the importance of examining AI within the context of specific comorbidities and affect types. Treatment and research addressing AI in the context of BPD-PTSD comorbidity may benefit from a focus on fear and sadness as separate from hostility or general negative affect. PMID:26904388

Stigmatizing attitudes differ across mental health disorders: a comparison of stigma across eating disorders, obesity, and major depressive disorder.

PubMed

Ebneter, Daria S; Latner, Janet D

2013-04-01

The aim of the current article was to compare stigmatizing attitudes toward eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), with stigma toward another weight-related condition (obesity) and a non-weight-related mental disorder (major depressive disorder [MDD]). Participants (N = 447) read five vignettes describing a woman with AN, BN, BED, obesity, or MDD and responded to questionnaires examining stigmatizing attitudes. The targets with EDs were blamed more for their condition than the targets with MDD, whereas persons with obesity were held more responsible for their condition than any other target. On the other hand, the target with MDD was perceived as more impaired than any other target. Lack of self-discipline was attributed more to the development of BED and obesity than to any other condition. Stigmatizing attitudes vary across mental health disorders, and future research should aim to specifically target stigmatizing beliefs to reduce and prevent discrimination toward mental health disorders and obesity.

Suicidal risk in young adult offspring of mothers with bipolar or major depressive disorder: a longitudinal family risk study.

PubMed

Klimes-Dougan, Bonnie; Lee, Chih-Yuan S; Ronsaville, Donna; Martinez, Pedro

2008-04-01

Recent evidence has highlighted suicidal risk associated with bipolar disorder (BD). Using a family risk approach, the goal of this study was to evaluate suicidal thoughts and behaviors longitudinally from childhood to young adulthood in children of mothers with BD, Major depressive disorder (MDD), and well mothers. Few group differences were found for cross-sectional assessments of suicidal thoughts and behavior in young adulthood; the offspring of MDD demonstrate an earlier onset and more persistent suicidality than other groups, but by young adulthood, BD offspring appear to be comparable to MDD offspring in their rates of suicidality. The longitudinal assessments reveal a pattern of higher suicidal risk in MDD offspring, more intermediate risk in BD offspring, and lower risk in well offspring. Precursors and correlates of suicidal thoughts and behaviors were also examined. These findings suggest diverse developmental trajectories based on family risk and have implications for planning preventive intervention.

Theory of mind in social anxiety disorder, depression, and comorbid conditions.

PubMed

Washburn, Dustin; Wilson, Gillian; Roes, Meighen; Rnic, Katerina; Harkness, Kate Leslie

2016-01-01

Social anxiety disorder is characterized by marked interpersonal impairment, particularly when presenting with comorbid major depression. However, the foundational social-cognitive skills that underlie interpersonal impairment in comorbid and non-comorbid manifestations of SAD has to date received very little empirical investigation. In a sample of 119 young adults, the current study examined differences in theory of mind (ToM), defined as the ability to decode and reason about others' mental states, across four groups: (a) non-comorbid SAD; (b) non-comorbid Lifetime MDD; (c) comorbid SAD and Lifetime MDD; and (d) healthy control. The non-comorbid SAD group was significantly less accurate at decoding mental states than the non-comorbid MDD and control groups. Further, both the comorbid and non-comorbid SAD groups made significantly more 'excessive' ToM reasoning errors than the non-comorbid MDD group, suggesting a pattern of over-mentalizing. Findings are discussed in terms of their implications for understanding the social cognitive foundations of social anxiety. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of antidepressants for major depressive disorder in children and adolescents: clinical considerations.

PubMed

Picouto, María Dolores; Braquehais, María Dolores

2013-01-01

Major depressive disorder (MDD) is a frequent condition among children and, especially, among adolescents. However, its clinical presentation usually differs from that of adults. It is also associated with other diagnoses and with an increased morbidity and mortality. However, MDD in this population remains underrecognized and undertreated. Antidepressants (ATDs) are chosen when psychoeducational, psychosocial and/or psychotherapeutic approaches have failed. ATDs are generally used in severe cases, and are always combined with psychological treatments. The objective of this work is to discuss the role of ATD in child and adolescent MDD. We focus on the recommendations of the most cited and updated clinical guidelines and discuss some controversial aspects with regards efficacy and safety issues that have been raised based on the information obtained from clinical trials. Finally, we offer some practical recommendations for clinicians. All these findings also pose some doubt on the hypothesis of MDD as a homogeneous phenomenon during the human life cycle.

Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome.

PubMed

Goldstein, Jill M; Holsen, Laura; Huang, Grace; Hammond, Bradley D; James-Todd, Tamarra; Cherkerzian, Sara; Hale, Taben M; Handa, Robert J

2016-12-01

Major depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature. Furthermore, these effects have lifelong consequences for shared sex-dependent risk of MDD and obesity/MetS. Thus, we propose that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.

Epigenetic differences in monozygotic twins discordant for major depressive disorder

PubMed Central

Malki, K; Koritskaya, E; Harris, F; Bryson, K; Herbster, M; Tosto, M G

2016-01-01

Although monozygotic (MZ) twins share the majority of their genetic makeup, they can be phenotypically discordant on several traits and diseases. DNA methylation is an epigenetic mechanism that can be influenced by genetic, environmental and stochastic events and may have an important impact on individual variability. In this study we explored epigenetic differences in peripheral blood samples in three MZ twin studies on major depressive disorder (MDD). Epigenetic data for twin pairs were collected as part of a previous study using 8.1-K-CpG microarrays tagging DNA modification in white blood cells from MZ twins discordant for MDD. Data originated from three geographical regions: UK, Australia and the Netherlands. Ninety-seven MZ pairs (194 individuals) discordant for MDD were included. Different methods to address non independently-and-identically distributed (non-i.i.d.) data were evaluated. Machine-learning methods with feature selection centered on support vector machine and random forest were used to build a classifier to predict cases and controls based on epivariations. The most informative variants were mapped to genes and carried forward for network analysis. A mixture approach using principal component analysis (PCA) and Bayes methods allowed to combine the three studies and to leverage the increased predictive power provided by the larger sample. A machine-learning algorithm with feature reduction classified affected from non-affected twins above chance levels in an independent training-testing design. Network analysis revealed gene networks centered on the PPAR−γ (NR1C3) and C-MYC gene hubs interacting through the AP-1 (c-Jun) transcription factor. PPAR−γ (NR1C3) is a drug target for pioglitazone, which has been shown to reduce depression symptoms in patients with MDD. Using a data-driven approach we were able to overcome challenges of non-i.i.d. data when combining epigenetic studies from MZ twins discordant for MDD. Individually, the studies yielded negative results but when combined classification of the disease state from blood epigenome alone was possible. Network analysis revealed genes and gene networks that support the inflammation hypothesis of MDD. PMID:27300265

Epigenetic differences in monozygotic twins discordant for major depressive disorder.

PubMed

Malki, K; Koritskaya, E; Harris, F; Bryson, K; Herbster, M; Tosto, M G

2016-06-14

Although monozygotic (MZ) twins share the majority of their genetic makeup, they can be phenotypically discordant on several traits and diseases. DNA methylation is an epigenetic mechanism that can be influenced by genetic, environmental and stochastic events and may have an important impact on individual variability. In this study we explored epigenetic differences in peripheral blood samples in three MZ twin studies on major depressive disorder (MDD). Epigenetic data for twin pairs were collected as part of a previous study using 8.1-K-CpG microarrays tagging DNA modification in white blood cells from MZ twins discordant for MDD. Data originated from three geographical regions: UK, Australia and the Netherlands. Ninety-seven MZ pairs (194 individuals) discordant for MDD were included. Different methods to address non independently-and-identically distributed (non-i.i.d.) data were evaluated. Machine-learning methods with feature selection centered on support vector machine and random forest were used to build a classifier to predict cases and controls based on epivariations. The most informative variants were mapped to genes and carried forward for network analysis. A mixture approach using principal component analysis (PCA) and Bayes methods allowed to combine the three studies and to leverage the increased predictive power provided by the larger sample. A machine-learning algorithm with feature reduction classified affected from non-affected twins above chance levels in an independent training-testing design. Network analysis revealed gene networks centered on the PPAR-γ (NR1C3) and C-MYC gene hubs interacting through the AP-1 (c-Jun) transcription factor. PPAR-γ (NR1C3) is a drug target for pioglitazone, which has been shown to reduce depression symptoms in patients with MDD. Using a data-driven approach we were able to overcome challenges of non-i.i.d. data when combining epigenetic studies from MZ twins discordant for MDD. Individually, the studies yielded negative results but when combined classification of the disease state from blood epigenome alone was possible. Network analysis revealed genes and gene networks that support the inflammation hypothesis of MDD.

Major depressive disorder: gender differences in symptoms, life quality, and sexual function.

PubMed

Lai, Chien-Han

2011-02-01

To investigate the gender differences of symptoms, life quality, functional impairment, and sexual function of patients with moderately severe major depressive disorder (MDD). One hundred forty-six outpatients with MDD were enrolled into this study with specific selection criteria (male, 57; female, 89; mean ± SD age, 38.30 ± 11.69 years). All the patients self-rated the Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR16) and the Integral Inventory for Depression (IID) for the assessment of symptoms assessment as well as the EuroQol life quality scale (EQ5D) was for the subjective life quality, the Sheehan disability scale was for the functional impairments, and the Arizona Sexual Experience Scale was for sexual function evaluation. All data were analyzed to estimate correlation and gender difference. Female patients had higher scores of the QIDS-SR16, IID, and Arizona Sexual Experience scales. Significant gender differences of sadness, sleep, appetite, calmness, painful symptoms, and sexual functioning were observed. The female-specific sexual dysfunctions included lower sexual drive, lower sexual arousal, lower horny feelings, lower orgasms, and lower satisfaction of orgasm. The MDD episodes were related to the EuroQol life quality scale and the SDS. Interepisode years were associated with the IID. The Sheehan disability scale was correlated with QIDS-SR16 with statistical significance. Patients with MDD showed a correlation between symptoms and functional impairment. Female patients might be more sexually impaired, more vegetative, more depressed, and experiencing more sadness and physical pain.

Ethnic Variations in Psychosocial and Health Correlates of Eating Disorders.

PubMed

Assari, Shervin; DeFreitas, Mariana R

2018-04-25

The aim of this study is to explore ethnic variations in psychosocial and health correlates of eating disorders in the United States, Specifically, we compared associations between gender, socioeconomic status (SES), body mass index (BMI), physical and mental self-rated health (SRH), and major depressive disorder (MDD) with eating disorders (EDs) across 10 different ethnic groups in the United States. Data was obtained from the Collaborative Psychiatric Epidemiology Surveys (CPES), a national household probability sample collected in 2001⁻2003. Data for this study included a sample of 17,729 individuals with the following ethnic profile: 520 Vietnamese, 508 Filipino, 600 Chinese, 656 Other Asian, 577 Cuban, 495 Puerto Rican, 1442 Mexican, 1106 Other Hispanic, 4746 African American, and 7587 Non-Latino Whites. Gender, SES (education and income), BMI, SRH, MDD, and presence of EDs were measured across different ethnic groups. Logistic regression analysis was conducted for each ethnic group with lifetime EDs as the main outcome. Ethnic group varied in psychosocial and health correlates of EDs. In most ethnic groups, gender and SES were not associated with EDs. In almost all ethnic groups, EDs were associated with MDD and BMI. EDs were found to be associated with SRH in half of the ethnic groups studied. The associations between gender, SES, BMI, SRH, MDD, and EDs vary across different ethnic groups. These differences must be considered in further studies and in clinical practice in order to improve our approach towards diagnosis and treatment of EDs.

Disentangling dysthymia from major depressive disorder in suicide attempters' suicidality, comorbidity and symptomatology.

PubMed

Holmstrand, Cecilia; Engström, Gunnar; Träskman-Bendz, Lil

2008-01-01

Dysthymia and major depressive disorder (MDD) are both risk diagnoses for suicidal behaviour. The aim of the present study was to identify clinical differences between these disorders, with a special reference to dysthymia. We studied suicidal behaviour, comorbidity and psychiatric symptoms of inpatient suicide attempters with dysthymia and MDD. We used DSM III-R diagnostics, the Suicide Assessment Scale (SUAS) and the Comprehensive Psychopathological Rating Scale (CPRS), part of which is the Montgomery and Asberg Depression Rating Scale (MADRS). Suicide mortality, number of repeated suicide attempts, method of suicide attempt and comorbidity of Axis I did not differ between the groups. Dysthymia patients, however, suffered more than MDD patients from DSM-III-R Axis II diagnoses (above all cluster B). There was no significant difference in Axis III comorbidity. Total SUAS, CPRS and MADRS scores did not differ significantly between the groups. When studying separate SUAS and CPRS items in a multivariate analysis, the CPRS items "aches and pains", "increased speech flow", increased "agitation" and "less tendency to worrying over trifles" as well as young age remained independently associated with dysthymia. Dysthymia patients, who later committed suicide, more often reported increased "aches and pains" than those who did not commit suicide. In this small sample of suicide attempters, we conclude that dysthymia suicide attempters, more often than MDD patients, have a comorbidity with personality disorders, which combined with a picture of aches and pains, could be factors explaining their suicidality.

Family history of completed suicide and characteristics of major depressive disorder: a STAR*D (sequenced treatment alternatives to relieve depression) study.

PubMed

Nierenberg, Andrew A; Alpert, Jonathan E; Gaynes, Bradley N; Warden, Diane; Wisniewski, Stephen R; Biggs, Melanie M; Trivedi, Madhukar H; Barkin, Jennifer L; Rush, A John

2008-05-01

Clinicians routinely ask patients with non-psychotic major depressive disorder (MDD) about their family history of suicide. It is unknown, however, whether patients with a family member who committed suicide differ from those without such a history. Patients were recruited for the STAR*D multicenter trial. At baseline, patients were asked to report first-degree relatives who had died from suicide. Differences in demographic and clinical features for patients with and without a family history of suicide were assessed. Patients with a family history of suicide (n=142/4001; 3.5%) were more likely to have a family history of MDD, bipolar disorder, or any mood disorder, and familial substance abuse disorder, but not suicidal thoughts as compared to those without such a history. The group with familial suicide had a more pessimistic view of the future and an earlier age of onset of MDD. No other meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. A history of completed suicide in a family member was associated with minimal clinical differences in the cross-sectional presentation of outpatients with MDD. Limitations of the study include lack of information about family members who had attempted suicide and the age of the probands when their family member died. STAR*D assessments were limited to those needed to ascertain diagnosis and treatment response and did not include a broader range of psychological measures.

Abnormalities in the fatty acid composition of the postmortem entorhinal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Hamazaki, Tomohito; Inadera, Hidekuni

2013-11-30

Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n-6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n-3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n-6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Family history of mood disorder and characteristics of major depressive disorder: a STAR*D (sequenced treatment alternatives to relieve depression) study.

PubMed

Nierenberg, Andrew A; Trivedi, Madhukar H; Fava, Maurizio; Biggs, Melanie M; Shores-Wilson, Kathy; Wisniewski, Stephen R; Balasubramani, G K; Rush, A John

2007-01-01

Clinicians routinely ask patients with major depressive disorder (MDD) about their family history. It is unknown, however, if patients who report a positive family history differ from those who do not. This study compared the demographic and clinical features of a large cohort of treatment-seeking outpatients with non-psychotic MDD who reported that they did or did not have at least one first-degree relative who had either MDD or bipolar disorder. Subjects were recruited for the STAR( *)D multicenter trial. Differences in demographic and clinical features for patients with and without a family history of mood disorders were assessed after correcting for age, sex, race, and ethnicity. Patients with a family history of mood disorder (n=2265; 56.5%) were more frequently women and had an earlier age of onset of depression, as compared to those without such a history (n=1740; 43.5%). No meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. Women were twice as likely as men to report a positive family history of mood disorder, and a positive family history was associated with younger age of onset of MDD in the proband. Consistent with prior research, early age of onset appears to define a familial and, by extension, genetic subtype of major depressive disorder.

Detrended fluctuation analysis for major depressive disorder.

PubMed

Mumtaz, Wajid; Malik, Aamir Saeed; Ali, Syed Saad Azhar; Yasin, Mohd Azhar Mohd; Amin, Hafeezullah

2015-01-01

Clinical utility of Electroencephalography (EEG) based diagnostic studies is less clear for major depressive disorder (MDD). In this paper, a novel machine learning (ML) scheme was presented to discriminate the MDD patients and healthy controls. The proposed method inherently involved feature extraction, selection, classification and validation. The EEG data acquisition involved eyes closed (EC) and eyes open (EO) conditions. At feature extraction stage, the de-trended fluctuation analysis (DFA) was performed, based on the EEG data, to achieve scaling exponents. The DFA was performed to analyzes the presence or absence of long-range temporal correlations (LRTC) in the recorded EEG data. The scaling exponents were used as input features to our proposed system. At feature selection stage, 3 different techniques were used for comparison purposes. Logistic regression (LR) classifier was employed. The method was validated by a 10-fold cross-validation. As results, we have observed that the effect of 3 different reference montages on the computed features. The proposed method employed 3 different types of feature selection techniques for comparison purposes as well. The results show that the DFA analysis performed better in LE data compared with the IR and AR data. In addition, during Wilcoxon ranking, the AR performed better than LE and IR. Based on the results, it was concluded that the DFA provided useful information to discriminate the MDD patients and with further validation can be employed in clinics for diagnosis of MDD.