Reduced Anterior Cingulate Glutamatergic Concentrations in Childhood Ocd and Major Depression Versus Healthy Controls

ERIC Educational Resources Information Center

Rosenberg, David R.; Mirza, Yousha; Russell, Aileen; Tang, Jennifer; Smith, Janet M.; Banerjee, Preeya S.; Bhandari, Rashmi; Rose, Michelle; Ivey, Jennifer; Boyd, Courtney; Moore, Gregory J.

2004-01-01

Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of pediatric patients with obsessive-compulsive disorder (OCD) without major depressive disorder (MDD) versus pediatric patients with MDD without OCD and healthy controls. Method: Single-voxel proton magnetic resonance spectroscopic examinations…

A comparison of the clinical characteristics of Chinese patients with recurrent major depressive disorder with and without dysthymia☆

PubMed Central

Sang, Wenhua; Li, Yihan; Su, Liang; Yang, Fuzhong; Wu, Wenyuan; Shang, Xiaofang; Zhang, Guanghua; Shen, Jianhua; Sun, Mengmeng; Guo, Liyang; Li, Zheng; Yan, Lijuan; Zhang, Bo; Wang, Gang; Liu, Guo; Liu, Tiebang; Zhang, Jinbei; Wang, Yanfang; Yu, Bin; Pan, Jiyang; Li, Yi; Hu, Chunmei; Yang, Lijun; Huang, Yongjin; Xie, Shoufu; Wang, Xueyi; Liu, Jiannin; Lv, Luxian; Chen, Yunchun; Zhang, Lina; Dang, Yamei; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S.; Flint, Jonathan; Li, Keqing

2011-01-01

Background The relationship between major depressive disorder (MDD) and dysthymia, a form of chronic depression, is complex. The two conditions are highly comorbid and it is unclear whether they are two separate disease entities. We investigated the extent to which patients with dysthymia superimposed on major depression can be distinguished from those with recurrent MDD. Methods We examined the clinical features in 1970 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and dysthymia and between dysthymia and disorders comorbid with major depression. Results The 354 cases with dysthymia had more severe MDD than those without, with more episodes of MDD and greater co-morbidity for anxiety disorders. Patients with dysthymia had higher neuroticism scores and were more likely to have a family history of MDD. They were also more likely to have suffered serious life events. Limitations Results were obtained in a clinically ascertained sample of Chinese women and may not generalize to community-acquired samples or to other populations. It is not possible to determine whether the associations represent causal relationships. Conclusions The additional diagnosis of dysthymia in Chinese women with recurrent MDD defines a meaningful and potentially important subtype. We conclude that in some circumstances it is possible to distinguish double depression from recurrent MDD. PMID:21824660

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.

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.

Lifetime comorbidities between phobic disorders and major depression in Japan: Results from the World Mental Health Japan 2002-2004 Survey

PubMed Central

Tsuchiya, Masao; Kawakami, Norito; Ono, Yutaka; Nakane, Yoshibumi; Nakamura, Yosikazu; Tachimori, Hisateru; Iwata, Noboru; Uda, Hidenori; Nakane, Hideyuki; Watanabe, Makoto; Naganuma, Yoichi; Furukawa, Toshiaki A.; Hata, Yukihiro; Kobayashi, Masayo; Miyake, Yuko; Takeshima, Tadashi; Kikkawa, Takehiko; Kessler, Ronald C.

2013-01-01

Background Although often considered of minor significance in themselves, evidence exists that early-onset phobic disorders might be predictors of later more serious disorders, such as major depressive disorder (MDD). The purpose of this study was to investigate the association of phobic disorders with the onset of MDD in the community in Japan. Methods Data from the World Mental Health Japan 2002-2004 Survey were analyzed. A total of 2,436 community residents aged 20 and older were interviewed using the WHO Composite International Diagnostic Interview 3.0 (response rate, 58.4%). A Cox proportional hazards model was used to predict the onset of MDD as a function of prior history of DSM-IV specific phobia, agoraphobia, or social phobia, adjusting for gender, birth cohort, other anxiety disorders, education, and marital status at survey. Results Social phobia was strongly associated with the subsequent onset of MDD (hazard ratio [HR] = 4.1 [95%CI: 2.0-8.7]) after adjusting for sex, birth cohort, and the number of other anxiety disorders. The association between agoraphobia or specific phobia and MDD was not statistically significant after adjusting for these variables. Conclusions Social phobia is a powerful predictor of the subsequent first onset of MDD in Japan. While this finding argues against a simple neurobiological model and in favor of a model in which the cultural meanings of phobia play a part in promoting MDD, an elucidation of causal pathways will require more fine-grained comparative research. PMID:19195005

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

The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study

PubMed Central

Nigatu, Yeshambel T.; Reijneveld, Sijmen A.; de Jonge, Peter; van Rossum, Elisabeth; Bültmann, Ute

2016-01-01

Background Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL), this study was aimed at examining these combined effects. Methods We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m2) as normal weight (18.5–24.99), overweight (25–29.9), mild obesity (30–34.9) and moderate/severe obesity (≥ 35); we measured abdominal obesity using a waist circumference of ≥102 and ≥ 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses. Results The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95%-confidence interval, 95%-CI) were: - 1.32 (-1.75; -0.90). However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL. Conclusions Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR-QoL. PMID:26866920

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

Age at onset of major depressive disorder in Han Chinese women: Relationship with clinical features and family history☆

PubMed Central

Yang, Fuzhong; Li, Yihan; Xie, Dong; Shao, Chunhong; Ren, Jianer; Wu, Wenyuan; Zhang, Ning; Zhang, Zhen; Zou, Ying; Zhang, Jiulong; Qiao, Dongdong; Gao, Chengge; Li, Youhui; Hu, Jian; Deng, Hong; Wang, Gang; Du, Bo; Wang, Xumei; Liu, Tiebang; Gan, Zhaoyu; Peng, Juyi; Wei, Bo; Pan, Jiyang; Chen, Honghui; Sun, Shufan; Jia, Hong; Liu, Ying; Chen, Qiaoling; Wang, Xueyi; Cao, Juling; Lv, Luxian; Chen, Yunchun; Ha, Baowei; Ning, Yuping; Chen, YiPing; Kendler, Kenneth S.; Flint, Jonathan; Shi, Shenxun

2011-01-01

Background Individuals with early-onset depression may be a clinically distinct group with particular symptom patterns, illness course, comorbidity and family history. This question has not been previously investigated in a Han Chinese population. Methods We examined the clinical features of 1970 Han Chinese women with DSM-IV major depressive disorder (MDD) between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models was used to determine the association between age at onset (AAO) with continuous, binary and discrete characteristic clinical features of MDD. Results Earlier AAO was associated with more suicidal ideation and attempts and higher neuroticism, but fewer sleep, appetite and weight changes. Patients with an earlier AAO were more likely to suffer a chronic course (longer illness duration, more MDD episodes and longer index episode), increased rates of MDD in their parents and a lower likelihood of marriage. They tend to have higher comorbidity with anxiety disorders (general anxiety disorder, social phobia and agoraphobia) and dysthymia. Conclusions Early AAO in MDD may be an index of a more severe, highly comorbid and familial disorder. Our findings indicate that the features of MDD in China are similar to those reported elsewhere in the world. PMID:21782247

The Bidirectional Relationships Between Alcohol, Cannabis, Co-occurring Alcohol and Cannabis Use Disorders with Major Depressive Disorder: Results From a National Sample

PubMed Central

Martins, Silvia S.; Crum, Rosa M.

2012-01-01

Introduction Alcohol use disorders (AUD) and cannabis use disorders (CUD) are common in the United States (US), and are associated with major depressive disorder (MDD). Co-occurring alcohol and cannabis use/use disorders (AUD+CUD), though understudied, have been found to be associated with greater adverse outcomes than alcohol or cannabis use/use disorders alone. There is a paucity of research on the co-occurring relationships of the two disorders with depression. Methods Data came from Waves 1 and 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a population-based longitudinal survey of the adult non-institutionalized, civilian population in the US. Logistic regression analyses were used to assess the associations between: 1) baseline AUD, CUD, and co-occurring AUD+CUD with incident MDD at follow-up and 2) baseline MDD with incident AUD, CUD, and co-occurring AUD+CUD at follow-up, adjusted for potential confounding variables. Results For Aim 1, most of the AUD and CUD were positively associated with MDD. The strongest associations with incident MDD were observed for cannabis dependence (OR=6.61, CI=1.67–26.21) and co-occurring alcohol and cannabis dependence (OR=2.34, CI=1.23–4.48). For Aim 2, baseline MDD was significantly associated with comparatively fewer cases of incident AUD and CUD but the strongest association was observed for new onset co-occurring alcohol and cannabis dependence (OR=4.51, CI=1.31–15.60). Limitations The present study is limited by the potential for social desirability and recall biases. Discussion Positive associations between AUD, CUD and MDD were observed bidirectionally. Findings have implications for preventive and treatment programs and initiatives. PMID:23260381

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

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.

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.

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.

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.

Escalation to Major Depressive Disorder among Adolescents with Subthreshold Depressive Symptoms: Evidence of Distinct Subgroups at Risk

PubMed Central

Hill, Ryan M.; Pettit, Jeremy W.; Lewinsohn, Peter M.; Seeley, John R.; Klein, Daniel N.

2014-01-01

Background The presence of subthreshold depressive symptoms (SubD) in adolescence is associated with high prospective risk of developing Major Depressive Disorder (MDD). Little is known about variables that predict escalation from SubD to MDD. This study used a longitudinal prospective design in a community sample of adolescents to identify combinations of risk factors that predicted escalation from SubD to MDD. Methods Classification tree analysis was used to identify combinations of risk factors that improved the sensitivity and specificity of prediction of MDD onset among 424 adolescents with a lifetime history of SubD. Results Of the 424, 144 developed MDD during the follow-up period. Evidence for multiple subgroups was found: Among adolescents with poor friend support, the highest risk of escalation was among participants with lifetime histories of an anxiety or substance use disorder. Among adolescents with high friend support, those reporting multiple major life events in the past year or with a history of an anxiety disorder were at highest risk of escalation. Limitations Study findings may not inform prevention efforts for individuals who first develop SubD during adulthood. This study did not examine the temporal ordering of predictors involved in escalation from SubD to MDD. Conclusions Adolescents with a history of SubD were at highest risk of escalation to MDD in the presence of poor friend support and an anxiety or substance use disorder, or in the presence of better friend support, multiple major life events, and an anxiety disorder. Findings may inform case identification approaches for adolescent depression prevention programs. PMID:24655777

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.

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.

Changed Hub and Corresponding Functional Connectivity of Subgenual Anterior Cingulate Cortex in Major Depressive Disorder

PubMed Central

Wu, Huawang; Sun, Hui; Xu, Jinping; Wu, Yan; Wang, Chao; Xiao, Jing; She, Shenglin; Huang, Jianwei; Zou, Wenjin; Peng, Hongjun; Lu, Xiaobing; Huang, Guimao; Jiang, Tianzi; Ning, Yuping; Wang, Jiaojian

2016-01-01

Major depressive disorder (MDD) is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS) map in each subject in 34 MDD patients and 34 gender-, age- and education level-matched healthy controls (HCs). Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decrease of FCS in subgenual anterior cingulate cortex (sgACC) in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS) scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD. PMID:28018183

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

Does comorbid Social Anxiety Disorder impact the clinical presentation of principal Major Depressive Disorder?

PubMed

Dalrymple, Kristy L; Zimmerman, Mark

2007-06-01

Although previous research has examined comorbidity in principal Social Anxiety Disorder (SAD), few studies have examined the disorders for which those with comorbid SAD seek treatment. Further, studies have shown that depressive disorders often are associated with SAD, but few have examined the clinical characteristics of patients with this particular comorbidity. The current study examined the prevalence of various principal Axis I disorders in 577 individuals diagnosed with comorbid SAD. Consistent with previous research, Major Depressive Disorder (MDD) was the most frequent principal diagnosis in patients with comorbid SAD. Those with principal MDD and comorbid SAD (MDD-SAD) were compared to those with MDD without SAD (MDD) on demographic and clinical characteristics. Patients with MDD-SAD versus those with MDD were more severe in terms of social functioning, duration of depressive episode, suicidal ideation, time out of work, presence of current alcohol abuse/dependence, and age of onset of MDD. Social functioning, duration of episode, suicidal ideation, and age of onset of MDD remained significant even after controlling for additional comorbid disorders. Findings suggest the need for future research to determine how treatments could be adapted for this commonly occurring comorbidity.

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.

The Prevalence and Specificity of Depression Diagnosis in a Clinic-Based Population of Adults With Type 2 Diabetes Mellitus

PubMed Central

Golden, Sherita Hill; Shah, Nina; Naqibuddin, Mohammad; Payne, Jennifer L.; Hill-Briggs, Felicia; Wand, Gary S.; Wang, Nae-Yuh; Langan, Susan; Lyketsos, Constantine

2018-01-01

Objective To estimate the crude prevalence of minor depressive disorder (MinD) in a clinic-based population of adults with type 2 diabetes. Methods We screened a clinical sample of 702 adults with type 2 diabetes for depressive symptoms using the Patient Health Questionnaire-2 and performed a structured diagnostic psychiatric interview on 52 screen-positive and a convenience sample of 51 screen-negative individuals. Depressive disorder diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria and categorized as MinD, major depressive disorder (MDD), or no depressive disorder. We estimated prevalence of MinD and MDD and derived 95% CIs. Results The crude prevalence of current, past, and current or past MinD was 4.3% (95% CI: 0.9–9.2%), 9.6% (95% CI: 3.9–15.9%), and 13.9% (95% CI: 7.7–21.2%), respectively. The crude prevalence of current, past, and current or past MDD was slightly higher—5.0% (95% CI: 1.9–9.4%), 12.0% (95% CI: 6.1–19.5%), and 17.0% (95% CI: 10.1–24.8%), respectively. There was a high prevalence of coexisting anxiety disorders in individuals with MinD (42.2%) and MDD (8.1%). Hemoglobin A1c levels were not significantly different in individuals with MinD or MDD compared to those without a depressive disorder. Conclusions MinD is comparably prevalent to MDD in patients with type 2 diabetes; both disorders are associated with concomitant anxiety disorders. MinD is not included in the DSM-5; however, our data support continuing to examine patients with chronic medical conditions for MinD. PMID:27692654

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

Plasma lipidomics reveals potential lipid markers of major depressive disorder.

PubMed

Liu, Xinyu; Li, Jia; Zheng, Peng; Zhao, Xinjie; Zhou, Chanjuan; Hu, Chunxiu; Hou, Xiaoli; Wang, Haiyang; Xie, Peng; Xu, Guowang

2016-09-01

Major depressive disorder (MDD) is a grave debilitating mental disease with a high incidence and severely impairs quality of life. Therefore, its physiopathological basis study and diagnostic biomarker discovery are extremely valuable. In this study, a non-targeted lipidomics strategy using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to reveal differential lipids between MDD (n = 60) and healthy controls (HCs, n = 60). Validation of changed lipid species was performed in an independent batch including 75 MDD and 52 HC using the same lipidomic method. Pronouncedly changed lipid species in MDD were discovered, which mainly were lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), 1-O-alkyl-2-acyl-PE (PE O), 1-O-alkyl-2-acyl-PC (PC O), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG). Among these lipid species, LPC, LPE, PC, PE, PI, TG, etc. remarkably increased in MDD and showed pronounced positive relationships with depression severity, while 1-O-alkyl-2-acyl-PE and SM with odd summed carbon number significantly decreased in MDD and demonstrated negative relationships with depression severity. A combinational lipid panel including LPE 20:4, PC 34:1, PI 40:4, SM 39:1, 2, and TG 44:2 was defined as potential diagnostic biomarker with a good sensitivity and specificity for distinguishing MDD from HCs. Our study brings insights into lipid metabolism disorder in MDD and provides a specific potential biomarker for MDD diagnose.

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

Regional brain volume in depression and anxiety disorders.

PubMed

van Tol, Marie-José; van der Wee, Nic J A; van den Heuvel, Odile A; Nielen, Marjan M A; Demenescu, Liliana R; Aleman, André; Renken, Remco; van Buchem, Mark A; Zitman, Frans G; Veltman, Dick J

2010-10-01

Major depressive disorder (MDD), panic disorder, and social anxiety disorder are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may have, at least in part, a common etiology. To identify the unique and shared neuroanatomical profile of depression and anxiety, controlling for illness severity, medication use, sex, age of onset, and recurrence. Cross-sectional study. Netherlands Study of Depression and Anxiety. Outpatients with MDD (n = 68), comorbid MDD and anxiety (n = 88), panic disorder, and/or social anxiety disorder without comorbid MDD (n = 68) and healthy controls (n = 65). Volumetric magnetic resonance imaging was conducted for voxel-based morphometry analyses. We tested voxelwise for the effects of diagnosis, age at onset, and recurrence on gray matter density. Post hoc, we studied the effects of use of medication, illness severity, and sex. We demonstrated lower gray matter volumes of the rostral anterior cingulate gyrus extending into the dorsal anterior cingulate gyrus in MDD, comorbid MDD and anxiety, and anxiety disorders without comorbid MDD, independent of illness severity, sex, and medication use. Furthermore, we demonstrated reduced right lateral inferior frontal volumes in MDD and reduced left middle/superior temporal volume in anxiety disorders without comorbid MDD. Also, patients with onset of depression before 18 years of age showed lower volumes of the subgenual prefrontal cortex. Our findings indicate that reduced volume of the rostral-dorsal anterior cingulate gyrus is a generic effect in depression and anxiety disorders, independent of illness severity, medication use, and sex. This generic effect supports the notion of a shared etiology and may reflect a common symptom dimension related to altered emotion processing. Specific involvement of the inferior frontal cortex in MDD and lateral temporal cortex in anxiety disorders without comorbid MDD, on the other hand, may reflect disorder-specific symptom clusters. Early onset of depression is associated with a distinct neuroanatomical profile that may represent a vulnerability marker of depressive disorder.

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.

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

Validity of a simpler definition of major depressive disorder.

PubMed

Zimmerman, Mark; Galione, Janine N; Chelminski, Iwona; Young, Diane; Dalrymple, Kristy; Witt, Caren Francione

2010-10-01

In previous reports from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we developed a briefer definition of major depressive disorder (MDD), and found high levels of agreement between the simplified and DSM-IV definitions of MDD. The goal of the present study was to examine the validity of the simpler definition of MDD. We hypothesized that compared to patients with adjustment disorder, patients with MDD would be more severely depressed, have poorer psychosocial functioning, have greater suicidal ideation at the time of the intake evaluation, and have an increased morbid risk for depression in their first-degree family members. We compared 1,486 patients who met the symptom criteria for current MDD according to either DSM-IV or the simpler definition to 145 patients with a current diagnosis of adjustment disorder with depressed mood or depressed and anxious mood. The patients with MDD were more severely depressed, more likely to have missed time from work due to psychiatric reasons, reported higher levels of suicidal ideation, and had a significantly higher morbid risk for depression in their first-degree family members. Both definitions of MDD were valid. The simpler definition of MDD was as valid as the DSM-IV definition. This new definition offers two advantages over the DSM-IV definition-it is briefer and therefore more likely to be recalled and applied in clinical practice, and it is free of somatic symptoms thereby making it easier to apply with medically ill patients. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.

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.

Major depressive disorder and suicide risk among adult outpatients at several general hospitals in a Chinese Han population

PubMed Central

Li, Haiyan; Luo, Xinni; Ke, Xiaoyin; Dai, Qing; Zheng, Wei; Zhang, Chanjuan; Cassidy, Ryan M.; Soares, Jair C.; Zhang, XiangYang

2017-01-01

Background Somatic complaints are often the presenting symptoms of major depressive disorder (MDD) in the outpatient context, because this may go unrecognized. It is well understood that MDD carries an increased risk of suicide. This study aimed to identify the risk factors and association with both MDD and suicidality among Han Chinese outpatients. Methods A multicenter study was carried out in 5189 outpatient adults (≥18 years old) in four general hospitals in Guangzhou, China. The 1392 patients who had the Patient Health Questionnaire-9 (PHQ-9) score ≥ 5, indicating depressive symptoms were offered an interview with a psychiatrist by the Mini International Neuropsychiatric Interview (MINI); 819 patients consented and completed the MINI interview. MINI module B was used to assess suicidality. Stepwise binary logistic models were used to estimate the relationship between a significant risk factor and suicide or MDD. According to with or without MDD, the secondary analysis was performed using the logistic regression model for the risk of suicidility. Results The current prevalence of MDD and the one month prevalence of suicidality were 3.7% and 2.3% respectively. The odds ratio of suicidality in women was more than twice that in men (OR = 2.62; 95% CI 1.45–4.76). Other risk factors which were significantly associated with suicidality were: living alone, higher education, self-reported depression, getting psychiatric diagnoses (MDD, anxiety disorders, and bipolar disorders). Significant risk factors for MDD were also noticed, such as comorbid anxiety disorders, self-reported anxiety, insomnia, suicidal ideation. Limitation It’s a cross-sectional study in outpatient clinics using self-report questionnaires. Conclusion This study provides valuable data about the risk factors and association of MDD and suicide risk in adult outpatients in Han Chinese. Those factors allow better the employment of preventative measures. PMID:29016669

Prospective, population-based study of the transition from major depressive disorder to bipolar disorder

PubMed Central

Gilman, Stephen E.; Dupuy, Jamie M.; Perlis, Roy H.

2013-01-01

Objective It is currently not possible to determine which individuals with unipolar depression are at highest risk for a manic episode. This study investigates clinical and psychosocial risk factors for mania among individuals with major depressive disorder (MDD), indicating diagnostic conversion from MDD to bipolar I disorder. Methods We fitted logistic regression models to predict the first onset of a manic episode among 6,214 cases of lifetime MDD according to DSM-IV criteria in the National Epidemiologic Survey on Alcohol and Related Conditions. Results Approximately 1 in 20 individuals with MDD transitioned to bipolar disorder during the study's 3-year follow-up period. Demographic risk factors for the transition from MDD to bipolar disorder included younger age, Black race/ethnicity, and less than high school education. Clinical characteristics of depression (e.g., age at first onset, presence of atypical features) were not associated with diagnostic conversion. However, prior psychopathology was associated with the transition to bipolar disorder: history of social phobia (Odds Ratio=2.20; 95% Confidence Interval=1.47, 3.30) and generalized anxiety disorder (OR=1.58; CI=1.06, 2.35). Lastly, we identified environmental stressors over the life course that predicted the transition to bipolar disorder: these include a history of child abuse (OR=1.26; CI=1.12, 1.42) and past-year problems with one's social support group (OR=1.79; CI=1.19, 2.68). The overall predictive power of these risk factors based on a receiver operating curve analysis is modest. Conclusions A wide range of demographic, clinical, and environmental risk factors were identified that indicate a heightened risk for the transition to bipolar disorder. Additional work is needed to further enhance the prediction of bipolar disorder among cases of MDD, and to determine whether interventions targeting these factors could reduce the risk of bipolar disorder. PMID:22394428

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.

Personality disorders, but not cancer severity or treatment type, are risk factors for later generalised anxiety disorder and major depressive disorder in non metastatic breast cancer patients.

PubMed

Champagne, Anne-Laure; Brunault, Paul; Huguet, Grégoire; Suzanne, Isabelle; Senon, Jean-Louis; Body, Gilles; Rusch, Emmanuel; Magnin, Guillaume; Voyer, Mélanie; Réveillère, Christian; Camus, Vincent

2016-02-28

This study aimed to determine whether personality disorders were associated with later Major Depressive Disorder (MDD) or Generalised Anxiety Disorder (GAD) in breast cancer patients. This longitudinal and multicentric study included 120 French non-metastatic breast cancer patients. After cancer diagnosis (T1) and 7 months after diagnosis (T3), we assessed MDD and GAD (Mini International Neuropsychiatric Interview 5.0). We assessed personality disorders 3 months after diagnosis (VKP). We used multiple logistic regression analysis to determine what were the factors associated with GAD and MDD at T3. At T3, prevalence rate was 10.8% for MDD and 19.2% for GAD. GAD at T3 was significantly and independently associated with GAD at T1 and with existence of a personality disorder, no matter the cluster type. MDD at T3 was significantly and independently associated with MDD at T1 and with the existence of a cluster C personality disorder. Initial cancer severity and the type of treatment used were not associated with GAD or MDD at T3. Breast cancer patients with personality disorders are at higher risk for GAD and MDD at the end of treatment. Patients with GAD should be screened for personality disorders. Specific interventions for patients with personality disorders could prevent psychiatric disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A mega-analysis of genome-wide association studies for major depressive disorder.

PubMed

Ripke, Stephan; Wray, Naomi R; Lewis, Cathryn M; Hamilton, Steven P; Weissman, Myrna M; Breen, Gerome; Byrne, Enda M; Blackwood, Douglas H R; Boomsma, Dorret I; Cichon, Sven; Heath, Andrew C; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A F; Martin, Nicholas G; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M; Penninx, Brenda P; Pergadia, Michele L; Potash, James B; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H; Preisig, Martin; Smoller, Jordan W; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R; Bettecken, Thomas; Binder, Elisabeth B; Breuer, René; Castro, Victor M; Churchill, Susanne E; Coryell, William H; Craddock, Nick; Craig, Ian W; Czamara, Darina; De Geus, Eco J; Degenhardt, Franziska; Farmer, Anne E; Fava, Maurizio; Frank, Josef; Gainer, Vivian S; Gallagher, Patience J; Gordon, Scott D; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A; Kohane, Isaac S; Kohli, Martin A; Korszun, Ania; Landen, Mikael; Lawson, William B; Lewis, Glyn; Macintyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M; Middleton, Lefkos; Montgomery, Grant M; Murphy, Shawn N; Nauck, Matthias; Nolen, Willem A; Nyholt, Dale R; O'Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A; Schulz, Andrea; Schulze, Thomas G; Shyn, Stanley I; Sigurdsson, Engilbert; Slager, Susan L; Smit, Johannes H; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B; Willemsen, Gonneke; Zitman, Frans G; Neale, Benjamin; Daly, Mark; Levinson, Douglas F; Sullivan, Patrick F

2013-04-01

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

Comparative cost analysis of generalized anxiety disorder and major depressive disorder patients in secondary care from a national hospital registry in Finland.

PubMed

Kujanpää, Tero; Ylisaukko-Oja, Tero; Jokelainen, Jari; Linna, Miika; Timonen, Markku

2014-07-01

Major depressive disorder (MDD) has shown to cause high costs to society. Earlier research indicates that generalized anxiety disorder (GAD) also causes high costs, but only limited data is available in varying settings. To analyse the secondary care costs of GAD compared with those of MDD. Retrospective database analysis from Finnish Hospital Discharge Registers (FHDR). All GAD and MDD patients diagnosed between 1 January 2007 and 31 December 2007 in FHDR were recorded and individual-level secondary care costs during a 48-month follow-up period were measured. The total mean cost of GAD with history of MDD or some other anxiety disorder was significantly higher than that of MDD with history of GAD or some other anxiety disorder during the 48-month follow-up period. The costs of pure GAD were comparable with those of pure MDD, but after adjusting for age and sex, the costs of pure MDD were higher than those of pure GAD. The economic burden of individual GAD patients is comparable with that of MDD patients in secondary care.

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.

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

Persistent Depression as a Novel Diagnostic Category: Results from the Menderes Depression Study

PubMed Central

ILDIRLI, Saliha; ŞAİR, Yaşan Bilge; DEREBOY, Ferhan

2015-01-01

Introduction Persistent depressive disorder (PDD) introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 as a novel diagnostic category represents a consolidation of two separate DSM-IV categories, chronic major depressive disorder (MDD) and dysthymic disorder. The present study aims to investigate the frequency and clinical as well as socio-demographic correlates of PDD in comparison with those of episodic MDD among patients seeking treatment for depressive symptoms. Methods Participants were 140 depressive out-and in-patients under treatment at the psychiatry clinic of the Adnan Menderes University Research Hospital. Each patient was assessed by means of a structured clinical interview (SCID-I) and relevant psychometric instruments including the Hamilton Depression Inventory and Eskin Suicidal Behavior Inventory. Results Among the depressive patients, 61% fulfilled the criteria for PDD and 39% for episodic MDD. As compared with patients with episodic MDD, the PDD patients were older (d=.54), lower in educational attainment (d=.55), more likely to have comorbid generalized anxiety disorder (OR=3.7), and more prone to report symptoms of anxiety, hopelessness, pessimism, and somatic complaints. Nevertheless, the PDD patients displayed heterogeneous characteristics with respect to clinical severity and suicidal behavior. Conclusion Our findings suggest that majority of depressive patients, including those fulfilling the criteria for MDD, have been suffering from a persistent ailment rather than an episodic disorder. Clinicians with a cross-sectional perspective are more likely to diagnose MDD, whereas those with a longitudinal perspective are more likely to identify PDD in the majority of depressive patients. The incorporation of both of these perspectives into DSM-5 in a complementary manner will possibly enhance our insight into depressive disorders and improve our treatment results. PMID:28360740

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.

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

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.

Subthreshold Substance Use and the Treatment of Resistant Depression in Adolescents

PubMed Central

Goldstein, Benjamin I.; Shamseddeen, Wael; Spirito, Anthony; Emslie, Graham; Clarke, Greg; Wagner, Karen Dineen; Asarnow, Joan Rosenbaum; Vitiello, Benedetto; Ryan, Neal; Birmaher, Boris; Mayes, Taryn; Onorato, Matthew; Zelazny, Jamies; Brent, David A.

2009-01-01

Objective Despite the known association between substance use disorders (SUD) and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. Method Youth with MDD who had not improved after an adequate SSRI trial (N = 334) were enrolled in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) trial. Analyses examined substance use (via the Drug Use Severity Index) and changes therein in relation to treatment and depressive symptoms. Adolescents meeting SUD criteria via the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version at baseline were excluded. Results Substance use was common: 28.1% reported repeated experimentation at baseline. Substance-related impairment was associated with baseline depression severity, older age, physical/sexual abuse, family conflict, hopelessness, and comorbid oppositional defiant disorder/conduct disorder. There was significant improvement in substance-related impairment among adolescents who responded to MDD treatment. Baseline suicidal ideation was higher among subjects who progressed to high substance-related impairment (≥75th percentile) versus those whose substance-related impairment remained low (<75th percentile), and parental depressive symptoms predicted persistence of high substance-related impairment during the study. MDD response was best among adolescents with low 12-week substance-related impairment scores regardless of whether they had high or low baseline substance-related impairment. There were no significant differential effects of specific treatments, pharmacological or CBT, on substance use. Conclusions Substance use is common among adolescents with treatment-resistant MDD. Subjects who had persistently low substance-related impairment or who demonstrated reduced substance-related impairment had better MDD treatment response, although the direction of this association is uncertain. PMID:19858762

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.

Major Depression in the National Comorbidity Survey- Adolescent Supplement: Prevalence, Correlates, and Treatment

PubMed Central

Avenevoli, Shelli; Swendsen, Joel; He, Jian-Ping; Burstein, Marcy; Merikangas, Kathleen

2015-01-01

Objective To present the 12-month prevalence of DSM-IV major depressive disorder (MDD) and severe MDD, examine sociodemographic correlates and comorbidity, and describe impairment and service utilization. Method Data are from the National Comorbidity Survey-Adolescent Supplement (NCS-A), a nationally representative survey of 10,123 adolescents aged 13 to 18 years that assesses DSM-IV disorders using the Composite International Diagnostic Interview (CIDI) Version 3.0. One parent or surrogate of each participating adolescent was also asked to complete a self-administered questionnaire. Results Lifetime and 12-month prevalence of MDD were 11.0% and 7.5%, respectively. The corresponding rates of severe MDD were 3.0% and 2.3%. The prevalence of MDD increased significantly across adolescence, with markedly greater increases among females than males. Most cases of MDD were associated with psychiatric comorbidity and severe role impairment, and a substantial minority reported suicidality. The prevalence of severe MDD was about a quarter of that of all MDD cases; estimates of impairment and clinical correlates were of 2- to 5-fold greater magnitude for severe versus mild/moderate depression, with markedly higher rates for suicidal thoughts and behaviors. Treatment in any form was received by the majority of adolescents with 12-month DSM-IV MDD (60.4%), but only a minority received treatment that was disorder-specific or from the mental health sector. Conclusion Findings underscore the important public health significance of depression among US adolescents and the urgent need to improve screening and treatment access in this population. PMID:25524788

Major depressive disorder following terrorist attacks: A systematic review of prevalence, course and correlates

PubMed Central

2011-01-01

Background Terrorist attacks are traumatic events that may result in a wide range of psychological disorders for people exposed. This review aimed to systematically assess the current evidence on major depressive disorder (MDD) after terrorist attacks. Methods A systematic review was performed. Studies included assessed the impact of human-made, intentional, terrorist attacks in direct victims and/or persons in general population and evaluated MDD based on diagnostic criteria. Results A total of 567 reports were identified, 11 of which were eligible for this review: 6 carried out with direct victims, 4 with persons in general population, and 1 with victims and general population. The reviewed literature suggests that the risk of MDD ranges between 20 and 30% in direct victims and between 4 and 10% in the general population in the first few months after terrorist attacks. Characteristics that tend to increase risk of MDD after a terrorist attack are female gender, having experienced more stressful situations before or after the attack, peritraumatic reactions during the attack, loss of psychosocial resources, and low social support. The course of MDD after terrorist attacks is less clear due to the scarcity of longitudinal studies. Conclusions Methodological limitations in the literature of this field are considered and potentially important areas for future research such as the assessment of the course of MDD, the study of correlates of MDD or the comorbidity between MDD and other mental health problems are discussed. PMID:21627850

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.

Performance on the Wisconsin card-sorting test and serum levels of glial cell line-derived neurotrophic factor in patients with major depressive disorder.

PubMed

Zhang, Xiaobin; Ru, Bu; Sha, Weiwei; Xin, Wang; Zhou, Honghui; Zhang, Yumei

2014-09-01

Some evidence suggests that neurotrophic growth factor systems might be involved in the etiology of major depressive disorder (MDD). Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor-β family that plays a role in the development and function of the brain. This study aimed to test whether GDNF in serum was abnormal in MDD, and whether it was related to the cognitive impairment of MDD. Serum GDNF levels in MDD patients (n = 32) and normal controls (n = 32) were measured with the enzyme-linked immunosorbent assay method. All subjects were assessed for performance on the Wisconsin card-sorting test (WCST). Performance on the WCST in MDD patients was significantly poorer than that in controls. Serum GDNF levels in MDD patients were significantly decreased compared to that of the control subjects (P < 0.001). Furthermore, the decrease in the serum GDNF levels positively correlated with performance in the WCST-% CONC and negatively with performance in the WCST-P in MDD patients. The findings suggest that MDD patients have extensive impairments of executive functioning, and lower serum GDNF might be involved in the pathogenesis of MDD, which may be associated with the cognitive dysfunction in MDD patients. © 2014 Wiley Publishing Asia Pty Ltd.

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.

Anxiety disorders, major depressive disorder and the dynamic relationship between these conditions: treatment patterns and cost analysis.

PubMed

François, Clément; Despiégel, Nicolas; Maman, Khaled; Saragoussi, Delphine; Auquier, Pascal

2010-03-01

To determine the treatment pattern and impact on healthcare costs of anxiety disorders and major depressive disorder (MDD), and influence of their concomitance and subsequence. A retrospective cohort study was conducted using a US reimbursement claims database. Adult patients with an incident diagnosis of anxiety or MDD (index date) were included. Their sociodemographic data, diagnoses, healthcare resource use and associated costs were collected over the 6 months preceding and 12 months following index date. A total of 599,624 patients were identified and included. Patients with phobia or post-traumatic stress disorder had the highest 12-month costs ($8,442 and $8,383, respectively). Patients with social anxiety disorder had the lowest costs ($3,772); generalized anxiety disorder ($6,472) incurred costs similar to MDD ($7,170). Costs were substantially increased with emergence of anxiety during follow-up in MDD patients ($10,031) or emergence of MDD in anxiety patients ($9,387). This was not observed in patients with both anxiety and MDD at index date ($6,148). This study confirms the high burden of costs of anxiety, which were within the same range as MDD. Interestingly, the emergence of anxiety or MDD in the year following a first diagnosis of MDD or anxiety, respectively, increased costs substantially. Major limitations were short follow-up and lack of absenteeism costs.

Aberrant functional connectivity for diagnosis of major depressive disorder: a discriminant analysis.

PubMed

Cao, Longlong; Guo, Shuixia; Xue, Zhimin; Hu, Yong; Liu, Haihong; Mwansisya, Tumbwene E; Pu, Weidan; Yang, Bo; Liu, Chang; Feng, Jianfeng; Chen, Eric Y H; Liu, Zhening

2014-02-01

Aberrant brain functional connectivity patterns have been reported in major depressive disorder (MDD). It is unknown whether they can be used in discriminant analysis for diagnosis of MDD. In the present study we examined the efficiency of discriminant analysis of MDD by individualized computer-assisted diagnosis. Based on resting-state functional magnetic resonance imaging data, a new approach was adopted to investigate functional connectivity changes in 39 MDD patients and 37 well-matched healthy controls. By using the proposed feature selection method, we identified significant altered functional connections in patients. They were subsequently applied to our analysis as discriminant features using a support vector machine classification method. Furthermore, the relative contribution of functional connectivity was estimated. After subset selection of high-dimension features, the support vector machine classifier reached up to approximately 84% with leave-one-out training during the discrimination process. Through summarizing the classification contribution of functional connectivities, we obtained four obvious contribution modules: inferior orbitofrontal module, supramarginal gyrus module, inferior parietal lobule-posterior cingulated gyrus module and middle temporal gyrus-inferior temporal gyrus module. The experimental results demonstrated that the proposed method is effective in discriminating MDD patients from healthy controls. Functional connectivities might be useful as new biomarkers to assist clinicians in computer auxiliary diagnosis of MDD. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

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.

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.

Distinguishing bipolar II depression from major depressive disorder with comorbid borderline personality disorder: demographic, clinical, and family history differences.

PubMed

Zimmerman, Mark; Martinez, Jennifer H; Morgan, Theresa A; Young, Diane; Chelminski, Iwona; Dalrymple, Kristy

2013-09-01

Because of the potential treatment implications, it is clinically important to distinguish between bipolar II depression and major depressive disorder with comorbid borderline personality disorder. The high frequency of diagnostic co-occurrence and resemblance of phenomenological features has led some authors to suggest that borderline personality disorder is part of the bipolar spectrum. Few studies have directly compared patients with bipolar disorder and borderline personality disorder. In the present study from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we compared these 2 groups of patients on demographic, clinical, and family history variables. From December 1995 to May 2012, 3,600 psychiatric patients presenting to the outpatient practice at Rhode Island Hospital (Providence, Rhode Island) were evaluated with semistructured diagnostic interviews for DSM-IV Axis I and Axis II disorders. The focus of the present study is the 206 patients with DSM-IV major depressive disorder and borderline personality disorder (MDD-BPD) and 62 patients with DSM-IV bipolar II depression without borderline personality disorder. The patients with MDD-BPD were significantly more often diagnosed with posttraumatic stress disorder (P < .001), a current substance use disorder (P < .01), somatoform disorder (P < .05), and other nonborderline personality disorder (P < .05). Clinical ratings of anger, anxiety, paranoid ideation, and somatization were significantly higher in the MDD-BPD group (all P < .01). The MDD-BPD patients were rated significantly lower on the Global Assessment of Functioning (P < .001), their current social functioning was poorer (P < .01), and they made significantly more suicide attempts (P < .01). The patients with bipolar II depression had a significantly higher morbid risk for bipolar disorder in their first-degree relatives than the MDD-BPD patients (P < .05). Patients diagnosed with bipolar II depression and major depressive disorder with comorbid borderline personality disorder differed on a number of clinical and family history variables, thereby supporting the validity of this distinction. © Copyright 2013 Physicians Postgraduate Press, Inc.

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

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.

Interoceptive Awareness, Positive Affect, and Decision Making in Major Depressive Disorder

PubMed Central

Furman, Daniella J.; Waugh, Christian E.; Bhattacharjee, Kalpa; Thompson, Renee J.; Gotlib, Ian H.

2013-01-01

Background Little work has examined the relation between interoceptive awareness and symptoms of Major Depressive Disorder (MDD). Existing research suggests that depressed individuals exhibit impaired heartbeat perception, though the results of this research have been equivocal. Importantly, depressed participants in these studies have had comorbid anxiety disorders, making it difficult to draw inferences about interoceptive awareness in MDD. The current study addresses this issue by assessing heartbeat perception in depressed women without current anxiety disorders and exploring the relation between interoception and perturbations in both affective intensity and decision making, components of MDD postulated to be related to bodily awareness. Methods Depressed women without concurrent anxiety disorders (n=25) and never-disordered controls (n=36) performed a heartbeat perception task. Participants completed the self-report Affect Intensity Measure (AIM), and decision-making difficulty was assessed in MDD participants using the Structured Clinical Interview for DSM-IV. Results Depressed women exhibited poorer heartbeat perception accuracy than did control participants. Impaired accuracy in MDD participants was associated with reduced positive affectivity and difficulty in decision making. Limitations Our sample was composed exclusively of females and was heterogeneous with respect to treatment status, thereby limiting our ability to generalize results to depressed males and to exclude the contribution of exogenous factors to the observed group differences. Conclusions Results of this study suggest that for depressed individuals without anxiety comorbidities, disrupted perception of bodily responses reduces both the experience of positive arousal and the ability to use interoceptive feedback to inform decision making. PMID:23972662

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.

Gene expression-based biological test for major depressive disorder: an advanced study.

PubMed

Watanabe, Shin-Ya; Numata, Shusuke; Iga, Jun-Ichi; Kinoshita, Makoto; Umehara, Hidehiro; Ishii, Kazuo; Ohmori, Tetsuro

2017-01-01

Recently, we could distinguished patients with major depressive disorder (MDD) from nonpsychiatric controls with high accuracy using a panel of five gene expression markers ( ARHGAP24, HDAC5, PDGFC, PRNP , and SLC6A4 ) in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder. We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR), and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD. This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively. Further research to identify MDD-specific markers is needed to improve the performance of this biological test.

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.

Hypomania spectrum disorder in adolescence: a 15-year follow-up of non-mood morbidity in adulthood

PubMed Central

2014-01-01

Background We investigated whether adolescents with hypomania spectrum episodes have an excess risk of mental and physical morbidity in adulthood, as compared with adolescents exclusively reporting major depressive disorder (MDD) and controls without a history of adolescent mood disorders. Methods A community sample of adolescents (N = 2 300) in the town of Uppsala, Sweden, was screened for depressive symptoms. Both participants with positive screening and matched controls (in total 631) were diagnostically interviewed. Ninety participants reported hypomania spectrum episodes (40 full-syndromal, 18 with brief episode, and 32 subsyndromal), while another 197 fulfilled the criteria for MDD without a history of a hypomania spectrum episode. A follow up after 15 years included a blinded diagnostic interview, a self-assessment of personality disorders, and national register data on prescription drugs and health services use. The participation rate at the follow-up interview was 71% (64/90) for the hypomania spectrum group, and 65.9% (130/197) for the MDD group. Multiple imputation was used to handle missing data. Results The outcomes of the hypomania spectrum group and the MDD group were similar regarding subsequent non-mood Axis I disorders in adulthood (present in 53 vs. 57%). A personality disorder was reported by 29% of the hypomania spectrum group and by 20% of the MDD group, but a statistically significant difference was reached only for obsessive-compulsive personality disorder (24 vs. 14%). In both groups, the risk of Axis I disorders and personality disorders in adulthood correlated with continuation of mood disorder. Prescription drugs and health service use in adulthood was similar in the two groups. Compared with adolescents without mood disorders, both groups had a higher subsequent risk of psychiatric morbidity, used more mental health care, and received more psychotropic drugs. Conclusions Although adolescents with hypomania spectrum episodes and adolescents with MDD do not differ substantially in health outcomes, both groups are at increased risk for subsequent mental health problems. Thus, it is important to identify and treat children and adolescents with mood disorders, and carefully follow the continuing course. PMID:24428938

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

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.

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.

Depression and major depressive disorder in patients with Parkinson's disease.

PubMed

Inoue, Takeshi; Kitagawa, Mayumi; Tanaka, Teruaki; Nakagawa, Shin; Koyama, Tsukasa

2010-01-15

The prevalence of depression in Parkinson's disease (PD) varies greatly. In this study, we investigated major depressive disorder (MDD) and depressive symptoms without MDD in patients with PD. The psychopathological characteristics of depressive symptoms were assessed by a psychiatric interview. A total of 105 Japanese patients with PD without dementia were included. The Japanese version of the Beck Depression Inventory-II (BDI-II) with a cutoff score of 13/14 was used to screen for depression. Using a structured interview, a comprehensive psychiatric evaluation of patients with BDI-II scores >13 (high BDI patients) was completed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR. Forty patients (38%) had a BDI-II >13, but 29 did not show any depressed mood. Five cases met the criteria for MDD (three current, two past) and one patient was diagnosed with minor depressive disorder. A slight depressed mood that was associated with worrying about PD was seen in 6 of 34 patients without any depressive disorder and fluctuated with aggravation of PD symptoms in two of these patients. For the diagnosis of MDD, the number of positive items from the DSM-IV-TR definition of MDD is most important and useful for differentiating MDD and non-MDD. The low-prevalence rate of MDD in our patient population suggests that PD may be a psychological stressor for MDD, but does not necessarily induce MDD.

Are flatter diurnal cortisol rhythms associated with major depression and anxiety disorders in late adolescence? The role of life stress and daily negative emotion.

PubMed

Doane, Leah D; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle; Griffith, James W; Adam, Emma K

2013-08-01

Alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning have been associated with major depression disorder (MDD) and some anxiety disorders. Few researchers have tested the possibility that high levels of recent life stress or elevations in negative emotion may partially account for the HPA axis alterations observed in these disorders. In a sample of 300 adolescents from the Youth Emotion Project, we examined associations between MDD and anxiety disorders, dimensional measures of internalizing symptomatology, life stress, mood on the days of cortisol testing, and HPA axis functioning. Adolescents with a past MDD episode and those with a recent MDD episode comorbid with an anxiety disorder had flatter diurnal cortisol slopes than adolescents without a history of internalizing disorders. Higher reports of general distress, a dimension of internalizing symptomatology, were also associated with flatter slopes. Negative emotion, specifically sadness and loneliness, was associated with flatter slopes and partially accounted for the associations between comorbid MDD and anxiety disorders and cortisol. The associations between past MDD and cortisol slopes were not accounted for by negative emotion, dimensional variation in internalizing symptomatology, or levels of life stress, indicating that flatter cortisol slopes may also be a "scar" marker of past experiences of MDD.

Joint source based analysis of multiple brain structures in studying major depressive disorder

NASA Astrophysics Data System (ADS)

Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

2014-03-01

We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

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.

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

Diagnosis of major depressive disorder by combining multimodal information from heart rate dynamics and serum proteomics using machine-learning algorithm.

PubMed

Kim, Eun Young; Lee, Min Young; Kim, Se Hyun; Ha, Kyooseob; Kim, Kwang Pyo; Ahn, Yong Min

2017-06-02

Major depressive disorder (MDD) is a systemic and multifactorial disorder that involves abnormalities in multiple biochemical pathways and the autonomic nervous system. This study applied a machine-learning method to classify MDD and control groups by incorporating data from serum proteomic analysis and heart rate variability (HRV) analysis for the identification of novel peripheral biomarkers. The study subjects consisted of 25 drug-free female MDD patients and 25 age- and sex-matched healthy controls. First, quantitative serum proteome profiles were analyzed by liquid chromatography-tandem mass spectrometry using pooled serum samples from 10 patients and 10 controls. Next, candidate proteins were quantified with multiple reaction monitoring (MRM) in 50 subjects. We also analyzed 22 linear and nonlinear HRV parameters in 50 subjects. Finally, we identified a combined biomarker panel consisting of proteins and HRV indexes using a support vector machine with recursive feature elimination. A separation between MDD and control groups was achieved using five parameters (apolipoprotein B, group-specific component, ceruloplasmin, RMSSD, and SampEn) at 80.1% classification accuracy. A combination of HRV and proteomic data achieved better classification accuracy. A high classification accuracy can be achieved by combining multimodal information from heart rate dynamics and serum proteomics in MDD. Our approach can be helpful for accurate clinical diagnosis of MDD. Further studies using larger, independent cohorts are needed to verify the role of these candidate biomarkers for MDD diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Abnormalities in the structural covariance of emotion regulation networks in major depressive disorder.

PubMed

Wu, Huawang; Sun, Hui; Wang, Chao; Yu, Lin; Li, Yilan; Peng, Hongjun; Lu, Xiaobing; Hu, Qingmao; Ning, Yuping; Jiang, Tianzi; Xu, Jinping; Wang, Jiaojian

2017-01-01

Major depressive disorder (MDD) is a common psychiatric disorder that is characterized by cognitive deficits and affective symptoms. To date, an increasing number of neuroimaging studies have focused on emotion regulation and have consistently shown that emotion dysregulation is one of the central features and underlying mechanisms of MDD. Although gray matter morphological abnormalities in regions within emotion regulation networks have been identified in MDD, the interactions and relationships between these gray matter structures remain largely unknown. Thus, in this study, we adopted a structural covariance method based on gray matter volume to investigate the brain morphological abnormalities within the emotion regulation networks in a large cohort of 65 MDD patients and 65 age- and gender-matched healthy controls. A permutation test with p < 0.05 was used to identify the significant changes in covariance connectivity strengths between MDD patients and healthy controls. The structural covariance analysis revealed an increased correlation strength of gray matter volume between the left angular gyrus and the left amygdala and between the right angular gyrus and the right amygdala, as well as a decreased correlation strength of the gray matter volume between the right angular gyrus and the posterior cingulate cortex in MDD. Our findings support the notion that emotion dysregulation is an underlying mechanism of MDD by revealing disrupted structural covariance patterns in the emotion regulation network. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Descriptive epidemiology of major depressive disorder in Canada in 2012.

PubMed

Patten, Scott B; Williams, Jeanne V A; Lavorato, Dina H; Wang, Jian Li; McDonald, Keltie; Bulloch, Andrew G M

2015-01-01

The epidemiology of major depressive disorder (MDD) was first described in the Canadian national population in 2002. Updated information is now available from a 2012 survey: the Canadian Community Health Study-Mental Health (CCHS-MH). The CCHS-MH employed an adaptation of the World Health Organization World Mental Health Composite International Diagnostic Interview and had a sample of n=25 113. Demographic variables, treatment, comorbidities, suicidal ideation, and perceived stigma were assessed. The analysis estimated adjusted and unadjusted frequencies and prevalence ratios. All estimates incorporated analysis methods to account for complex survey design effects. The past-year prevalence of MDD was 3.9% (95% CI 3.5% to 4.2%). Prevalence was higher in women and in younger age groups. Among respondents with past-year MDD, 63.1% had sought treatment and 33.1% were taking an antidepressant (AD); 4.8% had past-year alcohol abuse and 4.5% had alcohol dependence. Among respondents with past-year MDD, the prevalence of cannabis abuse was 2.5% and that of dependence was 2.9%. For drugs other than cannabis, the prevalence of abuse was 2.3% and dependence was 2.9%. Generalized anxiety disorder was present in 24.9%. Suicide attempts were reported by 6.6% of respondents with past-year MDD. Among respondents accessing treatment, 37.5% perceived that others held negative opinions about them or treated them unfairly because of their disorder. MDD is a common, burdensome, and stigmatized condition in Canada. Seeking help from professionals was reported at a higher frequency than in prior Canadian studies, but there has been no increase in AD use among Canadians with MDD.

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

Specificity of abnormal brain volume in major depressive disorder: a comparison with borderline personality disorder.

PubMed

Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Thomann, Philipp A; Christian Wolf, R

2015-03-15

Abnormal brain volume has been frequently demonstrated in major depressive disorder (MDD). It is unclear if these findings are specific for MDD since aberrant brain structure is also present in disorders with depressive comorbidity and affective dysregulation, such as borderline personality disorder (BPD). In this transdiagnostic study, we aimed to investigate if regional brain volume loss differentiates between MDD and BPD. Further, we tested for associations between brain volume and clinical variables within and between diagnostic groups. 22 Females with a DSM-IV diagnosis of MDD, 17 females with a DSM-IV diagnosis of BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls (HC) were investigated using magnetic resonance imaging. High-resolution structural data were analyzed using voxel-based morphometry. A significant (p<0.05, cluster-corrected) volume decrease of the anterior cingulate cortex (ACC) was found in MDD compared to HC, as opposed to volume decreases of the amygdala in BPD compared to both HC and MDD. Sensitivity and specificity of regional gray matter volume for a diagnosis of MDD were modest to fair. Amygdala volume was related to depressive symptoms across the entire patient sample. Potential limitations of this study include the modest sample size and the heterogeneous psychotropic drug treatment. ACC volume reduction is more pronounced in MDD with an intermediate degree of volume loss in BPD compared to HC. In contrast, amygdala volume loss is more pronounced in BPD compared to MDD, yet amygdala volume is associated with affective symptom expression in both disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

The Possible Role of the Kynurenine Pathway in Adolescent Depression with Melancholic Features

ERIC Educational Resources Information Center

Gabbay, Vilma; Klein, Rachel G.; Katz, Yisrael; Mendoza, Sandra; Guttman, Leah E.; Alonso, Carmen M.; Babb, James S.; Hirsch, Glenn S.; Liebes, Leonard

2010-01-01

Background: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features…

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.

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.

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

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

Coexistence of Urinary Incontinence and Major Depressive Disorder with Health-Related Quality of Life in Older Americans with and without Cancer

PubMed Central

White, Alexandra J.; Reeve, Bryce B.; Chen, Ronald C.; Stover, Angela M.; Irwin, Debra E.

2014-01-01

Purpose This study evaluates the prevalence and factors associated with major depressive disorder (MDD) in a population of cancer survivors and the impact of co-occurring MDD and urinary incontinence (UI) on health-related quality of life (HRQOL). Methods The prevalence of MDD risk among cancer survivors (breast, prostate, bladder, colorectal, lung and endometrial/uterine cancers) and those without cancer was estimated using the Surveillance, Epidemiology and End Results Program-Medicare Health Outcomes Survey (SEER-MHOS) linked database (n=9,282 with cancer/n=289,744 without cancer). Risk for MDD was measured using 3 items from the Diagnostic Interview Schedule and HRQOL was measured by the SF-36. UI was defined as self-reported leakage of urine causing a problem in previous 6 months. Factors associated with MDD were investigated using logistic regression and the impact of co-occurring MDD and UI on HRQOL scores was determined using linear regression. Results The prevalence of MDD risk ranged from 19.2% for prostate-34.1% for lung. Lung cancer diagnosis was associated with risk of MDD. Being ≥5 years from diagnosis was associated with decreased risk of MDD (Prevalence Odds Ratio (POR)=0.82, 95% Confidence Interval (95% CI): 0.71, 0.95). The coexistence of both UI and MDD was associated with a decrease across HRQOL subscales; including 40-points on role emotional (RE) score. Conclusions Cancer survivors reporting co-occurrence of UI and MDD experienced significant decrements in HRQOL. Implications of cancer survivors Understanding the combined effect of UI and MDD may help clinicians to better recognize and alleviate their effects on cancer survivors’ HRQOL. PMID:24770937

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.

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".

Association between eating disorders and migraine may be explained by major depression.

PubMed

Mustelin, Linda; Raevuori, Anu; Kaprio, Jaakko; Keski-Rahkonen, Anna

2014-12-01

The association between eating disorders and migraine remains unclear. We identified women with lifetime diagnoses of anorexia nervosa (AN) (N = 55) and bulimia nervosa (BN) (N = 60) and their co-twins from the FinnTwin16 cohort born in 1975-1979 (N = 2,825 women). Eating disorder and major depressive disorder (MDD) diagnoses were obtained from clinical interviews and data on migraine by self-report questionnaire. The women with eating disorders were compared with their unaffected co-twins and with unrelated women from the same birth cohorts. The prevalence of migraine was 12% in the general female population, but 22% for both AN and BN (odds ratio 2.0, p = .04). The prevalence of MDD was high in women with an eating disorder (42%). MDD was strongly associated with migraine (odds ratio 3.0, p < .0001) and explained the association between eating disorders and migraine. The highest migraine prevalence (36%) was found in women with both an eating disorder and MDD. Pairwise twin analyses also supported the clustering of migraine, MDD and eating disorders. Women with a lifetime diagnosis of an eating disorder were twice as likely to report a history of migraine as unrelated women from the same cohort; this relationship was explained by comorbid MDD. © 2014 Wiley Periodicals, Inc.

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.

Multifamily psychoeducation for improvement of mental health among relatives of patients with major depressive disorder lasting more than one year: study protocol for a randomized controlled trial.

PubMed

Katsuki, Fujika; Takeuchi, Hiroshi; Watanabe, Norio; Shiraishi, Nao; Maeda, Tohru; Kubota, Yosuke; Suzuki, Masako; Yamada, Atsurou; Akechi, Tatsuo

2014-08-12

Major depressive disorder (MDD) is a long-lasting disorder with frequent relapses that have significant effects on the patient's family. Family psychoeducation is recognized as part of the optimal treatment for patients with psychotic disorder. A previous randomized controlled trial has found that family psychoeducation is effective in enhancing the treatment of MDD. Although MDD can easily become a chronic illness, there has been no intervention study on the families of patients with chronic depression. In the present study, we design a randomized controlled trial to examine the effectiveness of family psychoeducation in improving the mental health of relatives of patients with MDD lasting more than one year. Participants are patients with MDD lasting more than one year and their relatives. Individually randomized, parallel-group trial design will be employed. Participants will be allocated to one of two treatment conditions: relatives will receive (a) family psychoeducation (four, two-hour biweekly multifamily psychoeducation sessions) plus treatment-as-usual for the patient (consultation by physicians), or (b) counseling for the family (one counseling session from a nurse) plus treatment-as-usual for the patient. The primary outcome measure will be relatives' mental health as measured by K6 that was developed to screen for DSM-IV depressive and anxiety disorder. Additionally, the severity of depressive symptoms in patients measured by the Beck Depression Inventory-II (BDI-II) scale will be assessed. Data from the intention-to-treat sample will be analyzed 16 weeks after randomization. This is the first study to evaluate the effectiveness of family psychoeducation for relatives of patients with MDD lasting more than one year. If this type of intervention is effective, it could be a new method of rehabilitation for patients with MDD lasting more than one year. Clinical Trials.gov NCT01734291 (registration date: 18 October 2012).

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

Excessive and premature new-onset cardiovascular disease among adults with bipolar disorder in the US NESARC cohort.

PubMed

Goldstein, Benjamin I; Schaffer, Ayal; Wang, Shuai; Blanco, Carlos

2015-02-01

Cross-sectional studies demonstrate increased prevalence of cardiovascular disease (CVD) among adults with bipolar disorder. However, there is a paucity of prospective data regarding new-onset CVD among adults with bipolar disorder. Analyses compared the 3-year incidence of CVD (via participant-reported physician diagnoses) among participants with DSM-IV diagnoses of bipolar I disorder (n = 1,047), bipolar II disorder (n = 392), major depressive disorder (MDD; n = 4,396), or controls (n = 26,266), who completed Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Analyses also compared the age of participants with new-onset CVD across groups. Multivariable analyses controlled for age, sex, race, cigarette smoking, hypertension, obesity, and alcohol and drug use disorders. The 3-year incidence of CVD among adults with bipolar I disorder, bipolar II disorder, MDD, and among controls was 6.30%, 5.74%, 3.98%, and 3.70%, respectively. The covariate-adjusted incidence of CVD was significantly greater among participants with bipolar I and II disorders versus controls and versus participants with MDD. Adjusted odds ratios (95% CI) were 2.58 (1.84-3.61; P < .0001) for bipolar I disorder vs controls; 2.76 (1.60-4.74; P = .0004) for bipolar II disorder vs controls; 2.11 (1.46-3.04; P = .0001) for bipolar I disorder vs MDD; 2.25 (1.26-4.01; P = .007) for bipolar II disorder vs MDD; and 1.22 (0.99-1.51; P = .06) for MDD vs controls. Bipolar I disorder participants with new-onset CVD were 10.70 ± 2.77 years younger than MDD participants with new-onset CVD and 16.78 ± 2.51 years younger than controls. Bipolar II disorder participants with new-onset CVD were 7.92 ± 3.27 years younger than MDD participants with new-onset CVD and 13.99 ± 2.79 years younger than controls. Adults with bipolar disorder are at significantly and meaningfully increased risk to develop CVD over the course of 3 years, even as compared to adults with MDD, and despite controlling for multiple potential confounds. Combined with very early age of CVD onset, this finding underscores the need for early and assertive CVD prevention strategies for people with bipolar disorder. © Copyright 2015 Physicians Postgraduate Press, Inc.

Modality-specific alterations in the perception of emotional stimuli in Bipolar Disorder compared to Healthy Controls and Major Depressive Disorder

PubMed Central

Vederman, Aaron C.; Weisenbach, Sara L.; Rapport, Lisa J.; Leon, Hadia M.; Haase, Brennan D.; Franti, Lindsay M.; Schallmo, Michael-Paul; Saunders, Erika F.H.; Kamali, Masoud M.; Zubieta, Jon-Kar; Langenecker, Scott A.; McInnis, Melvin G.

2013-01-01

Objectives Affect identification accuracy paradigms have increasingly been utilized to understand psychiatric illness including Bipolar Disorder (BD) and Major Depressive Disorder (MDD). This investigation focused on perceptual accuracy in affect identification in both visual and auditory domains among patients with BD, relative to Healthy Controls (HC) and patients with MDD. Demographic and clinical variables, in addition to medications were also investigated. Methods The visual Facial Emotion Perception Test (FEPT) and auditory Emotional Perception Test (EPT) were administered to adults with BD (n = 119) and MDD (n = 78) as well as HC (n = 66). Results Performance on the FEPT was significantly stronger than on the EPT irrespective of group. Performance on the EPT did not significantly differentiate the groups. On the FEPT, BD samples had the greatest difficulty relative to HC in identification of sad and fearful faces. BD participants also had greater difficulty identifying sad faces relative to MDD participants though not after controlling for severity of illness factors. For the BD (but not MDD) sample several clinical variables were also correlated with FEPT performance. Conclusions The findings suggest that disruptions in identification of negative emotions such as sadness and fear may be a characteristic trait of BD. However, this effect may be moderated by greater illness severity found in our BD sample. PMID:21683948

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.

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

PubMed Central

2013-01-01

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches. PMID:24289502

Discovery and validation of plasma biomarkers for major depressive disorder classification based on liquid chromatography-mass spectrometry.

PubMed

Liu, Xinyu; Zheng, Peng; Zhao, Xinjie; Zhang, Yuqing; Hu, Chunxiu; Li, Jia; Zhao, Jieyu; Zhou, Jingjing; Xie, Peng; Xu, Guowang

2015-05-01

Major depressive disorder (MDD) is a debilitating mental disease with a pronounced impact on the quality of life of many people; however, it is still difficult to diagnose MDD accurately. In this study, a nontargeted metabolomics approach based on ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to find the differential metabolites in plasma samples from patients with MDD and healthy controls. Furthermore, a validation analysis focusing on the differential metabolites was performed in another batch of samples using a targeted approach based on the dynamic multiple reactions monitoring method. Levels of acyl carnitines, ether lipids, and tryptophan pronouncedly decreased, whereas LPCs, LPEs, and PEs markedly increased in MDD subjects as compared with the healthy controls. Disturbed pathways, mainly located in acyl carnitine metabolism, lipid metabolism, and tryptophan metabolism, were clearly brought to light in MDD subjects. The binary logistic regression result showed that carnitine C10:1, PE-O 36:5, LPE 18:1 sn-2, and tryptophan can be used as a combinational biomarker to distinguish not only moderate but also severe MDD from healthy control with good sensitivity and specificity. Our findings, on one hand, provide critical insight into the pathological mechanism of MDD and, on the other hand, supply a combinational biomarker to aid the diagnosis of MDD in clinical usage.

Neuron-specific enolase levels in drug-naïve young adults with major depressive disorder.

PubMed

Wiener, Carolina David; Molina, Mariane Lopez; Passos, Miguel; Moreira, Fernanda Pedrotti; Bittencourt, Guilherme; de Mattos Souza, Luciano Dias; da Silva, Ricardo Azevedo; Jansen, Karen; Oses, Jean Pierre

2016-05-04

The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18-29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies

PubMed Central

Sharma, Ajaykumar N.; da Costa e Silva, Bruno Fernando Borges; Soares, Jair C.; Carvalho, André F.; Quevedo, Joao

2016-01-01

Rationale The neurotrophin hypothesis of major depressive disorder (MDD) postulates that this illness results from aberrant neurogenesis in brain regions that regulates emotion and memory. Notwithstanding this theory has primarily implicated BDNF in the neurobiology of MDD. Recent evidence suggests that other trophic factors namely GDNF, VEGF and IGF-1 may also be involved. Purpose The present review aimed to critically summarize evidence regarding changes in GDNF, IGF-1 and VEGF in individuals with MDD compared to healthy controls. In addition, we also evaluated the role of these mediators as potential treatment response biomarkers for MDD. Methods A comprehensive review of original studies studies measuring peripheral, central or mRNA levels of GDNF, IGF-1 or VEGF in patients with MDD was conducted. The PubMed/MEDLINE database was searched for peer-reviewed studies published in English through June 2nd, 2015. Results Most studies reported a reduction in peripheral GDNF and its mRNA levels in MDD patients versus controls. In contrast, IGF-1 levels in MDD patients compared to controls were discrepant across studies. Finally, most studies reported high peripheral VEGF levels and mRNA expression in MDD patients compared to healthy controls. Conclusions GDNF, IGF-1 and VEGF levels and their mRNA expression appear to be differentially altered in MDD patients compared to healthy individuals, indicating that these molecules might play an important role in the pathophysiology of depression and antidepressant action of therapeutic interventions. PMID:26956384

No association between serum cholesterol and death by suicide in patients with schizophrenia, bipolar affective disorder, or major depressive disorder

PubMed Central

2013-01-01

Background Previous research on serum total cholesterol and suicidality has yielded conflicting results. Several studies have reported a link between low serum total cholesterol and suicidality, whereas others have failed to replicate these findings, particularly in patients with major affective disorders. These discordant findings may reflect the fact that studies often do not distinguish between patients with bipolar and unipolar depression; moreover, definitions and classification schemes for suicide attempts in the literature vary widely. Methods Subjects were patients with one of the three major psychiatric disorders commonly associated with suicide: schizophrenia, bipolar affective disorder, and major depressive disorder (MDD). We compared serum lipid levels in patients who died by suicide (82 schizophrenia, 23 bipolar affective disorder, and 67 MDD) and non-suicide controls (200 schizophrenia, 49 bipolar affective disorder, and 175 MDD). Results Serum lipid profiles did not differ between patients who died by suicide and control patients in any diagnostic group. Conclusions Our results do not support the use of biological indicators such as serum total cholesterol to predict suicide risk among patients with a major psychiatric disorder. PMID:24308827

Undertreatment of people with major depressive disorder in 21 countries*

PubMed Central

Thornicroft, Graham; Chatterji, Somnath; Evans-Lacko, Sara; Gruber, Michael; Sampson, Nancy; Aguilar-Gaxiola, Sergio; Al-Hamzawi, Ali; Alonso, Jordi; Andrade, Laura; Borges, Guilherme; Bruffaerts, Ronny; Bunting, Brendan; de Almeida, Jose Miguel Caldas; Florescu, Silvia; de Girolamo, Giovanni; Gureje, Oye; Haro, Josep Maria; He, Yanling; Hinkov, Hristo; Karam, Elie; Kawakami, Norito; Lee, Sing; Navarro-Mateu, Fernando; Piazza, Marina; Posada-Villa, Jose; de Galvis, Yolanda Torres; Kessler, Ronald C.

2017-01-01

Background Major depressive disorder (MDD) is a leading cause of disability worldwide. Aims To examine the: (a) 12-month prevalence of DSM-IV MDD; (b) proportion aware that they have a problem needing treatment and who want care; (c) proportion of the latter receiving treatment; and (d) proportion of such treatment meeting minimal standards. Method Representative community household surveys from 21 countries as part of the World Health Organization World Mental Health Surveys. Results Of 51 547 respondents, 4.6% met 12-month criteria for DSM-IV MDD and of these 56.7% reported needing treatment. Among those who recognised their need for treatment, most (71.1%) made at least one visit to a service provider. Among those who received treatment, only 41.0% received treatment that met minimal standards. This resulted in only 16.5% of all individuals with 12-month MDD receiving minimally adequate treatment. Conclusions Only a minority of participants with MDD received minimally adequate treatment: 1 in 5 people in high-income and 1 in 27 in low-/lower-middle-income countries. Scaling up care for MDD requires fundamental transformations in community education and outreach, supply of treatment and quality of services. PMID:27908899

Co-morbid anxiety disorders in bipolar disorder and major depression: familial aggregation and clinical characteristics of co-morbid panic disorder, social phobia, specific phobia and obsessive-compulsive disorder.

PubMed

Goes, F S; McCusker, M G; Bienvenu, O J; Mackinnon, D F; Mondimore, F M; Schweizer, B; Depaulo, J R; Potash, J B

2012-07-01

Co-morbidity of mood and anxiety disorders is common and often associated with greater illness severity. This study investigates clinical correlates and familiality of four anxiety disorders in a large sample of bipolar disorder (BP) and major depressive disorder (MDD) pedigrees. The sample comprised 566 BP families with 1416 affected subjects and 675 MDD families with 1726 affected subjects. Clinical characteristics and familiality of panic disorder, social phobia, specific phobia and obsessive-compulsive disorder (OCD) were examined in BP and MDD pedigrees with multivariate modeling using generalized estimating equations. Co-morbidity between mood and anxiety disorders was associated with several markers of clinical severity, including earlier age of onset, greater number of depressive episodes and higher prevalence of attempted suicide, when compared with mood disorder without co-morbid anxiety. Familial aggregation was found with co-morbid panic and OCD in both BP and MDD pedigrees. Specific phobia showed familial aggregation in both MDD and BP families, although the findings in BP were just short of statistical significance after adjusting for other anxiety co-morbidities. We found no evidence for familiality of social phobia. Our findings suggest that co-morbidity of MDD and BP with specific anxiety disorders (OCD, panic disorder and specific phobia) is at least partly due to familial factors, which may be of relevance to both phenotypic and genetic studies of co-morbidity.

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.

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.

Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression

ERIC Educational Resources Information Center

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: A total of 51 children 7 through 11 years of age who had…

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

Intolerance of Uncertainty Mediates Reduced Reward Anticipation in Major Depressive Disorder

PubMed Central

Nelson, Brady D.; Shankman, Stewart A.; Proudfit, Greg H.

2014-01-01

Background Reduced reward sensitivity has long been considered a fundamental deficit of major depressive disorder (MDD). One way this deficit has been measured is by an asymmetry in electroencephalogram (EEG) activity between left and right frontal brain regions. MDD has been associated with a reduced frontal EEG asymmetry (i.e., decreased left relative to right) while anticipating reward. However, the mechanism (or mediator) of this association is unclear. The present study examined whether intolerance of uncertainty (IU) mediated the association between depression and reduced reward anticipation. Methods Data were obtained from a prior study reporting reduced frontal EEG asymmetry while anticipating reward in early-onset MDD. Participants included 156 individuals with early-onset MDD-only, panic disorder-only, both (comorbids), or controls. Frontal EEG asymmetry was recorded during an uncertain reward anticipation task. Participants completed a self-report measure of IU. Results All three psychopathology groups reported greater IU relative to controls. Across all participants, greater IU was associated with a reduced frontal EEG asymmetry. Furthermore, IU mediated the relationship between MDD and frontal EEG asymmetry and results remained significant after controlling for neuroticism, suggesting effects were not due to broad negative affectivity. Limitations MDD participants were limited to those with early-onset depression. Measures were collected cross-sectionally, precluding causal relationships. Conclusions IU mediated the relationship between MDD and reduced reward anticipation, independent of neuroticism. Explanations are provided regarding how IU may contribute to reduced reward anticipation in depression. Overall, IU appears to be an important mechanism for the association between depression and reduced reward anticipation. PMID:24655774

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.

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.

When social anxiety and depression go together: A population study of comorbidity and associated consequences.

PubMed

Adams, G Camelia; Balbuena, Lloyd; Meng, XiangFei; Asmundson, Gordon J G

2016-12-01

Despite several studies suggesting higher depression severity and dysfunction occurring in individuals with major depressive disorder (MDD) comorbid with social anxiety disorder (SAD), a clear understanding of the specific risks associated with this comorbidity is lacking. In this study we compared the disease characteristics and level of disability of individuals with MDD-SAD with other comorbidities between depression and anxiety. Data from the Collaborative Psychiatric Epidemiology Surveys (CPES) (N=20,013) were used. Individuals were divided in four groups comparing MDD-SAD with MDD alone, as well as other comorbidities between MDD and one anxiety (MDD-1ANX) or more than two anxiety disorders (MDD≥2ANX), with respect to several clinical, demographic, and functional characteristics. MDD-SAD comorbidity in the general population occurred in younger people, particularly men, and seemed to have an earlier onset of MDD. Occupational and social dysfunction was similar between individuals with MDD-SAD and those with MDD-1ANX. However, individuals with MDD≥2ANX had significantly higher severity as measured by suicidality as well as substance abuse and social and occupational dysfunction. SAD was the most prevalent comorbid anxiety in this group. The findings of this study were derived from the cross-sectional data. Our results suggest that the particular risks associated with MDD-SAD are the early onset and likelihood of additional anxiety, leading to higher severity and disability levels. Clinicians should increase the screening and treatment of SAD and other anxiety disorders in individuals with MDD given the higher associated health risk and functional impairment. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Major depressive disorder, cognitive symptoms, and neuropsychological performance among ethnically diverse HIV+ men and women.

PubMed

Fellows, Robert P; Byrd, Desiree A; Morgello, Susan

2013-02-01

Major depressive disorder (MDD), cognitive symptoms, and mild cognitive deficits commonly occur in HIV-infected individuals, despite highly active antiretroviral therapies. In this study, we compared neuropsychological performance and cognitive symptoms of 191 HIV-infected participants. Results indicated that participants with a formal diagnosis of current MDD performed significantly worse than participants without MDD in all seven neuropsychological domains evaluated, with the largest effect sizes in information processing speed, learning, and memory. In addition, a brief assessment of cognitive symptoms, derived from a comprehensive neuromedical interview, correlated significantly with neurocognitive functioning. Participants with MDD reported more cognitive symptoms and showed greater neurocognitive deficits than participants without MDD. These findings indicate that HIV-infected adults with MDD have more cognitive symptoms and worse neuropsychological performance than HIV-infected individuals without MDD. The results of this study have important implications for the diagnosis of HIV-associated neurocognitive disorders (HAND).

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.

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.

Challenging the unipolar-bipolar division: does mixed depression bridge the gap?

PubMed

Benazzi, Franco

2007-01-30

Mixed states, i.e., opposite polarity symptoms in the same mood episode, question the categorical splitting of mood disorders in bipolar disorders and unipolar depressive disorders, and may support a continuum between these disorders. Study aim was to find if there were a continuum between hypomania (defining BP-II) and depression (defining MDD), by testing mixed depression as a 'bridge' linking these two disorders. A correlation between intradepressive hypomanic symptoms and depressive symptoms could support such a continuum, but other explanations of a correlation are possible. Consecutive 389 BP-II and 261 MDD major depressive episode (MDE) outpatients were interviewed, cross-sectionally, with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide (to assess intradepressive hypomanic symptoms) and the Family History Screen, by a mood disorders specialist psychiatrist in a private practice. Patients presented voluntarily for treatment of depression when interviewed drug-free and had many subsequent follow-ups after treatment start. Mixed depression (depressive mixed state) was defined as the combination of MDE (depression) and three or more DSM-IV intradepressive hypomanic symptoms (elevated mood and increased self-esteem were always absent by definition), a definition validated by Akiskal and Benazzi. BP-II, versus MDD, had significantly lower age at onset, more recurrences, atypical and mixed depressions, bipolar family history, MDE symptoms and intradepressive hypomanic symptoms. Mixed depression was present in 64.5% of BP-II and in 32.1% of MDD (p=0.000). There was a significant correlation between number of MDE symptoms and number of intradepressive hypomanic symptoms. A dose-response relationship between frequency of mixed depression and number of MDE symptoms was also found. Differences on classic diagnostic validators could support a division between BP-II and MDD. Presence of intradepressive hypomanic symptoms by itself, and correlation between intradepressive hypomanic symptoms and depressive symptoms could instead support a continuum. Other explanations of such a correlation are possible. Depending on the method used, a BP-II-MDD continuum could be supported or not.

The temperament and character traits in patients with major depressive disorder and bipolar affective disorder with and without suicide attempt.

PubMed

Erić, Anamarija Petek; Erić, Ivan; Ćurković, Mario; Dodig-Ćurković, Katarina; Kralik, Kristina; Kovač, Vlatka; Filaković, Pavo

2017-06-01

Suicide and mood disorders (especially major depressive disorder (MDD) and bipolar affective disorder (BD)) represent a significant global health burden. Major depressive disorder and bipolar affective disorder have been associated with increased risk for suicide. Some specific suicide risk factors might be found in underlying individual personality traits. Specific personality features may predispose an individual to mood disorders (MDD or BD) hence increased suicide risk. The specificity of this research is in the assessment of personality features during the acute phase of illness immediately after suicide attempt which resulted in psychiatric inpatient treatment. The study included 119 unrelated Caucasian participants with MDD-severe depressive episode without psychotic symptoms (MDD) and BD-severe depressive episode without psychotic symptoms (BD-sDE). Both groups of patients with MDD and BD-sDE were divided into the suicide attempters and non-suicidal group. The diagnoses of the severe depressive episode without psychotic symptoms in major depressive disorder (MDD; F32.2) and bipolar disorder (BD-sDE; F31.4) were made according to ICD-10 (WHO 1992) diagnostic criteria. Methods of suicide attempts were also assessed according to ICD-10 and a self-report questionnaire, the Temperament and Character Inventory (TCI) was applied. The participants who exhibited suicide attempt had significantly higher scores on harm-avoidance (HA) (p<0.001), significantly lower score on persistence (PS) (p=0.037) and lower score, however not statistically significant, on novelty-seeking (NS) (p=0.319) regarding temperament dimensions. In character dimensions, the patients with suicidal attempt had significantly lower scores on self-directedness (SD) (p<0.001) and significantly lower scores on cooperativeness (CO) (p=0.001). Patients who had suicide attempt may have some significantly different personality traits than non-suicidal patients with mood disorders. The combination of high harm-avoidance (HA) and low self-directedness (SD) may be specific for depressive episode while the combination of high HA, novelty-seeking (NS), and self-transcendence (ST) with low SD may be related to suicide attempts during the depressive episode in bipolar disorder. The novelty-seeking (NS), self-transcendence (ST) and self-directedness (SD) may be specific for suicidal group of bipolar patients.

Burden of Depressive Disorders by Country, Sex, Age, and Year: Findings from the Global Burden of Disease Study 2010

PubMed Central

Ferrari, Alize J.; Charlson, Fiona J.; Norman, Rosana E.; Patten, Scott B.; Freedman, Greg; Murray, Christopher J.L.; Vos, Theo; Whiteford, Harvey A.

2013-01-01

Background Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease. Methods and Findings Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders. Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%–10.8%) of global YLDs and dysthymia for 1.4% (0.9%–2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%–3.2%) of global DALYs and dysthymia for 0.5% (0.3%–0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%–3.8%) to 3.8% (3.0%–4.7%) of global DALYs. Conclusions GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost-effective interventions to reduce its burden. Please see later in the article for the Editors' Summary PMID:24223526

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.

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.

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.

Neuropsychiatric Disorders Associated with Streptococcal Infection: A Case-Control Study among Privately Insured Children

PubMed Central

Leslie, Douglas L.; Kozma, Laura; Martin, Andrés; Landeros, Angeli; Katsovich, Liliya; King, Robert A.; Leckman, James F.

2009-01-01

Objective To assess whether antecedent streptococcal infection(s) increase the risk of subsequent diagnosis of obsessive-compulsive disorder (OCD), Tourette's syndrome (TS), other tic disorders, attention deficit hyperactivity disorder (ADHD) or major depressive disorder (MDD) in a national sample of privately insured children. Method Using health insurance claims data, we compared the prior-year occurrence of streptococcal infection in children aged 4–13 years with OCD, TS or tic disorder newly diagnosed between January 1998 and December 2004 to that of a cohort of matched controls. Conditional logistic regression models were used to determine the association of prior streptococcal sore throat or scarlet fever with a diagnosis of OCD, TS, or tic disorder. We repeated the analyses for two other infectious diseases (otitis media and sinusitis) and one non-infectious condition (migraine). We also investigated the potential specificity of this association by performing similar analyses focused on newly diagnosed attention deficit hyperactivity disorder (ADHD) and newly diagnosed major depressive disorder (MDD). Results Subjects with newly diagnosed OCD, TS, or tic disorder were more likely than controls to have had a diagnosis of streptococcal infection in the previous year (OR: 1.54, 95% CI: 1.29, 2.15). Prior streptococcal infection was also associated with incident diagnoses of ADHD (OR: 1.20, 95% CI: 1.06, 1.35) and MDD (OR=1.63, 95% CI: 1.12, 2.30). Conclusions These findings provide epidemiologic evidence that some pediatric onset neuropsychiatric disorders, including OCD, tic disorders, ADHD and MDD, may be temporally related to prior streptococcal infections. Whether this is the result of a non-specific stress response or secondary to an activation of the immune system remains to be determined. PMID:18724258

Anxiety Disorders in Adolescents and Psychosocial Outcomes at Age 30

PubMed Central

Essau, Cecilia A.; Lewinsohn, Peter M.; Olaya, Beatriz; Seeley, John R.

2014-01-01

Background Anxiety disorders are associated with adverse psychosocial functioning, and are predictive of a wide range of psychiatric disorders in adulthood. Objective The present study examined the associations between anxiety disorders during childhood and adolescence and psychosocial outcomes at age 30, and sought to address the extent to which psychopathology after age 19 mediated these relations. Method Eight hundred and sixteen participants from a large community sample were interviewed twice during adolescence, at age 24, and at age 30. They completed self-report measures of psychosocial functioning and semi-structured diagnostic interviews during adolescence and young adulthood. Results Childhood anxiety only predicted less years of completed education at age 30, whereas adolescent anxiety predicted income, unemployment, maladjustment, poor coping skills, more chronic stress and life events. Adult major depressive disorder (MDD) was the only disorder predicted by childhood anxiety, whereas adolescent anxiety predicted MDD, substance (SUD) and alcohol abuse/dependence (AUD) in adulthood. No adult psychopathology mediated the relationship between childhood anxiety disorders and psychosocial outcomes at age 30. Adult MDD, SUD and AUD partially or completely mediated the association between adolescent anxiety and most domains of psychosocial functioning at age 30. Limitations The participants are ethically and geographically homogenous, and changes in the diagnostic criteria and the interview schedules across the assessment periods. Conclusion Adolescent anxiety, compared to childhood anxiety, is associated with more adverse psychosocial outcomes at age 30. Adolescent anxiety affects negative outcomes at age 30 directly and through MDD, SUD and AUD. PMID:24456837

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

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

Comparison of treated and untreated major depressive disorder in a nationwide sample of Korean adults.

PubMed

Park, Subin; Cho, Maeng Je; Bae, Jae Nam; Chang, Sung Man; Jeon, Hong Jin; Hahm, Bong-Jin; Son, Jung-Woo; Kim, Shin Gyeom; Bae, Ahn; Hong, Jin Pyo

2012-06-01

We examined factors associated with lifetime treatment of major depressive disorder (MDD) in a nationwide sample of Korean adults. Of the 6,510 subjects aged 18-64 years who participated in the Korean Epidemiologic Catchment Area study, 362 (5.6%) with a lifetime diagnosis of MDD were analyzed. Diagnostic assessments were based on the Korean version of the Composite International Diagnostic Interview administered by lay interviewers. Of the 362 respondents with a lifetime diagnosis of MDD, 117 (32.3%) had been treated for psychiatric problems. Treated individuals with MDD were more likely to have chronic episode(s), more symptoms of depression, insomnia, and suicidal ideation, and were less likely to have feelings of guilt. In addition, treated individuals were more likely to have comorbid anxiety disorders, especially obsessive-compulsive disorder, post-traumatic stress disorder, and generalized anxiety disorder. Treatment-seeking by individuals with MDD is affected by socio-cultural factors such as misconception and stigma of mental illness, as well as severity of depression and comorbid conditions.

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.

Does Social Support Moderate the Association Among Major Depression, Generalized Anxiety Disorder, and Functional Disability in Adults With Diabetes?

PubMed

Levy, Melanie; Burns, Rachel J; Deschênes, Sonya S; Schmitz, Norbert

Diabetes requires complex self-management routines to prevent the development of functional disability. Relative to people without diabetes, those with diabetes are more likely to have comorbid major depressive disorder (MDD) and generalized anxiety disorder (GAD), which also increase the likelihood of functional disability. Social support is associated with positive health outcomes in people with comorbid diabetes and mental disorders and may serve as a buffer against functional disability, though this possibility has yet to be examined. This study examined whether social support moderates the association between MDD or GAD and functional disability in adults with diabetes. Adults with MDD or GAD were expected to report greater disability than those without MDD or GAD. This association was expected to be stronger in people reporting lower social support relative to those reporting higher social support. Data came from the cross-sectional 2012 Canadian Community Health Survey-Mental Health (n = 1764). Diabetes status, social support, and functional disability were assessed via self-report; past-year MDD and GAD were assessed with structured diagnostic interviews. Linear regression analyses, conducted separately for MDD and GAD, indicated main effects of past-year MDD and GAD, such that those with a mental disorder reported greater functional disability than those without a mental disorder. Social support did not moderate the associations between either MDD and functional disability or GAD and functional disability. In this nationally representative population study, both MDD and GAD predicted greater functional disability in adults with diabetes. Social support, however, did not moderate these associations. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

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.

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

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.

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

Altered brain network modules induce helplessness in major depressive disorder

PubMed Central

Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang

2017-01-01

Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474

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.

Remission of depression in patients with schizophrenia and comorbid major depressive disorder: results from the FACE-SZ cohort.

PubMed

Fond, Guillaume; Boyer, Laurent; Berna, Fabrice; Godin, Ophélia; Bulzacka, Ewa; Andrianarisoa, Méja; Brunel, Lore; Aouizerate, Bruno; Capdevielle, Delphine; Chereau, Isabelle; Coulon, Nathalie; D'Amato, Thierry; Dubertret, Caroline; Dubreucq, Julien; Faget, Catherine; Leignier, Sylvain; Lançon, Christophe; Mallet, Jasmina; Misdrahi, David; Passerieux, Christine; Rey, Romain; Schandrin, Aurélie; Urbach, Mathieu; Vidailhet, Pierre; Leboyer, Marion; Schürhoff, Franck; Llorca, Pierre-Michel

2018-06-06

Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.AimsTo determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD. Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6. 613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein. Antidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.Declaration of interestNone.

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.

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.

Emotional Variability and Clarity in Depression and Social Anxiety

PubMed Central

Thompson, Renee J.; Boden, Matthew Tyler; Gotlib, Ian H.

2016-01-01

Recent research has underscored the importance of elucidating specific patterns of emotion that characterize mental disorders. We examined two emotion traits, emotional variability and emotional clarity, in relation to both categorical (diagnostic interview) and dimensional (self-report) measures of Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD) in women diagnosed with MDD only (n=35), SAD only (n=31), MDD and SAD (n=26), or no psychiatric disorder (n=38). Results of the categorical analyses suggest that elevated emotional variability and diminished emotional clarity are transdiagnostic of MDD and SAD. More specifically, emotional variability was elevated for MDD and SAD diagnoses compared to no diagnosis, showing an additive effect for co-occurring MDD and SAD. Similarly diminished levels of emotional clarity characterized all three clinical groups compared to the healthy control group. Dimensional findings suggest that whereas emotional variability is associated more consistently with depression than with social anxiety, emotional clarity is associated more consistently with social anxiety than with depression. Results are interpreted using a threshold- and dose-response framework. PMID:26371579

Mixed features in major depressive disorder: diagnoses and treatments.

PubMed

Suppes, Trisha; Ostacher, Michael

2017-04-01

For the first time in 20 years, the American Psychiatric Association (APA) updated the psychiatric diagnostic system for mood disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Perhaps one of the most notable changes in the DSM-5 was the recognition of the possibility of mixed symptoms in major depression and related disorders (MDD). While MDD and bipolar and related disorders are now represented by 2 distinct chapters, the addition of a mixed features specifier to MDD represents a structural bridge between bipolar and major depression disorders, and formally recognizes the possibility of a mix of hypomania and depressive symptoms in someone who has never experienced discrete episodes of hypomania or mania. This article reviews historical perspectives on "mixed states" and the recent literature, which proposes a range of approaches to understanding "mixity." We discuss which symptoms were considered for inclusion in the mixed features specifier and which symptoms were excluded. The assumption that mixed symptoms in MDD necessarily predict a future bipolar course in patients with MDD is reviewed. Treatment for patients in a MDD episode with mixed features is critically considered, as are suggestions for future study. Finally, the premise that mood disorders are necessarily a spectrum or a gradient of severity progressing in a linear manner is argued.

Associations of current and remitted major depressive disorder with brain atrophy: the AGES-Reykjavik Study

PubMed Central

Geerlings, Mirjam I.; Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Garcia, Melissa E.; Harris, Tamara B.; Sigurdsson, Thordur; Gudnason, Vilmundur; Launer, Lenore J.

2014-01-01

Background To examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia. Methods Within the population-based AGES-Reykjavik Study 4,354 persons (mean age 76±5 years, 58% women) without dementia had a 1.5Tesla brain MRI. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the MINI International Neuropsychiatric Interview. Results Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy (B=−1.25%; 95%CI −2.05 to −0.44%), including more gray and white matter atrophy in most lobes as well as more atrophy of the hippocampus and thalamus. Participants with current, first onset, MDD also had more brain atrophy (B=−1.62%; 95%CI −3.30 to 0.05%), while those remitted did not (B=0.06%; 95%CI −0.54 to 0.66%). Conclusion In older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD, was associated with widespread gray and white matter brain atrophy. Prospective studies should examine whether MDD is a consequence of or contributes to brain volume loss and development of dementia. PMID:22647536

Medical expenditures associated with major depressive disorder among privately insured working-age adults with diagnosed diabetes in the United States, 2008

PubMed Central

Shrestha, Sundar S.; Zhang, Ping; Li, Rui; Thompson, Theodore J.; Chapman, Daniel P.; Barker, Lawrence

2017-01-01

Aim We aimed at estimating excess medical expenditures associated with major depressive disorder (MDD) among working-age adults diagnosed with diabetes, disaggregated by treatment mode: insulin-treated diabetes (ITDM) or non-insulin-treated diabetes (NITDM). Methods We analyzed data for over 500,000 individuals with diagnosed diabetes from the 2008 U.S. MarketScan claims database. We grouped diabetic patients first by treatment mode (ITDM or NITDM), then by MDD status (with or without MDD), and finally by whether those with MDD used antidepressant medication. We estimated annual mean excess outpatient, inpatient, prescription drug, and total expenditures using regression models, controlling for demographics, types of health coverage, and comorbidities. Results Among persons having ITDM, the estimated annual total mean expenditure for those with no MDD (the comparison group) was $19,625. For those with MDD, the expenditures were $12,406 (63%) larger if using antidepressant medication and $7322 (37%) larger if not using antidepressant medication. Among persons having NITDM, the corresponding estimated expenditure for the comparison group was $10,746, the excess expenditures were $10,432 (97%) larger if using antidepressant medication and $5579 (52%) larger if not using antidepressant medication, respectively. Inpatient excess expenditures were the largest of total excess expenditure for those with ITDM and MDD treated with antidepressant medication; for all others with diabetes and MDD, outpatient expenditures were the largest excess expenditure. Conclusions Among working-age adults with diabetes, MDD was associated with substantial excess medical expenditures. Implementing the effective interventions demonstrated in clinical trials and treatment guidelines recommended by professional organizations might reduce the economic burden of MDD in this population. PMID:23490596

The structural equation analysis of childhood abuse, adult stressful life events, and temperaments in major depressive disorders and their influence on refractoriness

PubMed Central

Toda, Hiroyuki; Inoue, Takeshi; Tsunoda, Tomoya; Nakai, Yukiei; Tanichi, Masaaki; Tanaka, Teppei; Hashimoto, Naoki; Nakato, Yasuya; Nakagawa, Shin; Kitaichi, Yuji; Mitsui, Nobuyuki; Boku, Shuken; Tanabe, Hajime; Nibuya, Masashi; Yoshino, Aihide; Kusumi, Ichiro

2015-01-01

Background Previous studies have shown the interaction between heredity and childhood stress or life events on the pathogenesis of a major depressive disorder (MDD). In this study, we tested our hypothesis that childhood abuse, affective temperaments, and adult stressful life events interact and influence the diagnosis of MDD. Patients and methods A total of 170 healthy controls and 98 MDD patients were studied using the following self-administered questionnaire surveys: the Patient Health Questionnaire-9 (PHQ-9), the Life Experiences Survey, the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire, and the Child Abuse and Trauma Scale (CATS). The data were analyzed with univariate analysis, multivariable analysis, and structural equation modeling. Results The neglect scores of the CATS indirectly predicted the diagnosis of MDD through cyclothymic and anxious temperament scores of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire in the structural equation modeling. Two temperaments – cyclothymic and anxious – directly predicted the diagnosis of MDD. The validity of this result was supported by the results of the stepwise multivariate logistic regression analysis as follows: three factors – neglect, cyclothymic, and anxious temperaments – were significant predictors of MDD. Neglect and the total CATS scores were also predictors of remission vs treatment-resistance in MDD patients independently of depressive symptoms. Limitations The sample size was small for the comparison between the remission and treatment-resistant groups in MDD patients in multivariable analysis. Conclusion This study suggests that childhood abuse, especially neglect, indirectly predicted the diagnosis of MDD through increased affective temperaments. The important role as a mediator of affective temperaments in the effect of childhood abuse on MDD was suggested. PMID:26316754

Lifetime comorbidities between phobic disorders and major depression in Japan: results from the World Mental Health Japan 2002-2004 Survey.

PubMed

Tsuchiya, Masao; Kawakami, Norito; Ono, Yutaka; Nakane, Yoshibumi; Nakamura, Yosikazu; Tachimori, Hisateru; Iwata, Noboru; Uda, Hidenori; Nakane, Hideyuki; Watanabe, Makoto; Naganuma, Yoichi; Furukawa, Toshiaki A; Hata, Yukihiro; Kobayashi, Masayo; Miyake, Yuko; Takeshima, Tadashi; Kikkawa, Takehiko; Kessler, Ronald C

2009-01-01

Although often considered of minor significance in themselves, evidence exists that early-onset phobic disorders might be predictors of later more serious disorders, such as major depressive disorder (MDD). The purpose of this study is to investigate the association of phobic disorders with the onset of MDD in the community in Japan. Data from the World Mental Health Japan 2002-2004 Survey were analyzed. A total of 2,436 community residents aged 20 and older were interviewed using the WHO Composite International Diagnostic Interview 3.0 (response rate, 58.4%). A Cox proportional hazard model was used to predict the onset of MDD as a function of prior history of DSM-IV specific phobia, agoraphobia, or social phobia, adjusting for gender, birth-cohort, other anxiety disorders, education, and marital status at survey. Social phobia was strongly associated with the subsequent onset of MDD (hazard ratio [HR]=4.1 [95% CI: 2.0-8.7]) after adjusting for sex, birth cohort, and the number of other anxiety disorders. The association between agoraphobia or specific phobia and MDD was not statistically significant after adjusting for these variables. Social phobia is a powerful predictor of the subsequent first onset of MDD in Japan. Although this finding argues against a simple neurobiological model and in favor of a model in which the cultural meanings of phobia play a part in promoting MDD, an elucidation of causal pathways will require more fine-grained comparative research.

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.

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

Relationship between white matter integrity and serum cortisol levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics.

PubMed

Liu, Xiaodan; Watanabe, Keita; Kakeda, Shingo; Yoshimura, Reiji; Abe, Osamu; Ide, Satoru; Hayashi, Kenji; Katsuki, Asuka; Umene-Nakano, Wakako; Watanabe, Rieko; Ueda, Issei; Nakamura, Jun; Korogi, Yukunori

2016-06-01

Higher daytime cortisol levels because of a hyperactive hypothalamic-pituitary-adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts. To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method. The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement. Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected). Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal-subcortical and frontal-limbic circuits. © The Royal College of Psychiatrists 2016.

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.

Psychosocial features associated with lifetime comorbidity of major depression and anxiety disorders among a community sample of mid-life women: the SWAN mental health study.

PubMed

Cyranowski, Jill M; Schott, Laura L; Kravitz, Howard M; Brown, Charlotte; Thurston, Rebecca C; Joffe, Hadine; Matthews, Karen A; Bromberger, Joyce T

2012-12-01

In clinical samples, comorbidity between depressive and anxiety disorders is associated with greater symptom severity and elevated suicide risk. Less is known, however, regarding the long-term psychosocial impact that a lifetime history of both major depressive disorder (MDD) and one or more anxiety disorders has in community samples. This report evaluates clinical, psychological, social, and stress-related characteristics associated with a lifetime history of MDD and anxiety. Data from 915 women aged 42-52 who were recruited as part of the the Study of Women's Health across the Nation (SWAN) Mental Health Study were used to examine clinical and psychosocial features across groups of women with a lifetime history of MDD alone, anxiety alone, both MDD and anxiety, or neither MDD nor anxiety. As compared with women with a history of either MDD or anxiety alone, women with a comorbid history were more likely to report recurrent MDD, multiple and more severe lifetime anxiety disorders, greater depressive and anxiety symptoms, diminished social support, and more past-year distressing life events. Exploratory analyses indicated that women with a comorbid history also report more childhood abuse/neglect and diminished self-esteem, as compared with women with a history of either disorder alone. Midlife women with a comorbid history that includes both MDD and anxiety disorders report diminished social support, more symptomatic distress, and a more severe and recurrent psychiatric history. Future research is needed to clarify the biological and psychosocial risk factors associated with this comorobid profile, and to develop targeted interventions for this at-risk group. Depression and Anxiety 00:1-8, 2012. © 2012 Wiley Periodicals, Inc. © 2012 Wiley Periodicals, Inc.

Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder.

PubMed

Chang, Cheng-Chen; Jou, Shaw-Hwa; Lin, Ta-Tsung; Lai, Te-Jen; Liu, Chin-San

2015-01-01

To compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with major depressive disorder (MDD). Patients met DSM-IV diagnostic criteria for MDD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any major psychiatric disorder and they were medically healthy. Peripheral blood leukocytes were analyzed to compare copy number, SNPs and oxidative damage of mtDNA between the two groups. 40 MDD patients and 70 comparison subjects were collected. The median age of the subjects was 42 years and 38 years in MDD and comparison groups, respectively. Leukocyte mtDNA copy number of MDD patients was significantly lower than that of the comparison group (p = 0.037). MDD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90, p<0.001). After generalized linear model adjusted for age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the MDD group (p<0.001). MtDNA oxidative damage was positively correlated with age (p<0.001) and MDD (p<0.001). Antipsychotic use was negatively associated with mtDNA copy number (p = 0.036). The study is cross-sectional with no longitudinal follow up. The cohort is clinically stable and generalizability of our result to other cohort should be considered. Our study suggests that oxidative stress and mitochondria may play a role in the pathophysiology of MDD. More large-scale studies are warranted to assess the interplay between oxidative stress, mitochondria dysfunction and MDD.

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.

Common Psychiatric Disorders and Caffeine Use, Tolerance, and Withdrawal: An Examination of Shared Genetic and Environmental Effects

PubMed Central

Bergin, Jocilyn E.; Kendler, Kenneth S.

2012-01-01

Background Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Method Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. Results GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation = 0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. Conclusions There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes. PMID:22854069

Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder.

PubMed

Chandley, Michelle J; Szebeni, Katalin; Szebeni, Attila; Crawford, Jessica; Stockmeier, Craig A; Turecki, Gustavo; Miguel-Hidalgo, Jose Javier; Ordway, Gregory A

2013-07-01

Norepinephrine and glutamate are among several neurotransmitters implicated in the neuropathology of major depressive disorder (MDD). Glia deficits have also been demonstrated in people with MDD, and glia are critical modulators of central glutamatergic transmission. We studied glia in men with MDD in the region of the brain (locus coeruleus; LC) where noradrenergic neuronal cell bodies reside and receive glutamatergic input. The expression of 3 glutamate-related genes (SLC1A3, SLC1A2, GLUL) concentrated in glia and a glia gene (GFAP) were measured in postmortem tissues from men with MDD and from paired psychiatrically healthy controls. Initial gene expression analysis of RNA isolated from homogenized tissue (n = 9-10 pairs) containing the LC were followed by detailed analysis of gene expressions in astrocytes and oligodendrocytes (n = 6-7 pairs) laser captured from the LC region. We assessed protein changes in GFAP using immunohistochemistry and immunoblotting (n = 7-14 pairs). Astrocytes, but not oligodendrocytes, demonstrated robust reductions in the expression of SLC1A3 and SLC1A2, whereas GLUL expression was unchanged. GFAP expression was lower in astrocytes, and we confirmed reduced GFAP protein in the LC using immunostaining methods. Reduced expression of protein products of SLC1A3 and SLC1A2 could not be confirmed because of insufficient amounts of LC tissue for these assays. Whether gene expression abnormalities were associated with only MDD and not with suicide could not be confirmed because most of the decedents who had MDD died by suicide. Major depressive disorder is associated with unhealthy astrocytes in the noradrenergic LC, characterized here by a reduction in astrocyte glutamate transporter expression. These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD.

The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study.

PubMed

Nigatu, Yeshambel T; Reijneveld, Sijmen A; de Jonge, Peter; van Rossum, Elisabeth; Bültmann, Ute

2016-01-01

Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL), this study was aimed at examining these combined effects. We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m2) as normal weight (18.5-24.99), overweight (25-29.9), mild obesity (30-34.9) and moderate/severe obesity (≥ 35); we measured abdominal obesity using a waist circumference of ≥102 and ≥ 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses. The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95%-confidence interval, 95%-CI) were: - 1.32 (-1.75; -0.90). However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL. Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR-QoL.

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

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.

Two-Year Course of Generalized Anxiety Disorder, Social Anxiety Disorder and Panic Disorder with Agoraphobia in a Sample of Latino Adults

PubMed Central

Bjornsson, Andri S.; Sibrava, Nicholas J.; Beard, Courtney; Moitra, Ethan; Weisberg, Risa B.; Pérez Benítez, Carlos I.; Keller, Martin B.

2014-01-01

Objective It is imperative to study the clinical course of anxiety disorders among Latinos, given the implications for culturally-sensitive treatment in this population. The current study is the first prospective, observational, longitudinal study of anxiety disorders among Latinos. Method Data are reported on 139 adult Latinos (mean age 34.65, SD =10.98, 70.5% female) diagnosed with social anxiety disorder (SAD, n = 86), generalized anxiety disorder (GAD, n = 90) or panic disorder with agoraphobia (PDA, n = 62). The participants were interviewed with standardized clinical interviews at intake and annually over two years of follow-up. Probabilities of recovery were calculated using standard survival analysis methods. Results The two-year recovery rates in this study were 0.07 for SAD, 0.14 for GAD, 0.03 for PDA, and 0.50 for major depressive disorder (MDD). Overall functioning, social adjustment and life satisfaction in this sample were poor. Conclusions The recovery rates for anxiety disorders in this Latino sample were markedly low. Although caution must be used in comparing these data with prior longitudinal studies, these recovery rates seem to be much lower than in non-Latino White samples. However, the clinical course of MDD in this sample was similar to its course among non-Latino Whites, invoking the pressing question of whether there is something about the experience of anxiety disorders (but not MDD) among Latinos that makes them more impairing and persistent. The answer to that question should inform future treatment development for this population. PMID:24731232

First psychiatric hospitalizations in the US military: the National Collaborative Study of Early Psychosis and Suicide (NCSEPS)

PubMed Central

HERRELL, RICHARD; HENTER, IOLINE D.; MOJTABAI, RAMIN; BARTKO, JOHN J.; VENABLE, DIANE; SUSSER, EZRA; MERIKANGAS, KATHLEEN R.; WYATT, RICHARD J.

2015-01-01

Background Military samples provide an excellent context to systematically ascertain hospitalization for severe psychiatric disorders. The National Collaborative Study of Early Psychosis and Suicide (NCSEPS), a collaborative study of psychiatric disorders in the US Armed Forces, estimated rates of first hospitalization in the military for three psychiatric disorders : bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia. Method First hospitalizations for BD, MDD and schizophrenia were ascertained from military records for active duty personnel between 1992 and 1996. Rates were estimated as dynamic incidence (using all military personnel on active duty at the midpoint of each year as the denominator) and cohort incidence (using all military personnel aged 18–25 entering active duty between 1992 and 1996 to estimate person-years at risk). Results For all three disorders, 8723 hospitalizations were observed in 8 120 136 person-years for a rate of 10·7/10 000 [95% confidence interval (CI) 10·5–11·0]. The rate for BD was 2·0 (95% CI 1·9–2·1), for MDD, 7·2 (95% CI 7·0–7·3), and for schizophrenia, 1·6 (95% CI 1·5–1·7). Rates for BD and MDD were greater in females than in males [for BD, rate ratio (RR) 2·0, 95% CI 1·7–2·2; for MDD, RR 2·9, 95% CI 2·7–3·1], but no sex difference was found for schizophrenia. Blacks had lower rates than whites of BD (RR 0·8, 95% CI 0·7–0·9) and MDD (RR 0·8, 95% CI 0·8–0·9), but a higher rate of schizophrenia (RR 1·5, 95% CI 1·3–1·7). Conclusions This study underscores the human and financial burden that psychiatric disorders place on the US Armed Forces. PMID:16879759

Anticipation-related brain connectivity in bipolar and unipolar depression: a graph theory approach

PubMed Central

Almeida, Jorge R. C.; Stiffler, Richelle; Lockovich, Jeanette C.; Aslam, Haris A.; Phillips, Mary L.

2016-01-01

Bipolar disorder is often misdiagnosed as major depressive disorder, which leads to inadequate treatment. Depressed individuals versus healthy control subjects, show increased expectation of negative outcomes. Due to increased impulsivity and risk for mania, however, depressed individuals with bipolar disorder may differ from those with major depressive disorder in neural mechanisms underlying anticipation processes. Graph theory methods for neuroimaging data analysis allow the identification of connectivity between multiple brain regions without prior model specification, and may help to identify neurobiological markers differentiating these disorders, thereby facilitating development of better therapeutic interventions. This study aimed to compare brain connectivity among regions involved in win/loss anticipation in depressed individuals with bipolar disorder (BDD) versus depressed individuals with major depressive disorder (MDD) versus healthy control subjects using graph theory methods. The study was conducted at the University of Pittsburgh Medical Center and included 31 BDD, 39 MDD, and 36 healthy control subjects. Participants were scanned while performing a number guessing reward task that included the periods of win and loss anticipation. We first identified the anticipatory network across all 106 participants by contrasting brain activation during all anticipation periods (win anticipation + loss anticipation) versus baseline, and win anticipation versus loss anticipation. Brain connectivity within the identified network was determined using the Independent Multiple sample Greedy Equivalence Search (IMaGES) and Linear non-Gaussian Orientation, Fixed Structure (LOFS) algorithms. Density of connections (the number of connections in the network), path length, and the global connectivity direction (‘top-down’ versus ‘bottom-up’) were compared across groups (BDD/MDD/healthy control subjects) and conditions (win/loss anticipation). These analyses showed that loss anticipation was characterized by denser top-down fronto-striatal and fronto-parietal connectivity in healthy control subjects, by bottom-up striatal-frontal connectivity in MDD, and by sparse connectivity lacking fronto-striatal connections in BDD. Win anticipation was characterized by dense connectivity of medial frontal with striatal and lateral frontal cortical regions in BDD, by sparser bottom-up striatum-medial frontal cortex connectivity in MDD, and by sparse connectivity in healthy control subjects. In summary, this is the first study to demonstrate that BDD and MDD with comparable levels of current depression differed from each other and healthy control subjects in density of connections, connectivity path length, and connectivity direction as a function of win or loss anticipation. These findings suggest that different neurobiological mechanisms may underlie aberrant anticipation processes in BDD and MDD, and that distinct therapeutic strategies may be required for these individuals to improve coping strategies during expectation of positive and negative outcomes. PMID:27368345

Anticipation-related brain connectivity in bipolar and unipolar depression: a graph theory approach.

PubMed

Manelis, Anna; Almeida, Jorge R C; Stiffler, Richelle; Lockovich, Jeanette C; Aslam, Haris A; Phillips, Mary L

2016-09-01

Bipolar disorder is often misdiagnosed as major depressive disorder, which leads to inadequate treatment. Depressed individuals versus healthy control subjects, show increased expectation of negative outcomes. Due to increased impulsivity and risk for mania, however, depressed individuals with bipolar disorder may differ from those with major depressive disorder in neural mechanisms underlying anticipation processes. Graph theory methods for neuroimaging data analysis allow the identification of connectivity between multiple brain regions without prior model specification, and may help to identify neurobiological markers differentiating these disorders, thereby facilitating development of better therapeutic interventions. This study aimed to compare brain connectivity among regions involved in win/loss anticipation in depressed individuals with bipolar disorder (BDD) versus depressed individuals with major depressive disorder (MDD) versus healthy control subjects using graph theory methods. The study was conducted at the University of Pittsburgh Medical Center and included 31 BDD, 39 MDD, and 36 healthy control subjects. Participants were scanned while performing a number guessing reward task that included the periods of win and loss anticipation. We first identified the anticipatory network across all 106 participants by contrasting brain activation during all anticipation periods (win anticipation + loss anticipation) versus baseline, and win anticipation versus loss anticipation. Brain connectivity within the identified network was determined using the Independent Multiple sample Greedy Equivalence Search (IMaGES) and Linear non-Gaussian Orientation, Fixed Structure (LOFS) algorithms. Density of connections (the number of connections in the network), path length, and the global connectivity direction ('top-down' versus 'bottom-up') were compared across groups (BDD/MDD/healthy control subjects) and conditions (win/loss anticipation). These analyses showed that loss anticipation was characterized by denser top-down fronto-striatal and fronto-parietal connectivity in healthy control subjects, by bottom-up striatal-frontal connectivity in MDD, and by sparse connectivity lacking fronto-striatal connections in BDD. Win anticipation was characterized by dense connectivity of medial frontal with striatal and lateral frontal cortical regions in BDD, by sparser bottom-up striatum-medial frontal cortex connectivity in MDD, and by sparse connectivity in healthy control subjects. In summary, this is the first study to demonstrate that BDD and MDD with comparable levels of current depression differed from each other and healthy control subjects in density of connections, connectivity path length, and connectivity direction as a function of win or loss anticipation. These findings suggest that different neurobiological mechanisms may underlie aberrant anticipation processes in BDD and MDD, and that distinct therapeutic strategies may be required for these individuals to improve coping strategies during expectation of positive and negative outcomes. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Major Depressive Disorder with Sub-threshold Bipolarity in the National Comorbidity Survey Replication

PubMed Central

Angst, Jules; Cui, Lihong; Swendsen, J. Joel; Rothen, S.; Cravchik, Anibal; Kessler, Ronald; Merikangas, Kathleen

2011-01-01

Objectives There is growing clinical and epidemiologic evidence indicating that major mood disorders form a spectrum from Major Depressive Disorder (MDD) to pure mania. The present investigation examined the prevalence and clinical correlates of MDD with sub-threshold bipolarity vs. pure MDD in the National Comorbidity Survey Replication (NCS-R). Methods The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February, 2001 and April, 2003. Lifetime history of mood disorders, symptoms and clinical indicators of severity were collected using version 3.0 of the WHO Composite International Diagnostic Interview, a fully structured lay-administered diagnostic interview. Results Nearly 40% of study participants with a history of major depressive disorder had a history of sub-threshold hypomania. This subgroup had a younger age of disorder onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania, and lower levels of clinical severity than those with bipolar II disorder. Conclusions The findings demonstrate heterogeneity of major depressive disorder and support the validity of inclusion of sub-threshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice. PMID:20713498

Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

PubMed

Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

2016-11-25

Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

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

A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies.

PubMed

Chang, Lun-Ching; Jamain, Stephane; Lin, Chien-Wei; Rujescu, Dan; Tseng, George C; Sibille, Etienne

2014-01-01

Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases. In support of the superior discriminative power of this novel approach, we observed no significant enrichment for GWAS-related genes in coexpression modules extracted from single studies or in meta-modules using gene expression data from non-psychiatric control subjects. Genes in the identified module encode proteins implicated in neuronal signaling and structure, including glutamate metabotropic receptors (GRM1, GRM7), GABA receptors (GABRA2, GABRA4), and neurotrophic and development-related proteins [BDNF, reelin (RELN), Ephrin receptors (EPHA3, EPHA5)]. These results are consistent with the current understanding of molecular mechanisms of MDD and provide a set of putative interacting molecular partners, potentially reflecting components of a functional module across cells and biological pathways that are synchronously recruited in MDD, other brain disorders and MDD-related illnesses. Collectively, this study demonstrates the importance of integrating transcriptome data, gene coexpression modules and GWAS results for providing novel and complementary approaches to investigate the molecular pathology of MDD and other complex brain disorders.

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.

Post-traumatic stress disorder and depression co-occurrence: Structural relations among disorder constructs and trait and symptom dimensions.

PubMed

Post, Loren M; Feeny, Norah C; Zoellner, Lori A; Connell, Arin M

2016-12-01

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) in response to trauma co-occur at high rates. A better understanding of the nature of this co-occurrence is critical to developing an accurate conceptualization of the disorders. This study examined structural relations among the PTSD and MDD constructs and trait and symptom dimensions within the framework of the integrative hierarchical model of anxiety and depression. Study participants completed clinician-rated and self-report measures during a pre-treatment assessment. The sample consisted of 200 treatment-seeking individuals with a primary DSM-IV PTSD diagnosis. Structural equation modelling was used to examine the relationship between the constructs. The trait negative affect/neuroticism construct had a direct effect on both PTSD and MDD. The trait positive affect/extraversion construct had a unique, negative direct effect on MDD, and PTSD had a unique, direct effect on the physical concerns symptoms construct. An alternative model with the PTSD and MDD constructs combined into an overall general traumatic stress construct produced a decrement in model fit. These findings provide a clearer understanding of the relationship between co-occurring PTSD and MDD as disorders with shared trait negative affect/neuroticism contributing to the overlap between them and unique trait positive affect/extraversion and physical concerns differentiating them. Therefore, PTSD and MDD in response to trauma may be best represented as two distinct, yet strongly related constructs. In assessing individuals who have been exposed to trauma, practitioners should recognize that co-occurring PTSD and MDD appears to be best represented as two distinct, yet strongly related constructs. Negative affect may be the shared vulnerability directly influencing both PTSD and MDD; however, in the presence of both PTSD and MDD, low positive affect appears to be more specifically related to MDD and fear of physical sensations to PTSD, which is information that could be used by practitioners in the determination of treatment approach. Overall, these findings are clinically relevant in that they may inform assessment, treatment planning, and ultimately diagnostic classification. © 2015 The British Psychological Society.

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

PubMed

Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

2011-04-01

The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that antidepressant therapy was significantly more effective than placebo in dysthymic disorder (risk ratio = 1.75; 95% CI, 1.49-2.04; P < .0001), while placebo response rates in dysthymic disorder trials were significantly lower compared to MDD trials (29.9% vs 37.9%, respectively; P = .042). Meta-regression suggested a statistically significant difference in the risk ratio of responding to antidepressants versus placebo when comparing studies either on dysthymic disorder or on MDD, suggesting a greater risk ratio for response in favor of antidepressant therapy versus placebo in patients with dysthymic disorder versus MDD (coefficient of -0.113; P = .007). These results support the utility of antidepressants for dysthymic disorder. In fact, the margin of efficacy of antidepressants for dysthymic disorder was larger than for MDD. Future studies providing longer-term data on the treatment of dysthymic disorder with antidepressants are essential. © Copyright 2011 Physicians Postgraduate Press, Inc.

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.

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.

The Costs of Depression

PubMed Central

Kessler, Ronald C.

2011-01-01

Brief summary Data are reviewed on the societal costs of major depressive disorder (MDD). Early-onset MDD is found to predict difficulties in subsequent role transitions, including low educational attainment, high risk of teen child-bearing, marital disruption, and unstable employment. Among people with specific social and productive roles, MDD is found to predict significant decrements in role functioning (e.g., low marital quality, low work performance, low earnings). MDD is also associated with elevated risk of onset, persistence, and severity of a wide range of chronic physical disorders as well as with increased early mortality due to an even wider range of physical disorders and to suicide. Although effectiveness trials show that expanded MDD treatment can reverse many of these adverse effects, only a minority of people with MDD receives treatment and the quality of treatment is unacceptably low among the majority of those in treatment. PMID:22370487

Altered slow wave activity in major depressive disorder with hypersomnia: a high density EEG pilot study

PubMed Central

Plante, David T.; Landsness, Eric C.; Peterson, Michael J.; Goldstein, Michael R.; Wanger, Tim; Guokas, Jeff J.; Tononi, Giulio; Benca, Ruth M.

2012-01-01

Hypersomnolence in major depressive disorder (MDD) plays an important role in the natural history of the disorder, but the basis of hypersomnia in MDD is poorly understood. Slow wave activity (SWA) has been associated with sleep homeostasis, as well as sleep restoration and maintenance, and may be altered in MDD. Therefore, we conducted a post-hoc study that utilized high density electroencephalography (hdEEG) to test the hypothesis that MDD subjects with hypersomnia (HYS+) would have decreased SWA relative to age and sex-matched MDD subjects without hypersomnia (HYS−) and healthy controls (n=7 for each group). After correcting for multiple comparisons using statistical non-parametric mapping, HYS+ subjects demonstrated significantly reduced parieto-occipital all-night SWA relative to HYS− subjects. Our results suggest hypersomnolence may be associated with topographic reductions in SWA in MDD. Further research using adequately powered prospective design is indicated to confirm these findings. PMID:22512951

Increased Ventricular Cerebrospinal Fluid Lactate in Depressed Adolescents

PubMed Central

Bradley, Kailyn A. L.; Mao, Xiangling; Case, Julia A. C.; Kang, Guoxin; Shungu, Dikoma C.; Gabbay, Vilma

2016-01-01

Background Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. Methods Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. Results Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1, 41) = 6.98, p = .01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. Conclusions Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function. PMID:26802978

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.

Face-memory and emotion: associations with major depression in children and adolescents.

PubMed

Pine, Daniel S; Lissek, Shmuel; Klein, Rachel G; Mannuzza, Salvatore; Moulton, John L; Guardino, Mary; Woldehawariat, Girma

2004-10-01

Studies in adults with major depressive disorder (MDD) document abnormalities in both memory and face-emotion processing. The current study used a novel face-memory task to test the hypothesis that adolescent MDD is associated with a deficit in memory for face-emotions. The study also examines the relationship between parental MDD and memory performance in offspring. Subjects were 152 offspring (ages 9-19) of adults with either MDD, anxiety disorders, both MDD and anxiety, or no disorder. Parents and offspring were assessed for mental disorders. Collection of face-memory data was blind to offspring and parent diagnosis. A computerized task was developed that required rating of facial photographs depicting 'happy,"fearful,' or 'angry' emotions followed by a memory recall test. Recall accuracy was examined as a function of face-emotion type. Age and gender independently predicted memory, with better recall in older and female subjects. Controlling for age and gender, offspring with a history of MDD (n = 19) demonstrated significant deficits in memory selectively for fearful faces, but not happy or angry faces. Parental MDD was not associated with face-memory accuracy. This study found an association between MDD in childhood or adolescence and perturbed encoding of fearful faces. MDD in young individuals may predispose to subtle anomalies in a neural circuit encompassing the amygdala, a brain region implicated in the processing of fearful facial expressions. These findings suggest that brain imaging studies using similar face-emotion paradigms should test whether deficits in processing of fearful faces relate to amygdala dysfunction in children and adolescents with 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

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

PubMed

Fond, G; Hamdani, N; Kapczinski, F; Boukouaci, W; Drancourt, N; Dargel, A; Oliveira, J; Le Guen, E; Marlinge, E; Tamouza, R; Leboyer, M

2014-03-01

To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prodromal Symptoms and Atypical Affectivity as Predictors of Major Depression in Juveniles: Implications for Prevention

ERIC Educational Resources Information Center

Kovacs, Maria; Lopez-Duran, Nestor

2010-01-01

Background: Given the long-term morbidity of juvenile-onset major depressive disorder (MDD), it is timely to consider whether more effort should be dedicated to its primary and secondary prevention. Methods: We reviewed studies of prodromal symptoms that may herald a first episode pediatric MDD and considered whether that literature has made an…

A diagnosis of bipolar spectrum disorder predicts diagnostic conversion from unipolar depression to bipolar disorder: a 5-year retrospective study.

PubMed

Woo, Young Sup; Shim, In Hee; Wang, Hee-Ryung; Song, Hoo Rim; Jun, Tae-Youn; Bahk, Won-Myong

2015-03-15

The major aims of this study were to identify factors that may predict the diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BP) and to evaluate the predictive performance of the bipolar spectrum disorder (BPSD) diagnostic criteria. The medical records of 250 patients with a diagnosis of MDD for at least 5 years were retrospectively reviewed for this study. The diagnostic conversion from MDD to BP was observed in 18.4% of 250 MDD patients, and the diagnostic criteria for BPSD predicted this conversion with high sensitivity (0.870) and specificity (0.917). A family history of BP, antidepressant-induced mania/hypomania, brief major depressive episodes, early age of onset, antidepressant wear-off, and antidepressant resistance were also independent predictors of this conversion. This study was conducted using a retrospective design and did not include structured diagnostic interviews. The diagnostic criteria for BPSD were highly predictive of the conversion from MDD to BP, and conversion was associated with several clinical features of BPSD. Thus, the BPSD diagnostic criteria may be useful for the prediction of bipolar diathesis in MDD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Sadness might isolate you in a non-smelling world: olfactory perception and depression

PubMed Central

Schablitzky, Sylvia; Pause, Bettina M.

2014-01-01

Major depressive disorder (MDD) occurs with a high prevalence among mental illnesses. MDD patients experience sadness and hopelessness, with blunted affective reactivity. However, such depressive episodes are also key symptoms in other depressive disorders, like Bipolar Disorder (BPD) or Seasonal Affective Disorder (SAD). Moreover, depressive symptoms can also be found in healthy individuals, but are experienced as less severe or for a shorter duration than in patients. Here, it is aimed to summarize studies investigating odor perception in depression, including depressive states in healthy individuals and patient populations. Odor perception in depression has been assessed with psychophysical methods (olfactory sensitivity, odor identification, and discrimination), and odor ratings (intensity, emotional valence, familiarity). In addition, some studies investigated affective reactions to odors, and physiological and anatomical correlates of odor perception in depression. The summary reveals that MDD is associated with reduced olfactory sensitivity. However, odor identification and discrimination scores seem to be unaffected by depression. The reduced olfactory sensitivity might be associated with a reduced ability to encode olfactory information and a reduced volume of the olfactory bulb. While similar processes seem to occur in healthy individuals experiencing depressive states, they have not been observed in BPD or SAD patients. However, in order to conclude that the reduced olfactory sensitivity is directly linked to depression, it is suggested that studies should implement control measures of cognitive performances or perceptual abilities in other stimulus modalities. It is concluded that the reduced olfactory performance in MDD patients seems to be disorder-, modality-, and test-specific, and that the application of an appropriate olfactory and cognitive test-battery might be highly useful in the differential diagnosis of MDD. PMID:24570666

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.

The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder.

PubMed

Lu, Yi; Liang, Hongmin; Han, Dan; Mo, Yin; Li, Zongfang; Cheng, Yuqi; Xu, Xiufeng; Shen, Zonglin; Tan, Chunyan; Zhao, Wei; Zhu, Yun; Sun, Xuejin

2016-01-01

Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05). Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05). Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.

A comparison of the clinical characteristics of Chinese patients with recurrent major depressive disorder with and without dysthymia.

PubMed

Sang, Wenhua; Li, Yihan; Su, Liang; Yang, Fuzhong; Wu, Wenyuan; Shang, Xiaofang; Zhang, Guanghua; Shen, Jianhua; Sun, Mengmeng; Guo, Liyang; Li, Zheng; Yan, Lijuan; Zhang, Bo; Wang, Gang; Liu, Guo; Liu, Tiebang; Zhang, Jinbei; Wang, Yanfang; Yu, Bin; Pan, Jiyang; Li, Yi; Hu, Chunmei; Yang, Lijun; Huang, Yongjin; Xie, Shoufu; Wang, Xueyi; Liu, Jiannin; Lv, Luxian; Chen, Yunchun; Zhang, Lina; Dang, Yamei; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S; Flint, Jonathan; Li, Keqing

2011-12-01

The relationship between major depressive disorder (MDD) and dysthymia, a form of chronic depression, is complex. The two conditions are highly comorbid and it is unclear whether they are two separate disease entities. We investigated the extent to which patients with dysthymia superimposed on major depression can be distinguished from those with recurrent MDD. We examined the clinical features in 1970 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and dysthymia and between dysthymia and disorders comorbid with major depression. The 354 cases with dysthymia had more severe MDD than those without, with more episodes of MDD and greater co-morbidity for anxiety disorders. Patients with dysthymia had higher neuroticism scores and were more likely to have a family history of MDD. They were also more likely to have suffered serious life events. Results were obtained in a clinically ascertained sample of Chinese women and may not generalize to community-acquired samples or to other populations. It is not possible to determine whether the associations represent causal relationships. The additional diagnosis of dysthymia in Chinese women with recurrent MDD defines a meaningful and potentially important subtype. We conclude that in some circumstances it is possible to distinguish double depression from recurrent MDD. Copyright © 2011 Elsevier B.V. All rights reserved.

Depressive Disorder Subtypes as Predictors of Incident Obesity in US Adults: Moderation by Race/Ethnicity

PubMed Central

Polanka, Brittanny M.; Vrany, Elizabeth A.; Patel, Jay; Stewart, Jesse C.

2017-01-01

Abstract We compared the relative importance of atypical major depressive disorder (MDD), nonatypical MDD, and dysthymic disorder in predicting 3-year obesity incidence and change in body mass index and determined whether race/ethnicity moderated these relationships. We examined data from 17,787 initially nonobese adults in the National Epidemiologic Survey on Alcohol and Related Conditions waves 1 (2001–2002) and 2 (2004–2005) who were representative of the US population. Lifetime subtypes of depressive disorders were determined using a structured interview, and obesity outcomes were computed from self-reported height and weight. Atypical MDD (odds ratio (OR) = 1.68, 95% confidence interval (CI): 1.43, 1.97; P < 0.001) and dysthymic disorder (OR = 1.66, 95% CI: 1.29, 2.12; P < 0.001) were stronger predictors of incident obesity than were nonatypical MDD (OR = 1.11, 95% CI: 1.01, 1.22; P = 0.027) and no history of depressive disorder. Atypical MDD (B = 0.41 (standard error, 0.15); P = 0.007) was a stronger predictor of increases in body mass index than were dysthymic disorder (B = −0.31 (standard error, 0.21); P = 0.142), nonatypical MDD (B = 0.007 (standard error, 0.06); P = 0.911), and no history of depressive disorder. Race/ethnicity was a moderator; atypical MDD was a stronger predictor of incident obesity in Hispanics/Latinos (OR = 1.97, 95% CI: 1.73, 2.24; P < 0.001) than in non-Hispanic whites (OR = 1.54, 95% CI: 1.25, 1.91; P < 0.001) and blacks (OR = 1.72, 95% CI: 1.31, 2.26; P < 0.001). US adults with atypical MDD are at particularly high risk of weight gain and obesity, and Hispanics/Latinos may be especially vulnerable to the obesogenic consequences of depressions. PMID:28369312

Major depressive disorder, anxiety disorders, and cardiac biomarkers in subjects at high risk of obstructive sleep apnea.

PubMed

Einvik, Gunnar; Hrubos-Strøm, Harald; Randby, Anna; Nordhus, Inger Hilde; Somers, Virend K; Omland, Torbjørn; Dammen, Toril

2011-06-01

Cardiac biomarkers may be valuable when exploring potential mechanisms for the association between cardiovascular disease and psychiatric disorders. In subjects at increased risk for obstructive sleep apnea, we examined whether major depressive disorder (MDD), anxiety disorders, or the combination of these was associated with circulating C-reactive protein (CRP), cardiac troponin T (cTnT), or heart rate variability (HRV). From the Akershus Sleep Apnea Project, 290 participants were assessed for MDD or any anxiety disorder by a physician using the Structured Clinical Interview for DSM-IV. Fasting blood samples were analyzed with high-sensitivity assays for CRP, cTnT, and HRV calculated from a Holter recording. Age, sex, hypertension, diabetes, hyperlipidemia, obesity, smoking, apnea-hypopnea index, and previous cardiovascular disease were adjusted for. The CRP levels (median [interquartile range], mg/L) were higher in depressive (2.7 [1.1-5.8]) versus nondepressive (1.3 [0.7-3.1], p = .02) and in anxious (2.8 [0.9-5.2]) versus nonanxious (1.3 [0.7-3.1], p = .01). MDD was independently associated with CRP (unstandardized β = 0.387, p = .04), but anxiety was not (unstandardized β = 0.298, p = .09). The CRP level was highest in subjects with comorbid MDD and anxiety (3.4 [1.1-7.8]). The unadjusted and adjusted odds ratios (95% confidence interval) for having measurable cTnT (> 3 ng/L) were 0.49 (0.24-1.07) and 0.92 (0.31-2.67) for MDD versus nondepressive and 0.38 (0.18-0.80) and 0.61 (0.30-2.05) for anxiety versus nonanxiety, respectively. HRV did not vary between groups. Although CRP was increased both in MDD and anxiety disorders, patients with comorbid MDD and anxiety may be particularly prone to increased systemic inflammation. Neither MDD nor anxiety disorders were associated with low-level myocardial damage or HRV.

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.

The bidirectional relationships between alcohol, cannabis, co-occurring alcohol and cannabis use disorders with major depressive disorder: results from a national sample.

PubMed

Pacek, Lauren R; Martins, Silvia S; Crum, Rosa M

2013-06-01

Alcohol use disorders (AUD) and cannabis use disorders (CUD) are common in the United States (US), and are associated with major depressive disorder (MDD). Co-occurring alcohol and cannabis use/use disorders (AUD+CUD), though understudied, have been found to be associated with greater adverse outcomes than alcohol or cannabis use/use disorders alone. There is a paucity of research on the co-occurring relationships of the two disorders with depression. Data came from Waves 1 and 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a population-based longitudinal survey of the adult non-institutionalized, civilian population in the US. Logistic regression analyses were used to assess the associations between: 1) baseline AUD, CUD, and co-occurring AUD+CUD with incident MDD at follow-up and 2) baseline MDD with incident AUD, CUD, and co-occurring AUD+CUD at follow-up, adjusted for potential confounding variables. For Aim 1, most of the AUD and CUD were positively associated with MDD. The strongest associations with incident MDD were observed for cannabis dependence (OR=6.61, CI=1.67-26.21) and co-occurring alcohol and cannabis dependence (OR=2.34, CI=1.23-4.48). For Aim 2, baseline MDD was significantly associated with comparatively fewer cases of incident AUD and CUD but the strongest association was observed for new onset co-occurring alcohol and cannabis dependence (OR=4.51, CI=1.31-15.60). The present study is limited by the potential for social desirability and recall biases. Positive associations between AUD, CUD and MDD were observed bidirectionally. Findings have implications for preventive and treatment programs and initiatives. Copyright © 2012 Elsevier B.V. All rights reserved.

Major depressive disorder and suicide risk among adult outpatients at several general hospitals in a Chinese Han population.

PubMed

Li, Haiyan; Luo, Xinni; Ke, Xiaoyin; Dai, Qing; Zheng, Wei; Zhang, Chanjuan; Cassidy, Ryan M; Soares, Jair C; Zhang, XiangYang; Ning, Yuping

2017-01-01

Somatic complaints are often the presenting symptoms of major depressive disorder (MDD) in the outpatient context, because this may go unrecognized. It is well understood that MDD carries an increased risk of suicide. This study aimed to identify the risk factors and association with both MDD and suicidality among Han Chinese outpatients. A multicenter study was carried out in 5189 outpatient adults (≥18 years old) in four general hospitals in Guangzhou, China. The 1392 patients who had the Patient Health Questionnaire-9 (PHQ-9) score ≥ 5, indicating depressive symptoms were offered an interview with a psychiatrist by the Mini International Neuropsychiatric Interview (MINI); 819 patients consented and completed the MINI interview. MINI module B was used to assess suicidality. Stepwise binary logistic models were used to estimate the relationship between a significant risk factor and suicide or MDD. According to with or without MDD, the secondary analysis was performed using the logistic regression model for the risk of suicidility. The current prevalence of MDD and the one month prevalence of suicidality were 3.7% and 2.3% respectively. The odds ratio of suicidality in women was more than twice that in men (OR = 2.62; 95% CI 1.45-4.76). Other risk factors which were significantly associated with suicidality were: living alone, higher education, self-reported depression, getting psychiatric diagnoses (MDD, anxiety disorders, and bipolar disorders). Significant risk factors for MDD were also noticed, such as comorbid anxiety disorders, self-reported anxiety, insomnia, suicidal ideation. It's a cross-sectional study in outpatient clinics using self-report questionnaires. This study provides valuable data about the risk factors and association of MDD and suicide risk in adult outpatients in Han Chinese. Those factors allow better the employment of preventative measures.

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.

Relationships of neuroticism and extraversion with axis I and II comorbidity among patients with DSM-IV major depressive disorder.

PubMed

Jylhä, Pekka; Melartin, Tarja; Isometsä, Erkki

2009-04-01

High comorbidity with axis I and II disorders among major depressive disorder (MDD) patients may in part be due to the predisposing personality dimensions of neuroticism and extraversion. However, a comprehensive view of this relationship is lacking. MDD patients (n=193) in the Vantaa Depression Study were interviewed at baseline and at 6 and 18 months with the SCAN and SCID-II, and a general population comparison group (n=388) surveyed by mail. Neuroticism and extraversion were measured with the Eysenck Personality Inventory. A dose-exposure relationship between standardized levels of neuroticism and extraversion and type and number of comorbid axis I and II disorders among patients with MDD was hypothesized. Prevalence and number of comorbid axis I and II disorders increased significantly with increasing level of neuroticism. In contrast, as the level of extraversion increased, the prevalences of social phobia and cluster C personality disorders decreased. Patients with pure MDD or with any comorbid axis I or II disorder had z-scores of neuroticism of +0.46, +0.90 and +1.30 and of extraversion of -0.34, -0.47 and -0.84, respectively. Patients' personality scores were not pre-morbid. Among MDD patients, a positive dose-exposure relationship appears to exist between neuroticism and prevalence and number of comorbid axis I and II disorders. A negative relationship exists between level of extraversion and prevalence of social phobia and cluster C personality disorders. These findings are consistent with the hypothesis that high neuroticism and low extraversion predispose to comorbid axis I and II disorders among patients with MDD.

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

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 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

The development of a novel high-precision major depressive disorder screening system using transient autonomic responses induced by dual mental tasks.

PubMed

Matsui, Takemi; Shinba, Toshikazu; Sun, Guanghao

2018-02-01

12.6% of major depressive disorder (MDD) patients have suicide intent, while it has been reported that 43% of patients did not consult their doctors for MDD, automated MDD screening is eagerly anticipated. Recently, in order to achieve automated screening of MDD, biomarkers such as multiplex DNA methylation profiles or physiological method using near infra-red spectroscopy (NIRS) have been studied, however, they require inspection using 96-well DNA ELIZA kit after blood sampling or significant cost. Using a single-lead electrocardiography (ECG), we developed a high-precision MDD screening system using transient autonomic responses induced by dual mental tasks. We developed a novel high precision MDD screening system which is composed of a single-lead ECG monitor, analogue to digital (AD) converter and a personal computer with measurement and analysis program written by LabView programming language. The system discriminates MDD patients from normal subjects using heat rate variability (HRV)-derived transient autonomic responses induced by dual mental tasks, i.e. verbal fluency task and random number generation task, via linear discriminant analysis (LDA) adopting HRV-related predictor variables (hear rate (HR), high frequency (HF), low frequency (LF)/HF). The proposed system was tested for 12 MDD patients (32 ± 15 years) under antidepressant treatment from Shizuoka Saiseikai General Hospital outpatient unit and 30 normal volunteers (37 ± 17 years) from Tokyo Metropolitan University. The proposed system achieved 100% sensitivity and 100% specificity in classifying 42 examinees into 12 MDD patients and 30 normal subjects. The proposed system appears promising for future HRV-based high-precision and low-cost screening of MDDs using only single-lead ECG.

Long-term outcome of major depressive disorder in psychiatric patients is variable.

PubMed

Holma, K Mikael; Holma, Irina A K; Melartin, Tarja K; Rytsälä, Heikki J; Isometsä, Erkki T

2008-02-01

The prevailing view of outcome of major depressive disorder (MDD), based on mostly inpatient cohorts sampled from tertiary centers, emphasizes chronicity and frequent recurrences. We investigated the long-term outcome of a regionally representative psychiatric MDD cohort comprising mainly outpatients. The Vantaa Depression Study included 163 patients with DSM-IV MDD (71.5% of those eligible) diagnosed using structured and semistructured interviews and followed up at 6 months, 18 months, and 5 years with a life chart between February 1, 1997, and April 30, 2004. The effects of comorbid disorders and other predictors on outcome were comprehensively investigated. Over the 5-year follow-up, 98.8% of patients achieved a symptom state below major depressive episode (MDE) criteria, and 88.4% reached full remission, with the median time to full remission being 11.0 months. Nearly one third (29.3%) had no recurrences, whereas 30.0% experienced 1, 12.9% experienced 2, and 27.9% experienced 3 or more recurrences. Preceding dysthymic disorder (p = .028), cluster C personality disorder (p = .041), and longer MDE duration prior to entry (p = .011) were the most significant predictors of longer time in achieving full remission. Severity of MDD and comorbidity, especially social phobia, predicted probability of, shorter time to, and number of recurrences. Previous literature on mostly inpatient MDD may have, by generalizing from patients with the most severe psychopathology, overemphasized chronicity of MDD. The long-term outcome of MDD in psychiatric care is variable, with about one tenth of patients having poor, one third having intermediate, and one half having favorable outcomes. In addition to known predictors, cluster C personality disorders and social phobia warrant further attention as predictors of MDD outcome among outpatients.

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).

Temporal sequencing of nicotine dependence and major depressive disorder: A U.S. national study.

PubMed

Martínez-Ortega, José M; Franco, Silvia; Rodríguez-Fernández, Jorge M; Gutiérrez-Rojas, Luis; Wang, Shuai; Gurpegui, Manuel

2017-04-01

Major Depressive Disorder (MDD) and Nicotine dependence (ND) often co-occur. However, little attention has been given to the temporal order between the two disorders. We compared the sociodemographic and clinical characteristics of individuals whose onset of ND preceded (ND-prior) or followed the onset of MDD (MDD-prior). Binary logistic regression models were computed to compare ND-prior (n=546) and MDD-prior (n=801) individuals from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n=43,093). We found that MDD-prior were more likely to have a history of suicide attempts and a family history of both depression and antisocial behavior, to have had psychiatric hospitalization, and to have an earlier age of onset of the first depressive episode; but a later age of onset for both daily smoking and ND. On average, MDD-prior individuals showed a significantly longer transition time from daily smoking to ND (15.6±0.6 vs. 6.9±0.4 years, P<0.001). In contrast, ND-prior subjects had a significantly greater proportion of withdrawal symptoms, and of lifetime alcohol use or alcohol use disorder. We conclude that the phenomenology and course of ND and MDD vary significantly, depending on which disorder had earlier onset. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Influence of Parental and Grandparental Major Depressive Disorder on Behavior Problems in Early Childhood: A Three-Generation Study

ERIC Educational Resources Information Center

Olino, Thomas M.; Pettit, Jeremy W.; Klein, Daniel N.; Allen, Nicholas B.; Seeley, John R.; Lewinsohn, Peter M.

2008-01-01

The study examines the influence of parental and grandparental major depressive disorder (MDD) on behavior problems in children. The results conclude that MDD in parents and grandparents may result in high levels of incorporation problems of MDD in children but don't indicate additional risk.

Major Depressive Disorder and Impulsive Reactivity to Emotion: Toward a Dual Process View of Depression

PubMed Central

Carver, Charles S.; Johnson, Sheri L.; Joormann, Jutta

2012-01-01

Objective Dual process theories of behavior have been used to suggest that vulnerability to depression involves elevated reactivity to emotions. This study tests that idea, examining self-reported reactivity. Design Comparison between persons with at least one lifetime episode of major depressive disorder (lifetime MDD) and those without this diagnosis, controlling for symptoms of alcohol use (a potential externalizing confound) and current symptoms of depression (a potential state-dependent confound). Methods Undergraduates (N = 120) completed a clinical interview to diagnose lifetime MDD and a series of self-reports bearing on diverse aspects of self-control, including reactivity to emotion. Thirty-four were diagnosed with lifetime MDD; 86 did not meet criteria for MDD. The groups were then compared on three factors underlying the scales assessing self-control. Results The MDD group had higher scores than controls on the two factors that reflect impulsive reactivity to diverse emotions, including emotions that are positive in valence. These effects were not explained by associations with either externalizing symptoms or current depressive symptoms. Conclusions Reflexive reactivity to emotions characterizes depression, in addition to some externalizing problems, and it may deserve study as a potential transdiagnostic feature. PMID:23865405

Patients with Posttraumatic Stress Disorder with Comorbid Major Depressive Disorder Require a Higher Dose of Psychotropic Drugs.

PubMed

Chiba, Hiromi; Oe, Misari; Uchimura, Naohisa

2016-01-01

Major depressive disorder (MDD) has been associated with stressful life events and with posttraumatic stress disorder (PTSD). PTSD and MDD comorbidity was also reported to be associated with greater symptom severity and lower levels of functioning. However, the characteristics of pharmacotherapy for PTSD with MDD are not fully understood. To understand this relationship, we conducted a retrospective review using medical charts at the Department of Neuropsychiatry, Kurume University Hospital. Information from 55 patients with PTSD was analyzed. Five cases were excluded after re-evaluation of the PTSD diagnosis. A higher rate of type II trauma was observed in the PTSD with MDD group (50.0%) than in the PTSD-only group [13.6%; χ(2) (1, n =50) = 7.26, p<0.01]. Patients with comorbid MDD were significantly older, had more severe PTSD symptomatology, and a longer duration of treatment. They also received higher doses of psychotropic drugs, regardless of the type (antidepressants, antipsychotics, benzodiazepines), than the PTSD-only group. Our results showed that comorbid MDD is associated with higher doses of psychotropic drugs, suggesting difficulties in treatment.

Patterns of cannabis use and clinical correlates among individuals with Major Depressive Disorder and Bipolar Disorder.

PubMed

Taub, Sharon; Feingold, Daniel; Rehm, Jürgen; Lev-Ran, Shaul

2018-01-01

Major Depressive Disorder (MDD) and Bipolar Disorder (BPD) are the most severe mood disorders globally. Previous reports indicate high co-occurrence of cannabis use and cannabis use disorders (CUDs) associated with both disorders, yet studies comparing patterns of cannabis use between individuals with MDD and BPD are scarce. Data were drawn from Wave 1 (2001-2002) of the National Epidemiologic survey on Alcohol and Related Conditions (NESARC). Cannabis users who qualified for a diagnosis of past-year MDD (N=217) were compared to those with BPD (N=168) in frequency and daily dose of cannabis use, rates of comorbid psychiatric disorders including specific criteria of CUDs, treatment utilization and suicidality. Among past-year cannabis users, individuals with BPD reported using cannabis more frequently and smoking more joints per day compared to those with MDD. They were also more likely to suffer from comorbid personality disorders and qualify for specific CUD-criteria, including use in physically hazardous situations and unsuccessful efforts to control substance use. Our results indicate that individuals with BPD may present more intensive patterns of cannabis use compared to those with MDD. This may have potential effects on the course of BPD and should be further explored in longitudinal studies. Copyright © 2017 Elsevier Inc. 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

Dose-response relationship between number of comorbid anxiety disorders in adolescent bipolar/unipolar disorders, and psychosis, suicidality, substance abuse and familiality.

PubMed

Dilsaver, Steven C; Akiskal, Hagop S; Akiskal, Kareen K; Benazzi, Franco

2006-12-01

To ascertain rates of panic, obsessive-compulsive (OCD) and social phobic disorders among adolescents with bipolar disorder (BP), unipolar major depressive disorder (MDD) and psychiatric comparison patients, to assess their relationships to suicidality, psychosis, comorbidity patterns and familiality. The first author (SCD) interviewed 313 Latino adolescents using a structured interview based on the SCID. Family history was ascertained by live interview or interview by proxy. Patients were classified as BP, MDD, or non-affectively ill comparison controls (CC). Data regarding suicidality and psychosis were collected. Regression analysis was used to test associations and control for confounding effects. Positive likelihood ratios were used to measure the dose-response relationships between number of anxiety disorders and measures of severity of illness and familial loading for affective illness. Of the total sample, 36.7% were BP, 44.7% MDD and 18.5% CC. In BP vs. MDD the odds of panic disorder were 4.4, of OCD 5.1, and of social phobia 3.3. MDD, in turn, were more likely to have these disorders than CC. BP (but not MDD) with panic disorder and social phobia, were more likely to have suicidal ideation; among the anxiety disorders, only social phobia was associated with having greater odds of suicide attempts. Among BP and MDD, patients with all three anxiety disorders were more likely to be psychotic. Presence of any mood disorder among first-degree relatives substantially increased the odds of having panic disorder and social phobia. The presence of one comorbid anxiety disorder increased the odds of having another. Finally, there were dose-response relationships between number of anxiety disorders and measures of severity of illness and familial loading for affective illness. Single interviewer using the SCID; cross sectional exploratory study. BP adolescents have a greater anxiety disorder burden than their MDD counterparts. The results are compatible with the hypothesis that heavy familial-genetic loading for affective illness in juveniles is associated with bipolarity, cumulative anxiety disorder comorbidity, suicidality and psychosis. These observations are in line with pioneering psychopathologic observation in the early 1900s by two French psychiatrists, Gilbert Ballet and Pierre Kahn, who saw common ground between what until then had been considered the distinct categories of the neuroses and cyclothymic (circular) psychoses. This perspective has much in common with current complex genetic models of anxious diatheses in bipolar disorder.

The impact of comorbid post-traumatic stress disorder in patients with major depressive disorder on clinical features, pharmacological treatment strategies, and treatment outcomes - Results from a cross-sectional European multicenter study.

PubMed

Dold, Markus; Bartova, Lucie; Kautzky, Alexander; Souery, Daniel; Mendlewicz, Julien; Serretti, Alessandro; Porcelli, Stefano; Zohar, Joseph; Montgomery, Stuart; Kasper, Siegfried

2017-07-01

This international, multicenter, cross-sectional study comprising 1346 adult in- and outpatients with major depressive disorder (MDD) investigated the association between MDD as primary diagnosis and comorbid post-traumatic stress disorder (PTSD). In a cross-sectional data collection process, the presence of comorbid PTSD was determined by the Mini International Neuropsychiatric Interview (MINI) and the patients' socio-demographic, clinical, psychopharmacological, and response information were obtained. Clinical features between MDD with and without concurrent PTSD were compared using descriptive statistics, analyses of covariance (ANCOVA), and binary logistic regression analyses. 1.49% of the MDD patients suffered from comorbid PTSD. Significantly more MDD + comorbid PTSD patients exhibited atypical features, comorbid anxiety disorders (any comorbid anxiety disorder, panic disorder, agoraphobia, and social phobia), comorbid bulimia nervosa, current suicide risk, and augmentation treatment with low-dose antipsychotic drugs. In the binary logistic regression analyses, the presence of atypical features (odds ratio (OR) = 4.49, 95%CI:1.01-20.12; p≤.05), any comorbid anxiety disorder (OR = 3.89, 95%CI:1.60-9.44; p = .003), comorbid panic disorder (OR = 6.45, 95%CI:2.52-16.51; p = .001), comorbid agoraphobia (OR = 6.51, 95%CI:2.54-16.68; p≤.001), comorbid social phobia (OR = 6.16, 95%CI:1.71-22.17; p≤.001), comorbid bulimia nervosa (OR = 10.39, 95%CI:1.21-88.64; p = .03), current suicide risk (OR = 3.58, 95%CI:1.30-9.91; p = .01), and augmentation with low-potency antipsychotics (OR = 6.66, 95%CI:2.50-17.77; p<.001) were associated with concurrent PTSD in predominant MDD. Major findings of this study were (1.) the much lower prevalence rate of comorbid PTSD in predominant MDD compared to the reverse prevalence rates of concurrent MDD in primary PTSD, (2.) the high association to comorbid anxiety disorders, and (3.) the increased suicide risk due to concurrent PTSD. Copyright © 2017 Elsevier B.V. and ECNP. 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.

Major depressive disorder subtypes to predict long-term course

PubMed Central

van Loo, Hanna M.; Cai, Tianxi; Gruber, Michael J.; Li, Junlong; de Jonge, Peter; Petukhova, Maria; Rose, Sherri; Sampson, Nancy A.; Schoevers, Robert A.; Wardenaar, Klaas J.; Wilcox, Marsha A.; Al-Hamzawi, Ali Obaid; Andrade, Laura Helena; Bromet, Evelyn J.; Bunting, Brendan; Fayyad, John; Florescu, Silvia E.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Levinson, Daphna; Medina-Mora, Maria Elena; Nakane, Yoshibumi; Posada-Villa, Jose; Scott, Kate M.; Xavier, Miguel; Zarkov, Zahari; Kessler, Ronald C.

2016-01-01

Background Variation in course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. Methods Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs) followed by k-means cluster analysis, are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) Surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM-IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode; number of with an episode lasting most of the year) and severity (hospitalization for MDD; disability due to MDD). Results Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness-worry-anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high-risk cluster (30.0% of respondents) accounted for 52.9-69.7% of high persistence and severity and was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor. Conclusions Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data. PMID:24425049

An Objective Screening Method for Major Depressive Disorder Using Logistic Regression Analysis of Heart Rate Variability Data Obtained in a Mental Task Paradigm.

PubMed

Sun, Guanghao; Shinba, Toshikazu; Kirimoto, Tetsuo; Matsui, Takemi

2016-01-01

Heart rate variability (HRV) has been intensively studied as a promising biological marker of major depressive disorder (MDD). Our previous study confirmed that autonomic activity and reactivity in depression revealed by HRV during rest and mental task (MT) conditions can be used as diagnostic measures and in clinical evaluation. In this study, logistic regression analysis (LRA) was utilized for the classification and prediction of MDD based on HRV data obtained in an MT paradigm. Power spectral analysis of HRV on R-R intervals before, during, and after an MT (random number generation) was performed in 44 drug-naïve patients with MDD and 47 healthy control subjects at Department of Psychiatry in Shizuoka Saiseikai General Hospital. Logit scores of LRA determined by HRV indices and heart rates discriminated patients with MDD from healthy subjects. The high frequency (HF) component of HRV and the ratio of the low frequency (LF) component to the HF component (LF/HF) correspond to parasympathetic and sympathovagal balance, respectively. The LRA achieved a sensitivity and specificity of 80.0 and 79.0%, respectively, at an optimum cutoff logit score (0.28). Misclassifications occurred only when the logit score was close to the cutoff score. Logit scores also correlated significantly with subjective self-rating depression scale scores ( p  < 0.05). HRV indices recorded during a MT may be an objective tool for screening patients with MDD in psychiatric practice. The proposed method appears promising for not only objective and rapid MDD screening but also evaluation of its severity.

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

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder

PubMed Central

Chen, Zi-Qi; Du, Ming-Ying; Zhao, You-Jin; Huang, Xiao-Qi; Li, Jing; Lui, Su; Hu, Jun-Mei; Sun, Huai-Qiang; Liu, Jia; Kemp, Graham J.; Gong, Qi-Yong

2015-01-01

Background Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. Methods Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. Results Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal–limbic–thalamic–striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. Limitations The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. Conclusion The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD. PMID:25853283

Is low cognitive functioning a predictor or consequence of major depressive disorder? A test in two longitudinal birth cohorts.

PubMed

Schaefer, Jonathan D; Scult, Matthew A; Caspi, Avshalom; Arseneault, Louise; Belsky, Daniel W; Hariri, Ahmad R; Harrington, Honalee; Houts, Renate; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E

2017-11-16

Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.

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

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.

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.

The genetic interacting landscape of 63 candidate genes in Major Depressive Disorder: an explorative study.

PubMed

Lekman, Magnus; Hössjer, Ola; Andrews, Peter; Källberg, Henrik; Uvehag, Daniel; Charney, Dennis; Manji, Husseini; Rush, John A; McMahon, Francis J; Moore, Jason H; Kockum, Ingrid

2014-01-01

Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear. This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and machine learning (MDR) approach. Although none of the interaction survived correction for multiple comparisons, the results provide important information for future genetic interaction studies in complex disorders. Among the 0.5% most significant observations, none had been reported previously for risk to MDD. Within this group of interactions, less than 0.03% would have been detectable based on main effect approach or an a priori algorithm. We evaluated correlations among the three different models and conclude that all three algorithms detected the same interactions to a low degree. Although the top interactions had a surprisingly large effect size for MDD (e.g. additive dominant model Puncorrected = 9.10E-9 with attributable proportion (AP) value = 0.58 and multiplicative recessive model with Puncorrected = 6.95E-5 with odds ratio (OR estimated from β3) value = 4.99) the area under the curve (AUC) estimates were low (< 0.54). Moreover, the population attributable fraction (PAF) estimates were also low (< 0.15). We conclude that the top interactions on their own did not explain much of the genetic variance of MDD. The different statistical interaction methods we used in the present study did not identify the same pairs of interacting markers. Genetic interaction studies may uncover previously unsuspected effects that could provide novel insights into MDD risk, but much larger sample sizes are needed before this strategy can be powerfully applied.

Mental Health Impact of Hosting Disaster Refugees: Analyses from a Random Sample Survey Among Haitians Living in Miami

PubMed Central

Messiah, Antoine; Lacoste, Jérôme; Gokalsing, Erick; Shultz, James M.; de la Vega, Pura Rodríguez; Castro, Grettel; Acuna, Juan M.

2016-01-01

Objectives Studies on the mental health of families hosting disaster refugees are lacking. This study compares participants in households that hosted 2010 Haitian earthquake disaster refugees with their nonhost counterparts. Methods A random sample survey was conducted from October 2011 through December 2012 in Miami-Dade County, Florida. Haitian participants were assessed regarding their 2010 earthquake exposure and impact on family and friends and whether they hosted earthquake refugees. Using standardized scores and thresholds, they were evaluated for symptoms of three common mental disorders (CMDs): posttraumatic stress disorder, generalized anxiety disorder, and major depressive disorder (MDD). Results Participants who hosted refugees (n = 51) had significantly higher percentages of scores beyond thresholds for MDD than those who did not host refugees (n = 365) and for at least one CMD, after adjusting for participants’ earthquake exposures and effects on family and friends. Conclusions Hosting refugees from a natural disaster appears to elevate the risk for MDD and possibly other CMDs, independent of risks posed by exposure to the disaster itself. Families hosting refugees deserve special attention. PMID:27490654

An Investigation of Depression, Trauma History, and Symptom Severity in Individuals Enrolled in a Treatment Trial for Chronic PTSD

PubMed Central

Bedard-Gilligan, Michele; Duax Jakob, Jeanne M.; Doane, Lisa Stines; Jaeger, Jeff; Eftekhari, Afsoon; Feeny, Norah; Zoellner, Lori A.

2015-01-01

Objectives To explore how factors such as major depressive disorder (MDD) and trauma history, including the presence of childhood abuse, influence diverse clinical outcomes such as severity and functioning in a sample with posttraumatic stress disorder (PTSD). Method In this study, 200 men and women seeking treatment for chronic PTSD in a clinical trial were assessed for trauma history and major depressive disorder and compared on symptom severity, psychosocial functioning, dissociation, treatment history, and extent of diagnostic co-occurrence. Results Overall, childhood abuse did not consistently predict clinical severity. However, co-occurring MDD, and to a lesser extent a high level of trauma exposure, did predict greater severity, worse functioning, greater dissociation, more extensive treatment history, and additional co-occurring disorders. Conclusions These findings suggest that presence of co-occurring depression may be a more critical marker of severity and impairment than history of childhood abuse or repeated trauma exposure. Furthermore, they emphasize the importance of assessing MDD and its impact on treatment seeking and treatment response for those with PTSD. PMID:25900026

The Prevalence of Stimulant and Antidepressant Use by Australian Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Major Depressive Disorder: A National Survey.

PubMed

Sawyer, Michael G; Reece, Christy E; Sawyer, Alyssa C P; Johnson, Sarah; Lawrence, David; Zubrick, Stephen R

2017-03-01

To identify the prevalence of stimulant and antidepressant medication use by children and adolescents with symptoms meeting the criteria for attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) in Australia. To identify factors associated with stimulant and antidepressant use by children and adolescents in Australia. Data are from a nationally representative sample of 4- to 17-year-olds (n = 6310). Parents completed the Diagnostic Interview Schedule for Children-Version IV (DISC-IV) and the Strengths and Difficulties Questionnaire. Eleven- to 17-year-olds completed a self-report version of the DISC-IV MDD module. Interviewers recorded prescribed medications used by participants in the previous 2 weeks. During a 2-week period, 1.3% of all 4- to 17-year-olds and 13.7% of those with symptoms meeting the criteria for ADHD had used stimulant medication, while 0.9% of all 4- to 17-year-olds and 13.4% with MDD had used antidepressants. In total, 22.6% of those using stimulant medications and 57.7% using antidepressant medications did not have symptoms meeting criteria for ADHD or MDD, respectively. Among 11- to 17-year-olds, 5.6% of those with adolescent-only-reported MDD, 10.9% of those with parent/carer-only-reported MDD, and 25.7% of those with MDD reported by both parents/carers and adolescents were using antidepressant medications. Only a minority of 4- to 17-year-olds with ADHD and MDD were being treated with stimulant or antidepressant medication. The percentage of adolescents with MDD using antidepressant medications varied depending on whether adolescents, parents/carers, or both identified the presence of MDD. This highlights the importance of using information from both these informants when assessing and treating adolescent depressive disorder.

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.

Face-Emotion Processing in Offspring at Risk for Panic Disorder.

ERIC Educational Resources Information Center

Pine, Daniel S.; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Lissek, Shmuel; Guardino, Mary; Woldehawariat, Girma

2005-01-01

Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no…

Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV.

PubMed

Uher, Rudolf; Payne, Jennifer L; Pavlova, Barbara; Perlis, Roy H

2014-06-01

The changes in diagnostic criteria for major depressive disorder (MDD) from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) may appear small but have important consequences for how the diagnosis is used. In DSM-5, MDD is part of the new "Depressive disorders" section, which is separate from "Bipolar disorders", marking a division in what had been known as "Mood disorders". A small wording change has expanded the core mood criterion to include hopelessness, potentially broadening the diagnosis. The replacement of an operationalized bereavement exclusion with a call for clinical judgment in distinguishing normal reactions to significant loss from a disorder in need of clinical attention makes the diagnosis less objective and complicates investigations of the relationship between adversity and depression. A new persistent depressive disorder category is intended to encompass both dysthymia and chronic depression, but its relationship to MDD is ambiguous with conflicting statements on whether the two diagnoses should be concurrent if both sets of criteria are fulfilled. Clarification is also needed on whether MDD can be concurrent with the new broad "other specified bipolar and related disorders". New specifiers of MDD "with anxious distress" and "with mixed features" allow characterization of additional symptoms. The specifier "with perinatal onset" expands on the DSM-IV "postnatal onset" to include onset during pregnancy. We review the changes in MDD definition, provide guidance on their implementation and discuss their implications for clinical practice and research. © 2013 Wiley Periodicals, Inc.

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.

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.

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.

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.

Clusters of Behaviors and Beliefs Predicting Adolescent Depression: Implications for Prevention

PubMed Central

Paunesku, David; Ellis, Justin; Fogel, Joshua; Kuwabara, Sachiko A; Gollan, Jackie; Gladstone, Tracy; Reinecke, Mark; Van Voorhees, Benjamin W.

2009-01-01

OBJECTIVE Risk factors for various disorders are known to cluster. However, the factor structure for behaviors and beliefs predicting depressive disorder in adolescents is not known. Knowledge of this structure can facilitate prevention planning. METHODS We used the National Longitudinal Study of Adolescent Health (AddHealth) data set to conduct an exploratory factor analysis to identify clusters of behaviors/experiences predicting the onset of major depressive disorder (MDD) at 1-year follow-up (N=4,791). RESULTS Four factors were identified: family/interpersonal relations, self-emancipation, avoidant problem solving/low self-worth, and religious activity. Strong family/interpersonal relations were the most significantly protective against depression at one year follow-up. Avoidant problem solving/low self-worth was not predictive of MDD on its own, but significantly amplified the risks associated with delinquency. CONCLUSION Depression prevention interventions should consider giving family relationships a more central role in their efforts. Programs teaching problem solving skills may be most appropriate for reducing MDD risk in delinquent youth. PMID:20502621

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

Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disorders: a meta-analysis of placebo-controlled randomized trials.

PubMed

Iovieno, Nadia; Tedeschini, Enrico; Bentley, Kate H; Evins, A Eden; Papakostas, George I

2011-08-01

Mood and alcohol use disorders are often co-occurring, each condition complicating the course and outcome of the other. The aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder with comorbid alcohol use disorders and to compare antidepressant and placebo response rates between depressed patients with or without comorbid alcohol use disorders. MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the acute-phase treatment of MDD and/or dysthymic disorder in patients with or without alcohol use disorders. The search term placebo was cross-referenced with each of the antidepressants approved by the US, Canadian, or European Union drug regulatory agencies for the treatment of MDD and/or dysthymic disorder. 195 articles were found eligible for inclusion in our analysis, 11 of which focused on the treatment of MDD/dysthymic disorder in patients with comorbid alcohol use disorders. The search was limited to articles published between January 1, 1980, and March 15, 2009 (inclusive). We found that antidepressant therapy was more effective than placebo in patients with comorbid alcohol use disorders (risk ratio of response = 1.336; P = .021). However, this was not the case when selective serotonin reuptake inhibitor (SSRI) antidepressants were examined alone (P > .05). There was no significant difference in the relative efficacy of antidepressants (versus placebo) when comparing studies in MDD/dysthymic disorder patients with or without alcohol use disorders (P = .973). Meta-regression analyses yielded no significant differences in the risk ratio of responding to antidepressants versus placebo in trials with comorbid alcohol use disorders, whether antidepressants were used alone or adjunctively to psychotherapy, whether they were used in patients actively drinking or recently sober, or whether they were used in pure MDD or in combined MDD and dysthymic disorder populations. These results support the utility of certain antidepressants (tricyclics, nefazodone) in treating depression in patients with comorbid alcohol use disorders. More data on the use of newer antidepressants, including the SSRIs, for this select patient population are needed. © Copyright 2011 Physicians Postgraduate Press, Inc.

[Heritability and genetic comorbidity of attention deficit disorder with hyperactivity].

PubMed

Puddu, Giannina; Rothhammer, Paula; Carrasco, Ximena; Aboitiz, Francisco; Rothhammer, Francisco

2017-03-01

This review aims to summarize information about the genetic etiology of attention deficit disorder with hyperactivity (ADHD), with particular reference to the contributions of our research group. We also discuss the genetic comorbidity estimated from genome-wide single nucleotide polymorphisms (SNP´s) between ADHD and major psychiatric disorders such as schizophrenia (E), major depressive disorder (MDD), bipolar disorder (BD) and autism spectrum disorders (ASD). A high genetic comorbidity was found between E and BD (46%), a moderate comorbidity between MDD and E, MDD and BD and MDD and ADHD (18%, 22% and 10% respectively) and a low comorbidity between E and ASD (2.5%). Furthermore, we show evidence concerning the genetic determination of psychiatric diseases, which is significantly lower when it is estimated from genome-wide SNP´s rather than using traditional quantitative genetic methodology (ADHD = E = 23%, BD = 25%, MDD = 21% and ASD = 17%). From an evolutionary perspective, we suggest that behavioral traits such as hyperactivity, inattention and impulsivity, which play a role in ADHD and perhaps also other hereditary traits which are part of major psychiatric disorders, could have had a high adaptive value during the early stages of the evolution of Homo sapiens. However, they became progressively less adaptive and definitively disadvantageous, to the extreme that they are involved in frequently diagnosed major psychiatric disorders.

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.

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.

Evaluation of periodontitis in hospital outpatients with major depressive disorder

PubMed Central

Solis, A. C. O.; Marques, A. H.; Pannuti, C. M.; Lotufo, R. F. M.; Lotufo-Neto, F.

2013-01-01

Background and Objective Major depressive disorder (MDD) has been associated with alterations in the neuroendocrine system and immune function and may be associated with an increased susceptibility to cardiovascular disease, cancer and autoimmune/inflammatory disease. This study was conducted to investigate the relationship between periodontitis and MDD in a convenience sample of hospital outpatients. Material and Methods The sample consisted of 72 physically healthy subjects (36 outpatients with MDD and 36 age-matched controls [± 3 years]). Patients with bipolar disorder, eating disorders and psychotic disorders were excluded. Probing pocket depth and clinical attachment level were recorded at six sites per tooth. Depression was assessed by means of Structured Clinical Interview for DSM-IV. Results Extent of clinical attachment level and probing pocket depth were not different between controls and subjects with depression for the following thresholds: ≥ 3 mm (Mann-Whitney, p = 0.927 and 0.756); ≥ 4 mm (Mann-Whitney, p = 0.656 and 0.373); ≥ 5 mm (Mann-Whitney, p = 0.518 and 0.870);, and ≥ 6 mm (Mann-Whitney, p = 0.994 and 0.879). Depression parameters were not associated with clinical attachment level ≥ 5 mm in this sample. Smoking was associated with loss of attachment ≥ 5 mm in the multi-variable logistic regression model (odds ratio = 6.99, 95% confidence interval = 2.00–24.43). Conclusions In this sample, periodontal clinical parameters were not different between patients with MDD and control subjects. There was no association between depression and periodontitis. PMID:23586804

Emotional reactivity to daily events in major and minor depression.

PubMed

Bylsma, Lauren M; Taylor-Clift, April; Rottenberg, Jonathan

2011-02-01

Although emotional dysfunction is an important aspect of major depressive disorder (MDD), it has rarely been studied in daily life. Peeters, Nicolson, Berkhof, Delespaul, and deVries (2003) observed a surprising mood-brightening effect when individuals with MDD reported greater reactivity to positive events. To better understand this phenomenon, we conducted a multimethod assessment of emotional reactivity to daily life events, obtaining detailed reports of appraisals and event characteristics using the experience-sampling method and the Day Reconstruction Method (Kahneman, Krueger, Schkade, Schwarz, & Stone, 2004) in 35 individuals currently experiencing a major depressive episode, 26 in a minor depressive (mD) episode, and 38 never-depressed healthy controls. Relative to healthy controls, both mood-disordered groups reported greater daily negative affect and lower positive affect and reported events as less pleasant, more unpleasant, and more stressful. Importantly, MDD and mD individuals reported greater reductions in negative affect following positive events, an effect that converged across assessment methods and was not explained by differences in prevailing affect, event appraisals, or medications. Implications of this curious mood-brightening effect are discussed. (c) 2010 APA, 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

Psychiatric Comorbidity in Depressed HIV-infected Individuals: Common and Clinically Consequential

PubMed Central

Gaynes, Bradley N.; O'Donnell, Julie; Nelson, Elise; Heine, Amy; Zinski, Anne; Edwards, Malaika; McGuinness, Teena; Riddhi, Modi A.; Montgomery, Charita; Pence, Brian W

2015-01-01

Objective To report on the prevalence of psychiatric comorbidity and its association with illness severity in depressed HIV patients. Methods As part of a multi-site randomized controlled trial of depression treatment for HIV patients, 304 participants meeting criteria for current Major Depressive Disorder (MDD) were assessed for other mood, anxiety and substance use disorders with the Mini-International Neuropsychiatric Interview, a structured psychiatric diagnostic interview. We also assessed baseline adherence, risk, and health measures. Results Complicated depressive illness was common. Only 18% of participants experienced MDD with no comorbid psychiatric diagnoses; 49% had comorbid dysthymia, 62% had ≥1 comorbid anxiety disorder, and 28% had a comorbid substance use disorder. Self-reported antiretroviral adherence did not differ by the presence of psychiatric comorbidity. However, psychiatric comorbidity was associated with worse physical health and functioning: compared to those with MDD alone, individuals with ≥1 comorbidity reported more HIV symptoms (5.1 vs. 4.1, p-value=0.01), and worse mental health-related quality of life on the SF-12 (29 vs. 35, p<0.01). Conclusion For HIV patients with MDD, chronic depression and psychiatric comorbidity are strikingly common, and this complexity is associated with greater HIV disease severity and worse quality of life. Appreciating this comorbidity can help clinicians better target those at risk of harder-to-treat HIV disease, and underscores the challenge of treating depression in this population. PMID:25892152

Co-altered functional networks and brain structure in unmedicated patients with bipolar and major depressive disorders.

PubMed

He, Hao; Sui, Jing; Du, Yuhui; Yu, Qingbao; Lin, Dongdong; Drevets, Wayne C; Savitz, Jonathan B; Yang, Jian; Victor, Teresa A; Calhoun, Vince D

2017-12-01

Bipolar disorder (BD) and major depressive disorder (MDD) share similar clinical characteristics that often obscure the diagnostic distinctions between their depressive conditions. Both functional and structural brain abnormalities have been reported in these two disorders. However, the direct link between altered functioning and structure in these two diseases is unknown. To elucidate this relationship, we conducted a multimodal fusion analysis on the functional network connectivity (FNC) and gray matter density from MRI data from 13 BD, 40 MDD, and 33 matched healthy controls (HC). A data-driven fusion method called mCCA+jICA was used to identify the co-altered FNC and gray matter components. Comparing to HC, BD exhibited reduced gray matter density in the parietal and occipital cortices, which correlated with attenuated functional connectivity within sensory and motor networks, as well as hyper-connectivity in regions that are putatively engaged in cognitive control. In addition, lower gray matter density was found in MDD in the amygdala and cerebellum. High accuracy in discriminating across groups was also achieved by trained classification models, implying that features extracted from the fusion analysis hold the potential to ultimately serve as diagnostic biomarkers for mood disorders.

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.

The Mediating Roles of Coping, Sleep, and Anxiety Motives in Cannabis Use and Problems among Returning Veterans with PTSD and MDD

PubMed Central

Metrik, Jane; Jackson, Kristina; Bassett, Shayna S.; Zvolensky, Michael J.; Seal, Karen; Borsari, Brian

2016-01-01

Veterans with posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), the two most prevalent mental health disorders in the Iraq and Afghanistan veterans, are at increased risk for cannabis use and problems including cannabis use disorder (CUD). The present study examined the relationship of PTSD and MDD with cannabis use frequency, cannabis problems, and CUD as well as the role of three coping-oriented cannabis use motives (coping with negative affect, situational anxiety, and sleep) that might underlie this relationship. Participants were veterans (N = 301) deployed post 9/11/2001 recruited from Veterans Health Administration facility in the Northeast US based on self-reported lifetime cannabis use. There were strong unique associations between PTSD and MDD and cannabis use frequency, cannabis problems, and CUD. Mediation analyses revealed the three motives accounted, in part, for the relationship between PTSD and MDD with three outcomes in all cases but for PTSD with cannabis problems. When modeled concurrently, sleep motives, but not situational anxiety or coping with negative affect motives, significantly mediated the association between PTSD and MDD with use. Together with coping motives, sleep motives also fully mediated the effects of PTSD and MDD on CUD and in part the effect of MDD on cannabis problems. Findings indicate the important role of certain motives for better understanding the relation between PTSD and MDD with cannabis use and misuse. Future work is needed to explore the clinical utility in targeting specific cannabis use motives in the context of clinical care for mental health and CUD. PMID:27786514

The network structure of major depressive disorder, generalized anxiety disorder and somatic symptomatology.

PubMed

Bekhuis, E; Schoevers, R A; van Borkulo, C D; Rosmalen, J G M; Boschloo, L

2016-10-01

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central in the processes behind the co-occurrence. This study explores associations between individual MDD/GAD symptoms and somatic symptoms by using the network approach. MDD/GAD symptoms were assessed in 2704 participants (mean age 41.7 years, 66.1% female) from the Netherlands Study of Depression and Anxiety using the Inventory of Depressive Symptomatology. Somatic symptoms were assessed with the somatization scale of the Four-Dimensional Symptom Questionnaire. The technique eLasso was used to estimate the network of MDD/GAD and somatic symptoms. The network structure showed numerous associations between MDD/GAD and somatic symptoms. In general, neurovegetative and cognitive/affective MDD/GAD symptoms showed a similar strength of connections to the somatic domain. However, associations varied substantially across individual symptoms. MDD/GAD symptoms with many and strong associations to the somatic domain included anxiety and fatigue, whereas hypersomnia and insomnia showed no connections to somatic symptoms. Among somatic symptoms, excessive perspiration and pressure/tight feeling in chest were associated with the MDD/GAD domain, while muscle pain and tingling in fingers showed only a few weak associations. Individual symptoms show differential associations in the co-occurrence of MDD/GAD with somatic symptomatology. Strongly interconnected symptoms are important in furthering our understanding of the interaction between the symptom domains, and may be valuable targets for future research and treatment.

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.

Comparison of automatical thoughts among generalized anxiety disorder, major depressive disorder and generalized social phobia patients.

PubMed

Gül, A I; Simsek, G; Karaaslan, Ö; Inanir, S

2015-08-01

Automatic thoughts are measurable cognitive markers of the psychopathology and coping styles of individuals. This study measured and compared the automatic thoughts of patients with generalized anxiety disorder (GAD), major depressive disorder (MDD), and generalized social phobia (GSP). Fifty-two patients with GAD, 53 with MDD, and 50 with GSP and 52 healthy controls completed the validated Automatic Thoughts Questionnaire (ATQ) and a structured psychiatric interview. Patients with GAD, MDD, and GSP also completed the validated Generalized Anxiety Disorder-7 questionnaire, the Beck Depression Inventory (BDI), and the Liebowitz Social Anxiety Scale (LSAS) to determine the severity of their illnesses. All scales were completed before treatment and after diagnosis. The ATQ scores of all pairs of groups were compared. The ATQ scores of the GAD, MDD, and GSP groups were significantly higher than were those of the control group. We also found significant correlations among scores on the GAD-7, BDI, and LSAS. The mean age of patients with GSP was lower than was that of the other groups (30.90 ± 8.35). The significantly higher ATQ scores of the MDD, GAD, and GSP groups, compared with the control group, underscore the common cognitive psychopathology characterizing these three disorders. This finding confirms that similar cognitive therapy approaches should be effective for these patients. This study is the first to compare GAD, MDD, and GSP from a cognitive perspective.

DNA Modification Study of Major Depressive Disorder: Beyond Locus-by-Locus Comparisons

PubMed Central

Oh, Gabriel; Wang, Sun-Chong; Pal, Mrinal; Chen, Zheng Fei; Khare, Tarang; Tochigi, Mamoru; Ng, Catherine; Yang, Yeqing A.; Kwan, Andrew; Kaminsky, Zachary A.; Mill, Jonathan; Gunasinghe, Cerisse; Tackett, Jennifer L.; Gottesman, Irving I.; Willemsen, Gonneke; de Geus, Eco J.C.; Vink, Jacqueline M.; Slagboom, P. Eline; Wray, Naomi R.; Heath, Andrew C.; Montgomery, Grant W.; Turecki, Gustavo; Martin, Nicholas G.; Boomsma, Dorret I.; McGuffin, Peter; Kustra, Rafal; Petronis, Art

2014-01-01

Background Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. Methods We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. Results In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Conclusions Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations. PMID:25108803

Age at onset of major depressive disorder in Han Chinese women: relationship with clinical features and family history.

PubMed

Yang, Fuzhong; Li, Yihan; Xie, Dong; Shao, Chunhong; Ren, Jianer; Wu, Wenyuan; Zhang, Ning; Zhang, Zhen; Zou, Ying; Zhang, Jiulong; Qiao, Dongdong; Gao, Chengge; Li, Youhui; Hu, Jian; Deng, Hong; Wang, Gang; Du, Bo; Wang, Xumei; Liu, Tiebang; Gan, Zhaoyu; Peng, Juyi; Wei, Bo; Pan, Jiyang; Chen, Honghui; Sun, Shufan; Jia, Hong; Liu, Ying; Chen, Qiaoling; Wang, Xueyi; Cao, Juling; Lv, Luxian; Chen, Yunchun; Ha, Baowei; Ning, Yuping; Chen, Yiping; Kendler, Kenneth S; Flint, Jonathan; Shi, Shenxun

2011-12-01

Individuals with early-onset depression may be a clinically distinct group with particular symptom patterns, illness course, comorbidity and family history. This question has not been previously investigated in a Han Chinese population. We examined the clinical features of 1970 Han Chinese women with DSM-IV major depressive disorder (MDD) between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models was used to determine the association between age at onset (AAO) with continuous, binary and discrete characteristic clinical features of MDD. Earlier AAO was associated with more suicidal ideation and attempts and higher neuroticism, but fewer sleep, appetite and weight changes. Patients with an earlier AAO were more likely to suffer a chronic course (longer illness duration, more MDD episodes and longer index episode), increased rates of MDD in their parents and a lower likelihood of marriage. They tend to have higher comorbidity with anxiety disorders (general anxiety disorder, social phobia and agoraphobia) and dysthymia. Early AAO in MDD may be an index of a more severe, highly comorbid and familial disorder. Our findings indicate that the features of MDD in China are similar to those reported elsewhere in the world. Copyright © 2011 Elsevier B.V. All rights reserved.

Predictors for switch from unipolar major depressive disorder to bipolar disorder type I or II: a 5-year prospective study.

PubMed

Holma, K Mikael; Melartin, Tarja K; Holma, Irina A K; Isometsä, Erkki T

2008-08-01

In this naturalistic study, we investigated the rate, time course, and predictors of a diagnostic switch from unipolar major depressive disorder (MDD) to bipolar disorder type I or II during a 5-year follow-up. The Vantaa Depression Study included at baseline 269 psychiatric outpatients (82.9%) and inpatients (17.1%) with DSM-IV MDD, diagnosed using structured and semi-structured interviews and followed up at 6 months, 18 months, and 5 years between February 1, 1997 and April 30, 2004. Information on 248 MDD patients (92.2%) was available for analyses of the risk of diagnostic switch. Cox proportional hazards models were used. Twenty-two subjects (8.9%) with previous unipolar MDD switched to bipolar disorder type II and 7 (2.8%) to type I. Median time for switch to bipolar type I was significantly shorter than to type II. In Cox proportional hazards analyses, severity of MDD (hazard ratio [HR] = 1.08, 95% CI = 1.00 to 1.15, p = .036), obsessive-compulsive disorder (OCD) (HR = 5.00, 95% CI = 2.04 to 12.5, p < .001), social phobia (HR = 2.33, 95% CI = 1.00 to 5.26, p = .050), and large number of cluster B personality disorder symptoms (HR = 1.10, 95% CI = 1.02 to 1.20, p = .022) predicted switch. Among outpatients with MDD in secondary level psychiatric settings, diagnostic switch to bipolar disorder usually refers to type II rather than type I. The few switching to bipolar type I do so relatively early. Predictors for diagnostic switch include not only features of mood disorder, such as severity, but may also include some features of psychiatric comorbidity, such as concurrent social phobia, OCD, and symptoms of cluster B personality disorders.

Major Depressive Disorder in Adolescence: The Role of Subthreshold Symptoms

ERIC Educational Resources Information Center

Georgiades, Katholiki; Lewinsohn, Peter M.; Monroe, Scott M.; Seeley, John R.

2006-01-01

Objective: To examine the longitudinal association between individual subthreshold symptoms and onset of major depressive disorder (MDD) in adolescence. Method: Data for analysis come from the Oregon Adolescent Depression Project, a prospective epidemiological study of psychological disorders among adolescents, ages 14 to 18 years, from the…

Prevalence and psychometric screening for the detection of major depressive disorder and post-traumatic stress disorder in adults injured in a motor vehicle crash who are engaged in compensation.

PubMed

Guest, Rebecca; Tran, Yvonne; Gopinath, Bamini; Cameron, Ian D; Craig, Ashley

2018-02-21

Physical injury and psychological disorder following a motor vehicle crash (MVC) is a public health concern. The objective of this research was to determine rates of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) in adults with MVC-related injury engaged in compensation, and to determine the capacity (e.g. sensitivity and specificity) of two psychometric scales for estimating the presence of MDD and PTSD. Participants included 109 adults with MVC-related injury engaged in compensation during 2015 to 2017, in Sydney, Australia. The mean time from MVC to baseline assessment was 11 weeks. Comprehensive assessment was conducted at baseline, and the Depression Anxiety Stress Scales (DASS-21) and the Impact of Event Scale-Revised (IES-R) were administered to determine probable MDD and PTSD. An online psychiatric interview, based on Diagnostic and Statistical Manual for Mental Disorders (DSM-5), was used to diagnose actual MDD and PTSD, acknowledged as gold standard diagnostic criteria. One-way multivariate analyses of variance established criterion validity of the DASS-21 and IES-R, and sensitivity and specificity analyses were conducted to determine the most sensitive cut-off points for detecting probable MDD and PTSD. Substantial rates of MDD (53.2%) and PTSD (19.3%) were found. The DASS-21 and IES-R were shown to have excellent criterion validity for detecting MDD and PTSD in injured participants. A range of cut-off points were investigated and shown to have acceptable sensitivity and specificity for detecting MDD and PTSD in an injured population engaged in compensation. The preferred cut-off points based on this study are: to detect MDD, a DASS-21 total score of 30 and/or a DASS-21 depression score of 10; to detect PTSD, IES-R scores of 33-40 and/or a DASS-21 anxiety score of 7-8. Major psychological disorder is prevalent following a MVC. Results suggest the DASS-21 and IES-R are suitable for use in clinical/compensation settings to detect probable MDD and PTSD soon after a MVC in physically injured people engaged in compensation. These results provide positive direction in the public health arena for improving mental health outcomes. Clinical Trials registration number: ANZCTR - ACTRN12615000326594 (9th April 2015).

Psychiatric phenomenology in Cushing's disease.

PubMed

Loosen, P T; Chambliss, B; DeBold, C R; Shelton, R; Orth, D N

1992-07-01

We evaluated 20 patients with Cushing's disease (i.e., Cushing's syndrome due to ACTH-secreting pituitary microadenoma) and 20 patients with Major Depressive Disorder (MDD) using the Structured Clinical Interview for DSM-III-R (SCID) and Research Diagnostic Criteria. The diagnosis of Generalized Anxiety Disorder (GAD) was most common in Cushing's disease (79%), followed by MDD (68%), and Panic Disorder (PD) including subthreshold PD (53%). The combination of MDD and GAD and/or PD was also common in Cushing's disease (63%). Behavioral symptoms, if present, usually first occurred at or after the onset of the first physical symptoms. However, the onset of PD was associated with more chronic stages of Cushing's disease. In both Cushing's disease and MDD, more female than male relatives suffered from MDD, whereas more male than female relatives suffered from substance abuse. The data demonstrate a syndrome of anxious depression in patients with active Cushing's disease; such comorbidility has not been previously noted. The data also point to intriguing epidemiological, clinical, and biological associations between Cushing's disease, MDD and substance abuse.

The impacts of migraine, anxiety disorders, and chronic depression on quality of life in psychiatric outpatients with major depressive disorder.

PubMed

Hung, Ching-I; Wang, Shuu-Jiun; Yang, Ching-Hui; Liu, Chia-Yih

2008-08-01

Our purpose was to determine if migraine, anxiety comorbidities, and chronic depression were independently related to health-related quality of life (HRQoL) in outpatients with major depressive disorder (MDD). Consecutive psychiatric outpatients with MDD in a medical center were enrolled. MDD, chronic depression, and seven anxiety disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR. Migraine was diagnosed based on the International Classification of Headache Disorders, 2nd edition. The acute version of the Short-Form 36 and the Hamilton Depression Rating Scale (HAMD) were used to evaluate the HRQoL and the severity of depression, respectively. Multiple linear regressions were used to determine the independent factors related to HRQoL. There were 135 participants (34 men, 101 women) with MDD. Subjects with migraine, anxiety comorbidities, or chronic depression had higher HAMD scores and poor HRQoL. Migraine, specific phobia, and panic disorder were important and independent comorbidities predicting HRQoL. The impact of migraine on HRQoL, especially on bodily pain, was not inferior to those of some anxiety comorbidities or chronic depression. Future studies related to HRQoL of MDD should consider migraine and anxiety comorbidities simultaneously.

Early developmental characteristics and features of major depressive disorder among child psychiatric patients in Hungary.

PubMed

Kapornai, Krisztina; Gentzler, Amy L; Tepper, Ping; Kiss, Eniko; Mayer, László; Tamás, Zsuzsanna; Kovacs, Maria; Vetró, Agnes

2007-06-01

We investigate the relations of early atypical characteristics (perinatal problems, developmental delay, and difficult temperament) and onset-age (as well as severity of) first major depressive disorder (MDD) and first internalizing disorder in a clinical sample of depressed children in Hungary. Participants were 371 children (ages 7-14) with MDD, and their biological mothers, recruited through multiple clinical sites. Diagnoses (via DSM-IV criteria) and onset dates of disorders were finalized "best estimate" psychiatrists, and based on multiple information sources. Mothers provided developmental data in a structured interview. Difficult temperament predicted earlier onset of MDD and first internalizing disorder, but its effect was ameliorated if the family was intact during early childhood. Further, the importance of difficult temperament decreased as a function of time. Perinatal problems and developmental delay did not impact onset ages of disorders, and none of the early childhood characteristics associated with MDD episode severity. Children with MDD may have added disadvantage of earlier onset if they had a difficult temperament in infancy. Because early temperament mirrors physiological reactivity and regulatory capacity, it can affect various areas of functioning related to psychopathology. Early caregiver stability may attenuate some adverse effects of difficult infant temperament.

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.

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.

The Neuroscience of Depression: Implications for Assessment and Intervention

PubMed Central

Singh, Manpreet K.; Gotlib, Ian H.

2014-01-01

Major Depressive Disorder (MDD) is among the most prevalent of all psychiatric disorders and is the single most burdensome disease worldwide. In attempting to understand the profound deficits that characterize MDD across multiple domains of functioning, researchers have identified aberrations in brain structure and function in individuals diagnosed with this disorder. In this review we synthesize recent data from human neuroimaging studies in presenting an integrated neural network framework for understanding the impairments experienced by individuals with MDD. We discuss the implications of these findings for assessment of and intervention for MDD. We conclude by offering directions for future research that we believe will advance our understanding of neural factors that contribute to the etiology and course of depression, and to recovery from this debilitating disorder. PMID:25239242

The clinical impact of mood disorder comorbidity on social anxiety disorder.

PubMed

Koyuncu, Ahmet; Ertekin, Erhan; Binbay, Zerrin; Ozyıldırım, Ilker; Yüksel, Cağrı; Tükel, Raşit

2014-02-01

High comorbidity rates of mood disorders have been reported in patients with social anxiety disorder (SAD). Our study aims to identify the frequency of comorbid Axis I disorders in patients with SAD and to investigate the impact of psychiatric comorbidity on SAD. The study included 247 patients with SAD. Thirty eight patients with bipolar depression (SAD-BD), 150 patients with major depressive disorder (SAD-MDD) and 25 patients who do not have any mood disorder comorbidity (SAD-NOMD) were compared. Around 90% of SAD patients had at least one comorbid disorder. Comorbidity rates of lifetime MDD and BD were 74.5% and 15.4%, respectively. There was no comorbidity in the SAD-NOMD group. Atypical depression, total number of depressive episodes and rate of PTSD comorbidity were higher in SAD-BD than in SAD-MDD. Additionally, OCD comorbidity was higher in SAD-BD than in SAD-NOMD. SAD-MDD group had higher social anxiety severity than SAD-NOMD. Mood disorder comorbidity might be associated with increased severity and decreased functionality in patients with SAD. © 2014.

Functional Biomarkers of Depression: Diagnosis, Treatment, and Pathophysiology

PubMed Central

Schmidt, Heath D; Shelton, Richard C; Duman, Ronald S

2011-01-01

Major depressive disorder (MDD) is a heterogeneous illness for which there are currently no effective methods to objectively assess severity, endophenotypes, or response to treatment. Increasing evidence suggests that circulating levels of peripheral/serum growth factors and cytokines are altered in patients with MDD, and that antidepressant treatments reverse or normalize these effects. Furthermore, there is a large body of literature demonstrating that MDD is associated with changes in endocrine and metabolic factors. Here we provide a brief overview of the evidence that peripheral growth factors, pro-inflammatory cytokines, endocrine factors, and metabolic markers contribute to the pathophysiology of MDD and antidepressant response. Recent preclinical studies demonstrating that peripheral growth factors and cytokines influence brain function and behavior are also discussed along with their implications for diagnosing and treating patients with MDD. Together, these studies highlight the need to develop a biomarker panel for depression that aims to profile diverse peripheral factors that together provide a biological signature of MDD subtypes as well as treatment response. PMID:21814182

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.

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

Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank.

PubMed

Hall, Lynsey S; Adams, Mark J; Arnau-Soler, Aleix; Clarke, Toni-Kim; Howard, David M; Zeng, Yanni; Davies, Gail; Hagenaars, Saskia P; Maria Fernandez-Pujals, Ana; Gibson, Jude; Wigmore, Eleanor M; Boutin, Thibaud S; Hayward, Caroline; Scotland, Generation; Porteous, David J; Deary, Ian J; Thomson, Pippa A; Haley, Chris S; McIntosh, Andrew M

2018-01-10

Few replicable genetic associations for Major Depressive Disorder (MDD) have been identified. Recent studies of MDD have identified common risk variants by using a broader phenotype definition in very large samples, or by reducing phenotypic and ancestral heterogeneity. We sought to ascertain whether it is more informative to maximize the sample size using data from all available cases and controls, or to use a sex or recurrent stratified subset of affected individuals. To test this, we compared heritability estimates, genetic correlation with other traits, variance explained by MDD polygenic score, and variants identified by genome-wide meta-analysis for broad and narrow MDD classifications in two large British cohorts - Generation Scotland and UK Biobank. Genome-wide meta-analysis of MDD in males yielded one genome-wide significant locus on 3p22.3, with three genes in this region (CRTAP, GLB1, and TMPPE) demonstrating a significant association in gene-based tests. Meta-analyzed MDD, recurrent MDD and female MDD yielded equivalent heritability estimates, showed no detectable difference in association with polygenic scores, and were each genetically correlated with six health-correlated traits (neuroticism, depressive symptoms, subjective well-being, MDD, a cross-disorder phenotype and Bipolar Disorder). Whilst stratified GWAS analysis revealed a genome-wide significant locus for male MDD, the lack of independent replication, and the consistent pattern of results in other MDD classifications suggests that phenotypic stratification using recurrence or sex in currently available sample sizes is currently weakly justified. Based upon existing studies and our findings, the strategy of maximizing sample sizes is likely to provide the greater gain.

Prevalence of ADHD symptoms across clinical stages of major depressive disorder.

PubMed

Bron, Tannetje I; Bijlenga, Denise; Verduijn, Judith; Penninx, Brenda W J H; Beekman, Aartjan T F; Kooij, J J Sandra

2016-06-01

Depression and ADHD often co-occur in clinical samples. Depression severity may be linked to ADHD symptomatology. We therefore assessed ADHD symptoms across clinical stages of major depressive disorder (MDD). We used 4-year follow-up data of the Netherlands Study of Depression and Anxiety (September 2008 until April 2011), including healthy controls, groups with remitted and current MDD (N=2053; age range 21-69 years; 66.8% females). Probable ADHD was defined as having current ADHD symptoms on the Conners Adult ADHD Rating Scale and a positive score on childhood or early-adolescent ADHD indicators. We examined ADHD symptom rates across (i) those with and without lifetime MDD, (ii) clinical characteristics of MDD including severity, course and outcomes, (iii) clinical stages of MDD. (i) The prevalence of ADHD symptoms was 0.4% in healthy controls, 5.7% in remitted MDD and 22.1% in current MDD (OR=4.5; 95% CI 3.1-6.5). (ii) ADHD symptom rates and odds were significantly increased among those with more severe depression (29.4%; OR=6.8; 95% CI 2.9-16.1), chronic depression (21.8%; OR=3.8; 95% CI 2.5-5.7), earlier age of onset of depressive symptoms (9.9%; OR=1.5; 95% CI 1.0-2.3), and comorbid anxiety disorders (29.0%; OR=3.4; 95% CI 2.0-5.7). (iii) ADHD symptom rates increased across clinical stages of MDD, up to 22.5% in chronic MDD. We used self-reports on ADHD symptoms. Also, clinical staging models have not yet been validated for mental disorders. ADHD symptoms are very common among MDD patients, especially among those in recurrent and chronic stages of MDD. Considering ADHD may be an important step forward in improving the treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Associations of Educational Attainment, Occupation, Social Class and Major Depressive Disorder among Han Chinese Women

PubMed Central

Liu, Feihu; Li, Yajuan; Wang, Junhui; Flint, Jonathan; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Shenxun; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; 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.

2014-01-01

Background The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. Principal findings We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25–0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77–0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86–0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. Conclusions In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype. PMID:24497966

Associations of educational attainment, occupation, social class and major depressive disorder among Han Chinese women.

PubMed

Shi, Jianguo; Zhang, Yan; Liu, Feihu; Li, Yajuan; Wang, Junhui; Flint, Jonathan; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Shenxun; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; 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

2014-01-01

The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25-0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77-0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86-0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype.

White matter abnormalities in major depressive disorder with melancholic and atypical features: A diffusion tensor imaging study.

PubMed

Ota, Miho; Noda, Takamasa; Sato, Noriko; Hattori, Kotaro; Hori, Hiroaki; Sasayama, Daimei; Teraishi, Toshiya; Nagashima, Anna; Obu, Satoko; Higuchi, Teruhiko; Kunugi, Hiroshi

2015-06-01

The DSM-IV recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes. Subjects were 21 patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy and mean diffusivity value derived from DTI data on a voxel-by-voxel basis among the two diagnostic groups and healthy subjects. There were significant decreases of fractional anisotropy and increases of mean diffusivity in patients with MDD compared with healthy subjects in the corpus callosum, inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD. Our results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

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.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

PubMed Central

McIntosh, Diane; Wang, JianLi; Enns, Murray W.; Kolivakis, Theo; Michalak, Erin E.; Sareen, Jitender; Song, Wei-Yi; Kennedy, Sidney H.; MacQueen, Glenda M.; Milev, Roumen V.; Parikh, Sagar V.; Ravindran, Arun V.

2016-01-01

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. This section is the first of six guidelines articles. Results: In Canada, the annual and lifetime prevalence of MDD was 4.7% and 11.3%, respectively. MDD represents the second leading cause of global disability, with high occupational and economic impact mainly attributable to indirect costs. DSM-5 criteria for depressive disorders remain relatively unchanged, but other clinical dimensions (sleep, cognition, physical symptoms) may have implications for depression management. e-Mental health is increasingly used to support clinical and self-management of MDD. In the 2-phase (acute and maintenance) treatment model, specific goals address symptom remission, functional recovery, improved quality of life, and prevention of recurrence. Conclusions: The burden attributed to MDD remains high, whether from individual distress, functional and relationship impairment, reduced quality of life, or societal economic cost. Applying core principles of care, including comprehensive assessment, therapeutic alliance, support of self-management, evidence-informed treatment, and measurement-based care, will optimize clinical, quality of life, and functional outcomes in MDD. PMID:27486151

Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala

PubMed Central

Murray, Elisabeth A.; Wise, Steven P.; Drevets, Wayne C.

2010-01-01

Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of ‘self’ underlies the core disorder in MDD; the medial frontal cortex represents ‘self’; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD. PMID:21111403

Epigenetic Modifications of Major Depressive Disorder

PubMed Central

Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A.

2016-01-01

Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders. PMID:27527165

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.

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.

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.

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.

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

An Investigation of the Relationship Between Alcohol Use and Major Depressive Disorder Across Hispanic National Groups.

PubMed

Jetelina, Katelyn K; Reingle Gonzalez, Jennifer M; Vaeth, Patrice A C; Mills, Britain A; Caetano, Raul

2016-03-01

There has been consistent epidemiological evidence of the association between drinking, alcohol dependence, and depression. However, most of the research has ignored potential diversity across Hispanic national subgroups. This study examines the prevalence of depression and explores its association with volume of drinking, age at first drink, binge drinking, and alcohol dependence across Mexican American, Puerto Rican, Cuban, and South/Central American Hispanic national groups. Data from more than 19,000 Hispanic adults were obtained from the 2010 to 2012 National Survey on Drug Use and Health. Survey logistic regression methods were used to test for differences in the relationship between major depressive disorder (MDD) and alcohol consumption across national groups. The prevalence of MDD varied significantly across Hispanic national groups (χ(2)  = 67.06, p < 0.001). Puerto Ricans (14%) and Mexican Americans (9%) were most likely to have MDD. Mexican Americans had the highest prevalence of alcohol dependence, volume of consumption, and youngest age at first drink compared to Puerto Ricans, Cuban Americans, and Central/South Americans. Multivariate results suggest that the odds of alcohol dependence were nearly 4 times greater among Hispanics with MDD compared to Hispanics who did not meet the criteria for MDD. Hispanic national origin did not modify the association between MDD and alcohol use. Although significant differences in the prevalence rates of MDD and alcohol-use measures emerged across Hispanic national groups, there was no evidence that the relationships between these measures were different across Hispanic national groups. Further research should investigate the root causes of these variable MDD prevalence rates to inform detection and intervention efforts targeted toward specific national groups. Copyright © 2016 by the Research Society on Alcoholism.

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

Re-examining the risk for switch from unipolar to bipolar major depressive disorder in youth with ADHD: a long term prospective longitudinal controlled study.

PubMed

Biederman, Joseph; Wozniak, Janet; Tarko, Laura; Serra, Giulia; Hernandez, Mariely; McDermott, Katie; Woodsworth, K Yvonne; Uchida, Mai; Faraone, Stephen V

2014-01-01

Recent studies have identified subthreshold forms of bipolar (BP)-I disorder and deficits in emotional regulation as risk factors for bipolar disorder in youth. The primary aim of this study was to investigate whether emotional dysregulation and subthreshold forms of BP-I disorder increase the risk for BP switches in ADHD youth with non-bipolar MDD. We used data from two large controlled longitudinal family studies of boys and girls with and without ADHD. Subjects (N=522) were followed prospectively and blindly over an average follow up period of 11.4 years. Comparisons were made between ADHD youth with unipolar major depression (MDD) who did (N=24) and did not (N=79) switch to BP-I disorder at follow-up. The rate of conversion to BP-I disorder at follow up was higher in MDD subjects with subthreshold BP-I disorder at baseline compared to those without (57% vs. 21%; OR=9.57, 95% CI=1.62-56.56, p=0.013) and in MDD subjects with deficient emotional self-regulation (OR=3.54, 95% CI=1.08-11.60, p=0.037). The sample was largely Caucasian, so these results may not generalize to minority groups. The sample of youth with SED was small, which limited the statistical power for some analyses. Switches from unipolar MDD to BP-I disorder in children with ADHD and MDD were predicted by baseline subthreshold BP-I disorder symptoms and baseline deficits in emotional regulation. More work is needed to assess whether these risk factors are operant outside the context of ADHD. © 2013 Published by Elsevier B.V.

The Prevalence and Specificity of Depression Diagnosis in a Clinic-Based Population of Adults With Type 2 Diabetes Mellitus.

PubMed

Golden, Sherita Hill; Shah, Nina; Naqibuddin, Mohammad; Payne, Jennifer L; Hill-Briggs, Felicia; Wand, Gary S; Wang, Nae-Yuh; Langan, Susan; Lyketsos, Constantine

To estimate the crude prevalence of minor depressive disorder (MinD) in a clinic-based population of adults with type 2 diabetes. We screened a clinical sample of 702 adults with type 2 diabetes for depressive symptoms using the Patient Health Questionnaire-2 and performed a structured diagnostic psychiatric interview on 52 screen-positive and a convenience sample of 51 screen-negative individuals. Depressive disorder diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria and categorized as MinD, major depressive disorder (MDD), or no depressive disorder. We estimated prevalence of MinD and MDD and derived 95% CIs. The crude prevalence of current, past, and current or past MinD was 4.3% (95% CI: 0.9-9.2%), 9.6% (95% CI: 3.9-15.9%), and 13.9% (95% CI: 7.7-21.2%), respectively. The crude prevalence of current, past, and current or past MDD was slightly higher-5.0% (95% CI: 1.9-9.4%), 12.0% (95% CI: 6.1-19.5%), and 17.0% (95% CI: 10.1-24.8%), respectively. There was a high prevalence of coexisting anxiety disorders in individuals with MinD (42.2%) and MDD (8.1%). Hemoglobin A1c levels were not significantly different in individuals with MinD or MDD compared to those without a depressive disorder. MinD is comparably prevalent to MDD in patients with type 2 diabetes; both disorders are associated with concomitant anxiety disorders. MinD is not included in the DSM-5; however, our data support continuing to examine patients with chronic medical conditions for MinD. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Onset of Alcohol or Substance Use Disorders Following Treatment for Adolescent Depression

ERIC Educational Resources Information Center

Curry, John; Silva, Susan; Rohde, Paul; Ginsburg, Golda; Kennard, Betsy; Kratochvil, Christopher; Simons, Anne; Kirchner, Jerry; May, Diane; Mayes, Taryn; Feeny, Norah; Albano, Anne Marie; Lavanier, Sarah; Reinecke, Mark; Jacobs, Rachel; Becker-Weidman, Emily; Weller, Elizabeth; Emslie, Graham; Walkup, John; Kastelic, Elizabeth; Burns, Barbara; Wells, Karen; March, John

2012-01-01

Objective: This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD). Method: For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in…

Depressive Disorder Subtypes as Predictors of Incident Obesity in US Adults: Moderation by Race/Ethnicity.

PubMed

Polanka, Brittanny M; Vrany, Elizabeth A; Patel, Jay; Stewart, Jesse C

2017-05-01

We compared the relative importance of atypical major depressive disorder (MDD), nonatypical MDD, and dysthymic disorder in predicting 3-year obesity incidence and change in body mass index and determined whether race/ethnicity moderated these relationships. We examined data from 17,787 initially nonobese adults in the National Epidemiologic Survey on Alcohol and Related Conditions waves 1 (2001-2002) and 2 (2004-2005) who were representative of the US population. Lifetime subtypes of depressive disorders were determined using a structured interview, and obesity outcomes were computed from self-reported height and weight. Atypical MDD (odds ratio (OR) = 1.68, 95% confidence interval (CI): 1.43, 1.97; P < 0.001) and dysthymic disorder (OR = 1.66, 95% CI: 1.29, 2.12; P < 0.001) were stronger predictors of incident obesity than were nonatypical MDD (OR = 1.11, 95% CI: 1.01, 1.22; P = 0.027) and no history of depressive disorder. Atypical MDD (B = 0.41 (standard error, 0.15); P = 0.007) was a stronger predictor of increases in body mass index than were dysthymic disorder (B = -0.31 (standard error, 0.21); P = 0.142), nonatypical MDD (B = 0.007 (standard error, 0.06); P = 0.911), and no history of depressive disorder. Race/ethnicity was a moderator; atypical MDD was a stronger predictor of incident obesity in Hispanics/Latinos (OR = 1.97, 95% CI: 1.73, 2.24; P < 0.001) than in non-Hispanic whites (OR = 1.54, 95% CI: 1.25, 1.91; P < 0.001) and blacks (OR = 1.72, 95% CI: 1.31, 2.26; P < 0.001). US adults with atypical MDD are at particularly high risk of weight gain and obesity, and Hispanics/Latinos may be especially vulnerable to the obesogenic consequences of depressions. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

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.

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

PubMed Central

Shi, Xian-Feng; Forrest, Lauren N.; Kuykendall, M. Danielle; Prescot, Andrew P.; Sung, Young-Hoon; Huber, Rebekah S.; Hellem, Tracy L.; Jeong, Eun-Kee; Renshaw, Perry F.; Kondo, Douglas G.

2015-01-01

Background Delayed diagnosis in bipolar disorder (BD) due to misdiagnosis as major depressive disorder (MDD) is a significant public health concern. Thus, identification of relevant diagnostic biomarkers is a critical unmet need, particularly early in the course of illness. The anterior cingulate cortex (ACC) is thought to play an important role in mood disorder pathophysiology. Case-control studies utilizing proton-1 magnetic resonance spectroscopy (1H-MRS) have found increased total choline levels in several brain regions in MDD. However, there are no published 1H-MRS reports directly comparing adolescents with MDD and BD. We hypothesized that ACC choline levels would be increased in adolescents with unipolar versus bipolar depression. Methods We studied depressed adolescents with MDD (n=28; mean age 17.0±2.1 years) and BD (n=9; 17.3±3.1 years). A Siemens Verio 3-Tesla clinical MRI system was used to acquire scans, using a single-voxel PRESS sequence. The voxel (18.75 cm3) was positioned on the ACC in the midsagittal plane. To remove potential gender effects, only female adolescent participants were included. Data were analyzed using the ANOVA and post-hoc Tukey tests. Results A significantly increased ACC choline/creatine ratio was observed in participants with MDD (mean=0.253±0.021) compared to BD (mean=0.219±0.020) (p=0.0002). There were no significant differences in the other 1H-MRS metabolites. Limitations Cross sectional design, single gender sample, limited sample size. Conclusions The present findings suggest that ACC total choline may have the potential to serve as a diagnostic biomarker in adolescent mood disorders. PMID:25082110

Reliability of DSM-III diagnoses for major depression and generalized anxiety disorder using the structured clinical interview for DSM-III.

PubMed

Riskind, J H; Beck, A T; Berchick, R J; Brown, G; Steer, R A

1987-09-01

This study examined the interrater reliability of generalized anxiety disorder (GAD) and major depressive disorder (MDD) diagnoses derived from the Structured Clinical Interview for DSM-III (SCID). Using videotaped interviews, paired raters made independent diagnoses of 75 psychiatric outpatients. The percent agreement of the raters was 82% for MDD and 86% for GAD; the respective kappa values were .72 and .79. The results indicated that the SCID can be employed reliably to differentiate MDD from GAD. The SCID is recommended for further research with these disorders.

Major Depression and Coronary Flow Reserve Detected by Positron Emission Tomography

PubMed Central

Vaccarino, Viola; Votaw, John; Faber, Tracy; Veledar, Emir; Murrah, Nancy V.; Jones, Linda R.; Zhao, Jinying; Su, Shaoyong; Goldberg, Jack; Raggi, J. Paolo; Quyyumi, Arshed A.; Sheps, David S.; Bremner, J. Douglas

2010-01-01

Background Major depressive disorder (MDD) is associated with coronary heart disease (CHD), but the mechanisms are unclear. The presence of MDD may increase CHD risk by affecting microvascular circulation. It is also plausible that genetic factors influencing MDD may overlap with those for CHD. We sought to examine the relationship between MDD and coronary flow reserve (CFR), the ratio of maximum flow during stress to flow at rest measured in milliliters per minute per gram of tissue. Methods We examined 289 male middle-aged twins, including 106 twins (53 twin pairs) discordant for a lifetime history of MDD and 183 control twins (unrelated to any twins in the experimental group) without MDD. To calculate CFR, we used positron emission tomography with nitrogen 13 (13N) ammonia to evaluate myocardial blood flow at rest and after adenosine stress. A standard perfusion defect score was also used to assess myocardial ischemia. Results There was no difference in myocardial ischemia between twins with and without MDD. Among the dizygotic twin pairs discordant for MDD, the CFR was 14% lower in the twins with MDD than in their brothers without MDD (2.36 vs 2.74) (P=.03). This association was not present in the monozygotic discordant pairs who were genetically matched (2.86 vs 2.64) (P = .19). The zygosity-MDD interaction after adjustment was significant (P=.006). The CFR in the dizygotic twins with MDD was also lower than in the control twins. Conclusions Our results provide evidence for a shared genetic pathway between MDD and microvascular dysfunction. Common pathophysiologic processes may link MDD and early atherosclerosis. PMID:19822823

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

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.

Specificity of posttraumatic stress disorder symptoms: an investigation of comorbidity between posttraumatic stress disorder symptoms and depression in treatment-seeking veterans.

PubMed

Gros, Daniel F; Simms, Leonard J; Acierno, Ron

2010-12-01

In response to high levels of comorbidity and symptom overlap between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and other disorders, much attention has been devoted to the role of specific and nonspecific symptoms among the disorders. The present study investigated the overlapping symptoms of PTSD and MDD in treatment-seeking veterans. Exploratory factor analyses were used to identify latent factors of both self-reported and clinician-rated symptoms of PTSD and MDD. Results of exploratory factor analyses supported a 2-factor model representing symptoms of depression and PTSD; however, a subset of PTSD symptoms, characterized by emotional numbing and dysphoria, loaded onto the depression factor, rather than the PTSD factor. These nonspecific PTSD symptoms were predictive of comorbid MDD and increased depression symptomatology in patients with PTSD. Together, these findings demonstrate the importance of accounting for nonspecific symptoms in diagnosis and treatment of PTSD, highlighting a need for revisions to our current diagnostics.

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.

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.

The impacts of migraine and anxiety disorders on painful physical symptoms among patients with major depressive disorder.

PubMed

Hung, Ching-I; Liu, Chia-Yih; Chen, Ching-Yen; Yang, Ching-Hui; Wang, Shuu-Jiun

2014-11-10

No study has simultaneously investigated the impacts of migraine and anxiety disorders on painful physical symptoms (PPS) among patients with major depressive disorder (MDD). The study aimed to investigate this issue. This open-label study enrolled 155 outpatients with MDD, who were then treated with venlafaxine 75 mg per day for four weeks. Eighty-five participants with good compliance completed the treatment. Migraine was diagnosed according to the International Classification of Headache Disorders. MDD and anxiety disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR. The visual analog scale (VAS) was used to evaluate the severity of eight PPS. Multiple linear and logistic regressions were used to investigate the impacts of migraine and anxiety disorders on PPS. Compared with patients without migraine, patients with migraine had a greater severity of PPS at baseline and post-treatment. After controlling for demographic variables and depressive severity, migraine independently predicted the intensities of eight PPS at baseline and four PPS post-treatment. Moreover, migraine independently predicted poorer treatment responses of chest pain and full remission of pains in the head, chest, neck and/or shoulder. Anxiety disorders predicted less full remission of pains in the abdomen and limbs. Migraine and anxiety disorders have negative impacts on PPS among patients with MDD. Integrating the treatment of migraine and anxiety disorders into the management of depression might help to improve PPS and the prognosis of MDD.

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.

Polygenic interactions with environmental adversity in the aetiology of major depressive disorder.

PubMed

Mullins, N; Power, R A; Fisher, H L; Hanscombe, K B; Euesden, J; Iniesta, R; Levinson, D F; Weissman, M M; Potash, J B; Shi, J; Uher, R; Cohen-Woods, S; Rivera, M; Jones, L; Jones, I; Craddock, N; Owen, M J; Korszun, A; Craig, I W; Farmer, A E; McGuffin, P; Breen, G; Lewis, C M

2016-03-01

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene-environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10(-6)). SLEs and CT were also associated with MDD status (p = 2.19 × 10(-4) and p = 5.12 × 10(-20), respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene-environment interactions in complex traits.

Reduced immunity to measles in adults with major depressive disorder.

PubMed

Ford, Bart N; Yolken, Robert H; Dickerson, Faith B; Teague, T Kent; Irwin, Michael R; Paulus, Martin P; Savitz, Jonathan

2018-03-19

Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination. IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963. Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24-0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26-0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles. Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.

Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States.

PubMed

Hasin, Deborah S; Sarvet, Aaron L; Meyers, Jacquelyn L; Saha, Tulshi D; Ruan, W June; Stohl, Malka; Grant, Bridget F

2018-04-01

No US national data are available on the prevalence and correlates of DSM-5-defined major depressive disorder (MDD) or on MDD specifiers as defined in DSM-5. To present current nationally representative findings on the prevalence, correlates, psychiatric comorbidity, functioning, and treatment of DSM-5 MDD and initial information on the prevalence, severity, and treatment of DSM-5 MDD severity, anxious/distressed specifier, and mixed-features specifier, as well as cases that would have been characterized as bereavement in DSM-IV. In-person interviews with a representative sample of US noninstitutionalized civilian adults (≥18 years) (n = 36 309) who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III). Data were collected from April 2012 to June 2013 and were analyzed in 2016-2017. Prevalence of DSM-5 MDD and the DSM-5 specifiers. Odds ratios (ORs), adjusted ORs (aORs), and 95% CIs indicated associations with demographic characteristics and other psychiatric disorders. Of the 36 309 adult participants in NESARC-III, 12-month and lifetime prevalences of MDD were 10.4% and 20.6%, respectively. Odds of 12-month MDD were significantly lower in men (OR, 0.5; 95% CI, 0.46-0.55) and in African American (OR, 0.6; 95% CI, 0.54-0.68), Asian/Pacific Islander (OR, 0.6; 95% CI, 0.45-0.67), and Hispanic (OR, 0.7; 95% CI, 0.62-0.78) adults than in white adults and were higher in younger adults (age range, 18-29 years; OR, 3.0; 95% CI, 2.48-3.55) and those with low incomes ($19 999 or less; OR, 1.7; 95% CI, 1.49-2.04). Associations of MDD with psychiatric disorders ranged from an aOR of 2.1 (95% CI, 1.84-2.35) for specific phobia to an aOR of 5.7 (95% CI, 4.98-6.50) for generalized anxiety disorder. Associations of MDD with substance use disorders ranged from an aOR of 1.8 (95% CI, 1.63-2.01) for alcohol to an aOR of 3.0 (95% CI, 2.57-3.55) for any drug. Most lifetime MDD cases were moderate (39.7%) or severe (49.5%). Almost 70% with lifetime MDD had some type of treatment. Functioning among those with severe MDD was approximately 1 SD below the national mean. Among 12.9% of those with lifetime MDD, all episodes occurred just after the death of someone close and lasted less than 2 months. The anxious/distressed specifier characterized 74.6% of MDD cases, and the mixed-features specifier characterized 15.5%. Controlling for severity, both specifiers were associated with early onset, poor course and functioning, and suicidality. Among US adults, DSM-5 MDD is highly prevalent, comorbid, and disabling. While most cases received some treatment, a substantial minority did not. Much remains to be learned about the DSM-5 MDD specifiers in the general population.

Escalation to Major Depressive Disorder among adolescents with subthreshold depressive symptoms: evidence of distinct subgroups at risk.

PubMed

Hill, Ryan M; Pettit, Jeremy W; Lewinsohn, Peter M; Seeley, John R; Klein, Daniel N

2014-04-01

The presence of subthreshold depressive symptoms (SubD) in adolescence is associated with high prospective risk of developing Major Depressive Disorder (MDD). Little is known about variables that predict escalation from SubD to MDD. This study used a longitudinal prospective design in a community sample of adolescents to identify combinations of risk factors that predicted escalation from SubD to MDD. Classification tree analysis was used to identify combinations of risk factors that improved the sensitivity and specificity of prediction of MDD onset among 424 adolescents with a lifetime history of SubD. Of the 424, 144 developed MDD during the follow-up period. Evidence for multiple subgroups was found: among adolescents with poor friend support, the highest risk of escalation was among participants with lifetime histories of an anxiety or substance use disorder. Among adolescents with high friend support, those reporting multiple major life events in the past year or with a history of an anxiety disorder were at highest risk of escalation. Study findings may not inform prevention efforts for individuals who first develop SubD during adulthood. This study did not examine the temporal ordering of predictors involved in escalation from SubD to MDD. Adolescents with a history of SubD were at highest risk of escalation to MDD in the presence of poor friend support and an anxiety or substance use disorder, or in the presence of better friend support, multiple major life events, and an anxiety disorder. Findings may inform case identification approaches for adolescent depression prevention programs. Copyright © 2014 Elsevier B.V. All rights reserved.

Generalized Anxiety Disorder and Major Depressive Disorder in Pregnant and Postpartum Women: Maternal Quality of Life and Treatment Outcomes.

PubMed

Misri, Shaila; Swift, Elena

2015-09-01

Comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD) in perinatal women is often under-diagnosed, resulting in suboptimal treatment and leading to significant maternal dysfunction. We describe a prospective, longitudinal study of the course, treatment outcomes, and quality of life (QoL) in pregnant and postpartum women with MDD and anxiety disorders. Two separate cohorts of women were recruited through the Reproductive Mental Health Program, Women's and Children's Hospital, Vancouver, British Columbia, for pharmacotherapy of depressed mood. One cohort was recruited during pregnancy and followed to one month postpartum; the other cohort was recruited postpartum and followed for 12 weeks. All women met the DSM-5 criteria for MDD and anxiety disorders. This non-lactating perinatal population completed measures of depression, anxiety, worry symptoms, and QoL at multiple study visits. Depressed women with GAD or excessive worry were compared to those without GAD in each cohort. Analysis revealed that despite the majority of women with MDD having remission of symptoms with treatment, those with postpartum GAD displayed a poorer quality of life, with persistent worry symptoms, and their illness was slower to remit. Pregnant depressed women with uncontrollable worry (a GAD indicator) showed a lower probability of achieving remission of symptoms with treatment than those without uncontrollable worry. All pregnant and postpartum women with GAD and MDD responded to pharmacotherapy, and the majority attained complete remission of MDD. However, their GAD symptoms persisted, and their QoL was compromised. Given the chronic debilitating course of concomitant MDD and GAD in the perinatal population, it is essential to focus on adjunctive therapies to aim for full recovery.

The potential impact of biochemical mediators on telomere attrition in major depressive disorder and implications for future study designs: A narrative review.

PubMed

Manoliu, Andrei; Bosch, Oliver G; Brakowski, Janis; Brühl, Annette B; Seifritz, Erich

2018-01-01

Major depressive disorder (MDD) has been proposed to represent a "disease of premature aging", which is associated with certain biomarkers of cellular ageing and numerous other age-related diseases. Over the last decade, telomere length (TL) arose as a surrogate for cellular aging. Recent data suggests that TL might be reduced in patients with MDD, however, results are still inconclusive. This might be explained by the lack of assessment of potential biochemical mediators that are directly associated with telomere shortening and frequently observed in patients with MDD. A narrative review was performed. The PubMed database was searched for relevant studies. We identified four major mediators, which are recurrently reported in patients with MDD and are associated with reduced TL: inflammation/oxidative stress, dysregulation of the hypothalamic-pituitary-adrenal axis, metabolic dysbalance including insulin resistance, and decreased brain-derived neurotrophic factor. These mediators are also mutually associated and were not systematically assessed in current studies investigating TL and MDD, which might explain inconclusive findings across current literature. Finally, we discuss possible ways to assess those mediators and potential implications of such approaches for future research. The majority of identified studies had cross-sectional designs and used heterogeneous methods to assess TL and associated relevant biochemical mediators. A better understanding of the complex interactions between biochemical mediators, somatic comorbidities and shortened telomeres in patients with MDD might further specify the pathophysiology-based conceptualization and, based on that, personalized treatment of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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.

Low comorbid obsessive-compulsive disorder in patients with major depressive disorder - Findings from a European multicenter study.

PubMed

Dold, Markus; Bartova, Lucie; Souery, Daniel; Mendlewicz, Julien; Porcelli, Stefano; Serretti, Alessandro; Zohar, Joseph; Montgomery, Stuart; Kasper, Siegfried

2018-02-01

This cross-sectional European multicenter study examined the association between major depressive disorder (MDD) and comorbid obsessive-compulsive disorder (OCD). Socio-demographic, clinical, and treatment features of 1346 adult MDD patients were compared between MDD subjects with and without concurrent OCD using descriptive statistics, analyses of covariance (ANCOVA), and binary logistic regression analyses. We determined a point prevalence of comorbid OCD in MDD of 1.65%. In comparison to the MDD control group without concurrent OCD, a higher proportion of patients in the MDD + comorbid OCD group displayed concurrent panic disorder (31.81% vs 7.77%, p<.001), suicide risk (52.80% vs 44.81%, p=.04), polypsychopharmacy (95.45% vs 60.21%, p=.001), and augmentation treatment with antipsychotics (50.00% vs 25.46%, p=.01) and benzodiazepines (68.18% vs 33.31%, p=.001). Moreover, they were treated with higher mean doses of their antidepressant drugs (in fluoxetine equivalents: 48.99mg/day ± 18.81 vs 39.68mg/day ± 20.75, p=.04). In the logistic regression analyses, comorbid panic disorder (odds ratio (OR)=4.17, p=.01), suicide risk (OR=2.56, p=.04), simultaneous treatment with more psychiatric drugs (OR=1.51, p=<.05), polypsychopharmacy (OR=14.29, p=.01), higher antidepressant dosing (OR=1.01, p=<.05), and augmentation with antipsychotics (OR=2.94, p=.01) and benzodiazepines (OR=4.35, p=.002) were significantly associated with comorbid OCD. In summary, our findings suggest that concurrent OCD in MDD (1) has a low prevalence rate compared to the reverse prevalence rates of comorbid MDD in OCD, (2) provokes higher suicide risk, and (3) is associated with a characteristic prescription pattern reflected by a high amount of polypsychopharmaceutical treatment strategies comprising particularly augmentation with antipsychotics and benzodiazepines. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of Comorbid Mental Disorders on Time to Treatment Seeking for Major Depressive Disorder

PubMed Central

Olfson, Mark; Liu, Shang-Min; Grant, Bridget F.; Blanco, Carlos

2012-01-01

Background Although treatment of depression has increased in recent years, long delays commonly separate disorder onset from first treatment contact. Objectives This study evaluates the effects of psychiatric comorbidities and socio-demographic characteristics on lifetime treatment seeking and speed to first treatment contact for major depressive disorder (MDD). Measures A cross-sectional epidemiological survey including retrospective structured assessments of DSM-IV MDD and other psychiatric disorders, respondent age at disorder onset, and age at first treatment contact. Subjects A nationally representative sample of 5,958 adults aged ≥18 years residing in households and group quarters who met lifetime criteria for MDD. Data Analysis The percentage of respondents with lifetime MDD who reported ever seeking treatment is reported overall and stratified by sociodemographic characteristics. Unadjusted and adjusted hazard ratios are presented of time to first depression treatment seeking by sociodemographic characteristics and comorbid psychiatric disorders. Results A majority (61.3%) of respondents with MDD reported having sought treatment for depression at some point in their lives. Time to first depression treatment contact was significantly related to the occurrence of comorbid panic disorder (AHR=2.01, 95%CI=1.69–2.39), generalized anxiety disorder (AHR=1.55, 95%CI=1.33–1.81), drug dependence (AHR=1.54, 95%CI=1.06–2.26), dysthymic disorder (AHR=1.54, 95%CI=1.35–1.76), and PTSD (AHR=1.34, 95%CI=1.13–1.59) and inversely related to male sex (AHR=0.74, 95%CI=0.66–0.82) and black race/ethnicity (AHR=0.69, 95%CI=0.59–0.81). Conclusion Comorbid psychiatric disorders, especially panic, generalized anxiety, substance use, and dysthymic disorders, appear to play an important role in accelerating treatment seeking for MDD. Outreach efforts should include a focus on depressed individuals without complicating psychiatric comorbidities. PMID:22186769

Ten-Year Course of Borderline Personality Disorder

PubMed Central

Gunderson, John G.; Stout, Robert L.; McGlashan, Thomas H.; Shea, M. Tracie; Morey, Leslie C.; Grilo, Carlos M.; Zanarini, Mary C.; Yen, Shirley; Markowitz, John C.; Sanislow, Charles; Ansell, Emily; Pinto, Anthony; Skodol, Andrew E.

2011-01-01

Context Borderline personality disorder (BPD) is traditionally considered chronic and intractable. Objective To compare the course of BPD’s psychopathology and social function with that of other personality disorders and with major depressive disorder (MDD) over 10 years. Design A collaborative study of treatment-seeking, 18-to 45-year-old patients followed up with standardized, reliable, and repeated measures of diagnostic remission and relapse and of both global social functioning and subtypes of social functioning. Setting Nineteen clinical settings (hospital and outpatient) in 4 northeastern US cities. Participants Three study groups, including 175 patients with BPD, 312 with cluster C personality disorders, and 95 with MDD but no personality disorder. Main Outcome Measures The Diagnostic Interview for DSM-IV Personality Disorders and its follow-along version (the Diagnostic Interview for DSM-IV Personality Disorders–Follow-Along Version) were used to diagnose personality disorders and assess changes in them. The Structured Clinical Interview for DSM-IV Axis I Disorders and the Longitudinal Interval Follow-up Evaluation were used to diagnose MDD and assess changes in MDD and in social function. Results Eighty-five percent of patients with BPD remitted. Remission of BPD was slower than for MDD (P<.001) and minimally slower than for other personality disorders (P<.03). Twelve percent of patients with BPD relapsed, a rate less frequent and slower than for patients with MDD (P<.001) and other personality disorders (P=.008). All BPD criteria declined at similar rates. Social function scores showed severe impairment with only modest albeit statistically significant improvement; patients with BPD remained persistently more dysfunctional than the other 2 groups (P<.001). Reductions in criteria predicted subsequent improvements in DSM-IV Axis V Global Assessment of Functioning scores (P<.001). Conclusions The 10-year course of BPD is characterized by high rates of remission, low rates of relapse, and severe and persistent impairment in social functioning. These results inform expectations of patients, families, and clinicians and document the severe public health burden of this disorder. PMID:21464343

Transdiagnostic and diagnosis-specific dynamic functional connectivity anchored in the right anterior insula in major depressive disorder and bipolar depression.

PubMed

Pang, Yajing; Chen, Heng; Wang, Yifeng; Long, Zhiliang; He, Zongling; Zhang, Huangbin; Liao, Wei; Cui, Qian; Chen, Huafu

2018-07-13

Dysfunctional and abnormal functional connectivity in the right anterior insula (rAI) may underlie the pathophysiology of depression episode in bipolar disorder (BD) and of major depressive disorder (MDD). In this study, we examined the dynamic functional connectivity (dFC) of the rAI of 30 patients with BD, 30 patients with MDD, and 30 healthy controls. In the functional separation of rAI, the right dorsal AI (rdAI) and ventral AI (rvAI) were defined as seed regions. Sliding-window correlation of rAI subregions was implemented to measure the variance of dFC. BD and MDD shared abnormality in dFC, such as the decreased dFC between the rvAI and right ventrolateral prefrontal cortex. Others were disorder-specific and included MDD-related increases in dFC between the rvAI and right precuneus, temporal pole, and left dorsolateral prefrontal cortex. This observation is in stark contrast to BD-related increases in the dFC between the rdAI and left inferior parietal lobule and right middle occipital gyrus. The abnormal dFC of rAI shared by BD and MDD supports the importance of rAI in the common pathophysiology of these disorders. Meanwhile, disorder-specific abnormalities that attribute to the dorsal and ventral divisions of rAI can be used as biomarkers to differentiate BD from MDD. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal Time Experiences in Major Depression: An Empirical Qualitative Study.

PubMed

Stanghellini, Giovanni; Ballerini, Massimo; Presenza, Simona; Mancini, Milena; Northoff, Georg; Cutting, John

2017-01-01

Phenomenological psychopathology, through theoretical and idiographic studies, conceptualizes major depressive disorder (MDD) as a disorder of time experience. Investigations on abnormal time experience (ATE) in MDD adopting methodologies requested by the standards of empirical sciences are still lacking. Our study aimed to provide a qualitative analysis, on an empirical ground and on a large scale, of narratives of temporal experiences of persons affected by MDD. We interviewed 550 consecutive patients affected by affective and schizophrenic disorders. Clinical files were analysed by means of consensual qualitative research. Out of 100 MDD patients, 96 reported at least 1 ATE. The principal categories of ATE are vital retardation - the experience of a stagnation of endogenous vital processes (37 patients), the experience of present and future dominated by the past (29 patients), and the experience of the slackening of the flow oftime (25 patients). A comparison with ATE in schizophrenia patients showed that in MDD, unlike in schizophrenia, there is no disarticulation of time experience (disorder of temporal synthesis) but rather a disorder of conation or inhibition of becoming. The interview style was not meant to make a quantitative assessment ("false negatives" cannot be excluded). Our findings confirm the relevance of distinctive features of ATE in MDD, support the hypothesis of an intrinsic disordered temporal structure in depressive symptoms, and may have direct implications in clinical practice, especially in relation to differential diagnosis, setting the boundaries between "true" and milder forms of depression, and neurobiological research. © 2016 S. Karger AG, Basel.

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.

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.

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.

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.

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.

Using patient self-reports to study heterogeneity of treatment effects in major depressive disorder

PubMed Central

Kessler, R.C.; van Loo, H.M.; Wardenaar, K.J.; Bossarte, R.M.; Brenner, L.A.; Ebert, D.D; de Jonge, P.; Nierenberg, A.A.; Rosellini, A.J.; Sampson, N.A.; Schoevers, R.A.; Wilcox, M.A.; Zaslavsky, A.M.

2016-01-01

Aims Clinicians need guidance to address the heterogeneity of treatment responses of patients with major depressive disorder (MDD). While prediction schemes based on symptom clustering and biomarkers have so far not yielded results of sufficient strength to inform clinical decision-making, prediction schemes based on big data predictive analytic models might be more practically useful. Methods We review evidence suggesting that prediction equations based on symptoms and other easily-assessed clinical features found in previous research to predict MDD treatment outcomes might provide a foundation for developing predictive analytic clinical decision support models that could help clinicians select optimal (personalized) MDD treatments. These methods could also be useful in targeting patient subsamples for more expensive biomarker assessments. Results Approximately two dozen baseline variables obtained from medical records or patient reports have been found repeatedly in MDD treatment trials to predict overall treatment outcomes (i.e., intervention versus control) or differential treatment outcomes (i.e., intervention A versus intervention B). Similar evidence has been found in observational studies of MDD persistence-severity. However, no treatment studies have yet attempted to develop treatment outcome equations using the full set of these predictors. Promising preliminary empirical results coupled with recent developments in statistical methodology suggest that models could be developed to provide useful clinical decision support in personalized treatment selection. These tools could also provide a strong foundation to increase statistical power in focused studies of biomarkers and MDD heterogeneity of treatment response in subsequent controlled trials. Conclusions Coordinated efforts are needed to develop a protocol for systematically collecting information about established predictors of heterogeneity of MDD treatment response in large observational treatment studies, applying and refining these models in subsequent pragmatic trials, carrying out pooled secondary analyses to extract the maximum amount of information from these coordinated studies, and using this information to focus future discovery efforts in the segment of the patient population in which continued uncertainty about treatment response exists. PMID:26810628

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.

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.

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.

Topographic and sex-related differences in sleep spindles in major depressive disorder: a high-density EEG investigation.

PubMed

Plante, D T; Goldstein, M R; Landsness, E C; Peterson, M J; Riedner, B A; Ferrarelli, F; Wanger, T; Guokas, J J; Tononi, G; Benca, R M

2013-03-20

Sleep spindles are believed to mediate several sleep-related functions including maintaining disconnection from the external environment during sleep, cortical development, and sleep-dependent memory consolidation. Prior studies that have examined sleep spindles in major depressive disorder (MDD) have not demonstrated consistent differences relative to control subjects, which may be due to sex-related variation and limited spatial resolution of spindle detection. Thus, this study sought to characterize sleep spindles in MDD using high-density electroencephalography (hdEEG) to examine the topography of sleep spindles across the cortex in MDD, as well as sex-related variation in spindle topography in the disorder. All-night hdEEG recordings were collected in 30 unipolar MDD participants (19 women) and 30 age and sex-matched controls. Topography of sleep spindle density, amplitude, duration, and integrated spindle activity (ISA) were assessed to determine group differences. Spindle parameters were compared between MDD and controls, including analysis stratified by sex. As a group, MDD subjects demonstrated significant increases in frontal and parietal spindle density and ISA compared to controls. When stratified by sex, MDD women demonstrated increases in frontal and parietal spindle density, amplitude, duration, and ISA; whereas MDD men demonstrated either no differences or decreases in spindle parameters. Given the number of male subjects, this study may be underpowered to detect differences in spindle parameters in male MDD participants. This study demonstrates topographic and sex-related differences in sleep spindles in MDD. Further research is warranted to investigate the role of sleep spindles and sex in the pathophysiology of MDD. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.

PubMed

Peyrot, W J; Lee, S H; Milaneschi, Y; Abdellaoui, A; Byrne, E M; Esko, T; de Geus, E J C; Hemani, G; Hottenga, J J; Kloiber, S; Levinson, D F; Lucae, S; Martin, N G; Medland, S E; Metspalu, A; Milani, L; Noethen, M M; Potash, J B; Rietschel, M; Rietveld, C A; Ripke, S; Shi, J; Willemsen, G; Zhu, Z; Boomsma, D I; Wray, N R; Penninx, B W J H

2015-06-01

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

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.

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.

Prescription patterns of Chinese herbal products for patients with sleep disorder and major depressive disorder in Taiwan.

PubMed

Chen, Yi-Lin; Lee, Chien-Ying; Huang, Kuang-Hua; Kuan, Yu-Hsiang; Chen, Ming

2015-08-02

Chinese herbal products (CHPs) are commonly prescribed for sleep disorder and major depressive disorder (MDD). The aim of this study was to investigate the prescription patterns of CHPs and Western medicine for patients with these disorders in Taiwan, and analyze the frequency of using single herbs (SHs) and herbal formulas (HFs). In this retrospective population-based study secondary data analysis was performed using data from Taiwan's Longitudinal Health Insurance Database (LHID) between January 2007 and December 2011. In total, 1000,000 beneficiaries from the LHID were randomly selected from the 2010 registry for beneficiaries of the National Health Insurance Research Database. Patients with sleep disorder and MDD according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 307.40 and 311, respectively. Among a total of 11,030 patients with sleep disorder, 9619 used Western medicine, 1334 used CHPs, and 77 used both, Among a total of 11,571 patients with MDD, 11,389 used Western medicine, 131 used CHPs, and 51 used both. Regardless of disorder type, women were predominant The majority of the patients were aged 22-44 years, had a monthly income of NT$17,281-NT$22,800, and lived in an area with Level 1 and Level 2 urbanization. Of the patients with sleep disorder, 1411 had used CHPs and visited a clinic 5298 times on average. Of the patients with MDD, 182 had used CHPs and visited a clinic 755 times on average. The three most commonly used SHs and HFs were Ziziphi Spinosae Semen, Polygoni Multiflori Caulis, and Polygalae Radix, and Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang, and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang, respectively. Chinese herbal products including SHs and HFs are prescribed for patients with sleep disorder and MDD. However, the efficacy and safety of CHPs for sleep disorder and MDD need to be further evaluated. Copyright © 2015. Published by Elsevier Ireland Ltd.

Behavioral Activation in the Treatment of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder

ERIC Educational Resources Information Center

Mulick, Patrick S.; Naugle, Amy E.

2009-01-01

This study investigated the efficacy of 10-weeks of Behavioral Activation (BA) in the treatment of comorbid Post-traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) in four adults using a nonconcurrent multiple baseline across participants design. All participants met full "DSM-IV" criteria for both MDD and PTSD at the…

The three-year naturalistic course of major depressive disorder, dysthymic disorder and double depression.

PubMed

Rhebergen, Didi; Beekman, Aartjan Tf; Graaf, Ron de; Nolen, Willem A; Spijker, Jan; Hoogendijk, Witte J; Penninx, Brenda Wjh

2009-06-01

Recent studies support a distinction between acute and chronic forms of depression, which contrasts the single-disease hypothesis for depressive disorders. Insight into the (determinants of) the 3-year naturalistic course of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD) may contribute to this debate. Data were derived from NEMESIS, an epidemiologic survey in the adult population of the Netherlands. 400 Respondents who met the Composite International Diagnostic Interview (CIDI) criteria of MDD and/or Dysth were selected. Cox proportional hazards analyses and Linear Mixed Models were conducted to examine 3-year course trajectories of MDD, Dysth and DD and determinants for course. Adjusted analyses showed similar course trajectories for Dysth and DD, which were significantly worse than the course for MDD. Determinants of unfavorable course were neuroticism and poor functioning. Attrition was higher among persons with Dysth. However, since attrition is generally associated with poorer outcome, this would indicate that differences in course may even have been larger in reality. Dysth and DD involve a similar course which is worse than the course of MDD only. These results do not support a distinction between Dysth and DD. Duration of symptoms and level of functioning may serve as two clinically relevant classifying dimensions within the broad category of depressive disorders.

Perseverative thought: a robust predictor of response to emotional challenge in generalized anxiety disorder and major depressive disorder.

PubMed

Ruscio, Ayelet Meron; Seitchik, Allison E; Gentes, Emily L; Jones, Jason D; Hallion, Lauren S

2011-12-01

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) frequently co-occur, yet the reasons for their comorbidity remain poorly understood. In the present experiment, we tested whether a tendency to engage in negative, repetitive thinking constitutes a common risk process for the two disorders. A mixed sample of adults with comorbid GAD-MDD (n=50), GAD only (n=35), MDD only (n=34), or no lifetime psychopathology (n=35) was administered noncontingent failure and success feedback on consecutive performance tasks. Perseverative thought (PT), measured by negative thought intrusions during a baseline period of focused breathing, emerged as a powerful prospective predictor of responses to this experimental challenge. Participants reporting more frequent negative thought intrusions at baseline, irrespective of thought content or diagnostic status, exhibited a stronger negative response to failure that persisted even after subsequent success. Higher PT over the course of the experiment was associated with later behavioral avoidance, with negative affect and other traits closely linked to anxiety and depression, and with the presence and severity of GAD and MDD. These findings provide evidence for a broadly-defined PT trait that is shared by GAD and MDD and contributes to adverse outcomes in these disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Behavioral avoidance mediates the relationship between anxiety and depressive symptoms among social anxiety disorder patients.

PubMed

Moitra, Ethan; Herbert, James D; Forman, Evan M

2008-10-01

This study investigated the relationship between social anxiety, depressive symptoms, and behavioral avoidance among adult patients with Social Anxiety Disorder (SAD). Epidemiological literature shows SAD is the most common comorbid disorder associated with Major Depressive Disorder (MDD), though the relationship between these disorders has not been investigated. In most cases, SAD onset precedes MDD, suggesting symptoms associated with SAD might lead to depression in some people. The present study addressed this question by investigating the mediational role of behavioral avoidance in this clinical phenomenon, using self-report data from treatment-seeking socially anxious adults. Mediational analyses were performed on a baseline sample of 190 individuals and on temporal data from a subset of this group. Results revealed behavioral avoidance mediated this relationship, and supported the importance of addressing such avoidance in the therapeutic setting, via exposure and other methods, as a possible means of preventing depressive symptom onset in socially anxious individuals.

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.

Lifetime Duration of Depressive Disorders in Patients With Type 2 Diabetes

PubMed Central

Crick, Kent A.; Long, Molly; Saha, Chandan; Shubrook, Jay H.

2016-01-01

OBJECTIVE Depression in patients with type 2 diabetes (T2D) is associated with long-term complications, disability, and early mortality. No studies have systematically examined the length of episodes and remission in adults with major depressive disorder (MDD) and T2D. This study examined the course of depressive disorders in patients with T2D and MDD. RESEARCH DESIGN AND METHODS Participants (N = 50) enrolled in a behavioral intervention for adults with T2D and MDD were interviewed using the Structured Clinical Interview for DSM-IV-TR to assess history of depressive disorders at baseline (lifetime history), postintervention, and 3-month follow-up. Onset and remission dates were recorded for all Axis I depressive disorders from birth to final interview. RESULTS Average number of MDD episodes was 1.8 with a mean duration of 23.4 months (SD 31.9; range 0.5–231.3). Over the life course, mean exposure to MDD was 43.1 months (SD 46.5; range 0.5–231.3). Kaplan-Meier survival curve analysis indicated median episode duration decreased with subsequent episodes (14 months, first episode; 9 months, second episode; P < 0.002). In patients with multiple depressive episodes, recovery time was shorter with each subsequent episode (P = 0.002). No differences in length of episode or remission were observed based on chronology of T2D diagnosis. CONCLUSIONS The overall exposure to depression in this sample of adults with T2D represents a substantial period of time that can contribute to negative medical and psychiatric outcomes. Recurrent episodes decrease in duration as do recovery periods, resulting in a waxing and waning pattern. Findings from this study underscore the need to effectively diagnose and treat depression in patients with T2D to minimize risk of future depressive episodes. PMID:27729427

How long should a trial of escitalopram treatment be in patients with major depressive disorder, generalised anxiety disorder or social anxiety disorder? An exploration of the randomised controlled trial database.

PubMed

Baldwin, David S; Stein, Dan J; Dolberg, Ornah T; Bandelow, Borwin

2009-06-01

To extend the knowledge of course of improvement in patients with major depressive disorder (MDD), social anxiety disorder (SAD) or generalised anxiety disorder (GAD) participating in randomised placebo-controlled trials (RCTs) and to infer the optimal duration of initial escitalopram treatment in clinical practice, after which intervention might be reasonable in case of non-response. Post hoc analysis of pooled clinical trial database for escitalopram in MDD (14 studies), GAD (4 studies) and SAD (2 studies). 'Onset' of action was defined as a 20% or more decrease from baseline score in disorder-specific psychopathological rating scales: 'response' as a 50% or more decrease from baseline score. In MDD, the probability of responding at week 8 if no onset was apparent at week 2 was 43%; in patients with an onset of effect the probability was nearly 80%. Similar patterns were observed in GAD and SAD. The chance of responding beyond week 4 in MDD, GAD and SAD was 20% or less if no effect had occurred by week 2. The pattern of response in these RCTs suggests that in patients with MDD, GAD or SAD in wider clinical practice, a period of at least 4 weeks is worthwhile before considering further intervention.

Anticipatory and consummatory pleasure and displeasure in major depressive disorder: An experience sampling study.

PubMed

Wu, Haijing; Mata, Jutta; Furman, Daniella J; Whitmer, Anson J; Gotlib, Ian H; Thompson, Renee J

2017-02-01

Pleasure and displeasure can be parsed into anticipatory and consummatory phases. However, research on pleasure and displeasure in major depressive disorder (MDD), a disorder characterized by anhedonia, has largely focused on deficits in the consummatory phase. Moreover, most studies in this area have been laboratory-based, raising the question of how component processes of pleasure and displeasure are experienced in the daily lives of depressed individuals. Using experience sampling, we compared anticipatory and consummatory pleasure and displeasure for daily activities reported by adults with MDD (n = 41) and healthy controls (n = 39). Participants carried electronic devices for one week and were randomly prompted eight times a day to answer questions about activities to which they most and least looked forward. Compared to healthy controls, MDD participants reported blunted levels of both anticipatory and consummatory pleasure and elevated levels of both anticipatory and consummatory displeasure for daily activities. Independent of MDD status, participants accurately predicted pleasure but overestimated displeasure. These results are the first to provide evidence that, across both anticipatory and consummatory phases, individuals with MDD experience blunted pleasure and elevated displeasure for daily activities. Our findings clarify the disturbances in pleasure and displeasure that characterize MDD and may inform treatment for this debilitating disorder. (PsycINFO Database Record (c) 2017 APA, 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.

Domain-Specific Impairment in Cognitive Control among Remitted Youth with a History of Major Depression

PubMed Central

Peters, Amy T.; Jacobs, Rachel H.; Crane, Natania A.; Ryan, Kelly A.; Weisenbach, Sara L.; Ajilore, Olusola; Lamar, Melissa; Kassel, Michelle T.; Gabriel, Laura B.; West, Amy E.; Zubieta, Jon-Kar; Langenecker, Scott A.

2016-01-01

Aim Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g., trait), scar, burden, or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set-shifting, and cognitive control in a unique population of young, remitted, un-medicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD. Methods Youth aged 18-23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD; verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and cognitive control. Results rMDD youth performed comparably to healthy controls on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and set-shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants. Conclusion MDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation PMID:26177674

Major Depression and Acute Coronary Syndrome-Related Factors

PubMed Central

Figueiredo, Jose Henrique Cunha; Silva, Nelson Albuquerque de Souza e; Pereira, Basilio de Bragança; de Oliveira, Glaucia Maria Moraes

2017-01-01

Background Major Depressive Disorder (MDD) is one of the most common mental illnesses in psychiatry, being considered a risk factor for Acute Coronary Syndrome (ACS). Objective To assess the prevalence of MDD in ACS patients, as well as to analyze associated factors through the interdependence of sociodemographic, lifestyle and clinical variables. Methods Observational, descriptive, cross-sectional, case-series study conducted on patients hospitalized consecutively at the coronary units of three public hospitals in the city of Rio de Janeiro over a 24-month period. All participants answered a standardized questionnaire requesting sociodemographic, lifestyle and clinical data, as well as a structured diagnostic interview for the DSM-IV regarding ongoing major depressive episodes. A general log-linear model of multivariate analysis was employed to assess association and interdependence with a significance level of 5%. Results Analysis of 356 patients (229 men), with an average and median age of 60 years (SD ± 11.42, 27-89). We found an MDD point prevalence of 23%, and a significant association between MDD and gender, marital status, sedentary lifestyle, Killip classification, and MDD history. Controlling for gender, we found a statistically significant association between MDD and gender, age ≤ 60 years, sedentary lifestyle and MDD history. The log-linear model identified the variables MDD history, gender, sedentary lifestyle, and age ≤ 60 years as having the greatest association with MDD. Conclusion Distinct approaches are required to diagnose and treat MDD in young women with ACS, history of MDD, sedentary lifestyle, and who are not in stable relationships. PMID:28443957

The role of genes and environment on brain alterations in Major Depressive Disorder: A review of twin studies: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

PubMed

Pigoni, A; Delvecchio, G; Altamura, A C; Soares, J C; Fagnani, C; Brambilla, P

2018-07-01

Although it has been consistently reported the important role of genetic and environmental risk factors on structural and functional alterations in Major Depressive Disorder (MDD), the mechanism and the magnitude of the interactions between specific genetic and/or environmental risk factors on brain structures in this disabling disorder are still elusive. Therefore, in the last two decades an increased interest has been devoted to neuroimaging investigations on monozygotic and dizygotic twin samples mainly because their intrinsic characteristics may help to separate the effects of genetic and environmental risk factors on clinical phenotypes, including MDD. In this context, the present review summarizes results from structural and functional Magnetic Resonance Imaging studies that investigated twin samples in correlation with MDD. Overall the results confirmed that a) MDD is characterized by significant alterations in selective brain areas presiding over emotion recognition and evaluation, including amygdala, insula and prefrontal cortices, and b) both genetic and environmental risk factors play a key role in the pathophysiology of this disorder. Few MRI studies exploring MDD in twin samples. The specific contribution of both aspects is still not fully elucidated especially because genes and environment have an impact on the same brain areas, which are particularly vulnerable in MDD. Expansion of the current twin sample sizes would help to clearly establish the potential relationship between risk factors and the development of MDD. Copyright © 2017 Elsevier B.V. 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.

Pilot Study of Treatment for Major Depression Among Women Prisoners with Substance Use Disorder

PubMed Central

Johnson, Jennifer E.; Zlotnick, Caron

2012-01-01

This study, the largest randomized controlled trial of treatment for major depressive disorder (MDD) in an incarcerated population to date, wave-randomized 38 incarcerated women (6 waves) in prison substance use treatment with MDD to group interpersonal psychotherapy (IPT) or to an attention-matched control. Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants. Control participants improved later, after prison release. IPT's rapid effect on MDD within prison may reduce serious in-prison consequences of MDD. PMID:22694906

Salivary Cortisol and Psychopathology in Adults Bereaved by the September 11, 2001 Terror Attacks

PubMed Central

Pfeffer, Cynthia R.; Altemus, Margaret; Heo, Moonseong; Jiang, Hong

2013-01-01

Objective This prospective study aimed to describe the nature and time course of HPA axis dysregulation and psychopathology among terror-bereaved spouses. Method Twenty-three spouses bereaved from September 11, 2001 terror attacks and 22 nonbereaved spouses were compared using a psychiatric diagnostic interview (SCID), three days of salivary cortisol collection, and a dexamethasone suppression test. Most subjects had repeated assessments at six month intervals during the two year study. Results After September 11, 2001, bereaved compared to nonbereaved had significantly higher rates of posttraumatic stress disorder (PTSD) (68.1% versus 0%) and major depressive disorder (MDD) (45.5% versus 9.5%). Bereaved had significantly higher morning basal cortisol and less afternoon postdexamethasone cortisol suppression than nonbereaved. Among bereaved, those with PTSD without comorbid MDD had significantly greater afternoon postdexamethasone cortisol suppression than those without psychiatric disorders. Conclusions Terror-related spouse death is a severe stressor associated with persistent HPA axis activation, PTSD, and MDD. However, bereaved spouses who developed PTSD and were not depressed had enhanced postdexamethasone cortisol suppression, evidence of heightened glucocorticoid receptor sensitivity. PMID:19967896

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

Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features.

PubMed

Rush, A John; Zimmerman, Mark; Wisniewski, Stephen R; Fava, Maurizio; Hollon, Steven D; Warden, Diane; Biggs, Melanie M; Shores-Wilson, Kathy; Shelton, Richard C; Luther, James F; Thomas, Brandi; Trivedi, Madhukar H

2005-07-01

This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive-compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD.

Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

PubMed

Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G

2013-06-01

The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

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.

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.

Examining the relationship between lifetime stressful life events and the onset of major depression in Chinese women☆

PubMed Central

Tao, Ming; Li, Yihan; Xie, Dong; Wang, Zhiyang; Qiu, Jianying; Wu, Wenyuan; Sun, Jing; Wang, Zhoubing; Tao, Danhong; Zhao, Hongsu; Tian, Tian; Zhang, Jingxuan; Gao, Chengge; Niu, Qihui; Li, Qiang; Liu, Shanming; Liu, Jia; Zhang, Yunshu; He, Qiang; Rong, Han; Gan, Zhaoyu; Li, Jianying; Chen, Xiansheng; Pan, Jiyang; Li, Yi; Cui, Yanping; Han, Wei; Ma, Huan; Xie, Shoufu; Jin, Guixing; Li, Ling; Zhang, Ruiling; Tan, Qingrong; Zhang, Jun; Guan, Jing; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S.; Flint, Jonathan; Gao, Jingfang

2011-01-01

Background In European and US studies, patients with major depressive disorder (MDD) report more stressful life events (SLEs) than controls, but this relationship has rarely been studied in Chinese populations. Methods Sixteen lifetime SLEs were assessed at interview in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MDD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. Results 60% of controls and 72% of cases reported at least one lifetime SLE. Fourteen of the sixteen SLEs occurred significantly more frequently in those with MDD (median odds ratio of 1.6). The three SLEs most strongly associated with risk for MDD (OR > 3.0) preceded the onset of MDD the majority of the time: rape (82%), physical abuse (100%) and serious neglect (99%). Limitations Our results may apply to females only. SLEs were rated retrospectively and are subject to biases in recollection. We did not assess contextual information for each life event. Conclusions More severe SLEs are more strongly associated with MDD. These results support the involvement of psychosocial adversity in the etiology of MDD in China. PMID:21821294

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.

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.

The Impact of a Single Nucleotide Polymorphism in SIGMAR1 on Depressive Symptoms in Major Depressive Disorder and Bipolar Disorder.

PubMed

Mandelli, Laura; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un; Serretti, Alessandro

2017-03-01

Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers. A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively. In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode. The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.

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.

Association of anxiety disorders and depression with incident heart failure.

PubMed

Garfield, Lauren D; Scherrer, Jeffrey F; Hauptman, Paul J; Freedland, Kenneth E; Chrusciel, Tim; Balasubramanian, Sumitra; Carney, Robert M; Newcomer, John W; Owen, Richard; Bucholz, Kathleen K; Lustman, Patrick J

2014-02-01

Depression has been associated with increased risk of heart failure (HF). Because anxiety is highly comorbid with depression, we sought to establish if anxiety, depression, or their co-occurrence is associated with incident HF. A retrospective cohort (N = 236,079) including Veteran's Administration patients (age, 50-80 years) free of cardiovascular disease (CVD) at baseline was followed up between 2001 and 2007. Cox proportional hazards models were computed to estimate the association between anxiety disorders alone, major depressive disorder (MDD) alone, and the combination of anxiety and MDD, with incident HF before and after adjusting for sociodemographics, CVD risk factors (Type 2 diabetes, hypertension, hyperlipidemia, obesity), nicotine dependence/personal history of tobacco use, substance use disorders (alcohol and illicit drug abuse/dependence), and psychotropic medication. Compared with unaffected patients, those with anxiety only, MDD only, and both disorders were at increased risk for incident HF in age-adjusted models (hazard ratio [HR] = 1.19 [ 95% confidence interval {CI} = 1.10-1.28], HR = 1.21 [95% CI = 1.13-1.28], and HR = 1.24 [95% CI = 1.17-1.32], respectively). After controlling for psychotropics in a full model, the association between anxiety only, MDD only, and both disorders and incident HF increased (HRs = 1.46, 1.56, and 1.74, respectively). Anxiety disorders, MDD, and co-occurring anxiety and MDD are associated with incident HF in this large cohort of Veteran's Administration patients free of CVD at baseline. This risk of HF is greater after accounting for protective effects of psychotropic medications. Prospective studies are needed to clarify the role of depression and anxiety and their pharmacological treatment in the etiology of HF.

First psychiatric hospitalizations in the US military: the National Collaborative Study of Early Psychosis and Suicide (NCSEPS).

PubMed

Herrell, Richard; Henter, Ioline D; Mojtabai, Ramin; Bartko, John J; Venable, Diane; Susser, Ezra; Merikangas, Kathleen R; Wyatt, Richard J

2006-10-01

Military samples provide an excellent context to systematically ascertain hospitalization for severe psychiatric disorders. The National Collaborative Study of Early Psychosis and Suicide (NCSEPS), a collaborative study of psychiatric disorders in the US Armed Forces, estimated rates of first hospitalization in the military for three psychiatric disorders: bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia. First hospitalizations for BD, MDD and schizophrenia were ascertained from military records for active duty personnel between 1992 and 1996. Rates were estimated as dynamic incidence (using all military personnel on active duty at the midpoint of each year as the denominator) and cohort incidence (using all military personnel aged 18-25 entering active duty between 1992 and 1996 to estimate person-years at risk). For all three disorders, 8723 hospitalizations were observed in 8,120,136 person-years for a rate of 10.7/10,000 [95% confidence interval (CI) 10.5-11.0]. The rate for BD was 2.0 (95% CI 1.9-2.1), for MDD, 7.2 (95% CI 7.0-7.3), and for schizophrenia, 1.6 (95% CI 1.5-1.7). Rates for BD and MDD were greater in females than in males [for BD, rate ratio (RR) 2.0, 95% CI 1.7-2.2; for MDD, RR 2.9, 95% CI 2.7-3.1], but no sex difference was found for schizophrenia. Blacks had lower rates than whites of BD (RR 0.8, 95% CI 0.7-0.9) and MDD (RR 0.8, 95% CI 0.8-0.9), but a higher rate of schizophrenia (RR 1.5, 95% CI 1.3-1.7). This study underscores the human and financial burden that psychiatric disorders place on the US Armed Forces.

The effects of dysthymic disorder on health-related quality of life and disability days in persons with comorbid medical conditions in the general population.

PubMed

Baune, Bernhard T; Caniato, Riccardo N; Arolt, Volker; Berger, Klaus

2009-01-01

We aimed to investigate in medical disorders the effects of comorbid dysthymic disorder as compared to major depressive disorder (MDD) on health-related quality of life (HR-QoL) and disability days in the general population. In a population-based study 4,181 individuals were assessed for the presence of dysthymic disorder and depression, utilizing the Composite International Diagnostic Interview. Each participant received a thorough medical examination to assess the presence of comorbid somatic conditions. HR-QoL was evaluated using the Medical Outcomes Survey Short-Form 36 (SF-36) and disability days were provided by self-report. Descriptive statistics, analysis of variance and multivariable logistic regression were used. Comorbidity with illnesses from a maximum of 6 somatic disease groups was more prevalent in persons with dysthymic disorder (78.7%) than in those with MDD (70.4%). Persons with dysthymic disorder had a significantly lower mental health summary score in the SF-36 and more disability days than those with MDD. The physical health summary scores were not significantly different between participants with dysthymic disorder and MDD (after Bonferroni correction), suggesting that limitations in physical functioning due to comorbid medical conditions were similar in both affective disorder groups. These results show that affective disorders comorbid with medical, somatic illnesses have a major impact on HR-QoL and disability with more pronounced effects in dysthymic disorder than in MDD. Differences in the time course of both conditions might contribute to this finding. Our results support the need for an improved identification and treatment of affective disorders in patients with somatic illnesses. Copyright (c) 2009 S. Karger AG, Basel.

The Influence of Gender, Age, Psychological Resilience and Family Interaction Factors upon Anxiety and Depression in Non-Autism Spectrum Disorder Siblings of Children with an Autism Spectrum Disorder

ERIC Educational Resources Information Center

Bitsika, Vicki; Sharpley, Christopher F.; Mailli, Rebecca

2015-01-01

The influence of gender, age, Psychological resilience and family interaction factors upon generalised anxiety disorder (GAD) and major depressive disorder (MDD) was investigated in 75 non-autism spectrum disorder (NASD) siblings who had a brother or sister with an autism spectrum disorder (ASD). GAD and MDD were much more prevalent than in…

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.

Noninvasive brain stimulation treatments for addiction and major depression

PubMed Central

Dunlop, Katharine; Hanlon, Colleen A.

2016-01-01

Major depressive disorder (MDD) and substance use disorders (SUDs) are prevalent, disabling, and challenging illnesses for which new treatment options are needed, particularly in comorbid cases. Neuroimaging studies of the functional architecture of the brain suggest common neural substrates underlying MDD and SUDs. Intrinsic brain activity is organized into a set of functional networks, of which two are particularly relevant to psychiatry. The salience network (SN) is crucial for cognitive control and response inhibition, and deficits in SN function are implicated across a wide variety of psychiatric disorders, including MDD and SUDs. The ventromedial network (VMN) corresponds to the classic reward circuit, and pathological VMN activity for drug cues/negative stimuli is seen in SUDs/MDD. Noninvasive brain stimulation (NIBS) techniques, including rTMS and tDCS, have been used to enhance cortico–striatal–thalamic activity through the core SN nodes in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and anterior insula. Improvements in both MDD and SUD symptoms ensue, including in comorbid cases, via enhanced cognitive control. Inhibition of the VMN also appears promising in preclinical studies for quenching the pathological incentive salience underlying SUDs and MDD. Evolving techniques may further enhance the efficacy of NIBS for MDD and SUD cases that are unresponsive to conventional treatments. PMID:26849183

Two-year course of generalized anxiety disorder, social anxiety disorder, and panic disorder with agoraphobia in a sample of Latino adults.

PubMed

Bjornsson, Andri S; Sibrava, Nicholas J; Beard, Courtney; Moitra, Ethan; Weisberg, Risa B; Benítez, Carlos I Pérez; Keller, Martin B

2014-12-01

It is imperative to study the clinical course of anxiety disorders among Latinos, given the implications for culturally sensitive treatment in this population. The current study is the first prospective, observational, longitudinal study of anxiety disorders among Latinos. Data are reported on 139 adult Latinos (M age = 34.65 years, SD = 10.98, 70.5% female) diagnosed with social anxiety disorder (SAD; n = 86), generalized anxiety disorder (GAD; n = 90), or panic disorder with agoraphobia (PDA; n = 62). The participants were interviewed with standardized clinical interviews at intake and annually over 2 years of follow-up. Probabilities of recovery were calculated using standard survival analysis methods. The 2-year recovery rates in this study were 0.07 for SAD, 0.14 for GAD, 0.03 for PDA, and 0.50 for major depressive disorder (MDD). Overall functioning, social adjustment, and life satisfaction in this sample were poor. The recovery rates for anxiety disorders in this Latino sample were markedly low. Although caution must be used in comparing these data with prior longitudinal studies, these recovery rates seem to be much lower than in non-Latino White samples. However, the clinical course of MDD in this sample was similar to its course among non-Latino Whites, invoking the pressing question of whether there is something about the experience of anxiety disorders (but not MDD) among Latinos that makes them more impairing and persistent. The answer to that question should inform future treatment development for this population.

Expert and self-assessment of lifetime symptoms and diagnosis of major depressive disorder in large-scale genetic studies in the general population: comparison of a clinical interview and a self-administered checklist.

PubMed

Martin, Jessica; Streit, Fabian; Treutlein, Jens; Lang, Maren; Frank, Josef; Forstner, Andreas J; Degenhardt, Franziska; Witt, Stephanie H; Schulze, Thomas G; Cichon, Sven; Nöthen, Markus M; Rietschel, Marcella; Strohmaier, Jana

2017-10-01

Major depression disorder (MDD) is a complex neuropsychiatric disorder and an increasing number of genetic risk variants are being identified. Investigation of their influence in the general population requires accurate and efficient assessment of depressive symptoms. Here, clinical interviews conducted by clinicians are the gold standard. We investigated whether valid and reliable clinical phenotypes can be obtained efficiently using self-administered instruments. Lifetime depressive symptoms and lifetime MDD diagnosis were assessed in 464 population-based individuals using a clinical interview and a structured, self-administered checklist. Analyses were carried out of the following: (i) intraclass correlations (ICC) between checklist and interview; (ii) sensitivity/specificity of the checklist; and (iii) the association of interview and checklist with a positive family history of MDD (FH-MDD+). The correspondence of the self-administered checklist with the clinical interview was good for most depressive symptoms (ICC=0.60-0.80) and moderate for MDD diagnosis (ICC=0.45). With the consecutive inclusion of MDD diagnostic criteria, sensitivity decreased from 0.67 to 0.46, whereas specificity remained high (0.95). For checklist and interview, strong associations were found between FH-MDD+ and most depressive symptoms and MDD diagnosis (all odds ratio≥1.83). The self-administered checklist showed high reliability for both the assessment of lifetime depressive symptoms and screening for individuals with no lifetime diagnosis of MDD. However, attention is warranted when the aim is to identify MDD cases. The positive association between depressive symptomatology and FH-MDD+ indicates the usefulness of both instruments to assess patients in genetic studies. Our data suggest that the more time-efficient and cost-efficient self-administered instruments also allow for the assessment of depressive symptoms accurate enough to investigate the influence of MDD genetic risk variants in the general population.

Expert and self-assessment of lifetime symptoms and diagnosis of major depressive disorder in large-scale genetic studies in the general population: comparison of a clinical interview and a self-administered checklist

PubMed Central

Martin, Jessica; Streit, Fabian; Treutlein, Jens; Lang, Maren; Frank, Josef; Forstner, Andreas J.; Degenhardt, Franziska; Witt, Stephanie H.; Schulze, Thomas G.; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella

2017-01-01

Major depression disorder (MDD) is a complex neuropsychiatric disorder and an increasing number of genetic risk variants are being identified. Investigation of their influence in the general population requires accurate and efficient assessment of depressive symptoms. Here, clinical interviews conducted by clinicians are the gold standard. We investigated whether valid and reliable clinical phenotypes can be obtained efficiently using self-administered instruments. Lifetime depressive symptoms and lifetime MDD diagnosis were assessed in 464 population-based individuals using a clinical interview and a structured, self-administered checklist. Analyses were carried out of the following: (i) intraclass correlations (ICC) between checklist and interview; (ii) sensitivity/specificity of the checklist; and (iii) the association of interview and checklist with a positive family history of MDD (FH-MDD+). The correspondence of the self-administered checklist with the clinical interview was good for most depressive symptoms (ICC=0.60–0.80) and moderate for MDD diagnosis (ICC=0.45). With the consecutive inclusion of MDD diagnostic criteria, sensitivity decreased from 0.67 to 0.46, whereas specificity remained high (0.95). For checklist and interview, strong associations were found between FH-MDD+ and most depressive symptoms and MDD diagnosis (all odds ratio≥1.83). The self-administered checklist showed high reliability for both the assessment of lifetime depressive symptoms and screening for individuals with no lifetime diagnosis of MDD. However, attention is warranted when the aim is to identify MDD cases. The positive association between depressive symptomatology and FH-MDD+ indicates the usefulness of both instruments to assess patients in genetic studies. Our data suggest that the more time-efficient and cost-efficient self-administered instruments also allow for the assessment of depressive symptoms accurate enough to investigate the influence of MDD genetic risk variants in the general population. PMID:28731911

Symptoms of Major Depressive Disorder Subsequent to Child Maltreatment: Examining Change across Multiple Levels of Analysis to Identify Transdiagnostic Risk Pathways

PubMed Central

Shenk, Chad E.; Griffin, Amanda M.; O’Donnell, Kieran J.

2016-01-01

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: 1) neuroendocrine, 2) autonomic, 3) affective, and 4) 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 eighteen 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. PMID:26535940

Premorbid Risk Factors for Major Depressive Disorder: Are They Associated With Early Onset and Recurrent Course?

PubMed Central

Wilson, Sylia; Vaidyanathan, Uma; Miller, Michael B.; McGue, Matt; Iacono, William G.

2014-01-01

Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age-11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual SNP-based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early-onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset. PMID:25422974

EEG sleep in Cushing's disease and Cushing's syndrome: comparison with patients with major depressive disorder.

PubMed

Shipley, J E; Schteingart, D E; Tandon, R; Pande, A C; Grunhaus, L; Haskett, R F; Starkman, M N

1992-07-15

Because patients with Cushing' syndrome (CS) and Major depressive disorder (MDD) share features of hypercortisolism and the depressive syndrome, we compared electro-encephalographic (EEG) sleep in patients with pituitary-ACTH-dependent Cushing's syndrome (Cushing's disease, CD), patients with ACTH-independent Cushing's syndrome (AICS), patients with major depressive disorder (MDD), and normal subjects. There were substantial similarities in the abnormal polysomnography profiles of patients with CD, AICS, and MDD. All three patient groups demonstrated poorer sleep continuity, shortened rapid eye movement (REM) latency, and increased first REM period density compared with normal subjects. In addition, AICS patients and MDD patients had elevated REM activity and density. These findings are discussed in terms of models of pathophysiology that relate abnormalities in sleep, mood, and hypothalamic-pituitary-adrenal function.

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.

Most of the genetic covariation between major depressive and alcohol use disorders is explained by trait measures of negative emotionality and behavioral control.

PubMed

Ellingson, J M; Richmond-Rakerd, L S; Statham, D J; Martin, N G; Slutske, W S

2016-10-01

Mental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD). A total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON. A statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD. This is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology.

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.

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.

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

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

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.

Apoptosis-related proteins and proliferation markers in the orbitofrontal cortex in major depressive disorder

PubMed Central

Miguel-Hidalgo, Jose J.; Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Meshram, Ashish; Pickett, Jason C.; Rajkowska, Grazyna; Stockmeier, Craig A.

2014-01-01

Background: In major depressive disorder (MDD), lowered neural activity and significant reductions of markers of cell resiliency to degeneration occur in the prefrontal cortex (PFC). It is still unclear whether changes in other relevant markers of cell vulnerability to degeneration and markers of cell proliferation are associated with MDD. Methods: Levels of caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA) and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured in postmortem samples of the left orbitofrontal cortex (OFC) of subjects with MDD, and psychiatrically-normal comparison subjects. Results: There was significant increase in C8, a higher ratio of DIABLO to XIAP, lower packing density of Ki-67-IR cells, and an unexpected age-dependent increase in PCNA in subjects with MDD vs. controls. PCNA levels were significantly higher in MDD subjects unresponsive to antidepressants or untreated with antidepressants. The DIABLO/XIAP ratio was higher in MDD subjects without antidepressants than in comparison subjects. Limitations: Qualitative nature of responsiveness assessments; Definition of resistance to antidepressant treatment is still controversial; Unclear role of PCNA. Conclusions: Markers of cell vulnerability to degeneration are increased and density of Ki67-positive cells is low MDD, but accompanied by normal XIAP levels. The results suggest increased vulnerability to cell pathology in depression that is insufficient to cause morphologically conspicuous cell death. Persistent but low-grade vulnerability to cell degeneration coexisting with reduced proliferation readiness may explain age-dependent reductions in neuronal densities in the OFC of depressed subjects. PMID:24655767

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.

Adolescent depression: clinical features and therapeutic strategies.

PubMed

Nardi, B; Francesconi, G; Catena-Dell'osso, M; Bellantuono, C

2013-06-01

Major depressive disorder (MDD) is a common disorder during adolescence and it is associated with an increased risk of suicide, poor school performance, impaired social skills, social withdrawal and substance abuse. Further, as many depressive episode in adolescents do not reach the diagnostic threshold for MDD, the disorder remains undetected. This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. We reviewed the international literature to identify studies focusing on clinical features and therapeutic options in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is present most frequently in female and it is related to the severity of MDD. Adolescent MDD is also characterized by a high rates of suicides. The therapeutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the traditional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is relevant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeutic program.

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.

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.

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.

Assessment of abnormal brain structures and networks in major depressive disorder using morphometric and connectome analyses.

PubMed

Chen, Vincent Chin-Hung; Shen, Chao-Yu; Liang, Sophie Hsin-Yi; Li, Zhen-Hui; Tyan, Yeu-Sheng; Liao, Yin-To; Huang, Yin-Chen; Lee, Yena; McIntyre, Roger S; Weng, Jun-Cheng

2016-11-15

It is hypothesized that the phenomenology of major depressive disorder (MDD) is subserved by disturbances in the structure and function of brain circuits; however, findings of structural abnormalities using MRI have been inconsistent. Generalized q-sampling imaging (GQI) methodology provides an opportunity to assess the functional integrity of white matter tracts in implicated circuits. The study population was comprised of 16 outpatients with MDD (mean age 44.81±2.2 years) and 30 age- and gender-matched healthy controls (mean age 45.03±1.88 years). We excluded participants with any other primary mental disorder, substance use disorder, or any neurological illnesses. We used T1-weighted 3D MRI with voxel-based morphometry (VBM) and vertex-wise shape analysis, and GQI with voxel-based statistical analysis (VBA), graph theoretical analysis (GTA) and network-based statistical (NBS) analysis to evaluate brain structure and connectivity abnormalities in MDD compared to healthy controls correlates with clinical measures of depressive symptom severity, Hamilton Depression Rating Scale 17-item (HAMD) and Hospital Anxiety and Depression Scale (HADS). Using VBM and vertex-wise shape analyses, we found significant volumetric decreases in the hippocampus and amygdala among subjects with MDD (p<0.001). Using GQI, we found decreases in diffusion anisotropy in the superior longitudinal fasciculus and increases in diffusion probability distribution in the frontal lobe among subjects with MDD (p<0.01). In GTA and NBS analyses, we found several disruptions in connectivity among subjects with MDD, particularly in the frontal lobes (p<0.05). In addition, structural alterations were correlated with depressive symptom severity (p<0.01). Small sample size; the cross-sectional design did not allow us to observe treatment effects in the MDD participants. Our results provide further evidence indicating that MDD may be conceptualized as a brain disorder with abnormal circuit structure and connectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Factors Associated with Mood Disorder Diagnosis Among a Population Based Cohort of Men and Women Living With and Without HIV in British Columbia Between 1998 and 2012.

PubMed

Closson, Kalysha; Osborne, Chuck; Smith, Danielle M; Kesselring, Sarah; Eyawo, Oghenowede; Card, Kiffer; Sereda, Paul; Jabbari, Shahab; Franco-Villalobos, Conrado; Ahmed, Tareq; Gabler, Karyn; Patterson, Thomas; Hull, Mark; Montaner, Julio S G; Hogg, Robert S

2018-05-01

Using data from the Comparison of Outcomes and Service Utilization Trends (COAST) study we examined factors associated with mood disorder diagnosis (MDD) among people living with HIV (PLHIV) and HIV-negative individuals in British Columbia, Canada. MDD cases were identified between 1998 and 2012 using International Classification of Disease 9 and 10 codes. A total of 491,796 individuals were included and 1552 (23.7%) and 60,097 (12.4%) cases of MDD were identified among the HIV-positive and HIV-negative populations, respectively. Results showed HIV status was associated with greater odds of MDD among men and lower odds among women. Among PLHIV, MDD was significantly associated with: identifying as gay, bisexual or other men who have sex with men compared to heterosexuals; higher viral load; history of injection drug use; and concurrent anxiety, dysthymia, and substance use disorders. Findings highlight the need for comprehensive and holistic HIV and mental health care.

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 in patients with type 2 diabetes mellitus: Prevalence and clinical characteristics.

PubMed

Huang, Chun-Jen; Hsieh, Hui-Min; Tu, Hung-Pin; Jiang, He-Jiun; Wang, Peng-Wei; Lin, Ching-Hua

2018-02-01

This study investigated the prevalence of major depressive disorder (MDD) among Taiwanese patients with type 2 diabetes mellitus (T2DM). We enrolled patients with at least one service claim for ambulatory or inpatient care with a principal diagnosis of MDD and at least two service claims for ambulatory care or one service claim for inpatient care with a principal diagnosis of T2DM, as listed in Taiwan's National Health Insurance database. We enrolled 715,756 people from the general population (GP), 61,589 patients with T2DM but without MDD, and 778 patients with both T2DM and MDD. The prevalence of MDD increased from 0.70% to 1.25% in the patients with T2DM, whereas it increased from 0.25% to 0.67% in the GP from 2000 to 2010. The higher prevalence of MDD was associated with the female sex, residing in the southern regions of Taiwan, and having comorbidities of cerebrovascular disease and anxiety disorder as well as higher comorbidity severity (Charlson comorbidity index, 1-2 and > 2). One limitation is the use of secondary data on diagnoses of MDD and T2DM. Another limitation is that we could not access some crucial related variables. The prevalence of MDD was higher in the patients with T2DM than in the GP. In this study, the prevalence of MDD in the patients with T2DM was lower than that reported in Western countries. Copyright © 2017 Elsevier B.V. All rights reserved.

Major depressive disorder and current psychological distress moderate the effect of polygenic risk for obesity on body mass index.

PubMed

Clarke, T-K; Hall, L S; Fernandez-Pujals, A M; MacIntyre, D J; Thomson, P; Hayward, C; Smith, B H; Padmanabhan, S; Hocking, L J; Deary, I J; Porteous, D J; McIntosh, A M

2015-06-30

Major depressive disorder (MDD) and obesity are frequently co-morbid and this correlation is partly due to genetic factors. Although specific genetic risk variants are associated with body mass index (BMI) and with larger effect sizes in depressed individuals, the genetic overlap and interaction with depression has not been addressed using whole-genome data. Polygenic profile scores for MDD and BMI were created in 13,921 members of Generation Scotland: the Scottish Family Health Study and tested for their association with BMI, MDD, neuroticism and scores on the General Health Questionnaire (GHQ) (current psychological distress). The association between BMI polygenic profile scores and BMI was tested fitting GHQ, neuroticism or MDD status as an interaction term to test for a moderating effect of mood disorder. BMI polygenic profile scores were not associated with lifetime MDD status or neuroticism although a significant positive association with GHQ scores was found (P = 0.0001, β = 0.034, r(2) = 0.001). Polygenic risk for MDD was not associated with BMI. A significant interaction between BMI polygenic profile scores and MDD (P = 0.0003, β = 0.064), GHQ (P = 0.0005, β = 0.027) and neuroticism (P = 0.003, β = 0.023) was found when BMI was the dependent variable. The effect of BMI-increasing alleles was greater in those with MDD, high neuroticism or current psychological distress. MDD, neuroticism and current psychological distress amplify the effect of BMI polygenic profile scores on BMI. Depressed individuals with a greater polygenic load for obesity are at greater risk of becoming obese than control individuals.

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

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.

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.

Pupillary reactivity to negative stimuli prospectively predicts recurrence of major depressive disorder in women.

PubMed

Kudinova, Anastacia Y; Burkhouse, Katie L; Siegle, Greg; Owens, Max; Woody, Mary L; Gibb, Brandon E

2016-12-01

There is a large body of research supporting the association between disrupted physiological reactivity to negative stimuli and depression. The present study aimed to examine whether physiological reactivity to emotional stimuli, assessed via pupil dilation, served as a biological marker of risk for depression recurrence among individuals who are known to be at a higher risk due to having previous history of depression. Participants were 57 women with a history of major depressive disorder (MDD). Pupil dilation to angry, happy, sad, and neutral faces was recorded. Participants' diagnoses and symptoms were assessed 24 months after the initial assessment. We found that women's pupillary reactivity to negative (sad or angry faces) but not positive stimuli prospectively predicted MDD recurrence. Additionally, we found that both hyper- and hypopupillary reactivity to angry faces predicted risk for MDD recurrence. These findings suggest that disrupted physiological response to negative stimuli indexed via pupillary dilation could serve as a physiological marker of MDD risk, thus presenting clinicians with a convenient and inexpensive method to predict which of the at-risk women are more likely to experience depression recurrence. © 2016 Society for Psychophysiological Research.

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

Prevalence of major depressive disorder and minor depressive disorder in an elderly Korean population: results from the Korean Longitudinal Study on Health and Aging (KLoSHA).

PubMed

Park, Joon Hyuk; Lee, Jung Jae; Lee, Seok Bum; Huh, Yoonseok; Choi, Eun Ae; Youn, Jong Choul; Jhoo, Jin Hyeong; Kim, Jin Sun; Woo, Jong Inn; Kim, Ki Woong

2010-09-01

We investigated the prevalence, risk factors and impact of major depressive disorder (MDD) and minor depressive disorder (MnDD) in a randomly selected community-dwelling Korean elderly population. This study was conducted as a part of the Korean Longitudinal Study on Health and Aging (KLoSHA). A study population of 1118 Korean elders was randomly sampled from residents of Seongnam, Korea aged 65 years or older. Standardized face-to-face interviews and neurological and physical examinations were conducted on 714 respondents using the Korean version of Mini International Neuropsychiatric Interview. MDD was diagnosed according to the DSM-IV criteria, and MnDD according to research criteria proposed in Appendix B of the DSM-IV criteria. Age-, gender- and education-standardized prevalence rates in Korean elders aged 65 years or older were estimated as 5.37% (95% CI=3.72-7.03) for MDD, 5.52% (95% CI=3.84-7.19) for MnDD, and 10.89% (95% CI=8.60-13.17) for overall late-life depression (LLD). A prior MDD episode (OR=3.07, 95% CI=1.38-6.82 in MDD, OR=3.44, 95% CI=1.49-7.94 in MnDD), female gender (OR=3.55, 95% CI=1.53-8.24 in MDD, OR=2.68, 95% CI=1.19-6.04 in MnDD) and history of stroke or TIA (OR=3.45, 95% CI=1.62-7.35 in MDD, OR=2.95, 95% CI=1.34-6.52 in MnDD) were associated with the risks of both MDD and MnDD. Lack of formal education (OR=2.75, 95% CI=1.30-5.85) and low income (OR=2.83, 95% CI=1.02-7.88) were associated with the risk of MDD only. Quality of life (QOL) of the MDD and MnDD patients was worse than that of non-depressed elders (P<0.001, ANOVA). MnDD was as prevalent as MDD in Korean elders and impacted QOL as MDD did. MnDD patients may increase in the future with accelerated population aging and westernization of lifestyle in Korea. 2010 Elsevier B.V. All rights reserved.

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.

Dehydroepiandrosterone Sulfate Level Varies Nonlinearly with Symptom Severity in Major Depressive Disorder

PubMed Central

Uh, Dasom; Jeong, Hyun-Ghang; Choi, Kwang-Yeon; Oh, So-Young; Lee, Suji; Kim, Seung-Hyun; Joe, Sook-Haeng

2017-01-01

Objective The pathophysiology of major depressive disorder (MDD) is still not well understood. Conflicting results for surrogate biomarkers in MDD have been reported, which might be a consequence of the heterogeneity of MDD patients. Therefore, we aim to investigate how the severity of depression and various symptom domains are related to the levels of dehydroepiandrosterone sulfate (DHEA-s) in MDD patients. Methods We recruited 117 subjects from a general practice. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Depressive symptoms were divided into three subdomains according to BDI items; somatic symptoms, guilt and failure, and mood and inhibition. Results In subjects with very-mild-to-moderate depression, the DHEA-s level increased as BDI score did. However, the DHEA-s levels in the subjects with severe depression were significantly lower than in subjects with moderate depression (p=0.003). DHEA-s level was correlated with the BDI subscore for guilt and failure in very-mild-to-moderate depression (r=0.365, p=0.006). Conclusion The DHEA-s level appears to be indicative of MDD severity with respect to depressive symptoms, especially regarding guilt and failure. Our findings suggest that the upregulation of DHEA-s may be a part of a compensatory process in very-mild-to-moderate depression, and the failure of this compensation mechanism may underlie the development of severe depression. PMID:28449564

Depression is more than the sum-score of its parts: individual DSM symptoms have different risk factors

PubMed Central

Fried, Eiko I.; Nesse, Randolph M.; Zivin, Kara; Guille, Constance; Sen, Srijan

2014-01-01

Background For diagnostic purposes, the nine symptoms that compose the DSM-5 criteria for Major Depressive Disorder (MDD) are assumed to be interchangeable indicators of one underlying disorder, implying that they should all have similar risk factors. The present study investigates this hypothesis, utilizing a population cohort that shifts from low to elevated depression levels. Methods We assessed the nine DSM-5 MDD criterion symptoms and seven depression risk factors (personal and family MDD history, sex, childhood stress, neuroticism, work hours, and stressful life events) in a longitudinal study of medical interns prior to and throughout internship (n=1289). We tested if risk factors varied across symptoms, and whether a latent disease model could account for heterogeneity between symptoms. Results All MDD symptoms increased significantly during residency training. Four risk factors predicted increases in unique subsets of PHQ-9 symptoms over time (depression history, childhood stress, sex, and stressful life events), while neuroticism and work hours predicted increases in all symptoms, albeit to varying magnitudes. MDD family history did not predict increases in any symptom. The strong heterogeneity of associations persisted after controlling for a latent depression factor. Conclusions The influence of risk factors varies substantially across DSM depression criterion symptoms. Since symptoms are etiologically heterogeneous, considering individual symptoms in addition to depression diagnosis might offer important insights obfuscated by symptom sum-scores. PMID:24289852

Sex- and age-specific associations between major depressive disorder and metabolic syndrome in two general population samples in Germany.

PubMed

Block, Andrea; Schipf, Sabine; Van der Auwera, Sandra; Hannemann, Anke; Nauck, Matthias; John, Ulrich; Völzke, Henry; Freyberger, Harald Jürgen; Dörr, Marcus; Felix, Stephan; Zygmunt, Marek; Wallaschofski, Henri; Grabe, Hans Jörgen

2016-11-01

Major depressive disorder (MDD) has been associated with the Metabolic Syndrome (MetS). As previous data strongly suggested sex and age effects on this association, this study aimed to analyse the association between MDD and MetS in two general population samples under explicit consideration of sex and age. This study analysed cross-sectional data based on two independent general population samples: SHIP-0 (n = 4083; 20-81 years; 49.4% male) and SHIP-TREND-0 (n = 3957; 20-83 years; 49.0% male) that were part of the Study of Health in Pomerania. MDD (SHIP-0: 12.6%; SHIP-TREND-0: 27.2%) was assessed using the Composite International Diagnostic-Screener (CID-S) in both samples. Interview assessment of MDD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria was performed in SHIP-TREND-0 (18.1% MDD). MetS was defined by abdominal obesity, elevated blood pressure, elevated glucose, elevated triglycerides and reduced high-density lipoprotein cholesterol according to established criteria. Data analysis was performed sex- and age-stratified. Prevalence of MetS was high in both samples: 19.4% of females and 30.2% of males in SHIP-0 and 22.1% and 33.2% in SHIP-TREND-0, respectively. Effect modifications were observed by sex and age on the association between MDD and MetS. Particularly, younger females (20-49 years) with MDD were more often affected by MetS than younger females without MDD: OR = 2.21 (95% CI = 1.39-3.50). This association vanished in elderly participants (50-82 years). The data suggest that especially younger (presumably pre-menopausal) females with MDD are more likely to have MetS than those without major depressive disorders, and that age extenuates this association.

Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity.

PubMed

Kaiser, Roselinde H; Andrews-Hanna, Jessica R; Wager, Tor D; Pizzagalli, Diego A

2015-06-01

Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. To investigate network dysfunction in MDD through a meta-analysis of rsFC studies. Seed-based voxelwise rsFC studies comparing individuals with MDD with healthy controls (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE) and authors contacted for additional data. Twenty-seven seed-based voxel-wise rsFC data sets from 25 publications (556 individuals with MDD and 518 healthy controls) were included in the meta-analysis. Coordinates of seed regions of interest and between-group effects were extracted. Seeds were categorized into seed-networks by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive or reduced negative connectivity) or hypoconnectivity (increased negative or reduced positive connectivity) with each seed-network. Major depressive disorder was characterized by hypoconnectivity within the frontoparietal network, a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network involved in attending to the external environment. Major depressive disorder was also associated with hyperconnectivity within the default network, a network believed to support internally oriented and self-referential thought, and hyperconnectivity between frontoparietal control systems and regions of the default network. Finally, the MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. Reduced connectivity within frontoparietal control systems and imbalanced connectivity between control systems and networks involved in internal or external attention may reflect depressive biases toward internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.

Stressful life events as predictors of functioning: findings from the Collaborative Longitudinal Personality Disorders Study

PubMed Central

Pagano, M. E.; Skodol, A. E.; Stout, R. L.; Shea, M. T.; Yen, S.; Grilo, C. M.; Sanislow, C. A.; Bender, D. S.; McGlashan, T. H.; Zanarini, M. C.; Gunderson, J. G.

2008-01-01

Objective Although much attention has been given to the effects of adverse childhood experiences on the development of personality disorders (PDs), we know far less about how recent life events influence the ongoing course of functioning. We examined the extent to which PD subjects differ in rates of life events and the extent to which life events impact psychosocial functioning. Method A total of 633 subjects were drawn from the Collaborative Longitudinal Personality Disorders Study (CLPS), a multi-site study of four personality disorders – schizotypal (STPD), borderline (BPD), avoidant (AVPD), obsessive-compulsive (OCPD) – and a comparison group of major depressive disorders (MDD) without PD. Results Borderline personality disorder subjects reported significantly more total negative life events than other PDs or subjects with MDD. Negative events, especially interpersonal events, predicted decreased psychosocial functioning over time. Conclusion Our findings indicate higher rates of negative events in subjects with more severe PDs and suggest that negative life events adversely impact multiple areas of psychosocial functioning. PMID:15521826

Psychopathology in the adolescent and young adult offspring of parents with dysthymic disorder and major depressive disorder.

PubMed

Lizardi, Humberto; Klein, Daniel N; Shankman, Stewart A

2004-03-01

This study addressed the following question: are the adolescent and young adult offspring of parents with early-onset dysthymic disorder (DD) at increased risk for psychopathology? Participants included 41 offspring of 21 outpatients with early-onset DD, 19 offspring of nine outpatients with episodic major depressive disorder (MDD), and 32 offspring of 11 normal controls (NCs). Lifetime best-estimate diagnoses were determined for each offspring using a team consensus method. Diagnoses were derived blind to all information about the index parents. The offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of a broad range of psychiatric disorders than the offspring of NCs. In addition, the offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of DD, anxiety disorders, and phobia than the offspring of outpatients with episodic MDD. These results support the importance of early-onset DD in parents as a risk factor for psychopathology in their offspring.

Reconsidering the prognosis of major depressive disorder across diagnostic boundaries: full recovery is the exception rather than the rule.

PubMed

Verduijn, Judith; Verhoeven, Josine E; Milaneschi, Yuri; Schoevers, Robert A; van Hemert, Albert M; Beekman, Aartjan T F; Penninx, Brenda W J H

2017-12-12

Major depressive disorder (MDD) is often handled as an episodic and isolated disorder, resulting in an optimistic view about its prognosis. Herein, we test the idea that the prognosis of MDD changes if we vary the perspective in terms of (1) a longer time frame and (2) a broader diagnostic conceptualisation including dysthymia, (hypo)mania and anxiety disorders as relevant outcomes. Patients with current MDD at baseline (n = 903) and available 2-, 4-, and/or 6-year follow-up assessments were selected from the Netherlands Study of Depression and Anxiety, a psychiatric cohort study. Combining psychiatric DSM-IV-based diagnoses and life-chart data, patient course trajectories were classified as (1) recovered (no diagnoses at 2-year follow-up or thereafter), (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic since baseline. A chronic episode was defined as having a current diagnosis at the follow-up assessment and consistent symptoms over 2 years. Proportions of course trajectories were provided moving from a short, narrow perspective (2-year follow-up, considering only MDD diagnosis) to a long, broad perspective (6-year follow-up, including MDD, dysthymia, (hypo)mania and anxiety diagnoses). With the short, narrow perspective, the recovery rate was 58% and 21% had a chronic episode. However, in the long, broad perspective the recovery rate was reduced to 17%, while 55% of the patients experienced chronic episodes. Results from a long and rigorous follow-up in a large cohort suggests that most MDD patients have an unfavourable prognosis. Longer follow-up and broader diagnostic conceptualisation show that the majority of patients have a disabling and chronic disorder. Conceptualising and handling MDD as a narrowly defined and episodic disorder may underestimate the prognosis of the majority of depressed patients and, consequently, the type of care that is appropriate.

Generalized anxiety and major depressive disorders, their comorbidity and hypertension in middle-aged men.

PubMed

Carroll, Douglas; Phillips, Anna C; Gale, Catharine R; Batty, G David

2010-01-01

To examine the cross-sectional associations between generalized anxiety disorder (GAD) and major depressive disorder (MDD), their comorbidity, and hypertension. Participants (n = 4180) were drawn from a cohort of men who were members of the U.S. army during the Vietnam war era. Occupational, sociodemographic, and health data were collected from military service files, telephone interviews, and medical examinations. Hypertension status was defined by the presence of one of the following: self-reports at interview of either a physician-diagnosis or taking antihypertensive medication; or an average systolic blood pressure > or = 140 mm Hg or an average diastolic blood pressure > or = 90 mm Hg at the medical examination. One-year prevalence of GAD and MDD was determined, using Diagnostic and Statistical Manual of Mental Disorders, Third Edition criteria. In separate regression models adjusting for age and then additionally for place of service, ethnicity, marital status, alcohol consumption, smoking, body mass index, household income, and education grade, both GAD and MDD were related positively to hypertension. In age-adjusted and fully adjusted models comparing comorbid GAD/MDD, GAD alone, MDD alone, and neither condition, comorbidity showed the strongest relationship with hypertension. Depression has been the main focus for research on mental health and physical health outcomes. The present results suggest that future research should pay equal attention to GAD and, in particular, the comorbidity of GAD and MDD.

Serum proteomic profiling of major depressive disorder

PubMed Central

Bot, M; Chan, M K; Jansen, R; Lamers, F; Vogelzangs, N; Steiner, J; Leweke, F M; Rothermundt, M; Cooper, J; Bahn, S; Penninx, B W J H

2015-01-01

Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P<0.05), whereas 10 partly overlapping markers differed significantly between rMDD cases and controls. Antidepressant medication use and comorbid anxiety status did not substantially impact on these findings. Sixteen of the cMDD-related markers had been assayed in the pooled validation cohorts, of which seven were associated with MDD. The analytes prominently associated with cMDD related to diverse cell communication and signal transduction processes (pancreatic polypeptide, macrophage migration inhibitory factor, ENRAGE, interleukin-1 receptor antagonist and tenascin-C), immune response (growth-regulated alpha protein) and protein metabolism (von Willebrand factor). Several proteins were implicated in depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology. PMID:26171980

Personality disorders and perceived stress in Major Depressive Disorder

PubMed Central

Candrian, Michele; Schwartz, Faye; Farabaugh, Amy; Perlis, Roy H.; Ehlert, Ulrike; Fava, Maurizio

2008-01-01

The investigation of comorbidity between major depressive disorder (MDD) and personality disorders (PDs) has attracted considerable interest. Whereas some studies found that the presence of PDs has adverse effects on the course and treatment of MDD, others have failed to demonstrate this link. These inconsistent findings suggest that specific PD comorbidity might affect the course of MDD by modulating factors that increase the overall risk of depression, including an elevated tendency to perceive stress. To investigate whether the presence of a specific PD cluster was associated with elevated levels of stress appraisal, we administered the Perceived Stress Scale (PSS) before and after treatment to 227 MDD outpatients enrolled in an 8-week open-label treatment with fluoxetine. Following treatment, multiple linear regression analyses revealed that the presence of Cluster A, but not Cluster B or C, was associated with higher levels of perceived stress, even after adjusting for baseline depression severity and PSS scores, as well as various sociodemographic variables. The presence of Cluster A PD comorbidity was uniquely associated with elevated stress appraisal after antidepressant treatment, raising the possibility that stress exacerbation might be an important factor linked to poor treatment outcome in MDD subjects with Cluster A pathology. PMID:18573540

Post-traumatic stress disorder among adolescents with bipolar disorder and its relationship to suicidality.

PubMed

Dilsaver, Steven C; Benazzi, Franco; Akiskal, Hagop S; Akiskal, Kareen K

2007-09-01

The aims of this cross-sectional pilot study were to ascertain the rates of post-traumatic stress disorder (PTSD) among adolescents with bipolar disorder (BPD) and major depressive disorder (MDD) relative to a comparison group comprised of non-affectively ill patients, and to determine whether PTSD is related to suicidal ideation and attempts. The impetus for the study was born of clinical impressions derived in the course of routine clinical practice. Patients were screened by a single interviewer for BPD, MDD and PTSD, panic disorder, obsessive-compulsive disorder (OCD) and social phobia using the apposite modules from the Structured Clinical Interview for DSM-IV (SCID) and histories of suicidal ideation and attempts. The data were subjected to analysis using a logistic regression model. The database included 34 patients with BPD, 79 with MDD and 26 with a non-affective disorder. The risk for PTSD for a patient with BPD significantly exceeded that for a patient with MDD [odds ratio (OR) = 4.9, 95% confidence interval (CI) = 1.9-12.2, p = 0.001]. Patients with PTSD had an insignificantly increased risk for suicidal ideation (OR = 2.8, 95% CI = 0.9-8.9, p = 0.069), and a 4.5-fold significantly increased risk of having had a suicide attempt (OR = 4.5, 95% CI = 1.7-11.7, p = 0.002). The relationship between PTSD and suicide attempts remained significant even after controlling for the confounding effects of concurrent panic disorder, OCD and social phobia (OR = 3.4, 95% CI = 1.1-10.0, p = 0.023). Patients with BPD have a greater risk for PTSD than those with MDD. Post-traumatic stress disorder is significantly related to history of suicide attempts.

Repetitive transcranial magnetic stimulation for treatment of major depressive disorder with comorbid generalized anxiety disorder.

PubMed

White, Daniela; Tavakoli, Sason

2015-08-01

Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating individuals with behavioral disorders such as major depressive disorder (MDD), posttraumatic stress disorder, obsessive-compulsive disorder, and social anxiety disorder. A number of applications of rTMS to different regions of the left and right prefrontal cortex have been used to treat these disorders, but no study of treatment for MDD with generalized anxiety disorder (GAD) has been conducted with application of rTMS to both the left and right prefrontal cortex. We hypothesized that applying low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC) before applying it to the left DLPFC for the treatment of depression would be anxiolytic in patients with MDD with GAD. Thirteen adult patients with comorbid MDD and GAD received treatment with rTMS in an outpatient setting. The number of treatments ranged from 24 to 36 over 5 to 6 weeks. Response was defined as a ≥ 50% reduction in symptoms from baseline, and remission was defined as a score of < 5 for anxiety symptoms on the 7-item Generalized Anxiety Disorder (GAD-7) scale and < 8 for depressive symptoms on the 21-item Hamilton Rating Scale for Depression (HAM-D-21). At the end of the treatment period, for the GAD-7 scale, 11 out of 13 (84.6%) patients' anxiety symptoms were in remission, achieving a score of < 5 on the GAD-7, and 10 out of 13 patients (76.9%) achieved a HAM-D-21 score of < 8 for depressive symptoms. In this small pilot study of 13 patients with comorbid MDD and GAD, significant improvement in anxiety symptoms along with depressive symptoms was achieved in a majority of patients after bilateral rTMS application.

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.

Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials.

PubMed

Thase, Michael E; Edwards, John; Durgam, Suresh; Chen, Changzheng; Chang, Cheng-Tao; Mathews, Maju; Gommoll, Carl P

2017-09-01

Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1-5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment.

Circuit to Construct Mapping: A Mathematical Tool for Assisting the Diagnosis and Treatment in Major Depressive Disorder

PubMed Central

Bielczyk, Natalia Z.; Buitelaar, Jan K.; Glennon, Jeffrey C.; Tiesinga, Paul H. E.

2015-01-01

Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of “constructs” as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning – cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD. PMID:25767450

Novel Variants in ZNF34 and Other Brain-Expressed Transcription Factors are Shared Among Early-Onset MDD Relatives

PubMed Central

Subaran, Ryan L.; Odgerel, Zagaa; Swaminathan, Rajeswari; Glatt, Charles E.; Weissman, Myrna M.

2018-01-01

There are no known genetic variants with large effects on susceptibility to major depressive disorder (MDD). Although one proposed study approach is to increase sensitivity by increasing sample sizes, another is to focus on families with multiple affected individuals to identify genes with rare or novel variants with strong effects. Choosing the family-based approach, we performed whole-exome analysis on affected individuals (n = 12) across five MDD families, each with at least five affected individuals, early onset, and prepubertal diagnoses. We identified 67 genes where novel deleterious variants were shared among affected relatives. Gene ontology analysis shows that of these 67 genes, 18 encode transcriptional regulators, eight of which are expressed in the human brain, including four KRAB-A box-containing Zn2+ finger repressors. One of these, ZNF34, has been reported as being associated with bipolar disorder and as differentially expressed in bipolar disorder patients compared to healthy controls. We found a novel variant—encoding a non-conservative P17R substitution in the conserved repressor domain of ZNF34 protein—segregating completely with MDD in all available individuals in the family in which it was discovered. Further analysis showed a common ZNF34 coding indel segregating with MDD in a separate family, possibly indicating the presence of an unobserved, linked, rare variant in that particular family. Our results indicate that genes encoding transcription factors expressed in the brain might be an important group of MDD candidate genes and that rare variants in ZNF34 might contribute to susceptibility to MDD and perhaps other affective disorders. PMID:26823146

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

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.

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

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

PubMed Central

Jiang, Jing; Zhao, You-Jin; Hu, Xin-Yu; Du, Ming-Ying; Chen, Zi-Qi; Wu, Min; Li, Kai-Ming; Zhu, Hong-Yan; Kumar, Poornima; Gong, Qi-Yong

2017-01-01

Background Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. Methods We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Results Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. Limitations The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. Conclusion By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD. PMID:27780031

Decreased interhemispheric resting-state functional connectivity in first-episode, drug-naive major depressive disorder.

PubMed

Guo, Wenbin; Liu, Feng; Dai, Yi; Jiang, Muliang; Zhang, Jian; Yu, Liuyu; Long, Liling; Chen, Huafu; Gao, Qing; Xiao, Changqing

2013-03-05

Major depressive disorder (MDD) is shown to have structural and functional abnormalities in specific brain areas and connections by recent neuroimaging studies. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in patients with MDD. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in patients with MDD at rest. Twenty-four first-episode, drug-naive patients with MDD and 24 age-, gender-, and education-matched healthy subjects underwent a resting-state functional magnetic resonance imaging (fMRI). An automated VMHC approach was used to analyze the data. Patients with MDD showed lower VMHC than healthy subjects in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex/precuneus (PCC/PCu), two core regions within default mode network (DMN). Both left and right MPFC showed reduced FC with the other frontal areas and with right anterior cingulate gyrus (ACC), while PCC/PCu exhibited abnormal FC with the frontal areas and thalamus in patient group. Significant positive correlation was observed between VMHC in MPFC and persistent error response of Wisconsin Card Sorting Test (WCST-Pre) in patients. Further ROC analysis revealed that VMHC in the MPFC and PCC/PCu could be used to differentiate the patients from healthy subjects with relatively high sensitivity and specificity. Our results suggest that decreased VMHC in brain regions within DMN may underlie the pathogenesis of MDD. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder.

PubMed

Chen, Zi-Qi; Du, Ming-Ying; Zhao, You-Jin; Huang, Xiao-Qi; Li, Jing; Lui, Su; Hu, Jun-Mei; Sun, Huai-Qiang; Liu, Jia; Kemp, Graham J; Gong, Qi-Yong

2015-11-01

Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.

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

Cognitive Behavioral Therapy Is Associated With Enhanced Cognitive Control Network Activity in Major Depression and Posttraumatic Stress Disorder

PubMed Central

Yang, Zhen; Oathes, Desmond J.; Linn, Kristin A.; Bruce, Steven E.; Satterthwaite, Theodore D.; Cook, Philip A.; Satchell, Emma K.; Shou, Haochang; Sheline, Yvette I.

2018-01-01

BACKGROUND Both major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are characterized by depressive symptoms, abnormalities in brain regions important for cognitive control, and response to cognitive behavioral therapy (CBT). However, whether a common neural mechanism underlies CBT response across diagnoses is unknown. METHODS Brain activity during a cognitive control task was measured using functional magnetic resonance imaging in 104 participants: 28 patients with MDD, 53 patients with PTSD, and 23 healthy control subjects; depression and anxiety symptoms were determined on the same day. A patient subset (n = 31) entered manualized CBT and, along with controls (n = 19), was rescanned at 12 weeks. Linear mixed effects models assessed the relationship between depression and anxiety symptoms and brain activity before and after CBT. RESULTS At baseline, activation of the left dorsolateral prefrontal cortex was negatively correlated with Montgomery–Åsberg Depression Rating Scale scores across all participants; this brain–symptom association did not differ between MDD and PTSD. Following CBT treatment of patients, regions within the cognitive control network, including ventrolateral prefrontal cortex and dorsolateral prefrontal cortex, showed a significant increase in activity. CONCLUSIONS Our results suggest that dimensional abnormalities in the activation of cognitive control regions were associated primarily with symptoms of depression (with or without controlling for anxious arousal). Furthermore, following treatment with CBT, activation of cognitive control regions was similarly increased in both MDD and PTSD. These results accord with the Research Domain Criteria conceptualization of mental disorders and implicate improved cognitive control activation as a transdiagnostic mechanism for CBT treatment outcome. PMID:29628063

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

Predictors of new-onset depressive disorders - Results from the longitudinal Finnish Health 2011 Study.

PubMed

Markkula, Niina; Marola, Niko; Nieminen, Tarja; Koskinen, Seppo; Saarni, Samuli I; Härkänen, Tommi; Suvisaari, Jaana

2017-01-15

Identifying risk factors for depression is important for understanding etiological mechanisms and targeting preventive efforts. No prior studies have compared risk factors of dysthymia and major depressive disorder (MDD) in a longitudinal setting. Predictors of new-onset MDD and dysthymia were examined in a longitudinal general population study (Health 2000 and 2011 Surveys, BRIF8901). 4057 persons free of depressive disorders at baseline were followed up for 11 years. DSM-IV MDD and dysthymia were diagnosed with the Composite International Diagnostic Interview. 126 persons (4.4%, 95%CI 3.6-5.2) were diagnosed with MDD or dysthymia at follow-up. Predictors of new-onset depressive disorders were younger age (adjusted OR 0.97, 95%CI 0.95-0.99 per year), female gender (aOR 1.46, 95%CI 1.01-2.12), multiple childhood adversities (aOR 1.76, 95%CI 1.10-2.83), low trust dimension of social capital (aOR 0.58, 95%CI 0.36-0.96 for high trust), baseline anxiety disorder (aOR 2.75, 95%CI 1.36-5.56), and baseline depressive symptoms (aOR 1.65, 95%CI 1.04-2.61 for moderate and aOR 2.49, 95%CI 1.20-5.17 for severe symptoms). Risk factors for MDD were younger age, female gender, anxiety disorder and depressive symptoms, whereas younger age, multiple childhood adversities, low trust, and having 1-2 somatic diseases predicted dysthymia. We only had one follow-up point at eleven years, and did not collect information on the subjects' health during the follow-up period. Persons with subclinical depressive symptoms, anxiety disorders, low trust, and multiple childhood adversities have a higher risk of depressive disorders. Predictors of MDD and dysthymia appear to differ. This information can be used to target preventive efforts and guide social policies. Copyright © 2016 Elsevier B.V. All rights reserved.

Self-stigma in borderline personality disorder – cross-sectional comparison with schizophrenia spectrum disorder, major depressive disorder, and anxiety disorders

PubMed Central

Grambal, Ales; Prasko, Jan; Kamaradova, Dana; Latalova, Klara; Holubova, Michaela; Marackova, Marketa; Ociskova, Marie; Slepecky, Milos

2016-01-01

Introduction Self-stigma arises from one’s acceptance of societal prejudices and is common in psychiatric patients. This investigation compares the self-stigma of a sample of patients with borderline personality disorder (BPD), schizophrenia spectrum disorder (SCH), major depressive disorder (MDD), bipolar affective disorder (BAD), and anxiety disorders (AD) and explores of the self-stigma with the subjective and objective measures of the severity of the disorder and demographic factors. Methods The total of 184 inpatients admitted to the psychotherapeutic department diagnosed with BPD, SCH, MDD, BAP, and AD were compared on the internalized stigma of mental illness (ISMI) scale. The ISMI-total score was correlated with the subjective and objective evaluation of the disorder severity (clinical global impression), and clinical and demographic factors. Results The self-stigma levels were statistically significantly different among the diagnostic groups (BPD 71.15±14.74; SCH 63.2±13.27; MDD 64.09±12.2; BAD 62.0±14.21; AD 57.62±15.85; one-way analysis of variance: F=8.698, df=183; P<0.005). However after applying the Bonferroni’s multiple comparison test, the only significant difference was between the BPD patients and the patients with AD (P<0.001). Stepwise regression analysis showed that the strongest factors connected with the higher level of self-stigma were being without partner, the number of hospitalization, and the severity of the disorder. Conclusion The BPD patients suffer from a higher level of self-stigma compared to patients with AD. In practice, it is necessary to address the reduction of self-stigma by using specific treatment strategies, such as cognitive therapy. PMID:27703362

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.

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

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.

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.

NIRS Study of the Effects of Computerized Brain Training Games for Cognitive Rehabilitation of Major Depressive Disorder Patients in Remission: A Pilot Study.

PubMed

Payzieva, Shaira; Maxmudova, D

2014-01-01

We used functional Near-Infrared Spectroscopy (fNIRS) to estimate brain activity in Major Depressive Disorder (MDD) patients (in remission), while they played a computerized brain training games for cognitive rehabilitation. MDD is characterized by marked deterioration in affect as well as significant impairment in cognitive function. It was found, that depressed patients showed long-lasting impaired cognitive performance on cognitive demanding tasks despite significant improvement in the depression symptoms. Previous studies have shown that video games can improve cognitive functions. But assessment was made only with cognitive tests. The main objective of this research was to study the effects of brain training games on cognitive functions of MDD patients in remission with objective instrumental NIRS method. Tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS) - Oxyprem (BORL, Zurich, Switzerland). Preliminary results are discussed.

Aversive Startle Potentiation and Fear Pathology: Mediating Role of Threat Sensitivity and Moderating Impact of Depression

PubMed Central

Yancey, James R.; Vaidyanathan, Uma; Patrick, Christopher J.

2015-01-01

Enhanced startle during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. PMID:25448265

Valence and agency influence striatal response to feedback in patients with major depressive disorder

PubMed Central

Späti, Jakub; Chumbley, Justin; Doerig, Nadja; Brakowski, Janis; Holtforth, Martin Grosse; Seifritz, Erich; Spinelli, Simona

2015-01-01

Background Reduced sensitivity to positive feedback is common in patients with major depressive disorder (MDD). However, findings regarding negative feedback are ambiguous, with both exaggerated and blunted responses being reported. The ventral striatum (VS) plays a major role in processing valenced feedback, and previous imaging studies have shown that the locus of controls (self agency v. external agency) over the outcome influences VS response to feedback. We investigated whether attributing the outcome to one’s own action or to an external agent influences feedback processing in patients with MDD. We hypothesized that depressed participants would be less sensitive to the feedback attribution reflected by an altered VS response to self-attributed gains and losses. Methods Using functional MRI and a motion prediction task, we investigated the neural responses to self-attributed (SA) and externally attributed (EA) monetary gains and losses in unmedicated patients with MDD and healthy controls. Results We included 21 patients and 25 controls in our study. Consistent with our prediction, healthy controls showed a VS response influenced by feedback valence and attribution, whereas in depressed patients striatal activity was modulated by valence but was insensitive to attribution. This attribution insensitivity led to an altered ventral putamen response for SA – EA losses in patients with MDD compared with healthy controls. Limitations Depressed patients with comorbid anxiety disorder were included. Conclusion These results suggest an altered assignment of motivational salience to SA losses in patients with MDD. Altered striatal response to SA negative events may reinforce the belief of not being in control of negative outcomes contributing to a cycle of learned helplessness. PMID:26107160

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

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.

Decreased prefrontal Myo-inositol in major depressive disorder.

PubMed

Coupland, Nick J; Ogilvie, Catherine J; Hegadoren, Kathleen M; Seres, Peter; Hanstock, Chris C; Allen, Peter S

2005-06-15

Postmortem studies have shown robust prefrontal cortex glial losses and more subtle neuronal changes in major depressive disorder (MDD). Earlier proton magnetic resonance spectroscopy (1H-MRS) studies of the glial marker myo-inositol in MDD were subject to potential confounds. The primary hypothesis of this study was that MDD patients would show reduced prefrontal/anterior cingulate cortex levels of myo-inositol. Thirteen nonmedicated moderate-severe MDD patients and 13 matched control subjects were studied (six male, seven female per group). Proton magnetic resonance spectroscopy stimulated echo acquisition mode spectra (3.0 T; echo time=168 msec; mixing time=28 msec; repetition time=3000 msec) were obtained from prefrontal/anterior cingulate cortex. Metabolite data were adjusted for tissue composition. Patients with MDD showed significantly lower myo-inositol/creatine ratios (.94+/-.23) than control subjects (1.32+/-.37) [F(1,23)=6.9; p=.016]. These data suggest a reduction of myo-inositol in prefrontal/anterior cingulate cortex in MDD, which could be a consequence of glial loss or altered glial metabolism. Additional in vivo studies of glial markers could add to the understanding of the pathophysiology of MDD.

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

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.

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.

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.

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.

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.

Prevalence and Predictors of Major Depressive Disorder for Fertility Treatment Patients and their Partners

PubMed Central

Holley, Sarah R.; Pasch, Lauri A.; Bleil, Maria E.; Gregorich, Steven; Katz, Patricia K.; Adler, Nancy E.

2015-01-01

Structured Abstract Objective To examine the prevalence and predictors of major depressive disorder (MDD) for women and their partners during the course of fertility treatment. Design Prospective cohort study over an 18-month period. Participants completed interviews and questionnaires at baseline and at 4, 10, and 18 months follow-up. Setting Five community and academic fertility practices. Patients 174 women and 144 of their male partners who did not have a successful child-related outcome during the timeframe of the study. Interventions No interventions administered. Main Outcome Measures MDD was assessed using the Composite International Diagnostic Interview (CIDI) Major Depression module, a structured diagnostic interview. Additional variables were assessed with self-report questionnaire measures. Results 39.1% of the women and 15.3% of the men met the criteria for MDD during the 18-month course of the study. A binary logistic covariate-adjusted model including showed that, for both women and men, past MDD was a significant predictor of MDD during treatment. Past MDD further predicted significant risk for MDD during treatment after controlling for other well-established risk factors (i.e., baseline levels of depression, anxiety, and partner support). Conclusions MDD was highly prevalent for fertility treatment patients and their partners. Past MDD predicted risk for MDD during treatment, and it contributed to MDD risk over and above other commonly-assessed risk factors. This suggests patients and their partners would benefit from being routinely assessed for a history of MDD prior to the start of treatment in order to best direct psychosocial support and interventions to those most in need. PMID:25796319

Mood disorders. Effective management of major depressive disorder in the geriatric patient.

PubMed

Evers, Martin M; Marin, Deborah B

2002-10-01

Major depressive disorder (MDD), commonly called depression, is characterized by a collection of psychologic, somatic, physical, behavioral, and cognitive symptoms that interfere with or prevent the execution of normal daily responsibilities and activities (e.g., work, exercise, hobbies, intellectual pursuits). Older persons with MDD are likely to present with weight loss and suicidal ideation or a preoccupation with death. Also common is irritability, anxiety, a change in functional ability, or some combination of these. Pharmacotherapy is an effective intervention for management of MDD symptoms. It can be used in combination with psychotherapy, or as monotherapy in patients who do not respond to psychotherapy and other nondrug interventions.

Autistic-Like Traits in Adult Patients with Mood Disorders and Schizophrenia

PubMed Central

Matsuo, Junko; Kamio, Yoko; Takahashi, Hidetoshi; Ota, Miho; Teraishi, Toshiya; Hori, Hiroaki; Nagashima, Anna; Takei, Reiko; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

2015-01-01

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed. PMID:25838109

Autistic-like traits in adult patients with mood disorders and schizophrenia.

PubMed

Matsuo, Junko; Kamio, Yoko; Takahashi, Hidetoshi; Ota, Miho; Teraishi, Toshiya; Hori, Hiroaki; Nagashima, Anna; Takei, Reiko; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

2015-01-01

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed.

Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies.

PubMed

Schür, Remmelt R; Draisma, Luc W R; Wijnen, Jannie P; Boks, Marco P; Koevoets, Martijn G J C; Joëls, Marian; Klomp, Dennis W; Kahn, René S; Vinkers, Christiaan H

2016-09-01

The inhibitory gamma-aminobutyric acid (GABA) system is involved in the etiology of most psychiatric disorders, including schizophrenia, autism spectrum disorder (ASD) and major depressive disorder (MDD). It is therefore not surprising that proton magnetic resonance spectroscopy ((1) H-MRS) is increasingly used to investigate in vivo brain GABA levels. However, integration of the evidence for altered in vivo GABA levels across psychiatric disorders is lacking. We therefore systematically searched the clinical (1) H-MRS literature and performed a meta-analysis. A total of 40 studies (N = 1,591) in seven different psychiatric disorders were included in the meta-analysis: MDD (N = 437), schizophrenia (N = 517), ASD (N = 150), bipolar disorder (N = 129), panic disorder (N = 81), posttraumatic stress disorder (PTSD) (N = 104), and attention deficit/hyperactivity disorder (ADHD) (N = 173). Brain GABA levels were lower in ASD (standardized mean difference [SMD] = -0.74, P = 0.001) and in depressed MDD patients (SMD = -0.52, P = 0.005), but not in remitted MDD patients (SMD = -0.24, P = 0.310) compared with controls. In schizophrenia this finding did not reach statistical significance (SMD = -0.23, P = 0.089). No significant differences in GABA levels were found in bipolar disorder, panic disorder, PTSD, and ADHD compared with controls. In conclusion, this meta-analysis provided evidence for lower brain GABA levels in ASD and in depressed (but not remitted) MDD patients compared with healthy controls. Findings in schizophrenia were more equivocal. Even though future (1) H-MRS studies could greatly benefit from a longitudinal design and consensus on the preferred analytical approach, it is apparent that (1) H-MRS studies have great potential in advancing our understanding of the role of the GABA system in the pathogenesis of psychiatric disorders. Hum Brain Mapp 37:3337-3352, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Testing a machine-learning algorithm to predict the persistence and severity of major depressive disorder from baseline self-reports.

PubMed

Kessler, R C; van Loo, H M; Wardenaar, K J; Bossarte, R M; Brenner, L A; Cai, T; Ebert, D D; Hwang, I; Li, J; de Jonge, P; Nierenberg, A A; Petukhova, M V; Rosellini, A J; Sampson, N A; Schoevers, R A; Wilcox, M A; Zaslavsky, A M

2016-10-01

Heterogeneity of major depressive disorder (MDD) illness course complicates clinical decision-making. Although efforts to use symptom profiles or biomarkers to develop clinically useful prognostic subtypes have had limited success, a recent report showed that machine-learning (ML) models developed from self-reports about incident episode characteristics and comorbidities among respondents with lifetime MDD in the World Health Organization World Mental Health (WMH) Surveys predicted MDD persistence, chronicity and severity with good accuracy. We report results of model validation in an independent prospective national household sample of 1056 respondents with lifetime MDD at baseline. The WMH ML models were applied to these baseline data to generate predicted outcome scores that were compared with observed scores assessed 10-12 years after baseline. ML model prediction accuracy was also compared with that of conventional logistic regression models. Area under the receiver operating characteristic curve based on ML (0.63 for high chronicity and 0.71-0.76 for the other prospective outcomes) was consistently higher than for the logistic models (0.62-0.70) despite the latter models including more predictors. A total of 34.6-38.1% of respondents with subsequent high persistence chronicity and 40.8-55.8% with the severity indicators were in the top 20% of the baseline ML-predicted risk distribution, while only 0.9% of respondents with subsequent hospitalizations and 1.5% with suicide attempts were in the lowest 20% of the ML-predicted risk distribution. These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models.

Testing a machine-learning algorithm to predict the persistence and severity of major depressive disorder from baseline self-reports

PubMed Central

Kessler, Ronald C.; van Loo, Hanna M.; Wardenaar, Klaas J.; Bossarte, Robert M.; Brenner, Lisa A.; Cai, Tianxi; Ebert, David Daniel; Hwang, Irving; Li, Junlong; de Jonge, Peter; Nierenberg, Andrew A.; Petukhova, Maria V.; Rosellini, Anthony J.; Sampson, Nancy A.; Schoevers, Robert A.; Wilcox, Marsha A.; Zaslavsky, Alan M.

2015-01-01

Heterogeneity of major depressive disorder (MDD) illness course complicates clinical decision-making. While efforts to use symptom profiles or biomarkers to develop clinically useful prognostic subtypes have had limited success, a recent report showed that machine learning (ML) models developed from self-reports about incident episode characteristics and comorbidities among respondents with lifetime MDD in the World Health Organization World Mental Health (WMH) Surveys predicted MDD persistence, chronicity, and severity with good accuracy. We report results of model validation in an independent prospective national household sample of 1,056 respondents with lifetime MDD at baseline. The WMH ML models were applied to these baseline data to generate predicted outcome scores that were compared to observed scores assessed 10–12 years after baseline. ML model prediction accuracy was also compared to that of conventional logistic regression models. Area under the receiver operating characteristic curve (AUC) based on ML (.63 for high chronicity and .71–.76 for the other prospective outcomes) was consistently higher than for the logistic models (.62–.70) despite the latter models including more predictors. 34.6–38.1% of respondents with subsequent high persistence-chronicity and 40.8–55.8% with the severity indicators were in the top 20% of the baseline ML predicted risk distribution, while only 0.9% of respondents with subsequent hospitalizations and 1.5% with suicide attempts were in the lowest 20% of the ML predicted risk distribution. These results confirm that clinically useful MDD risk stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models. PMID:26728563

Dementia and Cognitive Impairment Among U.S. Veterans With a History of MDD or PTSD: A Retrospective Cohort Study Based on Sex and Race.

PubMed

Bhattarai, Jagriti Jackie; Oehlert, Mary E; Multon, Karen D; Sumerall, Scott W

2018-06-01

The aim of this study was to examine major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) diagnosed at age < 55 as predictors, and sex and race as potential moderators, of dementia and other forms of cognitive impairment. Veterans ( N = 4,800) aged ⩾ 56 years were grouped by psychiatric history, sex, and race. Hierarchical and stepwise regression were employed to determine significant predictors. MDD and PTSD were associated with almost double the risk for developing dementia or cognitive impairment at age ⩾ 56. Sex, as a moderator, had small effects whereas race increased the risk almost twofold for Black veterans, given the presence of MDD history. MDD and PTSD act as significant risk factors for dementia and other forms of cognitive impairment, and Black veterans, given a history of MDD, may be at an increased risk. An important endeavor for future research is to examine how this risk may vary across dementia subtypes and related conditions.

Changes in heart rate variability during TOVA testing in patients with major depressive disorder.

PubMed

Shen, Tsu-Wang; Liu, Fang-Chih; Chen, Shaw-Ji; Chen, Shao-Tsu

2013-01-01

The aim of this study was to identify major depressive disorder (MDD) based on heart rate variability (HRV) during tests of variables of attention (TOVA). Forty-five MDD patients without cardiovascular disease and 45 controls matched by age and gender participated in this study. Compared to the controls, the MDD group had lower resting HRV parameters, more omissions and variability and longer response times on TOVA, and failure of attention employment to decrease HRV. The resting HRV parameters may provide easily measured, clinically useful ways to identify patients with MDD and to monitor their progress in treatment. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Treat the brain and treat the periphery: toward a holistic approach to major depressive disorder.

PubMed

Zheng, Xiao; Zhang, Xueli; Wang, Guangji; Hao, Haiping

2015-05-01

The limited medication for major depressive disorder (MDD) against an ever-rising disease burden presents an urgent need for therapeutic innovations. During recent years, studies looking at the systems regulation of mental health and disease have shown a remarkably powerful control of MDD by systemic signals. Meanwhile, the identification of a host of targets outside the brain opens the way to treat MDD by targeting systemic signals. We examine these emerging findings and consider the implications for current thinking regarding MDD pathogenesis and treatment. We highlight the opportunities and challenges of a periphery-targeting strategy and propose its incorporation into a holistic approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

Grandparents, parents, and grandchildren at high risk for depression: a three-generation study.

PubMed

Warner, V; Weissman, M M; Mufson, L; Wickramaratne, P J

1999-03-01

High-risk studies of psychiatric disorders in parents and offspring that include 3 generations are uncommon. Multigenerational studies can be clinically useful as they can provide information for risk prediction from one generation to another for the development of empirically based interventions. Using a high-risk design, this study examines the association of grandparent major depressive disorder (MDD) and parent MDD with psychopathology in grandchildren. Using Cox proportional hazards in a sample of 90 grandchildren at high and low risk for depression by virtue of their grandparents' and parents' depression status, the authors examined the risk for offspring depression and anxiety. Grandparent and parent MDD were associated with grandchild anxiety (relative risk [RR] = 5.51 and R = 3.09, respectively). Grandchildren with both a depressed parent and grandparent had the highest risk for anxiety. Parental MDD is associated with an increased risk for grandchild disruptive disorder (RR = 10.77). Forty-nine percent of the grandchildren in families in which both the parent and grandparent were depressed had some form of psychopathology. The grandchildren from those families were the most impaired. Prepubertal-onset anxiety disorder is a risk factor for the later development of clinically significant recurrent MDD across several generations of families at high risk for depression. Parental impaired functioning increases the risk for disruptive disorders. Children in families with multiple generations of depression are at particularly high risk for some form of psychopathology.

Extended family and friendship support networks are both protective and risk factors for major depressive disorder and depressive symptoms among African-Americans and black Caribbeans.

PubMed

Taylor, Robert Joseph; Chae, David H; Lincoln, Karen D; Chatters, Linda M

2015-02-01

This study explores relationships between lifetime and 12-month Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) major depressive disorder (MDD), depressive symptoms, and involvement with family and friends within a national sample of African-American and Black Caribbean adults (n = 5191). MDD was assessed using the DSM-IV World Mental Health Composite International Diagnostic Interview and depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression subscale and the K6. Findings indicated that among both populations, close supportive ties with family members and friends are associated with lower rates of depression and MDD. For African-Americans, closeness to family members was important for both 12-month and lifetime MDD, and both family and friend closeness were important for depressive symptoms. For Caribbean Blacks, family closeness had more limited associations with outcomes and was directly associated with psychological distress only. Negative interactions with family (conflict, criticisms), however, were associated with higher MDD and depressive symptoms among both African-Americans and Black Caribbeans.

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.

Imaging Phenotypes of Major Depressive Disorder: Genetic Correlates

PubMed Central

Savitz, Jonathan B; Drevets, Wayne C

2009-01-01

Imaging techniques are a potentially powerful method of identifying phenotypes that are associated with, or are indicative of a vulnerability to developing major depressive disorder (MDD). Here we identify seven promising MDD-associated traits identified by magnetic resonance imaging (MRI) or positron emission tomography (PET). We evaluate whether these traits are state-independent, heritable endophenotypes, or state-dependent phenotypes that may be useful markers of treatment efficacy. In MDD, increased activity of the amygdala in response to negative stimuli appears to be a mood-congruent phenomenon, and is likely moderated by the serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR). Hippocampal volume loss is characteristic of elderly or chronically-ill samples and may be impacted by the val66met brain-derived neurotrophic factor (BDNF) gene variant and the 5-HTTLPR SLC6A4 polymorphism. White matter pathology is salient in elderly MDD cohorts but is associated with cerebrovascular disease, and is unlikely to be a useful marker of a latent MDD diathesis. Increased blood flow or metabolism of the subgenual anterior cingulate cortex (sgACC), together with gray matter volume loss in this region, is a well-replicated finding in MDD. An attenuation of the usual pattern of fronto-limbic connectivity, particularly a decreased temporal correlation in amygdala-anterior cingulate cortex (ACC) activity, is another MDD-associated trait. Concerning neuroreceptor PET imaging, decreased 5-HT1A binding potential in the raphe, medial temporal lobe, and medial prefrontal cortex (mPFC) has been strongly associated with MDD, and may be impacted by a functional single nucleotide polymorphism in the promoter region of the 5-HT1A gene (HTR1A: –1019C/G; rs6295). Potentially indicative of inter-study variation in MDD etiology or mood state, both increased and decreased binding potential of the serotonin transporter has been reported. Challenges facing the field include the problem of phenotypic and etiological heterogeneity, technological limitations, the confounding effects of medication, and non-disease related inter-individual variation in brain morphology and function. Further advances are likely as epigenetic, copy-number variant, gene-gene interaction, and genome-wide association (GWA) approaches are brought to bear on imaging data. PMID:19358877

Ratio of mBDNF to proBDNF for Differential Diagnosis of Major Depressive Disorder and Bipolar Depression.

PubMed

Zhao, Guoqing; Zhang, Chen; Chen, Jun; Su, Yousong; Zhou, Rubai; Wang, Fan; Xia, Weiping; Huang, Jia; Wang, Zuowei; Hu, Yingyan; Cao, Lan; Guo, Xiaoyun; Yuan, Chengmei; Wang, Yong; Yi, Zhenghui; Lu, Weihong; Wu, Yan; Wu, Zhiguo; Hong, Wu; Peng, Daihui; Fang, Yiru

2017-09-01

There is a high rate of misdiagnosis between major depressive disorder (MDD) and bipolar disorder (BD) in clinical practice. Our previous work provided suggestive evidence for brain-derived neurotrophic factor (BDNF) in differentiating BD from MDD. In this study, we aimed to investigate the role of mature BDNF (mBDNF) and its precursor (proBDNF) in distinguishing bipolar depression (BP) from MDD during acute depressive episode. A total of 105 participants, including 44 healthy controls, 37 MDD patients and 24 BP patients, were recruited. Enzyme-linked immunosorbent assay kits were applied to measure plasma mBDNF levels and proBDNF levels of all participants. Plasma mBDNF levels were significantly decreased in BP group than those in MDD group (P = 0.001) and healthy controls (P = 0.002). Significantly higher ratio of mBDNF to proBDNF (M/P) at baseline was showed in MDD group than those in BP group as well as in healthy controls (P = 0.000 and P = 0.000, respectively). The optimal model for discriminating BP was the M/P ratio (area under the ROC curve = 0.858, 95 % CI 0.753-0.963). Furthermore, the M/P ratio was restored to normal levels after antidepressants treatment in MDD group. In summary, our data demonstrated that both plasma mBDNF levels and M/P ratio were lower in BP compared with MDD. These findings further support M/P ratio as a potential differential diagnostic biomarker for BP among patients in depressive episodes.

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.

An in-depth look into PTSD-depression comorbidity: A longitudinal study of chronically-exposed Detroit residents.

PubMed

Horesh, Danny; Lowe, Sarah R; Galea, Sandro; Aiello, Allison E; Uddin, Monica; Koenen, Karestan C

2017-01-15

Although PTSD-major depressive disorder (MDD) co-morbidity is well-established, the vast majority of studies have examined comorbidity at the level of PTSD total severity, rather than at the level of specific PTSD symptom clusters. This study aimed to examine the long-term associations between MDD and PTSD symptom clusters (intrusion, avoidance, hyperarousal), and the moderating role of gender in these associations. 942 residents of urban Detroit neighborhoods were interviewed at 3 waves, 1 year apart. At each wave, they were assessed for PTSD, depression, trauma exposure, and stressful life events. At all waves, hyperarousal was the PTSD cluster most strongly correlated with MDD. For the full sample, a reciprocal relationship was found between MDD and all three PTSD clusters across time. Interestingly, the relative strength of associations between MDD and specific PTSD clusters changed over time. Women showed the same bidirectional MDD-PTSD pattern as in the entire sample, while men sometimes showed non-significant associations between early MDD and subsequent PTSD clusters. First, our analyses are based on DSM-IV criteria, as this was the existing edition at the time of this study. Second, although this is a longitudinal study, inferences regarding temporal precedence of one disorder over another must be made with caution. Early identification of either PTSD or MDD following trauma may be crucial in order to prevent the development of the other disorder over time. The PTSD cluster of hyper-arousal may require special therapeutic attention. Also, professionals are encouraged to develop more gender-specific interventions post-trauma. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Major depressive disorder with anger attacks and cardiovascular risk factors.

PubMed

Fraguas, Renerio; Iosifescu, Dan V; Bankier, Bettina; Perlis, Roy; Clementi-Craven, Nicoletta; Alpert, Jonathan; Fava, Maurizio

2007-01-01

Depression and anger have been separately associated with cardiovascular risk factors. We investigated if major depressive disorder (MDD) with concomitant anger attacks was associated with cardiovascular risk factors. We measured total serum cholesterol, glycemia, resting blood pressure, and smoking parameters in 333 (52.9% women) MDD nonpsychotic outpatients, mean age of 39.4 years. MDD was diagnosed with the Structured Clinical Interview (SCID) in accordance with the Diagnostic and Statistic Manual of Mental Disorders, Third Edition, Revised (DSM-III-R). The presence of anger attacks was established with the Massachusetts General Hospital Anger Attacks Questionnaire. In a logistic regression analysis, anger attacks were independently associated with cholesterol levels > or = 200 mg/dL (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.18-3.94) and years of smoking > 11 (OR, 2.59; 95% CI, 1.32-5.04). MDD with anger attacks was significantly associated with increased cholesterol levels and years of smoking.

A morphometric, immunohistochemical, and in situ hybridization study of the dorsal raphe nucleus in major depression, bipolar disorder, schizophrenia, and suicide.

PubMed

Matthews, Paul R; Harrison, Paul J

2012-03-01

Several lines of evidence implicate 5-hydroxytryptamine (5-HT, serotonin) in the pathophysiology of mood disorders and suicide. However, it is unclear whether these conditions include morphological involvement of the dorsal raphe nucleus (DRN), the origin of most forebrain 5-HT innervation. We used morphometric, immunohistochemical, and molecular methods to compare the DRN in post-mortem tissue of 50 subjects (13 controls, 14 major depressive disorder [MDD], 13 bipolar disorder, 10 schizophrenia; 17 of the cases died by suicide). NeuN and PH8 antibodies were used to assess all neurons and serotonergic neurons respectively; 5-HT(1A) autoreceptor expression was investigated by regional and cellular in situ hybridization. Measurements were made at three rostrocaudal levels of the DRN. In MDD, the area of the DRN was decreased. In bipolar disorder, serotonergic neuronal size was decreased. Suicide was associated with an increased DRN area, and with a higher density but decreased size of serotonergic neurons. Total neuronal density and 5-HT(1A) receptor mRNA abundance were unaffected by diagnosis or suicide. No changes were seen in schizophrenia. The results show that mood disorders and suicide are associated with differential, limited morphological alterations of the DRN. The contrasting influences of MDD and suicide may explain some of the discrepancies between previous studies, since their design precluded detection of the effect. Copyright © 2011 Elsevier B.V. All rights reserved.

Korean Medication Algorithm for Depressive Disorders 2017: Third Revision

PubMed Central

Seo, Jeong Seok; Wang, Hee Ryung; Woo, Young Sup; Park, Young-Min; Jeong, Jong-Hyun; Kim, Won; Shim, Se-Hoon; Lee, Jung Goo; Jon, Duk-In

2018-01-01

Objective In 2002, the Korean Society for Affective Disorders developed the guidelines for the treatment of major depressive disorder (MDD), and revised it in 2006 and 2012. The third revision of these guidelines was undertaken to reflect advances in the field. Methods Using a 44-item questionnaire, an expert consensus was obtained on pharmacological treatment strategies for MDD 1) without or 2) with psychotic features, 3) depression subtypes, 4) maintenance, 5) special populations, 6) the choice of an antidepressant (AD) regarding safety and adverse effects, and 7) non-pharmacological biological therapies. Recommended first, second, and third-line strategies were derived statistically. Results AD monotherapy is recommended as the first-line strategy for non-psychotic depression in adults, children/adolescents, elderly adults, patient with persistent depressive disorder, and pregnant women or patients with postpartum depression or premenstrual dysphoric disorder. The combination of AD and atypical antipsychotics (AAP) was recommended for psychotic depression in adult, child/adolescent, postpartum depression, and mixed features or anxious distress. Most experts recommended stopping the ongoing initial AD and AAP after a certain period in patients with one or two depressive episodes. As an MDD treatment modality, 92% of experts are considering electroconvulsive therapy and 46.8% are applying it clinically, while 86% of experts are considering repetitive transcranial magnetic stimulation but only 31.6% are applying it clinically. Conclusion The pharmacological treatment strategy in 2017 is similar to that of Korean Medication Algorithm for Depressive Disorder 2012. The preference of AAPs was more increased. PMID:29397669

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.

Cortisol stress reactivity across psychiatric disorders: A systematic review and meta-analysis.

PubMed

Zorn, Jelle V; Schür, Remmelt R; Boks, Marco P; Kahn, René S; Joëls, Marian; Vinkers, Christiaan H

2017-03-01

The hypothalamus-pituitary-adrenal (HPA) axis and its end product cortisol are essential for an adequate response to stress. Considering the role of stress as a risk factor for psychiatric disorders, it is not surprising that cortisol stress reactivity has frequently been investigated in patients versus healthy individuals. However, the large heterogeneity in measures of the cortisol stress response has hampered a systematic evaluation of the evidence. We here report of a systematic literature review and meta-analysis on cortisol reactivity to psychosocial stress across psychiatric disorders. Original data from authors were obtained to construct standardized cortisol outcomes (the areas under the curve with respect to increase (AUCi) and ground (AUCg)) and to examine the influence of sex and symptomatic state on cortisol stress reactivity. Fourteen studies on major depressive disorder (MDD) (n=1129), 9 on anxiety disorders (n=732, including social anxiety disorder (SAD), posttraumatic stress disorder, panic disorder and mixed samples of anxiety disorders) and 4 on schizophrenia (n=180) were included that used the Trier Social Stress Test or an equivalent psychosocial stress task. Sex-dependent changes in stress reactivity were apparent in MDD and anxiety disorders. Specifically, women with current MDD or an anxiety disorder exhibited a blunted cortisol stress response, whereas men with current MDD or SAD showed an increased cortisol response to psychosocial stress. In individuals with remitted MDD, altered cortisol stress reactivity was less pronounced in women and absent in men. For schizophrenia, cortisol stress reactivity was blunted in both men and women, but the number of studies was limited and showed evidence for publication bias. These findings illustrate that sharing individual data to disentangle the effects of sex, symptom levels and other factors is essential for further understanding of the alterations in cortisol stress reactivity across psychiatric disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Automaticity in Anxiety Disorders and Major Depressive Disorder

PubMed Central

Teachman, Bethany A.; Joormann, Jutta; Steinman, Shari; Gotlib, Ian H.

2012-01-01

In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is not sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation. PMID:22858684

T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder

PubMed Central

Patas, Kostas; Willing, Anne; Demiralay, Cüneyt; Engler, Jan Broder; Lupu, Andreea; Ramien, Caren; Schäfer, Tobias; Gach, Christian; Stumm, Laura; Chan, Kenneth; Vignali, Marissa; Arck, Petra C.; Friese, Manuel A.; Pless, Ole; Wiedemann, Klaus; Agorastos, Agorastos; Gold, Stefan M.

2018-01-01

While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross-sectional case–control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities (n = 20), who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject (n = 20). T cell phenotype and repertoire were interrogated using a combination of flow cytometry, gene expression analysis, and next generation sequencing. T cells from MDD patients showed significantly lower surface expression of the chemokine receptors CXCR3 and CCR6, which are known to be central to T cell differentiation and trafficking. In addition, we observed a shift within the CD4+ T cell compartment characterized by a higher frequency of CD4+CD25highCD127low/− cells and higher FOXP3 mRNA expression in purified CD4+ T cells obtained from patients with MDD. Finally, flow cytometry-based TCR Vβ repertoire analysis indicated a less diverse CD4+ T cell repertoire in MDD, which was corroborated by next generation sequencing of the TCR β chain CDR3 region. Overall, these results suggest that T cell phenotype and TCR utilization are skewed on several levels in patients with MDD. Our study identifies putative cellular and molecular signatures of dysregulated adaptive immunity and reinforces the notion that T cells are a pathophysiologically relevant cell population in this disorder. PMID:29515587

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association.

PubMed

Goldstein, Benjamin I; Carnethon, Mercedes R; Matthews, Karen A; McIntyre, Roger S; Miller, Gregory E; Raghuveer, Geetha; Stoney, Catherine M; Wasiak, Hank; McCrindle, Brian W

2015-09-08

In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications. © 2015 American Heart Association, Inc.

Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials

PubMed Central

Edwards, John; Durgam, Suresh; Chen, Changzheng; Chang, Cheng-Tao; Mathews, Maju; Gommoll, Carl P.

2017-01-01

Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1–5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment. PMID:28538024

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.

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.

A longitudinal study of posttraumatic stress disorder, depression, and generalized anxiety disorder in Israeli civilians exposed to war trauma.

PubMed

Neria, Yuval; Besser, Avi; Kiper, Dasha; Westphal, Maren

2010-06-01

This 3-wave longitudinal study examined the mental health consequences of the Israel-Gaza 2008-2009 war among young Israeli civilians. Data on posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD), and their predictors were collected during the war, and 2 and 4 months after cease fire. Results showed a sharp decline in symptom levels of PTSD, MDD, and GAD over time. Perceived social support during the war moderated the effects of immediate emotional response on subsequent levels of PTSD, MDD, and GAD. These findings underscore the importance of social support and immediate emotional response to trauma in predicting trauma-related psychopathology, and highlight the potential need for providing early care to exposed individuals exhibiting immediate and severe emotional responses.

Quality of life in treatment-seeking patients with obsessive-compulsive disorder with and without major depressive disorder.

PubMed

Cassin, Stephanie E; Richter, Margaret A; Zhang, K Anne; Rector, Neil A

2009-07-01

To compare the quality of life of patients with obsessive-compulsive disorder (OCD) with and without depression comorbidity. Treatment-seeking outpatients (n = 56) with OCD (n = 28) or comorbid OCD and major depressive disorder (MDD) (n = 28), matched by age, sex, and antidepressant medication use, completed a multidimensional measure of quality of life. Patients with comorbid OCD and MDD reported significantly greater decrements in their subjective feelings, social relations, and a composite measure of general activities (for example, overall well-being and life satisfaction) in comparison with patients with OCD without MDD. These differences were not owing to the presence of other Axis I comorbid disorders. Treatments addressing depression comorbidity in the context of primary OCD are required to improve the quality of life of this severely affected population of OCD sufferers.

Abnormal screening for gestational diabetes, maternal mood disorder, and preterm birth

PubMed Central

Sit, Dorothy; Luther, James; Dills, Jesse; Eng, Heather; Wisniewski, Stephen; Wisner, Katherine L

2013-01-01

Objective Gestational diabetes (GDM) affects 7% of pregnant mothers and those with GDM have increased rates of perinatal complications. Major depressive disorder (MDD) and its pharmacologic treatments are associated with obesity and adverse pregnancy outcomes. In this prospective study, we investigated the relationship between abnormal GDM screens, maternal mood disorders, and adverse outcomes. Methods We examined mothers with MDD, bipolar disorder (BD), and healthy controls (HC) at 20, 30, and 36 weeks gestation and delivery. We obtained demographic data and pre-pregnancy body mass index (BMI), and confirmed diagnoses with the Structured Clinical Interview for DSM-IV. We evaluated smoking, alcohol, substance use, and medication treatments with the Longitudinal Interval Follow-up Evaluation interview. Mothers received the one-hour 50 g glucose challenge test (GCT) at 26–28 weeks gestation. Outcome variables were preterm birth, birth weight (BW) and peripartum events. Results We enrolled 62 HC, 50 BD, 41 past MDD, and 39 current MDD mother–infant pairs. Mean GCT levels and the frequency of abnormal GCT (> 140 mg/dL) did not differ across groups. Rates of smoking (χ2 = 20.68, df = 3, p < 0.001), substance use (χ2 = 21.76, df = 3, p < 0.001), and pre-pregnancy obesity [BMI ≥ 30 (χ2 = 9.97, df = 3, p = 0.019)] differed significantly across groups. Mothers with BD received medications associated with weight gain significantly more often than others [13/45 (29%), p < 0.001). After adjusting for group differences, GCT levels were associated significantly with increased odds for preterm birth (odds ratio = 1.29, 95% confidence interval: 1.0–1.7; p = 0.05) and increased perinatal events (beta = 0.11, p = 0.04) but not associated with BW. Conclusions In mothers with or without mood disorders, having increased GCT levels contributes to a higher likelihood for adverse pregnancy outcomes. Mothers with BD or current MDD can have additional risks for adverse outcomes and may benefit from early referral for high-risk services and supportive management in pregnancy. PMID:24164892

The NEO Five-Factor Inventory: latent structure and relationships with dimensions of anxiety and depressive disorders in a large clinical sample.

PubMed

Rosellini, Anthony J; Brown, Timothy A

2011-03-01

The present study evaluated the latent structure of the NEO Five-Factor Inventory (NEO FFI) and relations between the five-factor model (FFM) of personality and dimensions of DSM-IV anxiety and depressive disorders (panic disorder, generalized anxiety disorder [GAD], obsessive-compulsive disorder, social phobia [SOC], major depressive disorder [MDD]) in a large sample of outpatients (N = 1,980). Exploratory structural equation modeling (ESEM) was used to show that a five-factor solution provided acceptable model fit, albeit with some poorly functioning items. Neuroticism demonstrated significant positive associations with all but one of the disorder constructs whereas Extraversion was inversely related to SOC and MDD. Conscientiousness was inversely related to MDD but demonstrated a positive relationship with GAD. Results are discussed in regard to potential revisions to the NEO FFI, the evaluation of other NEO instruments using ESEM, and clinical implications of structural paths between FFM domains and specific emotional disorders.

The NEO Five-Factor Inventory: Latent Structure and Relationships With Dimensions of Anxiety and Depressive Disorders in a Large Clinical Sample

PubMed Central

Rosellini, Anthony J.; Brown, Timothy A.

2017-01-01

The present study evaluated the latent structure of the NEO Five-Factor Inventory (NEO FFI) and relations between the five-factor model (FFM) of personality and dimensions of DSM-IV anxiety and depressive disorders (panic disorder, generalized anxiety disorder [GAD], obsessive–compulsive disorder, social phobia [SOC], major depressive disorder [MDD]) in a large sample of outpatients (N = 1,980). Exploratory structural equation modeling (ESEM) was used to show that a five-factor solution provided acceptable model fit, albeit with some poorly functioning items. Neuroticism demonstrated significant positive associations with all but one of the disorder constructs whereas Extraversion was inversely related to SOC and MDD. Conscientiousness was inversely related to MDD but demonstrated a positive relationship with GAD. Results are discussed in regard to potential revisions to the NEO FFI, the evaluation of other NEO instruments using ESEM, and clinical implications of structural paths between FFM domains and specific emotional disorders. PMID:20881102

The effect of comorbid major depressive disorder or bipolar disorder on cognitive behavioral therapy for social anxiety disorder.

PubMed

Fracalanza, Katie; McCabe, Randi E; Taylor, Valerie H; Antony, Martin M

2014-06-01

Major depressive disorder (MDD) and bipolar disorder (BD) commonly co-occur in individuals with social anxiety disorder (SAD), yet whether these comorbidities influence the outcomes of cognitive behavioral therapy (CBT) for SAD is unclear. The present study examined the degree to which individuals with SAD and comorbid MDD (SAD+MDD; n=76), comorbid BD (SAD+BD; n=19), a comorbid anxiety disorder (SAD+ANX; n=27), or no comorbid diagnoses (SAD+NCO; n=41) benefitted from CBT for SAD. Individuals were screened using the Structured Clinical Interview for DSM-IV and then completed the Social Phobia Inventory and the Depression Anxiety Stress Scales before and after 12-weeks of group CBT for SAD. At pretreatment the SAD+MDD and SAD+BD groups reported higher social anxiety symptoms than the SAD+ANX and SAD+NCO groups. All groups reported large and significant improvement in social anxiety with CBT. However, at posttreatment the SAD+MDD and SAD+BD groups continued to have higher social anxiety symptoms than the SAD+NCO group, and the SAD+ANX group did not differ in social anxiety symptoms from any group. The sample also showed small and statistically significant improvement in depressive symptoms with CBT for SAD. Information about medication was not collected in the present study, and we did not assess the long-term effects of CBT. Our results suggest that CBT for SAD is an effective treatment even in the presence of comorbid mood disorders in the short-term, although extending the course of treatment may be helpful for this population and should be investigated in future research. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Major depressive disorder, antidepressant use, and subsequent 2-year weight change patterns in the Netherlands Study of Depression and Anxiety.

PubMed

Gibson-Smith, Deborah; Bot, Mariska; Milaneschi, Yuri; Twisk, Jos W; Visser, Marjolein; Brouwer, Ingeborg A; Penninx, Brenda W J H

2016-02-01

Although depression and obesity are bidirectionally associated, little is known about weight changes following major depressive disorder (MDD). This study compared 2-year weight changes between patients with current MDD (cMDD), patients with remitted MDD (rMDD), and healthy controls. Additionally, we examined the relationship between antidepressant medication use and 2-year weight change. Data from 2,542 adults aged 18-65 y were sourced from the Netherlands Study of Depression and Anxiety. Data were collected at baseline and after 2, 4, and 6 years (September 2004-April 2013). Depression status (DSM-IV criteria for MDD) was established with the Composite International Diagnostic Interview. Subsequent 2-year weight changes were categorized as weight loss (> 5% loss), weight stable (within 5% weight loss or gain), and weight gain (> 5% gain). The association of depression status with subsequent weight change, with weight stable as reference category, was studied by combining all repeated measurements in a mixed multinomial logistical regression model. cMDD, but not rMDD, was significantly associated with both weight gain and weight loss over a 2-year period after adjustment for covariates (odds ratio [OR] = 1.67; 95% confidence interval [CI], 1.37-2.03; P < .001; and OR = 1.27; 95% CI 1.01-1.61; P = .045, respectively). Antidepressant use was associated with weight gain (SSRIs: OR = 1.26; 95% CI, 1.05-1.52; other antidepressants: OR = 1.36; 95% CI, 1.00-1.84; P < .05 for both), but not after considering depression status. Compared to cMDD patients who lost weight, those who gained weight had lower initial weight, were younger, had more comorbid anxiety disorders, and reported poorer quality of mood and reduced appetite as depressive symptoms. Compared to controls, cMDD participants have greater odds of either gaining or losing weight over a 2-year period, regardless of antidepressant use. © Copyright 2015 Physicians Postgraduate Press, Inc.

Effects of dopamine and glutamate on synaptic plasticity: a computational modeling approach for drug abuse as comorbidity in mood disorders.

PubMed

Qi, Z; Kikuchi, S; Tretter, F; Voit, E O

2011-05-01

Major depressive disorder (MDD) affects about 16% of the general population and is a leading cause of death in the United States and around the world. Aggravating the situation is the fact that "drug use disorders" are highly comorbid in MDD patients, and VICE VERSA. Drug use and MDD share a common component, the dopamine system, which is critical in many motivation and reward processes, as well as in the regulation of stress responses in MDD. A potentiating mechanism in drug use disorders appears to be synaptic plasticity, which is regulated by dopamine transmission. In this article, we describe a computational model of the synaptic plasticity of GABAergic medium spiny neurons in the nucleus accumbens, which is critical in the reward system. The model accounts for effects of both dopamine and glutamate transmission. Model simulations show that GABAergic medium spiny neurons tend to respond to dopamine stimuli with synaptic potentiation and to glutamate signals with synaptic depression. Concurrent dopamine and glutamate signals cause various types of synaptic plasticity, depending on input scenarios. Interestingly, the model shows that a single 0.5 mg/kg dose of amphetamine can cause synaptic potentiation for over 2 h, a phenomenon that makes synaptic plasticity of medium spiny neurons behave quasi as a bistable system. The model also identifies mechanisms that could potentially be critical to correcting modifications of synaptic plasticity caused by drugs in MDD patients. An example is the feedback loop between protein kinase A, phosphodiesterase, and the second messenger cAMP in the postsynapse. Since reward mechanisms activated by psychostimulants could be crucial in establishing addiction comorbidity in patients with MDD, this model might become an aid for identifying and targeting specific modules within the reward system and lead to a better understanding and potential treatment of comorbid drug use disorders in MDD. © Georg Thieme Verlag KG Stuttgart · New York.

Functional Neurosurgery in the Treatment of Severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician

PubMed Central

Shah, Dhwani B.; Pesiridou, Angeliki; Baltuch, Gordon H.; Malone, Donald A.; O’Reardon, John P.

2008-01-01

Over the past 20 years, there has been a concerted effort to expand our understanding of the neural circuitry involved in the pathogenesis of psychiatric disorders. Distinct neuronal circuits and networks have been implicated in obsessive compulsive disorder (OCD) and major depressive disorder (MDD) involving feedback loops between the cortex, striatum, and thalamus. When neurosurgery is used as a therapeutic tool in severe OCD and MDD, the goal is to modulate specific targets or nodes within these networks in an effort to produce symptom relief. Currently, four lesioning neurosurgical procedures are utilized for treatment refractory OCD and MDD: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. Deep brain stimulation (DBS) is a novel neurosurgical approach that has some distinct advantages over lesioning procedures. With DBS, the desired clinical effect can be achieved by reversible, high frequency stimulation in a nucleus or at a node in the circuit without the need to produce an irreversible lesion. Recent trials of deep brain stimulation in both OCD and MDD at several neuroanatomical targets have reported promising early results in highly refractory patients and with a good safety profile. Future definitive trials in MDD and OCD are envisaged. PMID:19727257

Effect of adolescent substance use and antisocial behavior on the development of early adulthood depression.

PubMed

Choi, Tai Kiu; Worley, Matthew J; Trim, Ryan S; Howard, David; Brown, Sandra A; Hopfer, Christian J; Hewitt, John K; Wall, Tamara L

2016-04-30

Major depressive disorder (MDD) is a prevalent and frequently comorbid psychiatric disorder. This study evaluates the development of depressive symptoms, MDD diagnosis, and suicidal ideation in a high-risk sample (N=524) diagnosed with conduct disorder (CD) and substance use disorder (SUD) symptoms as youth and re-assessed approximately 6.5 years later. Dual trajectory classes of both alcohol and other drug use (AOD) and antisocial behavior (ASB), previously identified using latent class growth analyses (LCGA), were used to predict depression outcomes. The Dual Chronic, Increasing AOD/Persistent ASB, and Decreasing Drugs/Persistent ASB classes had higher past-week depression scores, more past-year MDD symptoms, and were more likely to have past-year MDD than the Resolved class. The Dual Chronic and Decreasing Drugs/Persistent ASB classes also had more past-year MDD symptoms than the Persistent AOD/Adolescent ASB class. Youth at highest risk for developing or maintaining depression in adulthood had the common characteristic of persistent antisocial behavior. This suggests young adulthood depression is associated more with persistent antisocial behavior than with persistent substance use in comorbid youth. As such, interventions targeting high-risk youth, particularly those with persistent antisocial behavior, are needed to help reduce the risk of severe psychosocial consequences (including risk for suicide) in adulthood. Published by Elsevier Ireland Ltd.

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.

A machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD).

PubMed

Mumtaz, Wajid; Ali, Syed Saad Azhar; Yasin, Mohd Azhar Mohd; Malik, Aamir Saeed

2018-02-01

Major depressive disorder (MDD), a debilitating mental illness, could cause functional disabilities and could become a social problem. An accurate and early diagnosis for depression could become challenging. This paper proposed a machine learning framework involving EEG-derived synchronization likelihood (SL) features as input data for automatic diagnosis of MDD. It was hypothesized that EEG-based SL features could discriminate MDD patients and healthy controls with an acceptable accuracy better than measures such as interhemispheric coherence and mutual information. In this work, classification models such as support vector machine (SVM), logistic regression (LR) and Naïve Bayesian (NB) were employed to model relationship between the EEG features and the study groups (MDD patient and healthy controls) and ultimately achieved discrimination of study participants. The results indicated that the classification rates were better than chance. More specifically, the study resulted into SVM classification accuracy = 98%, sensitivity = 99.9%, specificity = 95% and f-measure = 0.97; LR classification accuracy = 91.7%, sensitivity = 86.66%, specificity = 96.6% and f-measure = 0.90; NB classification accuracy = 93.6%, sensitivity = 100%, specificity = 87.9% and f-measure = 0.95. In conclusion, SL could be a promising method for diagnosing depression. The findings could be generalized to develop a robust CAD-based tool that may help for clinical purposes.

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

Regional homogeneity associated with overgeneral autobiographical memory of first-episode treatment-naive patients with major depressive disorder in the orbitofrontal cortex: A resting-state fMRI study.

PubMed

Liu, Yansong; Zhao, Xudong; Cheng, Zaohuo; Zhang, Fuquan; Chang, Jun; Wang, Haosen; Xie, Rukui; Wang, Zhiqiang; Cao, Leiming; Wang, Guoqiang

2017-02-01

Overgeneral autobiographical memory (OGM) is involved in the onset and maintenance of depression. Recent studies have shown correlations between OGM and alterations of some brain regions by using task-state functional magnetic resonance imaging (fMRI). However, the correlation between OGM and spontaneous brain activity in depression remains unclear. The purpose of this study was to determine whether patients with major depressive disorder (MDD) show abnormal regional homogeneity (ReHo) and, if so, whether the brain areas with abnormal ReHo are associated with OGM. Twenty five patients with MDD and 25 age-matched, sex-matched, and education-matched healthy controls underwent resting-state fMRI. All participants were also assessed by 17-item Hamilton Depression Rating Scale and autobiographical memory test. The ReHo method was used to analyze regional synchronization of spontaneous neuronal activity. Patients with MDD, compared to healthy controls, exhibited extensive ReHo abnormalities in some brain regions, including the frontal, temporal, and occipital cortex. Moreover, ReHo value of the orbitofrontal cortex was negatively correlated with OGM scores in patients with MDD. The sample size of this study was relatively small, and the influence of physiological noise was not completely excluded. These results suggest that abnormal ReHo of spontaneous brain activity in the orbitofrontal cortex may be involved in the pathophysiology of OGM in patients with MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased anterior default-mode network homogeneity in first-episode, drug-naive major depressive disorder: A replication study.

PubMed

Guo, Wenbin; Cui, Xilong; Liu, Feng; Chen, Jindong; Xie, Guangrong; Wu, Renrong; Zhang, Zhikun; Chen, Huafu; Zhao, Jingping

2018-01-01

Abnormal default-mode network (DMN) homogeneity has been involved in the neurophysiology of major depressive disorder (MDD) with inconsistent findings. The inconsistency may be due to clinical and methodological variability, and the reproducibility of the findings is limited. The present study aimed to examine alterations of the DMN homogeneity in two independent samples of patients with first-episode, drug-naive MDD. The samples included 59 patients with MDD and 31 comparison subjects from Sample 1 and 29 patients with MDD and 24 comparison subjects from Sample 2. Network homogeneity (NH) was computed with an overlapping technique, which was employed to define brain regions with abnormal NH common to the MDD samples. Compared with comparison subjects, patients with MDD exhibited increased NH in an overlapped brain region of the left superior medial prefrontal cortex (MPFC). No correlations were found between abnormal NH and HAMD total/subscale scores in the patients of each sample and in the combined patients from both samples. This study is the first to examine alterations of DMN homogeneity in first-episode, drug-naive patients with MDD in two independent samples by using an overlapping technique. Patients with MDD exhibit increased NH in an overlapped region in the anterior DMN. The present study thus highlights the importance of the DMN in the neurophysiology of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Utility of self-reported sleep disturbances as a marker for major depressive disorder (MDD): Findings from the World Mental Health Japan Survey 2002–2006

PubMed Central

Kawakami, Norito

2013-01-01

Although major depressive disorder (MDD) is a serious common disease, many depressive patients attend primary care complaining sleep disturbances and remain undiagnosed. The purpose of this study was to investigate the utility of self-reported sleep disturbances as a marker for MDD. This study investigated the association between 12-month prevalence of self-reported sleep disturbances and MDD using data from a cross-sectional survey in Japan. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiver operating characteristic curve (AUC) of self-reported sleep disturbances as a marker for MDD were 58.9%, 73.4%, 6.9%, 98.1%, and 0.66, respectively. Self-reported sleep disturbances showed highest utility for the youngest group. Among four types of sleep disturbances, problem of daytime sleepiness was most useful as a marker for MDD. Combined with at least moderate role impairment, self-reported sleep disturbances became more informative with higher specificity (99.6%) and PPV (80.0%) as a marker for MDD. Self-reported sleep disturbances cannot be a marker for MDD in isolation. Comorbid role impairment increases probability of MDD. Clinicians should be cautious about young people who have sleep disturbances. Daytime sleepiness should be included in the question asking about sleep disturbances. PMID:22377572

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.

Discrimination, arrest history, and major depressive disorder in the U.S. Black population.

PubMed

Anglin, Deidre M; Lighty, Quenesha; Yang, Lawrence H; Greenspoon, Michelle; Miles, Rashun J; Slonim, Tzachi; Isaac, Kathleen; Brown, Monique J

2014-09-30

Everyday discrimination contributes negatively to depressive symptomatology among Blacks in the US and being arrested could add to this depression. Using data from the National Survey on American Life, the present study determined the association between an arrest history and major depressive disorder (MDD), while accounting for discrimination among African Americans, US-born Afro-Caribbeans and first-generation Black immigrants. Findings from logistic regression analyses adjusted for discrimination suggested an arrest history is associated with 12-month MDD (Adjusted OR=1.47; 95% CI=1.02-2.10) and lifetime MDD (Adjusted OR=1.56 CI=1.17-2.09). Accounting for drug and alcohol dependence attenuated the association between arrest history and 12-month MDD, but not lifetime MDD. The associations between arrest history and both 12-month and lifetime MDD, and discrimination and lifetime MDD varied by ethnic/immigrant group. Specifically, while the association between arrest history and MDD (both 12-month and lifetime) was strongest among US-born Afro-Caribbeans, evidence consistent with the immigrant paradox, the association between discrimination and lifetime MDD was particularly relevant for first-generation Black immigrants, suggesting discrimination may hinder the protection of first-generation status. Mental health prevention and treatment programs should target the stress associated with being arrested and experiencing discrimination among US Blacks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Meta-analysis indicates that SNP rs9939609 within FTO is not associated with major depressive disorder (MDD) in Asian population.

PubMed

Yao, Yao; Wen, Yueqiang; Du, Tingfu; Sun, Ning; Deng, Hong; Ryan, Joanne; Rao, Shuquan

2016-03-15

Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with heritability of up to 38%. The fat mass- and obesity-associated (FTO) gene, in particular the single nucleotide polymorphism (SNP) rs9939609, has been identified as a genetic risk loci associated with MDD. However, most prior studies have involved European and American populations. Whether rs9939609 is an true risk SNP for MDD in Asian populations remains inconclusive. In the present study, we conducted a meta-analysis of the association between rs9939609 and MDD in Asian populations by combining 5 available case-control samples totaling 6531 cases and 12,359 controls. Our meta-analysis suggests that rs9939609 is not a risk SNP for MDD in Asian populations by fixed effect model (Z=1.04, P=0.30, OR=0.96, 95% CI=0.90-1.03). The age distribution and gender ratios were not matched well in the combined samples of cases and controls. Publication bias might be also considered with only a relatively small number of association studies of FTO rs9939609 with MDD in Asian populations. The absence of association of rs9939609 with MDD in our Asian populations suggests a potential genetic heterogeneity in the susceptibility of MDD on this locus. Copyright © 2015 Elsevier B.V. All rights reserved.

Regulatory T Cells As Supporters of Psychoimmune Resilience: Toward Immunotherapy of Major Depressive Disorder

PubMed Central

Ellul, Pierre; Mariotti-Ferrandiz, Encarnita; Leboyer, Marion; Klatzmann, David

2018-01-01

There is growing evidence that inflammation plays a role in major depressive disorder (MDD). As the main role of regulatory T cells (Tregs) is to control inflammation, this might denote a Treg insufficiency in MDD. However, neither a qualitative nor a quantitative defect of Tregs has been ascertained and no causality direction between inflammation and depression has been established. Here, after reviewing the evidence supporting a relation between Treg insufficiency and MDD, we conclude that a novel therapeutic approach based on Treg stimulation could be valuable in at least the subset of patients with inflammatory MDD. Low-dose interleukin-2 appears to be a good candidate as it is not only a safe stimulator of Tregs in humans but also an inhibitor of pro-inflammatory Th17 lymphocytes. Here, we discuss that a thorough immune investigation as well as immunotherapy will be heuristic for deciphering the pathophysiology of MDD. PMID:29615964

Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update

PubMed Central

Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Jun, Tae-Youn; Patkar, Ashwin A; Masand, Prakash S

2016-01-01

Less than one third of patients who suffer from major depressive disorder (MDD) report remission following antidepressant treatments requiring more diverse treatment approaches. Augmentation of second generation antipsychotics (SGAs) has been increasingly recognized as an important treatment option. The authors have previously provided a comprehensive review of SGAs for the treatment of MDD in 2013. Since then, numerous additional clinical trials have been conducted to investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new SGA, brexpiprazole, was recently approved by the Food and Drug Administration in July 2015 for the treatment of MDD as an augmentation agent to antidepressants. Thus, the aim of this study was to provide a concise update of all the available SGAs for the treatment of MDD, in particular on the additional clinical trials which have been published since 2013. PMID:27689026

Adapting Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression

ERIC Educational Resources Information Center

Eisendrath, Stuart; Chartier, Maggie; McLane, Maura

2011-01-01

Major depressive disorder (MDD) is currently ranked the third leading cause of disability in the world. Treatment-resistant depression (TRD) causes the majority of MDD disability. Strikingly, 50% of individuals with MDD will fail to remit with 2 adequate trials of antidepressant medications, thus qualifying as treatment resistant. Current…

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.

Odour recognition memory and odour identification in patients with mild and severe major depressive disorders.

PubMed

Zucco, Gesualdo M; Bollini, Fabiola

2011-12-30

Olfactory deficits, in detection, recognition and identification of odorants have been documented in ageing and in several neurodegenerative and psychiatric conditions. However, olfactory abilities in Major Depressive Disorder (MDD) have been less investigated, and available studies have provided inconsistent results. The present study assessed odour recognition memory and odour identification in two groups of 12 mild MDD patients (M age 41.3, range 25-57) and 12 severe MDD patients (M age, 41.9, range 23-58) diagnosed according to DSM-IV criteria and matched for age and gender to 12 healthy normal controls. The suitability of olfactory identification and recognition memory tasks as predictors of the progression of MDD was also addressed. Data analyses revealed that Severe MDD patients performed significantly worse than Mild MDD patients and Normal controls on both tasks, with these last groups not differing significantly from one another. The present outcomes are consistent with previous studies in other domains which have shown reliable, although not conclusive, impairments in cognitive function, including memory, in patients with MDD, and highlight the role of olfactory identification and recognition tasks as an important additional tool to discriminate between patients characterised by different levels of severity of MDD. Copyright © 2011 Elsevier Ltd. All rights reserved.