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  1. Major depression

    MedlinePlus

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... Doctors do not know the exact causes of depression. It is believed that chemical changes in the ...

  2. The Latent Symptom Structure of the Beck Depression Inventory-II in Outpatients with Major Depression

    ERIC Educational Resources Information Center

    Quilty, Lena C.; Zhang, K. Anne; Bagby, R. Michael

    2010-01-01

    The Beck Depression Inventory-II (BDI-II) is a self-report instrument frequently used in clinical and research settings to assess depression severity. Although investigators have examined the factor structure of the BDI-II, a clear consensus on the best fitting model has not yet emerged, resulting in different recommendations regarding how to best…

  3. Major depression.

    PubMed

    Bentley, Susan M; Pagalilauan, Genevieve L; Simpson, Scott A

    2014-09-01

    Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co-morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered. PMID:25134869

  4. Major depression

    MedlinePlus

    ... is very severe, you may have hallucinations and delusions (false beliefs). This condition is called depression with ... This helps relieve your symptoms. If you have delusions or hallucinations, your provider may prescribe additional medicines. ...

  5. Do You Have Major Depression?

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Depression Do You Have Major Depression? Past Issues / Fall 2009 Table of Contents Simple ... member may have major depression. —NIMH Types of Depression Just like other illnesses, such as heart disease, ...

  6. Oxidative Stress and Major Depression

    PubMed Central

    Verma, Akhilesh Kumar; Srivastava, Mona; Srivastava, Ragini

    2014-01-01

    Background: Major causative factor for major depression is inflammation, autoimmune tissue damage and prolonged psychological stress, which leads to oxidative stress. The aim of this study was to know the association of free radicals and antioxidant status in subjects suffering from major depression. Materials and Methods: Sixty patients diagnosed as a case of unipolar depression as per DSM IV, fulfilling the inclusion and exclusion criteria were compared with 40 healthy age and sex matched controls. The sera of both the groups were collected taking aseptic precautions and were evaluated for the markers of oxidative stress and for the antioxidants. The age group of the sample and the controls was between 18-60 y, both males and females were equally represented in the groups. Results: A significantly high level of malondialdehyde (MDA) was found in the patients with major depression (1.95 ± 1.04 mmol/L) as compared to healthy controls (0.366 ± 0.175 mmol/L) (p < 0.0001). The serum level of nitrite was found to be lower in cases (23.18 ± 12.08 μmol/L) in comparison to controls (26.18 ± 8.68 μmol/L) (p = 0.1789). Similarly the serum level of ascorbic acid and superoxide dismutase (SOD) were significantly below as compared to healthy controls (all p < 0.0001). Ceruloplasmin levels were also depressed in cases (p = 0.3943). Conclusion: The study concluded that in the absence of known oxidative injury causative agents, the lowered levels of antioxidants and higher levels of MDA implicate the high degree of oxidative stress in unipolar depression. PMID:25653939

  7. Major Depression Can Be Prevented

    ERIC Educational Resources Information Center

    Munoz, Ricardo F.; Beardslee, William R.; Leykin, Yan

    2012-01-01

    The 2009 Institute of Medicine report on prevention of mental, emotional, and behavioral disorders (National Research Council & Institute of Medicine, 2009b) presented evidence that major depression can be prevented. In this article, we highlight the implications of the report for public policy and research. Randomized controlled trials have shown…

  8. Molecular signatures of major depression.

    PubMed

    Cai, Na; Chang, Simon; Li, Yihan; Li, Qibin; Hu, Jingchu; Liang, Jieqin; Song, Li; Kretzschmar, Warren; Gan, Xiangchao; Nicod, Jerome; Rivera, Margarita; Deng, Hong; Du, Bo; Li, Keqing; Sang, Wenhu; Gao, Jingfang; Gao, Shugui; Ha, Baowei; Ho, Hung-Yao; Hu, Chunmei; Hu, Jian; Hu, Zhenfei; Huang, Guoping; Jiang, Guoqing; Jiang, Tao; Jin, Wei; Li, Gongying; Li, Kan; Li, Yi; Li, Yingrui; Li, Youhui; Lin, Yu-Ting; Liu, Lanfen; Liu, Tiebang; Liu, Ying; Liu, Yuan; Lu, Yao; Lv, Luxian; Meng, Huaqing; Qian, Puyi; Sang, Hong; Shen, Jianhua; Shi, Jianguo; Sun, Jing; Tao, Ming; Wang, Gang; Wang, Guangbiao; Wang, Jian; Wang, Linmao; Wang, Xueyi; Wang, Xumei; Yang, Huanming; Yang, Lijun; Yin, Ye; Zhang, Jinbei; Zhang, Kerang; Sun, Ning; Zhang, Wei; Zhang, Xiuqing; Zhang, Zhen; Zhong, Hui; Breen, Gerome; Wang, Jun; Marchini, Jonathan; Chen, Yiping; Xu, Qi; Xu, Xun; Mott, Richard; Huang, Guo-Jen; Kendler, Kenneth; Flint, Jonathan

    2015-05-01

    Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual's somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 × 10(-14), odds ratio 0.85 [95% CI = 0.81-0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease. PMID:25913401

  9. Recurrence in Major Depression: A Conceptual Analysis

    ERIC Educational Resources Information Center

    Monroe, Scott M.; Harkness, Kate L.

    2011-01-01

    Theory and research on major depression have increasingly assumed a recurrent and chronic disease model. Yet not all people who become depressed suffer recurrences, suggesting that depression is also an acute, time-limited condition. However, few if any risk indicators are available to forecast which of the initially depressed will or will not…

  10. Do You Have Major Depression?

    MedlinePlus

    ... often with periods of normal mood in between. Postpartum depression can make new mothers feel restless, anxious, fatigued, ... themselves or their babies. Unlike the "baby blues," postpartum depression does not go away quickly. Researchers think that ...

  11. Major depression with psychotic features

    MedlinePlus

    ... loss of contact with reality. It usually includes: Delusions: False beliefs about what is taking place or ... things that aren't there The types of delusions and hallucinations are often related to your depressed ...

  12. Delayed mood transitions in major depressive disorder.

    PubMed

    Korf, Jakob

    2014-05-01

    The hypothesis defended here is that the process of mood-normalizing transitions fails in a significant proportion of patients suffering from major depressive disorder. Such a failure is largely unrelated to the psychological content. Evidence for the hypothesis is provided by the highly variable and unpredictable time-courses of the depressive episodes. The main supporting observations are: (1) mood transitions within minutes or days have been reported during deep brain stimulation, naps after sleep deprivation and bipolar mood disorders; (2) sleep deprivation, electroconvulsive treatment and experimental drugs (e.g., ketamine) may facilitate mood transitions in major depressive disorder within hours or a few days; (3) epidemiological and clinical studies show that the time-to-recovery from major depressive disorder can be described with decay models implying very short depressive episodes; (4) lack of relationship between the length of depression and recovery episodes in recurrent depression; (5) mood fluctuations predict later therapeutic success in major depressive disorder. We discuss some recent models aimed to describe random mood transitions. The observations together suggest that the mood transitions have a wide variety of apparently unrelated causes. We suggest that the mechanism of mood transition is compromised in major depressive disorder, which has to be recognized in diagnostic systems. PMID:24613736

  13. Examining Minor and Major Depression in Adolescents

    ERIC Educational Resources Information Center

    Gonzalez-Tejera, Gloria; Canino, Glorisa; Ramirez, Rafael; Chavez, Ligia; Shrout, Patrick; Bird, Hector; Bravo, Milagros; Martinez-Taboas, Alfonso; Ribera, Julio; Bauermeister, Jose

    2005-01-01

    Background: Research has shown that a large proportion of adolescents with symptoms of depression and substantial distress or impairment fail to meet the diagnostic criteria for a major depressive disorder (MDD). However, many of these undiagnosed adolescents may meet criteria for a residual category of the "Diagnostic and Statistical Manual of…

  14. Seasonal Variation of Depressive Symptoms in Unipolar Major Depressive Disorder

    PubMed Central

    Cobb, Bryan S.; Coryell, William H.; Cavanaugh, Joseph; Keller, Martin; Solomon, David A.; Endicott, Jean; Potash, James B.; Fiedorowicz, Jess G.

    2014-01-01

    Objectives Retrospective and cross-sectional studies of seasonal variation of depressive symptoms in unipolar major depression have yielded conflicting results. We examined seasonal variation of mood symptoms in a long-term prospective cohort – the Collaborative Depression Study (CDS). Methods The sample included 298 CDS participants from five academic centers with a prospectively derived diagnosis of unipolar major depression who were followed for at least ten years of annual or semi-annual assessments. Generalized linear mixed models were utilized to investigate the presence of seasonal patterns. In a subset of 271 participants followed for at least 20 years, the stability of a winter depressive pattern was assessed across the first two decades of follow-up. Results A small increase in proportion of time depressed was found in the months surrounding the winter solstice, although the greatest symptom burden was seen in December through April with a peak in March. The relative burden of winter depressive symptoms in the first decade demonstrated no relationship to that of the second decade. The onset of new episodes was highest October through January, peaking in January. Conclusions There exists a small but statistically significant peak in depressive symptoms from the month of the winter solstice to the month of the spring equinox. However, the predominance of winter depressive symptoms did not appear stable over the long-term course of illness. PMID:25176622

  15. Emerging from Depression: Treatment of Adolescent Depression Using the Major Treatment Models of Adult Depression.

    ERIC Educational Resources Information Center

    Long, Kathleen M.

    Noting that adolescents who commit suicide are often clinically depressed, this paper examines various approaches in the treatment of depression. Major treatment models of adult depression, which can be directly applied to the treatment of the depressed adolescent, are described. Major treatment models and selected research studies are reviewed in…

  16. Major depression with psychotic features

    MedlinePlus

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major ...

  17. Interpersonal psychotherapy (IPT) in major depressive disorder.

    PubMed

    Brakemeier, Eva-Lotta; Frase, Lukas

    2012-11-01

    In this article, we will introduce interpersonal psychotherapy as an effective short-term treatment strategy in major depression. In IPT, a reciprocal relationship between interpersonal problems and depressive symptoms is regarded as important in the onset and as a maintaining factor of depressive disorders. Therefore, interpersonal problems are the main therapeutic targets of this approach. Four interpersonal problem areas are defined, which include interpersonal role disputes, role transitions, complicated bereavement, and interpersonal deficits. Patients are helped to break the interactions between depressive symptoms and their individual interpersonal difficulties. The goals are to achieve a reduction in depressive symptoms and an improvement in interpersonal functioning through improved communication, expression of affect, and proactive engagement with the current interpersonal network. The efficacy of this focused and structured psychotherapy in the treatment of acute unipolar major depressive disorder is summarized. This article outlines the background of interpersonal psychotherapy, the process of therapy, efficacy, and the expansion of the evidence base to different subgroups of depressed patients. PMID:22955493

  18. [Cognition - the core of major depressive disorder].

    PubMed

    Polosan, M; Lemogne, C; Jardri, R; Fossati, P

    2016-02-01

    Cognitive deficits have been only recently recognized as a major phenotype determinant of major depressive disorder, although they are an integral part of the definition of the depressive state. Congruent evidence suggest that these cognitive deficits persist beyond the acute phase and may be identified at all ages. The aim of the current study was to review the main meta-analyses on cognition and depression, which encompasses a large range of cognitive domains. Therefore, we discuss the "cold" (attention, memory, executive functions) and "hot" (emotional bias) cognitive impairments in MDD, as well as those of social cognition domains (empathy, theory of mind). Several factors interfere with cognition in MDD such as clinical (melancholic, psychotic...) features, age, age of onset, illness severity, medication and comorbid condition. As still debated in the literature, the type of relationship between the severity of cognitive symptoms and functioning in depression is detailed, thus highlighting their predictive value of functional outcome, independently of the affective symptoms. A better identification of the cognitive deficits in MDD and a monitoring of the effects of different treatments require appropriate instruments, which may be developed by taking advantage of the increasing success of computing tools. Overall, current data suggest a core role for different cognitive deficits in MDD, therefore opening new perspectives for optimizing the treatment of depression. PMID:26879254

  19. Vortioxetine for the treatment of major depression.

    PubMed

    Dhir, A

    2013-12-01

    Vortioxetine (Lu-AA-21004; 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide) is a novel orally active molecule that is being investigated by Lundbeck and Takeda for the treatment of major depression and generalized anxiety disorders. Vortioxetine has a unique "multi-modal" mechanism of action. It inhibits the activity of serotonin transporters and is an agonist of serotonin 5-HT1A receptor, partial agonist of 5-HT1B and antagonist of 5-HT3A, 5-HT7 and 5-HT1D receptors. Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day. Vortioxetine reverses cognitive decline in patients with depression making it a unique molecule. The molecule lacks any serious side effects and drug-drug interactions. However, dose adjustments are required if vortioxetine is co-administered with rifampicin or bupropion. The molecule is under review by various regulatory agencies around the world for the treatment of major depression. PMID:24524096

  20. Feeling blue or turquoise? Emotional differentiation in major depressive disorder.

    PubMed

    Demiralp, Emre; Thompson, Renee J; Mata, Jutta; Jaeggi, Susanne M; Buschkuehl, Martin; Barrett, Lisa Feldman; Ellsworth, Phoebe C; Demiralp, Metin; Hernandez-Garcia, Luis; Deldin, Patricia J; Gotlib, Ian H; Jonides, John

    2012-01-01

    Some individuals have very specific and differentiated emotional experiences, such as anger, shame, excitement, and happiness, whereas others have more general affective experiences of pleasure or discomfort that are not as highly differentiated. Considering that individuals with major depressive disorder (MDD) have cognitive deficits for negative information, we predicted that people with MDD would have less differentiated negative emotional experiences than would healthy people. To test this hypothesis, we assessed participants' emotional experiences using a 7-day experience-sampling protocol. Depression was assessed using structured clinical interviews and the Beck Depression Inventory-II. As predicted, individuals with MDD had less differentiated emotional experiences than did healthy participants, but only for negative emotions. These differences were above and beyond the effects of emotional intensity and variability. PMID:23070307

  1. Epigenetic Modifications of Major Depressive Disorder.

    PubMed

    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

  2. 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

  3. Maternal Depressive Symptoms in Pediatric Major Depressive Disorder: Relationship to Acute Treatment Outcome

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Hughes, Jennifer L.; Stewart, Sunita M.; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J.

    2008-01-01

    A study examined maternal depressive symptoms at the beginning and end of acute pediatric treatment of children with major depressive disorder (MDD). Results suggested a direct and possible reciprocal association between maternal and child depression severity.

  4. Metabolic depression in hibernation and major depression: an explanatory theory and an animal model of depression.

    PubMed

    Tsiouris, John A

    2005-01-01

    Metabolic depression, an adaptive biological process for energy preservation, is responsible for torpor, hibernation and estivation. We propose that a form of metabolic depression, and not mitochondrial dysfunction, is the process underlying the observed hypometabolism, state-dependent neurobiological changes and vegetative symptoms of major depression in humans. The process of metabolic depression is reactivated via differential gene expression in response to perceived adverse stimuli in predisposed persons. Behavior inhibition by temperament, anxiety disorders, genetic vulnerabilities, and early traumatic experiences predispose persons to depression. The proposed theory is supported by similarities in the presentation and neurobiology of hibernation in bears and major depression and explains the yet unexplained neurobiological changes of depression. Although, gene expression is suppressed in other hibernators by deep hypothermia, bears were chosen because they hibernate with mild hypothermia. Pre-hibernation in bears and major depression with atypical features are both characterized by fat storage through overeating, oversleeping, and decreased mobility. Hibernation in bears and major depression with melancholic features are characterized by withdrawal from the environment, lack of energy, loss of weight from not eating and burning stored fat, changes in sleep pattern, and the following similar neurobiological findings: reversible subclinical hypothyroidism; increased concentration of serum cortisol; acute phase protein response; low respiratory quotient; oxidative stress response; decreased neurotransmitter levels; and changes in cyclic-adenosine monophosphate-binding activity. Signaling systems associated with protein phosphorylation, transcription factors, and gene expression are responsible for the metabolic depression process during pre-hibernation and hibernation. Antidepressants and mood stabilizers interfere with the hibernation process and produce their

  5. Polygenic dissection of major depression clinical heterogeneity.

    PubMed

    Milaneschi, Y; Lamers, F; Peyrot, W J; Abdellaoui, A; Willemsen, G; Hottenga, J-J; Jansen, R; Mbarek, H; Dehghan, A; Lu, C; Boomsma, D I; Penninx, B W J H

    2016-04-01

    The molecular mechanisms underlying major depressive disorder (MDD) are largely unknown. Limited success of previous genetics studies may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the polygenic features of MDD and two common clinical subtypes (typical and atypical) defined by symptom profiles in a large sample of adults with established diagnoses. Data were from 1530 patients of the Netherlands Study of Depression and Anxiety (NESDA) and 1700 controls mainly from the Netherlands Twin Register (NTR). Diagnoses of MDD and its subtypes were based on DSM-IV symptoms. Genetic overlap of MDD and subtypes with psychiatric (MDD, bipolar disorder, schizophrenia) and metabolic (body mass index (BMI), C-reactive protein, triglycerides) traits was evaluated via genomic profile risk scores (GPRS) generated from meta-analysis results of large international consortia. Single nucleotide polymorphism (SNP)-heritability of MDD and subtypes was also estimated. MDD was associated with psychiatric GPRS, while no association was found for GPRS of metabolic traits. MDD subtypes had differential polygenic signatures: typical was strongly associated with schizophrenia GPRS (odds ratio (OR)=1.54, P=7.8e-9), while atypical was additionally associated with BMI (OR=1.29, P=2.7e-4) and triglycerides (OR=1.21, P=0.006) GPRS. Similar results were found when only the highly discriminatory symptoms of appetite/weight were used to define subtypes. SNP-heritability was 32% for MDD, 38% and 43% for subtypes with, respectively, decreased (typical) and increased (atypical) appetite/weight. In conclusion, MDD subtypes are characterized by partially distinct polygenic liabilities and may represent more homogeneous phenotypes. Disentangling MDD heterogeneity may help the psychiatric field moving forward in the search for molecular roots of depression. PMID:26122587

  6. Glutamate Metabolism in Major Depressive Disorder

    PubMed Central

    Abdallah, Chadi G.; Jiang, Lihong; De Feyter, Henk M.; Fasula, Madonna; Krystal, John H.; Rothman, Douglas L.; Mason, Graeme F.; Sanacora, Gerard

    2015-01-01

    Objective Emerging evidence suggests abnormalities in amino acid neurotransmitter function and impaired energy metabolism contribute to the underlying pathophysiology of Major Depressive Disorder (MDD). To test whether impairments in energetics and glutamate neurotransmitter cycling are present in MDD we used in vivo 13C magnetic resonance spectroscopy (13C MRS) to measure these fluxes in individuals diagnosed with MDD relative to non-depressed subjects. Method 1H MRS and 13C MRS data were collected on 23 medication-free MDD and 17 healthy subjects. 1H MRS provided total glutamate and GABA concentrations, and 13C MRS, coupled with intravenous infusion of [1-13C]-glucose, provided measures of the neuronal tricarboxylic acid cycle (VTCAN) for mitochondrial energy production, GABA synthesis, and glutamate/glutamine cycling, from voxels placed in the occipital cortex. Results Our main finding was that mitochondrial energy production of glutamatergic neurons was reduced by 26% in MDD subjects (t = 2.57, p = 0.01). Paradoxically we found no difference in the rate of glutamate/glutamine cycle (Vcycle). We also found a significant correlation between glutamate concentrations and Vcycle considering the total sample. Conclusions We interpret the reduction in mitochondrial energy production as being due to either mitochondrial dysfunction or a reduction in proper neuronal input or synaptic strength. Future MRS studies could help distinguish these possibilities. PMID:25073688

  7. [Sequence learning in major depressive disorder].

    PubMed

    Borbély-Ipkovich, Emöke; Németh, Dezsö; Janacsek, Karolina; Gonda, Xénia

    2014-01-01

    Major Depressive Disorder (MDD) is one of the most common psychiatric diagnoses, accompanied by several psychological, behavioural and emotional symptoms, and in addition to the symptoms affecting the quality of life, it can lead to severe consequences, including suicide. Sequence learning plays a key role in adapting to the environment, neural plasticity, first language acquisition, social learning and skills, at the same time it defines the behaviour of the patient and also therapeutic possibilities. The aim of this paper is to review sequence learning and its consolidation in MDD. We know little about the effects of mood disorders on sequence learning; the results are contradictory, therefore, further studies are needed to test the effects of MDD on sequence learning and on the consolidation of implicitly acquired sequence knowledge. PMID:25411225

  8. The Bipolar II Depression Questionnaire: A Self-Report Tool for Detecting Bipolar II Depression.

    PubMed

    Leung, Chi Ming; Yim, Chi Lap; Yan, Connie T Y; Chan, Cheuk Chi; Xiang, Yu-Tao; Mak, Arthur D P; Fok, Marcella Lei-Yee; Ungvari, Gabor S

    2016-01-01

    Bipolar II (BP-II) depression is often misdiagnosed as unipolar (UP) depression, resulting in suboptimal treatment. Tools for differentiating between these two types of depression are lacking. This study aimed to develop a simple, self-report screening instrument to help distinguish BP-II depression from UP depressive disorder. A prototype BP-II depression questionnaire (BPIIDQ-P) was constructed following a literature review, panel discussions and a field trial. Consecutively assessed patients with a diagnosis of depressive disorder or BP with depressive episodes completed the BPIIDQ-P at a psychiatric outpatient clinic in Hong Kong between October and December 2013. Data were analyzed using discriminant analysis and logistic regression. Of the 298 subjects recruited, 65 (21.8%) were males and 233 (78.2%) females. There were 112 (37.6%) subjects with BP depression [BP-I = 42 (14.1%), BP-II = 70 (23.5%)] and 182 (62.4%) with UP depression. Based on family history, age at onset, postpartum depression, episodic course, attacks of anxiety, hypersomnia, social phobia and agoraphobia, the 8-item BPIIDQ-8 was constructed. The BPIIDQ-8 differentiated subjects with BP-II from those with UP depression with a sensitivity/specificity of 0.75/0.63 for the whole sample and 0.77/0.72 for a female subgroup with a history of childbirth. The BPIIDQ-8 can differentiate BP-II from UP depression at the secondary care level with satisfactory to good reliability and validity. It has good potential as a screening tool for BP-II depression in primary care settings. Recall bias, the relatively small sample size, and the high proportion of females in the BP-II sample limit the generalization of the results. PMID:26963908

  9. The Bipolar II Depression Questionnaire: A Self-Report Tool for Detecting Bipolar II Depression

    PubMed Central

    Leung, Chi Ming; Yim, Chi Lap; Yan, Connie T. Y.; Chan, Cheuk Chi; Xiang, Yu-Tao; Mak, Arthur D. P.; Fok, Marcella Lei-Yee; Ungvari, Gabor S.

    2016-01-01

    Bipolar II (BP-II) depression is often misdiagnosed as unipolar (UP) depression, resulting in suboptimal treatment. Tools for differentiating between these two types of depression are lacking. This study aimed to develop a simple, self-report screening instrument to help distinguish BP-II depression from UP depressive disorder. A prototype BP-II depression questionnaire (BPIIDQ-P) was constructed following a literature review, panel discussions and a field trial. Consecutively assessed patients with a diagnosis of depressive disorder or BP with depressive episodes completed the BPIIDQ-P at a psychiatric outpatient clinic in Hong Kong between October and December 2013. Data were analyzed using discriminant analysis and logistic regression. Of the 298 subjects recruited, 65 (21.8%) were males and 233 (78.2%) females. There were 112 (37.6%) subjects with BP depression [BP-I = 42 (14.1%), BP-II = 70 (23.5%)] and 182 (62.4%) with UP depression. Based on family history, age at onset, postpartum depression, episodic course, attacks of anxiety, hypersomnia, social phobia and agoraphobia, the 8-item BPIIDQ-8 was constructed. The BPIIDQ-8 differentiated subjects with BP-II from those with UP depression with a sensitivity/specificity of 0.75/0.63 for the whole sample and 0.77/0.72 for a female subgroup with a history of childbirth. The BPIIDQ-8 can differentiate BP-II from UP depression at the secondary care level with satisfactory to good reliability and validity. It has good potential as a screening tool for BP-II depression in primary care settings. Recall bias, the relatively small sample size, and the high proportion of females in the BP-II sample limit the generalization of the results. PMID:26963908

  10. Psychopathological symptoms of depression in Parkinson's disease compared to major depression.

    PubMed

    Merschdorf, U; Berg, D; Csoti, I; Fornadi, F; Merz, B; Naumann, M; Becker, G; Supprian, T

    2003-01-01

    Parkinson's disease is frequently associated with depressive symptoms. When depression occurs at early stages and before the onset of characteristic motor symptoms of the disease, differential diagnosis of major depression may be difficult. Differences in psychopathological features of depression in Parkinson's disease and major depression have been reported by some authors. This study presents data of 49 patients with depression in Parkinson's disease and 38 patients with major depression. The severity of depressive symptoms was equivalent in both groups. Depressive features did not differ between the two groups with exception of affective flattening, delusional ideas and suicide attempts. In conclusion, this investigation gives support to the assumption of a common neurobiological origin of depression in Parkinson's disease and major depression. PMID:14571050

  11. Gene expression in major depressive disorder.

    PubMed

    Jansen, R; Penninx, B W J H; Madar, V; Xia, K; Milaneschi, Y; Hottenga, J J; Hammerschlag, A R; Beekman, A; van der Wee, N; Smit, J H; Brooks, A I; Tischfield, J; Posthuma, D; Schoevers, R; van Grootheest, G; Willemsen, G; de Geus, E J; Boomsma, D I; Wright, F A; Zou, F; Sun, W; Sullivan, P F

    2016-03-01

    The search for genetic variants underlying major depressive disorder (MDD) has not yet provided firm leads to its underlying molecular biology. A complementary approach is to study gene expression in relation to MDD. We measured gene expression in peripheral blood from 1848 subjects from The Netherlands Study of Depression and Anxiety. Subjects were divided into current MDD (N=882), remitted MDD (N=635) and control (N=331) groups. MDD status and gene expression were measured again 2 years later in 414 subjects. The strongest gene expression differences were between the current MDD and control groups (129 genes at false-discovery rate, FDR<0.1). Gene expression differences across MDD status were largely unrelated to antidepressant use, inflammatory status and blood cell counts. Genes associated with MDD were enriched for interleukin-6 (IL-6)-signaling and natural killer (NK) cell pathways. We identified 13 gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD, FDR=5.8 × 10(-5)) and IL-6 pathways (upregulated in current MDD, FDR=3.2 × 10(-3)). Longitudinal analyses largely confirmed results observed in the cross-sectional data. Comparisons of gene expression results to the Psychiatric Genomics Consortium (PGC) MDD genome-wide association study results revealed overlap with DVL3. In conclusion, multiple gene expression associations with MDD were identified and suggest a measurable impact of current MDD state on gene expression. Identified genes and gene clusters are enriched with immune pathways previously associated with the etiology of MDD, in line with the immune suppression and immune activation hypothesis of MDD. PMID:26008736

  12. Does escitalopram reduce neurotoxicity in major depression?

    PubMed

    Halaris, Angelos; Myint, Aye-Mu; Savant, Vidushi; Meresh, Edwin; Lim, Edwin; Guillemin, Gilles; Hoppensteadt, Debra; Fareed, Jawed; Sinacore, James

    2015-01-01

    A pro-inflammatory state and a dysregulation in the tryptophan/kynurenine pathway have been documented in depression. This study examined whether treatment with the SSRI, escitalopram (ESC), could suppress inflammation and favorably shift metabolites of the kynurenine pathway in patients with major depressive disorder (MDD) within the utilized treatment period. Twenty seven healthy control subjects were included for comparison. Thirty patients were enrolled after completing baseline assessments. They received a 12-week ESC monotherapy. Twenty subjects were completers. Clinical assessments were carried out at each visit using the HAM-D, HAM-A, CGI and BDI rating scales. Blood samples were collected at each assessment and stored until analyzed. Cytokines were analyzed with Randox multiplex assay and tryptophan and kynurenine metabolites were analyzed using HPLC/GCMS. Baseline plasma concentrations of hsCRP, TNFα, IL6 and MCP-1 were significantly higher in patients compared to healthy controls. IL10 trended toward an increase. Baseline plasma IL1β correlated significantly with IL1α, and IL4. Patients showed significant improvement in all outcome measures with a high remission rate. Significant correlations were obtained between specific symptoms and certain biomarkers at baseline but these correlations must be viewed as very preliminary. During ESC treatment concentrations of inflammatory biomarkers did not change except for TNFα that trended lower. Metabolites and ratios of the tryptophan/kynurenine pathway showed reductions of the neurotoxic metabolites, 3-hydroxykynurenine and quinolinic acid, 3-hydroxykynurenine/kynurenine, quinolinic acid/tryptophan, kynurenic acid/quinolinic acid and quinolinic acid/3-hydroxykynurenine. The results indicate that ESC may exert its antidepressant effect in part through inhibition of synthesis of certain neurotoxic kynurenine metabolites and possibly also through reduction of the inflammatory response, although there was no

  13. Current Major Depression Among Smokers Using a State Quitline

    PubMed Central

    Hebert, Kiandra K.; Cummins, Sharon E.; Hernandez, Sandra; Tedeschi, Gary J.; Zhu, Shu-Hong

    2010-01-01

    Background Smokers seeking treatment to quit smoking are generally not assessed for current depression, yet depression among smokers may influence quitting outcome. Purpose This study aims to formally assess current major depression among smokers calling a state tobacco quitline. Methods A total of 844 smokers calling the California Smokers’ Helpline in 2007 were screened for depression by the mood module of the Patient Health Questionnaire (PHQ-9). The Social Functioning Questionnaire (SFQ) was also administered to these callers. Two months after the screening, follow-up evaluations were conducted to assess cessation outcome. Results In all, 24.2% of smokers met criteria for current major depression and 16.5% reported symptoms indicating mild depression. Callers with current major depression were more likely to be heavy smokers and on Medicaid. Moreover, 74.0% of smokers with current major depression had substantial social and occupational functioning deficits. Two months later, those with major depression at baseline were significantly less likely to have quit smoking (18.5% vs 28.4%). Conclusions Almost one in four smokers to the California Smokers’ Helpline met criteria for current major depression. Over 400,000 smokers call state quitlines in the U.S. for help with quitting each year, which means that as many as 100,000 smokers with serious depressive symptoms are using these services annually. The large number of depressed smokers who seek help suggests a need to develop appropriate interventions to help them quit successfully. PMID:21146767

  14. Major depression, parental mental disorder and early family relationships.

    PubMed

    Hällström, T

    1987-03-01

    Sixty middle-aged urban women with a major depressive episode diagnosed in a community survey were compared with those 400 participants of the study who had no history of major depression. The study design is retrospective. The depressed women's parents had been in contact with psychiatric services twice as often as those of never depressed women. The rate of paternal alcoholism was however the same in both groups. As compared with the controls, women with major depression reported significantly more often frequent corporal punishment, poor relationship with mother, having been misunderstood by parents, and unhappy childhood. PMID:3591408

  15. Deep brain stimulation for major depression.

    PubMed

    Schlaepfer, T E; Bewernick, B H

    2013-01-01

    A third of patients suffering from major depression cannot be helped by conventional treatment methods. These patients face reduced quality of life, high risk of suicide, and little hope of recovery. Deep brain stimulation (DBS) is under scientific evaluation as a new treatment option for these treatment-resistant patients. First clinical studies with small samples have been stimulated at the subgenual cingulate gyrus (Cg25/24), the anterior limb of the capsula interna (ALIC), and the nucleus accumbens (NAcc). Long-term antidepressant effects, augmentation of social functioning, and normalization of brain metabolism have been shown in about 50% of patients. Cognitive safety regarding attention, learning, and memory has been reported. Adverse events were wound infection, suicide, and hypomania, amongst others. Larger studies are under way to confirm these preliminary encouraging results. New hypothesis-guided targets (e.g., medial forebrain bundle, habenula) are about to be assessed in clinical trials. The application of DBS for other psychiatric diseases (e.g., bipolar disorder, alcohol dependency, opioid addiction, schizophrenia) is debated and single case studies are under way. Standards are needed for study registration, target selection, patient inclusion and monitoring, and publication of results to guarantee safety for the patients and scientific exchange. PMID:24112897

  16. A Genetic Susceptibility Mechanism for Major Depression

    PubMed Central

    Wang, Yanfang; Sun, Ning; Li, Suping; Du, Qiaorong; Xu, Yong; Liu, Zhifeng; Zhang, Kerang

    2015-01-01

    Abstract Major Depression (MD) is a highly inherited psychiatric disorder. The norepinephrine transporter (NET) gene plays important role in pathophysiology of MD. This study attempted to examine the relationship between polymorphisms of NET gene and MD. Patients with MD and healthy controls were recruited and subgrouped. The T-182C and G1287A polymorphisms of NET gene were genotyped by direct sequencing. The genotypic and allelic frequencies were compared using the Pearson χ2 analysis. The linkage disequilibrium was analyzed using the UNPHASED program. Significant differences in genotypic and allelic frequencies of T-182C polymorphism were observed between MD subgroups and controls. When referenced by TT genotype, the OR value increased gradient from TC to CC genotype; when referenced by T allele, the odds ratio value of C allele also increased. Compared with those having both −182 T/T and 1287 G/G genotypes, in patients with MD, early-onset MD, and MD with suicide concept group, the −182 C/C and 1287 G/A combinatorial genotype has significant risk; yet in patients with MD family history, the −182 C/C and 1287 A/A combinatorial genotype has significant risk. Different combinations of T-182C and the G1287A polymorphisms of NET gene might increase morbidity risk of MD subpopulations. PMID:26061302

  17. Predicting symptoms in major depression after inpatient treatment: the role of alexithymia.

    PubMed

    Günther, Vivien; Rufer, Michael; Kersting, Anette; Suslow, Thomas

    2016-07-01

    Alexithymia has been considered to have a negative influence on the course of symptoms in various psychiatric disorders. Only a few studies of depressed patients have examined whether alexithymia predicts the outcome of therapeutic interventions or the course of symptoms in naturalistic settings. This prospective study investigated whether alexithymia is associated with depressive symptoms after a multimodal inpatient treatment. Forty-five inpatients suffering from acute major depression were examined in the initial phase of treatment and then again after seven weeks. Patients took part in a multimodal treatment programme comprising psychodynamic-interactional oriented individual and group therapy. The majority of patients were taking antidepressants during study participation. To assess alexithymia and depressive symptoms, the 20-item Toronto Alexithymia Scale (TAS-20), the Beck Depression Inventory II (BDI-II) and the Hamilton Depression Scale (HAMD) were administered at baseline and follow-up. When controlling for baseline depressive symptoms along with trait anxiety, high scores in the externally oriented thinking (EOT) facet of alexithymia at baseline predicted high severity of depressive symptoms at follow-up (for self-reported as well as interviewer-based scores). Inpatients suffering from major depression with a more pronounced external cognitive style might benefit less from a routine multimodal treatment approach (including psychodynamic interactional therapy, antidepressant medication, and complementary therapies). Intervention programmes might modify or account for alexithymic characteristics to improve the course of depressive symptoms in these patients. PMID:26935972

  18. Motor Imagery in Unipolar Major Depression

    PubMed Central

    Bennabi, Djamila; Monnin, Julie; Haffen, Emmanuel; Carvalho, Nicolas; Vandel, Pierre; Pozzo, Thierry; Papaxanthis, Charalambos

    2014-01-01

    Background: Motor imagery is a potential tool to investigate action representation, as it can provide insights into the processes of action planning and preparation. Recent studies suggest that depressed patients present specific impairment in mental rotation. The present study was designed to investigate the influence of unipolar depression on motor imagery ability. Methods: Fourteen right-handed patients meeting DSM-IV criteria for unipolar depression were compared to 14 matched healthy controls. Imagery ability was accessed by the timing correspondence between executed and imagined movements during a pointing task, involving strong spatiotemporal constraints (speed/accuracy trade-off paradigm). Results: Compared to controls, depressed patients showed marked motor slowing on both actual and imagined movements. Furthermore, we observed greater temporal discrepancies between actual and mental movements in depressed patients than in healthy controls. Lastly, depressed patients modulated, to some extent, mental movement durations according to the difficulty of the task, but this modulation was not as strong as that of healthy subjects. Conclusion: These results suggest that unipolar depression significantly affects the higher stages of action planning and point out a selective decline of motor prediction. PMID:25538580

  19. Examining the role of neuroinflammation in major depression.

    PubMed

    Furtado, Melissa; Katzman, Martin A

    2015-09-30

    Recent findings have established a connection between inflammation and major depression and specifically the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression. This article reviews clinical and experimental studies examining the role of the HPA axis, HPA hyperactivity (resulting in increased cortisol levels), as well as the proinflammatory cytokines tumor necrosis factor, C-reactive protein, and the interleukins, in depressed patients. Similarly this paper will review data supporting increased cytokine levels in depression and specifically differential effects in treatment-resistant patients, as well as potentially distinguishing in particular depression subtypes. Understanding the role of the immune system and inflammation in patients with major depression is essential in order to develop efficacious treatments potentially targeting inflammation in relation to the depression in order to reduce patient symptomatology and comorbidities. PMID:26187338

  20. Perinatal Major Depression Biomarkers: A systematic review.

    PubMed

    Serati, M; Redaelli, M; Buoli, M; Altamura, A C

    2016-03-15

    Postpartum depression, now termed perinatal depression by the DSM-5, is a clinically relevant disorder reaching 15% of incidence. Although it is quite frequent and associated with high social dysfunction, only recently its underpinning biological pathways have been explored, while multiple and concomitant risk factors have been identified (e.g. psychosocial stress). Peripartum depression usually has its onset during the third trimester of pregnancy or in the postpartum, being one of the most common medical complications in new mothers. Purpose of the present review is to summarize the state of art of biological biomarkers involved in the pathogenesis of perinatal depression, in view of the fact that suboptimal prenatal milieu can induce permanent damage in subsequent offspring life and have a negative impact on mother-child relationship. Furthermore, parents' biological changes due to medical/psychiatric disorders or stress exposure could influence offspring life: a concept known as 'intergenerational transmission', acting by variations into gametes and the gestational uterine environment. Given the evidence that perinatal mental disorders involve risks for the mother and offspring, the search for reliable biomarkers in high-risk mothers actually represents a medical priority to prevent perinatal depression. PMID:26802316

  1. Comorbid Problem Gambling and Major Depression in a Community Sample.

    PubMed

    Quigley, Leanne; Yakovenko, Igor; Hodgins, David C; Dobson, Keith S; El-Guebaly, Nady; Casey, David M; Currie, Shawn R; Smith, Garry J; Williams, Robert J; Schopflocher, Don P

    2015-12-01

    Major depression is among the most common comorbid conditions in problem gambling. However, little is known about the effects of comorbid depression on problem gambling. The present study examined the prevalence of current major depression among problem gamblers (N = 105) identified from a community sample of men and women in Alberta, and examined group differences in gambling severity, escape motivation for gambling, family functioning, childhood trauma, and personality traits across problem gamblers with and without comorbid depression. The prevalence of major depression among the sample of problem gamblers was 32.4%. Compared to problem gamblers without depression (n = 71), problem gamblers with comorbid depression (n = 34) reported more severe gambling problems, greater history of childhood abuse and neglect, poorer family functioning, higher levels of neuroticism, and lower levels of extraversion, agreeableness, and conscientiousness. Furthermore, the problem gamblers with comorbid depression had greater levels of childhood abuse and neglect, worse family functioning, higher neuroticism, and lower agreeableness and conscientiousness than a comparison sample of recreational gamblers with depression (n = 160). These findings underscore the need to address comorbid depression in assessment and treatment of problem gambling and for continued research on how problem gambling is related to frequently co-occurring disorders such as depression. PMID:25112217

  2. Benchmarks for Psychotherapy Efficacy in Adult Major Depression

    ERIC Educational Resources Information Center

    Minami, Takuya; Wampold, Bruce E.; Serlin, Ronald C.; Kircher, John C.; Brown, George S.

    2007-01-01

    This study estimates pretreatment-posttreatment effect size benchmarks for the treatment of major depression in adults that may be useful in evaluating psychotherapy effectiveness in clinical practice. Treatment efficacy benchmarks for major depression were derived for 3 different types of outcome measures: the Hamilton Rating Scale for Depression…

  3. Theory of mind disability in major depression with or without psychotic symptoms: a componential view.

    PubMed

    Wang, Yong-Guang; Wang, Yi-Qiang; Chen, Shu-Lin; Zhu, Chun-Yan; Wang, Kai

    2008-11-30

    Previous reports have conceptualized theory of mind (ToM) as comprising two components and questioned whether ToM deficits are associated with psychotic symptoms. We investigated 33 nonpsychotic depressed inpatients, 23 psychotic depressed inpatients, and 53 normal controls with the following measures: Eyes Task, Faux pas Task, Verbal Fluency Test (VFT), Digit Span Test (DST) and WAIS-IQ. The depressed patients were also evaluated with the Beck Depression Inventory-II (BDI-II) and the Brief Psychiatric Rating Scale (BPRS). The nonpsychotic depressed patients and the psychotic depressed individuals were significantly impaired on tasks involving ToM social-perceptual and social-cognitive components, as well as the VFT. The psychotic depressed patients performed significantly worse than nonpsychotic depressed patients on ToM tasks. An association was found between ToM performances and both BPRS total and hostile-suspiciousness scores in the depressed group. Both of the ToM components were impaired in depressed patients. Similar mechanisms and neurobiological substrate may contribute to schizophrenia and major depression. PMID:18926572

  4. Vagus Nerve Stimulation for Major Depressive Episodes.

    PubMed

    Eljamel, Sam

    2015-01-01

    Stimulation of the left vagus nerve is a novel antidepressive therapy that relies upon the vagal projections to the brain stem to modulate brain circuits involved in mood regulation. There is cumulative evidence from prospective and long-term studies that has demonstrated tolerability and effectiveness of vagus nerve stimulation (VNS) in major depressive episodes (MDE). VNS in MDE has the following advantages: symptomatic response (defined as at least a 50% improvement in MDE severity) occurs in at least 15-17% of patients after 10 weeks of VNS treatment and in at least 22-37% of patients after 12 months of VNS treatment, remissions are observed in at least 15-17% of patients after 12 months of treatment, there is a sustained response in 13-27% of patients during 12 months of VNS, and successful maintenance of the initial improvement is observed in a high percentage of patients (73-77% of patients who had meaningful or greater benefit after 3 months of treatment maintained at least meaningful benefit after 12 months of treatment). VNS is a well-tolerated treatment as indicated by the high continuation rates of VNS therapy in the D01 and D02 studies after 12 months of therapy (90-98%) and the low rate of adverse event-related study discontinuations through 12 months or more in these studies (3%). Adverse effects are characterized by the absence of systemic effects associated with drug therapy and are primarily limited to those related to stimulation of the vagus nerve; many of the common adverse effects only occurred when VNS was on with the ability to stop acute stimulation-related adverse effects immediately through the use of magnet deactivation of the VNS device. More importantly, there were no adverse cognitive and psychomotor effects observed with antidepressant drugs and electroconvulsive therapy, no overdose toxicity observed with antidepressant drugs, favorable findings in animal reproductive studies, and an ability to add VNS therapy to antidepressant drug

  5. Mechanisms Underlying Neurocognitive Dysfunctions in Recurrent Major Depression

    PubMed Central

    Gałecki, Piotr; Talarowska, Monika; Anderson, George; Berk, Michael; Maes, Michael

    2015-01-01

    Recent work shows that depression is intimately associated with changes in cognitive functioning, including memory, attention, verbal fluency, and other aspects of higher-order cognitive processing. Changes in cognitive functioning are more likely to occur when depressive episodes are recurrent and to abate to some degree during periods of remission. However, with accumulating frequency and duration of depressive episodes, cognitive deficits can become enduring, being evident even when mood improves. Such changes in cognitive functioning give depression links to mild cognitive impairment and thereby with neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, and multiple sclerosis. Depression may then be conceptualized on a dimension of depression – mild cognitive impairment – dementia. The biological underpinnings of depression have substantial overlaps with those of neurodegenerative conditions, including reduced neurogenesis, increased apoptosis, reactive oxygen species, tryptophan catabolites, autoimmunity, and immune-inflammatory processes, as well as decreased antioxidant defenses. These evolving changes over the course of depressive episodes drive the association of depression with neurodegenerative conditions. As such, the changes in cognitive functioning in depression have important consequences for the treatment of depression and in reconceptualizing the role of depression in wider neuroprogressive conditions. Here we review the data on changes in cognitive functioning in recurrent major depression and their association with other central conditions. PMID:26017336

  6. Brain Structural Effects of Antidepressant Treatment in Major Depression

    PubMed Central

    Dusi, Nicola; Barlati, Stefano; Vita, Antonio; Brambilla, Paolo

    2015-01-01

    Depressive disorder is a very frequent and heterogeneous syndrome. Structural imaging techniques offer a useful tool in the comprehension of neurobiological alterations that concern depressive disorder. Altered brain structures in depressive disorder have been particularly located in the prefrontal cortex (medial prefrontal cortex and orbitofrontal cortex, OFC) and medial temporal cortex areas (hippocampus). These brain areas belong to a structural and functional network related to cognitive and emotional processes putatively implicated in depressive symptoms. These volumetric alterations may also represent biological predictors of response to pharmacological treatment. In this context, major findings of magnetic resonance (MR) imaging, in relation to treatment response in depressive disorder, will here be presented and discussed. PMID:26412065

  7. Major Depressive Disorder and Kappa Opioid Receptor Antagonists

    PubMed Central

    Li, Wei; Sun, Huijiao; Chen, Hao; Yang, Xicheng; Xiao, Li; Liu, Renyu; Shao, Liming; Qiu, Zhuibai

    2016-01-01

    Major depressive disorder (MDD) is a common psychiatric disease worldwide. The clinical use of tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs)/serotonin–norepinephrine reuptake inhibitor (SNRIs) for this condition have been widely accepted, but they were challenged by unacceptable side-effects, potential drug-drug interactions (DDIs) or slow onset/lack of efficacy. The endogenous opioid system is involved in stress and emotion regulatory processes and its role in MDD has been implicated. Although several KOR antagonists including JDTic and PF-04455242 were discontinued in early clinical trials, ALKS 5461 and CERC-501(LY-2456302) survived and entered into Phase-III and Phase-II trials, respectively. Considering the efficacy and safety of early off-label use of buprenorphine in the management of the treatment-resistant depression (TRD), it will be not surprising to predict the potential success of ALKS 5461 (a combination of buprenorphine and ALKS-33) in the near future. Moreover, CERC-501 will be expected to be available as monotherapy or adjuvant therapy with other first-line antidepressants in the treatment of TRD, if ongoing clinical trials continue to provide positive benefit-risk profiles. Emerging new researches might bring more drug candidates targeting the endogenous opioid system to clinical trials to address current challenges in MDD treatment in clinical practice. PMID:27213169

  8. The Relationship Between Borderline Personality Disorder and Major Depression in Later Life: Acute Versus Temperamental Symptoms

    PubMed Central

    Galione, Janine N.; Oltmanns, Thomas F.

    2012-01-01

    Objective A recent issue in the personality disorder field is the prevalence and course of Axis II symptoms in later life. Focusing on the presentation of personality disorder criteria over time may have some utility in exploring the relationship between borderline personality disorder (BPD) and major depression in older adults. Temperamental personality symptoms are relatively resistant to change but tend to be nonspecific to disorders, while acute symptoms remit relatively quickly. We predicted that temperamental BPD symptoms would be positively correlated with a history of depression and did not expect to find a relationship between major depression and acute BPD symptoms. Method One thousand six hundred and thirty participants between the ages of 55 and 64 were recruited to participate in a community-based longitudinal study representative of the St. Louis area. Participants completed a battery of assessments at baseline, including diagnostic interviews for all ten personality disorders and major depressive disorder. Results Temperamental and acute BPD symptoms were significantly correlated with a history of major depression. After adjustments were made for the effects of temperamental symptoms on depression, acute symptoms were no longer correlated with a history of depression. As predicted, temperamental symptoms remained significantly related to depression, even after controlling for the effects of acute symptoms. BPD acute symptoms showed a unique negative correlation with the amount of time following remission from a depressive episode. Conclusions Overall, this study supports associations between major depression and borderline personality in older adults. The findings indicate that a history of major depression is primarily related to stable BPD symptoms related to emotional distress, which are more prevalent in older adults compared to acute features. PMID:23567384

  9. Neurobiology of chronic mild stress: Parallels to major depression

    PubMed Central

    Hill, Matthew N.; Hellemans, Kim G.C.; Verma, Pamela; Gorzalka, Boris B.; Weinberg, Joanne

    2016-01-01

    The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression. PMID:22776763

  10. Interaction of posttraumatic stress disorder and major depressive disorder among older combat veterans.

    PubMed

    Hyer, L; Stanger, E

    1997-06-01

    This study investigated the interaction of PTSD and major depressive disorder with common aging-related variables for a community sample of older World War II and Korean War veterans. Older veterans (N = 139) were divided into PTSD and depressed groups on the basis of interviewers' measures and compared on overall adjustment, social support, and health status. Only PTSD affected adjustment and health status. PMID:9198379

  11. Additive genetic contribution to symptom dimensions in major depressive disorder.

    PubMed

    Pearson, Rahel; Palmer, Rohan H C; Brick, Leslie A; McGeary, John E; Knopik, Valerie S; Beevers, Christopher G

    2016-05-01

    Major depressive disorder (MDD) is a phenotypically heterogeneous disorder with a complex genetic architecture. In this study, genomic-relatedness-matrix restricted maximum-likelihood analysis (GREML) was used to investigate the extent to which variance in depression symptoms/symptom dimensions can be explained by variation in common single nucleotide polymorphisms (SNPs) in a sample of individuals with MDD (N = 1,558) who participated in the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A principal components analysis of items from the Hamilton Rating Scale for Depression (HRSD) obtained prior to treatment revealed 4 depression symptom components: (a) appetite, (b) core depression symptoms (e.g., depressed mood, anhedonia), (c) insomnia, and (d) anxiety. These symptom dimensions were associated with SNP-based heritability (hSNP2) estimates of 30%, 14%, 30%, and 5%, respectively. Results indicated that the genetic contribution of common SNPs to depression symptom dimensions were not uniform. Appetite and insomnia symptoms in MDD had a relatively strong genetic contribution whereas the genetic contribution was relatively small for core depression and anxiety symptoms. While in need of replication, these results suggest that future gene discovery efforts may strongly benefit from parsing depression into its constituent parts. (PsycINFO Database Record PMID:27124715

  12. Collective efficacy and major depression in urban neighborhoods.

    PubMed

    Ahern, Jennifer; Galea, Sandro

    2011-06-15

    Depression contributes substantially to the global burden of disease and disability. Population-level factors that shape depression may be efficient targets for intervention to decrease the depression burden. The authors aimed to identify the relation between neighborhood collective efficacy and major depression. Analyses were conducted on data from the New York Social Environment Study (n = 4,000), a representative study of residents of New York, New York, conducted in 2005. Neighborhood collective efficacy was measured as the average neighborhood response on a well-established scale. Major depression was assessed with the Patient Health Questionnaire. A marginal modeling approach was applied to present results on the additive scale relevant to public health and intervention. Analyses were adjusted for demographic and socioeconomic characteristics, recent life events that could contribute to both depression and change in residence, and individual perception of collective efficacy. Collective efficacy was related to major depression among older adults; marginal models estimated a 6.2% (95% confidence interval: 0.1, 17.5) lower prevalence of depression if all older adults (65 years and older) had lived in high versus low collective efficacy neighborhoods. Similar results were suggested among younger adults; however, the confidence interval crossed the null. These and other study findings suggest that community-randomized trials targeting collective efficacy merit consideration. PMID:21527512

  13. Discriminating Between Bipolar Disorder and Major Depressive Disorder.

    PubMed

    Vöhringer, Paul A; Perlis, Roy H

    2016-03-01

    Rates of misdiagnosis between major depressive disorder and bipolar disorder have been reported to be substantial, and the consequence of such misdiagnosis is likely to be a delay in achieving effective control of symptoms, in some cases spanning many years. Particularly in the midst of a depressive episode, or early in the illness course, it may be challenging to distinguish the 2 mood disorders purely on the basis of cross-sectional features. To date, no useful biological markers have been reliably shown to distinguish between bipolar disorder and major depressive disorder. PMID:26876315

  14. Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder

    PubMed Central

    Wittenborn, A. K.; Rahmandad, H.; Rick, J.; Hosseinichimeh, N.

    2016-01-01

    Background Depression is a complex public health problem with considerable variation in treatment response. The systemic complexity of depression, or the feedback processes among diverse drivers of the disorder, contribute to the persistence of depression. This paper extends prior attempts to understand the complex causal feedback mechanisms that underlie depression by presenting the first broad boundary causal loop diagram of depression dynamics. Method We applied qualitative system dynamics methods to map the broad feedback mechanisms of depression. We used a structured approach to identify candidate causal mechanisms of depression in the literature. We assessed the strength of empirical support for each mechanism and prioritized those with support from validation studies. Through an iterative process, we synthesized the empirical literature and created a conceptual model of major depressive disorder. Results The literature review and synthesis resulted in the development of the first causal loop diagram of reinforcing feedback processes of depression. It proposes candidate drivers of illness, or inertial factors, and their temporal functioning, as well as the interactions among drivers of depression. The final causal loop diagram defines 13 key reinforcing feedback loops that involve nine candidate drivers of depression. Conclusions Future research is needed to expand upon this initial model of depression dynamics. Quantitative extensions may result in a better understanding of the systemic syndrome of depression and contribute to personalized methods of evaluation, prevention and intervention. PMID:26621339

  15. Risk Factors for Anxiety in Major Depressive Disorder Patients

    PubMed Central

    Xin, Li-Min; Chen, Lin; Ji, Zhen-Peng; Zhang, Suo-Yuan; Wang, Jun; Liu, Yan-Hong; Chen, Da-Fang; Yang, Fu-De; Wang, Gang; Fang, Yi-Ru; Lu, Zheng; Yang, Hai-Chen; Hu, Jian; Chen, Zhi-Yu; Huang, Yi; Sun, Jing; Wang, Xiao-Ping; Li, Hui-Chun; Zhang, Jin-Bei; Si, Tian-Mei

    2015-01-01

    Objective To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). Methods This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. Results Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=−4.39, p<0.001), were older (t=−4.69, p<0.001), reported more lifetime depressive episodes (z=−3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ2=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p<0.001), and were more likely to have a family history of psychiatric disorders (χ2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. Conclusion These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD. PMID:26598584

  16. A Review of the Role of Social Cognition in Major Depressive Disorder

    PubMed Central

    Weightman, Michael James; Air, Tracy Michele; Baune, Bernhard Theodor

    2014-01-01

    Background: Social cognition – the ability to identify, perceive, and interpret socially relevant information – is an important skill that plays a significant role in successful interpersonal functioning. Social cognitive performance is recognized to be impaired in several psychiatric conditions, but the relationship with major depressive disorder is less well understood. The aim of this review is to characterize the current understanding of: (i) the different domains of social cognition and a possible relationship with major depressive disorder, (ii) the clinical presentation of social cognition in acute and remitted depressive states, and (iii) the effect of severity of depression on social cognitive performance. Methods: Electronic databases were searched to identify clinical studies investigating social cognition in a major depressive disorder population, yielding 31 studies for this review. Results: Patients with major depressive disorder appear to interpret social cognitive stimuli differently to healthy controls: depressed individuals may interpret emotion through a mood-congruent bias and have difficulty with cognitive theory of mind tasks requiring interpretation of complex mental states. Social cognitive performance appears to be inversely associated with severity of depression, whilst the bias toward negative emotions persists even in remission. Some deficits may normalize following effective pharmacotherapy. Conclusions: The difficulties with social interaction observed in major depressive disorder may, at least in part, be due to an altered ability to correctly interpret emotional stimuli and mental states. These features seem to persist even in remission, although some may respond to intervention. Further research is required in this area to better understand the functional impact of these findings and the way in which targeted therapy could aid depressed individuals with social interactions. PMID:25566100

  17. Comprehensive behavioral analysis of patients with a major depressive episode

    PubMed Central

    Rothuber, Helfried; Mitterauer, Bernhard

    2011-01-01

    Summary Background A major depressive episode diagnosed according to DSM-IV criteria can be accompanied by symptoms that DSM-IV does not include. These symptoms are sometimes classified as comorbidities. Our study assessed altered behavioral modes during a major depressive episode; ie, if 1 or more modes of behavior operated less or even not at all (“never”), or if the operation of others was more frequent or even constant (“always”). We hypothesize that these altered behavioral modes, especially the extreme positions “never” (hypomodes) and “always” (hypermodes) might correlate with depression scores and thus represent a typical symptom of depression. Material/Methods We used the 35-item Salzburg Subjective Behavioral Analysis (SSBA) questionnaire to measure altered behavioral modes in 63 depressed patients and 87 non-depressed controls. Depression was assessed using the Hamilton Depression Scale. Results In our test group (n=63) we found a total of 888 extreme positions. The mean number of extreme positions per patient was 11.15±5.173 (SD). Extreme positions were found in all 35 behavioral modes. The mean Hamilton score was 22.08±7.35 (SD). The association of the incidence of extreme positions and the Hamilton score in our test group was highly significant (Spearman’s Rho=0.41; p=.001). In the control group (n=87), only 11 persons were found to display extreme positions, with a total of only 25. Conclusions Although this study has several limitations, such as the small sample or the use of a questionnaire in the validation procedure, the significant correlation of extreme positions and the Hamilton score indicate that altered modes of behavior as detected with the SSBA might be typical symptoms in a major depressive episode. PMID:21525807

  18. Sensitivity and specificity of the Major Depression Inventory in outpatients

    PubMed Central

    Cuijpers, Pim; Dekker, Jack; Noteboom, Annemieke; Smits, Niels; Peen, Jaap

    2007-01-01

    Background The Major Depression Inventory (MDI) is a new, brief, self-report measure for depression based on the DSM-system, which allows clinicians to assess the presence of a depressive disorder according to the DSM-IV, but also to assess the severity of the depressive symptoms. Methods We examined the sensitivity, specificity, and psychometric qualities of the MDI in a consecutive sample of 258 psychiatric outpatients. Of these patients, 120 had a mood disorder (70 major depression, 49 dysthymia). A total of 139 subjects had a comorbid axis-I diagnosis, and 91 subjects had a comorbid personality disorder. Results Crohnbach's alpha of the MDI was a satisfactory 0.89, and the correlation between the MDI and the depression subscale of the SCL-90 was 0.79 (p < .001). Subjects with major depressive disorder (MDD) had a significantly higher MDI score than subjects with anxiety disorders (but no MDD), dysthymias, bipolar, psychotic, other neurotic disorders, and subjects with relational problems. In ROC analysis we found that the area under the curve was 0.68 for the MDI. A good cut-off point for the MDI seems to be 26, with a sensitivity of 0.66, and a specificity of 0.63. The indication of the presence of MDD based on the MDI had a moderate agreement with the diagnosis made by a psychiatrist (kappa: 0.26). Conclusion The MDI is an attractive, brief depression inventory, which seems to be a reliable tool for assessing depression in psychiatric outpatients. PMID:17688685

  19. Immune system dysregulation in adolescent major depressive disorder

    PubMed Central

    Gabbay, Vilma; Klein, Rachel G.; Alonso, Carmen M.; Babb, James S.; Nishawala, Melissa; De Jesus, Georgette; Hirsch, Glenn S.; Hottinger-Blanc, Pauline M.Z.; Gonzalez, Charles J.

    2009-01-01

    Background A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon [IFN]-γ, tumor necrosis factor-α, interleukin [IL]-6, IL-1β, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-γ/IL-4. Method Thirty adolescents with MDD (19 females; 13 medication-free/naïve; ages 12–19) of at least 6 weeks duration and a minimum severity score of 40 on the Children’s Depression Rating Scale—Revised, and 15 healthy comparisons (8 females), group-matched for age, were enrolled. Plasma cytokines were examined using enzyme-linked immunosorbent assay. Mann–Whitney test was used to compare subjects with MDD and controls. Results Adolescents with MDD had significantly elevated plasma IFN-γ levels (3.38 ± 11.8 pg/ml versus 0.37 ± 0.64 pg/ml; p<0.003), and IFN-γ/IL-4 ratio (16.6 ± 56.5 versus 1.76 ± 2.28; p = 0.007). A trend for IL-6 to be elevated in the MDD group was also observed (1.52 ± 2.88 pg/ml versus 0.49 ± 0.90 pg/ml; p=0.09). Importantly, findings remained evident when medicated subjects were excluded. Conclusions Findings suggest that immune system dysregulation may be associated with adolescent MDD, with an imbalance of Th1/Th2 shifted toward Th1, as documented in adult MDD. Larger studies with medication-free adolescents should follow. PMID:18790541

  20. Transcranial magnetic stimulation for the treatment of major depression

    PubMed Central

    Janicak, Philip G; Dokucu, Mehmet E

    2015-01-01

    Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (eg, psychotherapy, medications, or their combination) are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse). Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability. PMID:26170668

  1. Major depressive disorder induced by prolactinoma--a case report.

    PubMed

    Liao, Wei-Ting; Bai, Ya-Mei

    2014-01-01

    Prolactinomas, the most common type of pituitary tumor, can induce hyperprolactinemia and cause some psychiatric symptoms, such as anxiety, depression and even psychotic symptoms. However, in previous case reports, no information about estrogen levels was mentioned. Here, we present a 48-year-old female patient who had a recurrent episode of major depressive disorder (MDD) and amenorrhea. Hyperprolactinemia (167 ng/ml), low estrogen (15.31 pg/ml) and a pituitary prolactinoma were found by MRI. After a dopamine agonist (Dostinex) and aripiprazole were prescribed, the patient's depressed mood remitted and her menstruation normalized. The possible mechanism of MDD induced by prolactinoma is discussed. PMID:24182617

  2. The Functional Anatomy of Psychomotor Disturbances in Major Depressive Disorder

    PubMed Central

    Liberg, Benny; Rahm, Christoffer

    2015-01-01

    Psychomotor disturbances (PMD) are a classic feature of depressive disorder that provides rich clinical information. The aim our narrative review was to characterize the functional anatomy of PMD by summarizing findings from neuroimaging studies. We found evidence across several neuroimaging modalities that suggest involvement of fronto-striatal neurocircuitry, and monoaminergic pathways and metabolism. We suggest that PMD in major depressive disorder emerge from an alteration of limbic signals, which influence emotion, volition, higher-order cognitive functions, and movement. PMID:25806006

  3. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    PubMed

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status. PMID:26122586

  4. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

    PubMed Central

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-01-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen's d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen's d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status. PMID:26122586

  5. Serum 25-Hydroxyvitamin D in Patients with Major Depressive Disorder

    PubMed Central

    DANA-ALAMDARI, Leila; KHEIROURI, Sorayya; NOORAZAR, Seyed Gholamreza

    2015-01-01

    Background: We investigated the association between serum 25(OH) D levels and depressive symptoms in patients with major depressive disorder (MDD). Methods: Eighty-five adults, 44 drug free patients with MDD and 41 apparently healthy controls, participated in the study. The Hamilton Depression Rating Scale was used to assess severity of major depression. Mental health of the controls was assessed according to DSM-IV criteria. Stress level of the participants was assessed by the Holmes and Rahe stress scale. Serum 25(OH) D levels was measured by immunochemiluminescence assay. Vitamin D deficiency was defined as a serum 25(OH) D concentration of lower than 20 ng/ml. Results: Depressed patients had the higher levels of stress. There was a positive correlation between stress level and disease severity (r= 0.32, P= 0.03). In total participants, mean percentage of vitamin D deficiency was 77.6% with 75% in patients and 80.5% in the healthy subjects. There were no differences between the two groups in serum 25(OH) D levels and percentage of subjects with the vitamin deficiency. A negative correlation was observed between disease severity and serum 25(OH) D level of patients with depression episodes < 2 y (r= −0.38, P = 0.08) and winter samples (samples collected and measured from December to march, r= −0.62, P = 0.004). Conclusion: Serum 25(OH) D levels were not associated with depression. However, the inverse relationship between levels of vitamin D and depressive symptoms in current depression episodes and in sun-deprived season warrants further investigation. PMID:26284211

  6. A meta-analysis of chemokines in major depression.

    PubMed

    Eyre, Harris A; Air, Tracy; Pradhan, Alyssa; Johnston, James; Lavretsky, Helen; Stuart, Michael J; Baune, Bernhard T

    2016-07-01

    Chemokines are increasingly recognised as playing a role in depression. Here we meta-analyse the data on concentrations of all chemokines in patients diagnosed with a major depression versus healthy controls. We included studies which utilised Diagnostic and Statistical Manual (DSM)-IV diagnostic criteria for major depression, participants free from major medical conditions, studies with healthy controls, and unstimulated measurements of chemokines. We only included chemokines which had ≥3 studies performed. Two chemokines and 15 studies in total met criteria for this meta-analysis; 8 for Monocyte Chemotactic Protein (MCP)-1/CCL2 (n=747), and 7 for Interleukin (IL)-8/CXCL8 (n=560). There were significantly higher concentrations of CCL2/MCP-1 in depressed subjects compared with control subjects - overall mean difference of 36.43pg/mL (95% CI: 2.43 to 70.42). There was significant heterogeneity across these studies (I2=98.5%). The estimates of mean difference between the control and depression groups did not remain significant when the trim-and-fill procedure was used to correct for publication bias. There was no significant difference in concentrations of IL-8/CXCL8 in depressed subjects compared with control subjects. Significant heterogeneity was found across these studies (I2=96.7%). The estimates of mean difference between the control and depression groups remained non-significant when the trim-and-fill procedure was used to correct for publication bias. This meta-analysis reports significantly heterogeneity in this field among studies. There are higher concentrations of the chemokine MCP-1/CCL2 in depressed subjects compared with control subjects, and no differences for IL-8/CXCL8. More high quality research and consistent methodologies are needed in this important area of enquiry. PMID:26903140

  7. The cortisol awakening response and major depression: examining the evidence

    PubMed Central

    Dedovic, Katarina; Ngiam, Janice

    2015-01-01

    A vast body of literature has revealed that dysregulation of the hypothalamic–pituitary–adrenal (HPA) stress axis is associated with etiology of major depressive disorder (MDD). There are many ways that the dysregulation of the HPA axis can be assessed: by sampling diurnal basal secretion and/or in response to a stress task, pharmacological challenge, and awakening. Here, we focus on the association between cortisol awakening response (CAR), as one index of HPA axis function, and MDD, given that the nature of this association is particularly unclear. Indeed, in the following selective review, we attempt to reconcile sometimes-divergent evidence of the role of CAR in the pathway to depression. We first examine association of CAR with psychological factors that have been linked with increased vulnerability to develop depression. Then, we summarize the findings regarding the CAR profile in those with current depression, and evaluate evidence for the role of CAR following depression resolution and continued vulnerability. Finally, we showcase longitudinal studies showing the role of CAR in predicting depression onset and recurrence. Overall, the studies reveal an important, but complex, association between CAR and vulnerability to depression. PMID:25999722

  8. Functional and structural brain correlates of risk for major depression in children with familial depression

    PubMed Central

    Chai, Xiaoqian J.; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia A.; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de los Angeles, Carlo; Whitfield-Gabrieli, Susan; Gabrieli, John D.E.

    2015-01-01

    Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group) and a group of children of parents without a history of major depression (control group). Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression. PMID:26106565

  9. Attachment as Moderator of Treatment Outcome in Major Depression: A Randomized Control Trial of Interpersonal Psychotherapy versus Cognitive Behavior Therapy

    ERIC Educational Resources Information Center

    McBride, Carolina; Atkinson, Leslie; Quilty, Lena C.; Bagby, R. Michael

    2006-01-01

    Anxiety and avoidance dimensions of adult attachment insecurity were tested as moderators of treatment outcome for interpersonal psychotherapy (IPT) and cognitive-behavioral therapy (CBT). Fifty-six participants with major depression were randomly assigned to these treatment conditions. Beck Depression Inventory-II, Six-Item Hamilton Rating Scale…

  10. Diagnosing Depression in Chronic Pain Patients: DSM-IV Major Depressive Disorder vs. Beck Depression Inventory (BDI)

    PubMed Central

    2016-01-01

    Background Diagnosing depression in chronic pain is challenging due to overlapping somatic symptoms. In questionnaires, such as the Beck Depression Inventory (BDI), responses may be influenced more by pain than by the severity of depression. In addition, previous studies have suggested that symptoms of negative self-image, a key element in depression, are uncommon in chronic pain-related depression. The object of this study is to assess the relationship of the somatic and cognitive-emotional items of BDI with the diagnosis of depression, pain intensity, and disability. Methods One hundred consecutive chronic pain patients completed the Structured Clinical Interview for DSM Disorders (SCID) for the diagnosis of major depressive disorder (MDD) according to DSM-IV. Two subscales of BDI (negative view of self and somatic-physical function) were created according to the factor model presented by Morley. Results In the regression analysis, the somatic-physical function factor associated with MDD, while the negative view of self factor did not. Patients with MDD had higher scores in several of the BDI items when analysed separately. Insomnia and weight loss were not dependent on the depression diagnosis. Limitations The relatively small sample size and the selected patient sample limit the generalisability of the results. Conclusions Somatic symptoms of depression are also common in chronic pain and should not be excluded when diagnosing depression in pain patients. Regardless of the assessment method, diagnosing depression in chronic pain remains a challenge and requires careful interpretation of symptoms. PMID:27008161

  11. Phonologically-based biomarkers for major depressive disorder

    NASA Astrophysics Data System (ADS)

    Trevino, Andrea Carolina; Quatieri, Thomas Francis; Malyska, Nicolas

    2011-12-01

    Of increasing importance in the civilian and military population is the recognition of major depressive disorder at its earliest stages and intervention before the onset of severe symptoms. Toward the goal of more effective monitoring of depression severity, we introduce vocal biomarkers that are derived automatically from phonologically-based measures of speech rate. To assess our measures, we use a 35-speaker free-response speech database of subjects treated for depression over a 6-week duration. We find that dissecting average measures of speech rate into phone-specific characteristics and, in particular, combined phone-duration measures uncovers stronger relationships between speech rate and depression severity than global measures previously reported for a speech-rate biomarker. Results of this study are supported by correlation of our measures with depression severity and classification of depression state with these vocal measures. Our approach provides a general framework for analyzing individual symptom categories through phonological units, and supports the premise that speaking rate can be an indicator of psychomotor retardation severity.

  12. Impaired social decision making in patients with major depressive disorder.

    PubMed

    Zhang, Hui-Jun; Sun, Delin; Lee, Tatia M C

    2012-07-01

    Research on how depression influences social decision making has been scarce. This study investigated how people with depression make decisions in an interpersonal trust-reciprocity game. Fifty female patients diagnosed with major depressive disorders (MDDs) and 49 healthy women participated in this study. The experiment was conducted on a one-to-one basis. Participants were asked to play the role of a trustee responsible for investing money given to them by an anonymous female investor playing on another computer station. In each trial, the investor would send to a participant (the trustee) a request for a certain percentage of the appreciated investment (repayment proportion). Since only the participant knew the exact amount of the appreciated investment, she could decide to pay more (altruistic act), the same, or less (deceptive act) than the requested amount. The participant's money acquired in the trial would be confiscated if her deceptive act was caught. The frequency of deceptive or altruistic decisions and relative monetary gain in each decision choice were examined. People with depression made fewer deceptive and fewer altruistic responses than healthy controls in all conditions. Moreover, the specific behavioral pattern presented by people with depression was modulated by the task factors, including the risk of deception detection and others' intentions (benevolence vs. malevolence). Findings of this study contribute to furthering our understanding of the specific pattern of social behavioral changes associated with depression. PMID:22950045

  13. Consumers with Major Depressive Disorder: Factors Influencing Job Placement

    ERIC Educational Resources Information Center

    Hergenrather, Kenneth C.; Haase, Eileen; Zeglin, Robert J.; Rhodes, Scott D.

    2013-01-01

    The theory of planned behavior (TPB) was applied to study the factors that influence the intention of public rehabilitation placement professionals to place consumers with major depressive disorder (MDD) in jobs. A sample of 108 public rehabilitation placement professionals in the Mid-Atlantic region of the United States completed the MDD…

  14. Interpersonal Pathoplasticity in the Course of Major Depression

    ERIC Educational Resources Information Center

    Cain, Nicole M.; Ansell, Emily B.; Wright, Aidan G. C.; Hopwood, Christopher J.; Thomas, Katherine M.; Pinto, Anthony; Markowitz, John C.; Sanislow, Charles A.; Zanarini, Mary C.; Shea, M. Tracie; Morey, Leslie C.; McGlashan, Thomas H.; Skodol, Andrew E.; Grilo, Carlos M.

    2012-01-01

    Objective: The identification of reliable predictors of course in major depressive disorder (MDD) has been difficult. Evidence suggests that the co-occurrence of personality pathology is associated with longer time to MDD remission. Interpersonal pathoplasticity, the mutually influencing nonetiological relationship between psychopathology and…

  15. Reduced Anterior Cingulate Cortex Glutamatergic Concentrations in Childhood Major Depression

    ERIC Educational Resources Information Center

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

    2004-01-01

    Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of children with major depressive disorder (MDD). Method: Single-voxel proton magnetic resonance spectroscopic ([.sup.1]H-MRS) examinations of the anterior cingulate cortex were conducted in 13 psychotropic-naive children and adolescents with MDD…

  16. Medial temporal N-acetyl aspartate in pediatric major depression

    PubMed Central

    MacMaster, Frank P.; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S. Preeya; Buhagiar, Christian; Rosenberg, David R.

    2008-01-01

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD-case control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  17. Medial temporal N-acetyl-aspartate in pediatric major depression.

    PubMed

    MacMaster, Frank P; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S Preeya; Buhagiar, Christian; Rosenberg, David R

    2008-10-30

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD case-control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in the left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  18. Selective Neurocognitive Impairments in Adolescents with Major Depressive Disorder

    ERIC Educational Resources Information Center

    Han, Georges; Klimes-Dougan, Bonnie; Jepsen, Susie; Ballard, Kristin; Nelson, Megan; Houri, Alaa; Kumra, Sanjiv; Cullen, Kathryn

    2012-01-01

    This study investigated whether major depression in adolescence is characterized by neurocognitive deficits in attention, affective decision making, and cognitive control of emotion processing. Neuropsychological tests including the Wechsler Abbreviated Scale of Intelligence, the Continuous Performance Test-Identical Pairs, the Attention Network…

  19. Abnormal Temporal Difference Reward-Learning Signals in Major Depression

    ERIC Educational Resources Information Center

    Kumar, P.; Waiter, G.; Ahearn, T.; Milders, M.; Reid, I.; Steele, J. D.

    2008-01-01

    Anhedonia is a core symptom of major depressive disorder (MDD), long thought to be associated with reduced dopaminergic function. However, most antidepressants do not act directly on the dopamine system and all antidepressants have a delayed full therapeutic effect. Recently, it has been proposed that antidepressants fail to alter dopamine…

  20. Sertraline in Children and Adolescents with Major Depressive Disorder

    ERIC Educational Resources Information Center

    Donnelly, Craig L.; Wagner, Karen Dineen; Rynn, Moira; Ambrosini, Paul; Landau, Phyllis; Yang, Ruoyong; Wohlberg, Christopher J.

    2006-01-01

    Objective: To explore time to first response and time to first persistent response of sertraline versus placebo and compare these parameters between children (6-11 years old, n = 177) and adolescents (12-17 years old, n = 199) with major depressive disorder. Method: A 10-week placebo-controlled treatment was followed by a 24-week open-label…

  1. Neuroendocrine response to L-5-hydroxytryptophan challenge in prepubertal major depression. Depressed vs normal children.

    PubMed

    Ryan, N D; Birmaher, B; Perel, J M; Dahl, R E; Meyer, V; al-Shabbout, M; Iyengar, S; Puig-Antich, J

    1992-11-01

    The neuroendocrine response to L-5-hydroxytryptophan was compared in 37 prepubertal children who met the Research Diagnostic Criteria for major depressive disorder with that in 23 normal children with no lifetime history of any psychiatric disorder and very low rates of depression in both first- and second-degree relatives. Intravenous L-5-hydroxytryptophan (0.8 mg/kg) was given over a 1-hour interval after preloading with oral carbidopa, an inhibitor of peripheral but not central L-5-hydroxytryptophan metabolism. L-5-Hydroxytryptophan, a precursor of serotonin, increases serotonin turnover in the central nervous system when given after carbidopa. Seven (19%) of the 37 children with major depressive disorder and two (9%) of the 23 normal children had nausea or vomiting and therefore did not complete the full infusion. They were subsequently excluded from data analysis. After this stimulation, prolactin, cortisol, and growth hormone secretion were compared between diagnostic groups. The depressed children secreted significantly less cortisol (effect size, 0.70) and significantly more prolactin (effect size, 0.83). There was a sex-by-diagnosis interaction in prolactin response to L-5-hydroxytryptophan and, on examination, the prolactin hypersecretion was seen in depressed girls but not in depressed boys compared with same-sex controls. There was no significant stimulation of growth hormone in either group. These findings are consistent with dysregulation of central serotonergic systems in childhood major depression. PMID:1444721

  2. The genetics of major depression: Moving beyond the monoamine hypothesis

    PubMed Central

    Shyn, Stanley I.; Hamilton, Steven P.

    2009-01-01

    SYNOPSIS Efforts to unlock the biology of major depressive disorder (MDD) are proceeding on multiple fronts. In this article, we review our current understanding of epidemiologic evidence for a heritable component to MDD risk, as well as recent advances in linkage, candidate gene, and genome-wide association analyses of MDD and related disease subtypes and endophenotypes. While monoamine signaling has preoccupied the bulk of scientific investigation to date, non-traditional gene candidates such as PCLO and GRM7 are now emerging and beginning to change the landscape for future human and animal research on depression. PMID:20159343

  3. Predicting clinical responses in major depression using intrinsic functional connectivity.

    PubMed

    Qin, Jian; Shen, Hui; Zeng, Ling-Li; Jiang, Weixiong; Liu, Li; Hu, Dewen

    2015-08-19

    There has been increasing interest in multivariate pattern analysis (MVPA) as a means of distinguishing psychiatric patients from healthy controls using brain imaging. However, it remains unclear whether MVPA methods can accurately estimate the medication status of psychiatric patients. This study aims to develop an MVPA approach to accurately predict the antidepressant medication status of individuals with major depression on the basis of whole-brain resting-state functional connectivity MRI (rs-fcMRI). We investigated data from rs-fcMRI of 24 medication-naive depressed patients, 16 out of whom subsequently underwent antidepressant treatment and achieved clinical recovery, and 29 demographically similar controls. By training a linear support vector machine classifier and combining it with principal component analysis, the medication-naive patients were identified from the healthy controls with 100% accuracy. In addition, we found reliable correlations between MVPA prediction scores and clinical symptom severity. Moreover, the most discriminative functional connections were located within or across the cerebellum and default mode, affective, and sensorimotor networks, indicating that these networks may play important roles in major depression. Most importantly, only ∼30% of these discriminative connections were normalized in clinically recovered patients after antidepressant treatment. The current study may not only show the feasibility of estimating medication status by MVPA of whole-brain rs-fcMRI data in major depression but also shed new light on the pathological mechanism of this disorder. PMID:26164454

  4. Differences in depressive symptoms between Korean and American outpatients with major depressive disorder.

    PubMed

    Jeon, Hong Jin; Walker, Rosemary S; Inamori, Aya; Hong, Jin Pyo; Cho, Maeng Je; Baer, Lee; Clain, Alisabet; Fava, Maurizio; Mischoulon, David

    2014-05-01

    Previous epidemiologic studies have revealed that East-Asian populations experience fewer depressive symptoms than American populations do. However, it is unclear whether this difference applies to clinical patients with major depressive disorder (MDD). This present study included 1592 Korean and 3744 American outpatients who were 18 years of age or older and met the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria for single or recurrent episodes of nonpsychotic MDD, and evaluated their symptoms of depression using the Hamilton Depression Rating Scale and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form. Korean patients scored significantly lower for guilt and depressed mood items, and higher for hypochondriasis and suicidality items than American patients did, after adjusting for total Hamilton Depression Rating Scale scores. Conversely, no significant differences were found in quality and function of daily life between groups. Multivariate logistic regression analyses revealed that Korean patients experienced less frequent depressed mood and guilt, including verbal and nonverbal expression of depressed mood [adjusted odds ratio (AOR) = 0.14, 95% confidence interval (CI) 0.08-0.23] and feelings of punishment (AOR = 0.036, 95% CI 0.025-0.054) when compared with Americans after adjusting for age and sex. Conversely, Korean patients experienced more frequent suicidality and hypochondriasis, including suicidal ideas or gestures (AOR = 2.10, 95% CI 1.60-2.76) and self-absorption of hypochondriasis (AOR = 1.94, 95% CI 1.70-2.20). In conclusion, decreased expression of depressed mood and guilt may cause underdiagnosis of MDD in Korean patients. Early diagnosis of and intervention for depression and suicide may be delayed because of this specific cross-cultural difference in depression symptoms. PMID:24323201

  5. Dental management of the geriatric patient with major depression.

    PubMed

    Friedlander, A H; Kawakami, K K; Ganzell, S; Fitten, L J

    1993-01-01

    Major depression is a psychiatric disorder in which mood, thought content, and behavioral patterns are impaired, often for an extended period of time. The condition is encountered among elderly persons admitted to the hospital and those residing in nursing homes. Major depression is predominantly biologic in origin and may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. It is associated with personal neglect, including a disinterest in performing appropriate preventive oral hygiene techniques. The majority of antidepressant medications cause xerostomia and magnify the incidence of dental disease. Appropriate dental management of patients with the disorder necessitates the use of anti-caries agents containing fluoride, saliva substitutes, and special precautions when analgesics and local anesthetics are being prescribed or administered. Dental treatment helps to improve the patient's self-image and quality of life. PMID:8042134

  6. Reduced Venous Blood Basophil Count and Anxious Depression in Patients with Major Depressive Disorder

    PubMed Central

    Baek, Ji Hyun; Kim, Hee-Jin; Fava, Maurizio; Mischoulon, David; Papakostas, George I; Nierenberg, Andrew; Heo, Jung-Yoon

    2016-01-01

    Objective Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between white blood cell (WBC) subset counts and anxiety in individuals with major depressive disorder (MDD). Methods A total of 709 patients who were newly diagnosed with MDD were recruited. Anxiety levels of participants were evaluated using the Anxiety/ Somatization subitem of the Hamilton Depression Rating Scale. The association between WBC subset fraction and anxiety was evaluated. Results Basophil and eosinophil sub-fractions showed significant negative correlations with HAM-D anxiety/somatization factor scores (basophils: r=-0.092, p=0.014 and eosinophils: r=-0.075, p=0.046). When an anxiety score (a sum of somatic and psychic anxiety) was entered as a dependent variable, only basophils showed significant negative association with the anxiety scores after adjusting for all other WBC subset counts and demographic factors (t=-2.57, p=0.010). Conclusion This study showed that anxious depression had a decreased basophil subfraction, which might be associated with involvement of inflammation in development of anxious depression. PMID:27247599

  7. Imaging genetics studies on monoaminergic genes in major depressive disorder.

    PubMed

    Won, Eunsoo; Ham, Byung-Joo

    2016-01-01

    Although depression is the leading cause of disability worldwide, current understanding of the neurobiology of depression has failed to be translated into clinical practice. Major depressive disorder (MDD) pathogenesis is considered to be significantly influenced by multiple risk genes, however genetic effects are not simply expressed at a behavioral level. Therefore the concept of endophenotype has been applied in psychiatric genetics. Imaging genetics applies anatomical or functional imaging technologies as phenotypic assays to evaluate genetic variation and their impact on behavior. This paper attempts to provide a comprehensive review of available imaging genetics studies, including reports on genetic variants that have most frequently been linked to MDD, such as the monoaminergic genes (serotonin transporter gene, monoamine oxidase A gene, tryptophan hydroxylase-2 gene, serotonin receptor 1A gene and catechol-O-methyl transferase gene), with regard to key structures involved in emotion processing, such as the hippocampus, amygdala, anterior cingulate cortex and orbitofrontal cortex. PMID:25828849

  8. Vortioxetine for the treatment of major depressive disorder.

    PubMed

    Tritschler, Laurent; Felice, Daniela; Colle, Romain; Guilloux, Jean-Philippe; Corruble, Emmanuelle; Gardier, Alain Michel; David, Denis Joseph

    2014-11-01

    Vortioxetine (Brintellix(®), 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a multimodal antidepressant targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin (5-HT) transporter (5-HTT). Vortioxetine administration induces antidepressant- and anxiolytic-like effects, and can enhance cognitive performance in rodents. Several clinical trials have reported the efficiency and a satisfactory tolerability of vortioxetine treatment in depressed patients. Remarkably, vortioxetine has a specific positive impact on cognitive symptoms in depressed patients. Overall, vortioxetine is an efficacious antidepressant drug for the treatment of patients with a major depressive episode and has a unique mechanism of action offering a new therapeutic option. PMID:25166025

  9. A Review of Vilazodone, Serotonin, and Major Depressive Disorder

    PubMed Central

    Thase, Michael E.

    2014-01-01

    Objective: To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission, focusing on serotonin 1A (5-HT1A) autoreceptors, which are proposed to be involved in delaying therapeutic efficacy. Vilazodone was specifically designed to function both as an SSRI and a partial agonist at 5-HT1A receptors. This combined mechanism is proposed to decrease time to efficacy, minimize sexual side effects, and provide concomitant anxiolytic properties. Data Sources: A PubMed search of all English-language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A, depression and buspirone, depression and pindolol, and vilazodone. Study Selection: We found 47 articles and abstracts that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol, buspirone, and vilazodone in depression. Data Extraction: This review summarizes current literature involving antidepressant activity, the role of 5-HT1A autoreceptors, and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists, with a focus on vilazodone. Results:Vilazodone has demonstrated efficacy in 2 large, randomized, double-blind, placebo-controlled trials in major depressive disorder. Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety. A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy. Conclusions: If future studies corroborate the clinical benefits attributed to its mechanism of action, vilazodone may show potential advantages in terms of onset of action, sexual side effects, and anxiolytic activity in patients with major depressive disorder. PMID:24940527

  10. Executive Attention Impairment in Adolescents With Major Depressive Disorder.

    PubMed

    Sommerfeldt, Sasha L; Cullen, Kathryn R; Han, Georges; Fryza, Brandon J; Houri, Alaa K; Klimes-Dougan, Bonnie

    2016-01-01

    Neural network models that guide neuropsychological assessment practices are increasingly used to explicate depression, though a paucity of work has focused on regulatory systems that are under development in adolescence. The purpose of this study was to evaluate subsystems of attention related to executive functioning including alerting, orienting, and executive attention networks, as well as sustained attention with varying working memory load, in a sample of depressed and well adolescents. Neuropsychological functioning in 99 adolescents diagnosed with major depressive disorder (MDD) and 63 adolescent healthy controls (M = 16.6 years old) was assessed on the Attention Network Test (ANT) and the Continuous Performance Test, Identical Pairs. Adolescents with MDD, particularly those who were not medicated, were slower to process conflict (slower reaction time on the Executive Attention scale of the ANT) compared to controls, particularly for those who were not undergoing psychopharmacological treatment. Tentative evidence also suggests that within the MDD group, orienting performance was more impaired in those with a history of comorbid substance use disorder, and alerting was more impaired in those with a history of a suicide attempt. Adolescents with depression showed impaired executive attention, although cognitive performance varied across subgroups of patients. These findings highlight the importance of examining neurocognitive correlates associated with features of depression and suggest an avenue for future research to help guide the development of interventions. PMID:26566871

  11. Altered fecal microbiota composition in patients with major depressive disorder.

    PubMed

    Jiang, Haiyin; Ling, Zongxin; Zhang, Yonghua; Mao, Hongjin; Ma, Zhanping; Yin, Yan; Wang, Weihong; Tang, Wenxin; Tan, Zhonglin; Shi, Jianfei; Li, Lanjuan; Ruan, Bing

    2015-08-01

    Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker. PMID:25882912

  12. Executive Attention Impairment in Adolescents with Major Depressive Disorder

    PubMed Central

    Sommerfeldt, Sasha L.; Cullen, Kathryn R.; Han, Georges; Fryza, Brandon J.; Houri, Alaa K.; Klimes-Dougan, Bonnie

    2015-01-01

    Objective Neural network models that guide neuropsychological assessment practices are increasingly used to explicate depression, though a paucity of work has focused on regulatory systems that are under development in adolescence. The purpose of this study was to evaluate subsystems of attention related to executive functioning including alerting, orienting, and executive attention networks, as well as sustained attention with varying working memory load, in a sample of depressed and well adolescents. Method Neuropsychological functioning in 99 adolescents diagnosed with major depressive disorder (MDD) and 63 adolescent healthy controls (M = 16.6 years old) was assessed on the Attention Network Task (ANT) and the Continuous Performance Test, Identical Pairs (CPT). Results Adolescents with MDD, particularly those who were not medicated, were slower to process conflict (slower reaction time on the executive attention scale of the ANT) compared to controls, particularly for those who were not undergoing psychopharmacological treatment. Tentative evidence also suggests that within the MDD group, orienting performance was more impaired in those with a history of comorbid substance use disorder, and alerting was more impaired in those with a history of a suicide attempt. Conclusions Adolescents with depression showed impaired executive attention, although cognitive performance varied across subgroups of patients. These findings highlight the importance of examining neurocognitive correlates associated with features of depression and suggest an avenue for future research to help guide the development of interventions. PMID:26566871

  13. Rapid recovery from major depression using magnesium treatment.

    PubMed

    Eby, George A; Eby, Karen L

    2006-01-01

    Major depression is a mood disorder characterized by a sense of inadequacy, despondency, decreased activity, pessimism, anhedonia and sadness where these symptoms severely disrupt and adversely affect the person's life, sometimes to such an extent that suicide is attempted or results. Antidepressant drugs are not always effective and some have been accused of causing an increased number of suicides particularly in young people. Magnesium deficiency is well known to produce neuropathologies. Only 16% of the magnesium found in whole wheat remains in refined flour, and magnesium has been removed from most drinking water supplies, setting a stage for human magnesium deficiency. Magnesium ions regulate calcium ion flow in neuronal calcium channels, helping to regulate neuronal nitric oxide production. In magnesium deficiency, neuronal requirements for magnesium may not be met, causing neuronal damage which could manifest as depression. Magnesium treatment is hypothesized to be effective in treating major depression resulting from intraneuronal magnesium deficits. These magnesium ion neuronal deficits may be induced by stress hormones, excessive dietary calcium as well as dietary deficiencies of magnesium. Case histories are presented showing rapid recovery (less than 7 days) from major depression using 125-300 mg of magnesium (as glycinate and taurinate) with each meal and at bedtime. Magnesium was found usually effective for treatment of depression in general use. Related and accompanying mental illnesses in these case histories including traumatic brain injury, headache, suicidal ideation, anxiety, irritability, insomnia, postpartum depression, cocaine, alcohol and tobacco abuse, hypersensitivity to calcium, short-term memory loss and IQ loss were also benefited. Dietary deficiencies of magnesium, coupled with excess calcium and stress may cause many cases of other related symptoms including agitation, anxiety, irritability, confusion, asthenia, sleeplessness

  14. The GABAergic Deficit Hypothesis of Major Depressive Disorder

    PubMed Central

    Luscher, Bernhard; Shen, Qiuying; Sahir, Nadia

    2012-01-01

    Increasing evidence points to an association between major depressive disorders (MDDs) and diverse types of GABAergic deficits. Here we summarize clinical and preclinical evidence supporting a central and causal role of GABAergic deficits in the etiology of depressive disorders. Studies of depressed patients indicate that MDDs are accompanied by reduced brain concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) as well as alterations in the subunit composition of the principal receptors (GABAA receptors) mediating GABAergic inhibition. In addition, there is abundant evidence that GABA plays a prominent role in the brain control of stress, the most important vulnerability factor in mood disorders. Furthermore, preclinical evidence suggests that currently used antidepressant drugs designed to alter monoaminergic transmission as well as non-pharmacologic therapies may ultimately act to counteract GABAergic deficits. In particular, GABAergic transmission plays an important role in the control of hippocampal neurogenesis and neural maturation, which are now established as cellular substrates of most if not all antidepressant therapies. Lastly, comparatively modest deficits in GABAergic transmission in GABAA-receptor-deficient mice are sufficient to cause behavioral, cognitive, neuroanatomical, and neuroendocrine phenotypes as well as antidepressant drug response characteristics expected of an animal model of MDD. The GABAergic hypothesis of MDD suggests that alterations in GABAergic transmission represent fundamentally important aspects of the etiological sequelae of major depressive disorders that are reversed by monoaminergic antidepressant drug action. PMID:21079608

  15. Major depression epidemiology from a diathesis-stress conceptualization

    PubMed Central

    2013-01-01

    Background Major depression is a widely used diagnostic category but there is increasing dissatisfaction with its performance. The diathesis-stress model is an alternative approach that does not require the (sometimes arbitrary) imposition of categories onto the spectrum of depressive morbidity. However, application of this model has not been well explored and its consistency with available epidemiologic data is uncertain. Methods Simulation provides an opportunity to explore these issues. In this study, a simulation model based on an intuitive representation of diathesis-stress interaction was developed. Both diathesis and stress were represented using continuous distributions, without categorization. A diagnostic threshold was then applied to the simulation output to create nominal categories and to explore their consistency with available information. Results An apparently complex epidemiologic pattern emerged from the diathesis-stress interaction when thresholds were applied: incidence was time dependent, recurrence depended on the number of past episodes, baseline symptoms were associated with an increased risk of subsequent episodes and the remission rate declined with increasing episode duration. Conclusions A diathesis-stress conceptualization coupled with application of a threshold-based diagnostic definition may explain several of the apparent complexities of major depression epidemiology. Some of these complexities may be artifacts of the nominal diagnostic approach. These observations should encourage an empirical exploration of whether diathesis-stress interactions provide a more parsimonious framework for understanding depression than current approaches. PMID:23305517

  16. [Bipolarity correlated factors in major depression: about 155 Tunisian inpatients].

    PubMed

    Gassab, L; Mechri, A; Gaha, L; Khiari, G; Zaafrane, F; Zougaghi, L

    2002-01-01

    The distinction between the depressive troubles according to their inclusion in bipolar disorders or in recurrent depressive disorders offers an evident practical interest. In fact, the curative and mainly the preventive treatment of these troubles are different. So it is necessary to identify the predictive factors of bipolar development in case of inaugural depressive episode. In 1983, Akiskal was the first who identified those factors: pharmacological hypomania, puerperal depression, onset at early age (<25 years), presence of psychotic characteristics, hypersomnia and psychomotor inhibition. Through this study, the authors try to compare the epidemiological, clinical and evolution characteristics of major depression in bipolar disorders to recurrent depressive disorders in order to indicate the correlated factors with bipolarity. It is a retrospective and comparative study based on about 155 inpatients for major depressive episode during the period between January 1994 and December 1998. These patients were divided into two groups according the DSM IV criteria: bipolar group (96 patients) and recurrent depressive group (59 patients). Both groups were compared according to socio-demographic data, life events in childhood, personal and family history, clinical and evolution characteristics of the index depressive episode. The predictive factors proposed by Akiskal were systematically examined. It was found out that the following factors were correlated with bipolarity: high rate of separation and divorce (17.7% versus 5.1%; p=0.02), family history of psychiatric disorders (56.3% versus 35.6%; p=0.012) especially bipolar ones (29.2% versus 3.4%; p=0,00008), onset at early age (mean age of onset: 24.8 8.2 years versus 34.1 12.6 years; p=0.000004), number of affective episode significantly more frequent (mean 3.6 versus 2.5; p=0.03), sudden onset of depressive episode (44.8% versus 15.9%; p=0.0003) and presence of psychotic characteristics (69.8% versus 16.7%; p=0

  17. Neural origins of psychosocial functioning impairments in major depression.

    PubMed

    Pulcu, Erdem; Elliott, Rebecca

    2015-09-01

    Major depressive disorder, a complex neuropsychiatric condition, is associated with psychosocial functioning impairments that could become chronic even after symptoms remit. Social functioning impairments in patients could also pose coping difficulties to individuals around them. In this Personal View, we trace the potential neurobiological origins of these impairments down to three candidate domains-namely, social perception and emotion processing, motivation and reward value processing, and social decision making. We argue that the neural basis of abnormalities in these domains could be detectable at different temporal stages during social interactions (eg, before and after decision stages), particularly within frontomesolimbic networks (ie, frontostriatal and amygdala-striatal circuitries). We review some of the experimental designs used to probe these circuits and suggest novel, integrative approaches. We propose that an understanding of the interactions between these domains could provide valuable insights for the clinical stratification of major depressive disorder subtypes and might inform future developments of novel treatment options in return. PMID:26360902

  18. Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder.

    PubMed

    Rethorst, Chad D; Tu, Jian; Carmody, Thomas J; Greer, Tracy L; Trivedi, Madhukar H

    2016-08-01

    Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise. PMID:27136412

  19. Achieving adolescent adherence to treatment of major depression

    PubMed Central

    Staton, Dennis

    2010-01-01

    When treatments are ordered for adolescent major depression, or for other adolescent medical illnesses, adherence and clinical outcomes are likely to be unsatisfactory, unless 4 basic principles of the medical treatment of adolescent illness are implemented. These comprise providing effective patient and parent/caregiver education, establishing effective patient and caregiver therapeutic alliances, providing effective treatment, and managing other factors associated with treatment adherence as indicated. The goals of treatment are to achieve the earliest possible response and remission. Failure to treat adolescent major depression successfully has potentially serious consequences, including worsened adherence, long-term morbidity, and suicide attempt. Accordingly, prescribed treatment must be aggressively managed. Doses of an antidepressant medication should be increased as rapidly as can be tolerated, preferably every 1–2 weeks, until full remission is achieved or such dosing is limited by the emergence of unacceptable adverse effects. A full range of medication treatment options must be employed if necessary. Treatment adherence, occurrence of problematic adverse effects, clinical progress, and safety must be systematically monitored. Adolescents with major depression must be assessed for risk of harm to self or others. When this risk appears significant, likelihood of successful outcomes will be enhanced by use of treatment plans that comprehensively address factors associated with treatment nonadherence. Abbreviated and comprehensive plans for the treatment of potentially fatal adolescent illnesses are outlined in this review. PMID:24600263

  20. Levomilnacipran for the treatment of major depressive disorder: a review.

    PubMed

    Asnis, Gregory M; Henderson, Margaret A

    2015-01-01

    Levomilnacipran (LVM, Fetzima(®)) was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. It is a unique dual neurotransmitter reuptake inhibitor. In contrast with other selective serotonin norepinephrine reuptake inhibitors, including duloxetine, venlafaxine, and desvenlafaxine, it has greater selectivity for inhibiting norepinephrine reuptake than serotonin reuptake. Our review focuses on the efficacy, safety, and tolerability data for five double-blind, placebo-controlled, short-term studies and two long-term studies. In the short-term studies, LVM was found to be more effective than placebo in reducing depression (Montgomery-Åsberg Depression Rating Scale) scores as well as improving functional impairment (Sheehan Disability Scale) scores. Long-term studies found LVM to be similarly effective but in the only placebo-controlled long-term study, LVM was not significantly superior to placebo. LVM is fairly well tolerated, with the most common adverse events being nausea, headache, dry mouth, hyperhidrosis, and constipation. Discontinuation rates were mildly increased in those being treated with LVM (9%) versus placebo (3%). Adverse events were not dose-related except for urinary hesitancy and erectile dysfunction. LVM was weight neutral, was not toxic to the liver, and did not cause clinically significant QTc prolongation. Consistent with being a predominant potentiator of norepinephrine, pulse and blood pressure were significantly elevated by LVM but rarely induced tachycardia or hypertension. LVM is a relatively safe alternative antidepressant treatment with minimal drug-drug interactions. It is the only antidepressant that has in its labeling that it is not only effective in improving depression but also effective in improving impaired functioning. Whether this important effect on functioning is unique to LVM must be researched. In addition, whether LVM might be effective in norepinephrine

  1. Levomilnacipran for the treatment of major depressive disorder: a review

    PubMed Central

    Asnis, Gregory M; Henderson, Margaret A

    2015-01-01

    Levomilnacipran (LVM, Fetzima®) was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. It is a unique dual neurotransmitter reuptake inhibitor. In contrast with other selective serotonin norepinephrine reuptake inhibitors, including duloxetine, venlafaxine, and desvenlafaxine, it has greater selectivity for inhibiting norepinephrine reuptake than serotonin reuptake. Our review focuses on the efficacy, safety, and tolerability data for five double-blind, placebo-controlled, short-term studies and two long-term studies. In the short-term studies, LVM was found to be more effective than placebo in reducing depression (Montgomery-Åsberg Depression Rating Scale) scores as well as improving functional impairment (Sheehan Disability Scale) scores. Long-term studies found LVM to be similarly effective but in the only placebo-controlled long-term study, LVM was not significantly superior to placebo. LVM is fairly well tolerated, with the most common adverse events being nausea, headache, dry mouth, hyperhidrosis, and constipation. Discontinuation rates were mildly increased in those being treated with LVM (9%) versus placebo (3%). Adverse events were not dose-related except for urinary hesitancy and erectile dysfunction. LVM was weight neutral, was not toxic to the liver, and did not cause clinically significant QTc prolongation. Consistent with being a predominant potentiator of norepinephrine, pulse and blood pressure were significantly elevated by LVM but rarely induced tachycardia or hypertension. LVM is a relatively safe alternative antidepressant treatment with minimal drug–drug interactions. It is the only antidepressant that has in its labeling that it is not only effective in improving depression but also effective in improving impaired functioning. Whether this important effect on functioning is unique to LVM must be researched. In addition, whether LVM might be effective in norepinephrine

  2. Smoking and Major Depressive Disorder in Chinese Women

    PubMed Central

    Shi, Shenxun; Gao, Jingfang; Tao, Ming; Zhang, Kerang; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; 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, Ying; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S.; Wang, Xumei; Li, Youhui; Flint, Jonathan

    2014-01-01

    Objective To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers. Methods We examined the smoking status and clinical features in 6120 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 smoking status and between risk factors for MDD and smoking status. Results Among the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias), with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence. Conclusions Although depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors. PMID:25180682

  3. BDNF plasma levels variations in major depressed patients receiving duloxetine.

    PubMed

    Fornaro, Michele; Escelsior, Andrea; Rocchi, Giulio; Conio, Benedetta; Magioncalda, Paola; Marozzi, Valentina; Presta, Andrea; Sterlini, Bruno; Contini, Paola; Amore, Mario; Fornaro, Pantaleo; Martino, Matteo

    2015-05-01

    It has been frequently reported that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of major depressive disorder (MDD). Objective of the study was to investigate BDNF levels variations in MDD patients during antidepressant treatment with duloxetine. 30 MDD patients and 32 healthy controls were assessed using Hamilton Depression Scale (HAM-D) and monitored for BDNF plasma levels at baseline, week 6 and week 12 of duloxetine treatment (60 mg/day) and at baseline, respectively. According to early clinical response to duloxetine (defined at week 6 by reduction >50 % of baseline HAM-D score), MDD patients were distinguished in early responders (ER) and early non-responders (ENR), who reached clinical response at week 12. Laboratory analysis showed significant lower baseline BDNF levels among patients compared to controls. During duloxetine treatment, in ENR BDNF levels increased, reaching values not significantly different compared to controls, while in ER BDNF levels remained nearly unchanged. Lower baseline BDNF levels observed in patients possibly confirm an impairment of the NEI stress-adaptation system and neuroplasticity in depression, while BDNF increase and normalization observed only in ENR might suggest differential neurobiological backgrounds in ER vs. ENR within the depressive syndrome. PMID:25501804

  4. Discrimination, Family Relationships, and Major Depression Among Asian Americans

    PubMed Central

    Chae, David H.; Lee, Sunmin; Lincoln, Karen D.; Ihara, Emily S.

    2012-01-01

    Background Depression represents a growing concern among Asian Americans. This study examined whether discrimination and family dynamics are associated with depression in this population. Methods Weighted logistic regressions using nationally representative data on Asian American adults (N = 2095) examining associations between discrimination, negative interactions with relatives, family support, and 12-month major depressive disorder (MDD). Results Discrimination (odds ratio [OR] = 2.13, 95% confidence interval [CI] = 1.67, 2.71) and negative interactions with relatives (OR = 1.28, 95% CI = 1.03, 1.58) were positively associated with MDD. Family support was associated with lower MDD (OR = 0.73, 95% CI = 0.59, 0.89), and buffered lower levels of discrimination. Discussion Results suggest that discrimination may have negative mental health implications, and also point to the importance of family relationships for depression among Asian Americans. Findings suggest that providers may consider stress experienced at multiple ecological levels to address Asian American mental health needs. PMID:22083344

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

    PubMed Central

    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

    2014-01-01

    Objectives Despite different treatments and course 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). Methods 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. Results 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. Conclusions 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. PMID:24990479

  6. Sensitivity and Specificity of the Beck Depression Inventory-II in Persons With Traumatic Brain Injury

    PubMed Central

    Homaifar, Beeta Y.; Brenner, Lisa A.; Gutierrez, Peter M.; Harwood, Jeri F.; Thompson, Caitlin; Filley, Christopher M.; Kelly, James P.; Adler, Lawrence E.

    2016-01-01

    Objectives Our objective was to examine the Beck Depression Inventory-II (BDI-II) in a traumatic brain injury (TBI) sample using a receiver operating characteristic (ROC) curve to determine how well the BDI-II identifies depression. An ROC curve allows for analysis of the sensitivity and specificity of a diagnostic test using various cutoff points to determine the number of true positives, true negatives, false positives, and false negatives. Design This was a secondary analysis of data gathered from an observational study. We examined BDI-II scores in a sample of 52 veterans with remote histories of TBI. Setting This study was completed at a Veterans Affairs (VA) Medical Center. Participants Participants were veterans eligible to receive VA health care services. Interventions Not applicable. Main Outcome Measures Outcome measures included the BDI-II and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-IV). Results We generated an ROC curve to determine how well the BDI-II identifies depression using the SCID-IV as the criterion standard for diagnosing depression, defined here as a diagnosis of major depressive disorder. Results indicated a cutoff score of at least 19 if one has a mild TBI or at least 35 if one has a moderate or severe TBI. These scores maximize sensitivity (87%) and specificity (79%). Conclusions Clinicians working with persons with TBI can use the BDI-II to determine whether depressive symptoms warrant further assessment. PMID:19345782

  7. Branched-Chain Amino Acids as New Biomarkers of Major Depression - A Novel Neurobiology of Mood Disorder

    PubMed Central

    Baranyi, Andreas; Amouzadeh-Ghadikolai, Omid; von Lewinski, Dirk; Rothenhäusler, Hans-Bernd; Theokas, Simon; Robier, Christoph; Mangge, Harald; Reicht, Gerhard; Hlade, Peter; Meinitzer, Andreas

    2016-01-01

    Background The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are altered in patients with major depression and might thus be appropriate biomarkers for major depression. Methods The concentrations of valine, leucine and isoleucine were determined in 71 in-patients with major depression and 48 healthy controls by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at the time of in-patient admittance. Results The BCAAs are significantly decreased in patients with major depression in comparison with healthy subjects (valine: Mann-Whitney-U: 968.0; p <0.0001, leucine: Mann-Whitney-U: 1246.5; p = 0.013, isoleucine: Mann-Whitney-U: 1252.5; p = 0.014). Furthermore, as shown by Spearman's rank correlation coefficients, there is a significant negative correlation between valine, leucine and isoleucine concentrations and the Hamilton Depression Rating Scale (HAMD-17) as well as Beck Depression Inventory (BDI-II) scores. Conclusions Our study results are strong evidence that in patients with major depression, BCAAs might be appropriate biomarkers for depression. Reduced activation of the mammalian target of rapamycin (mTor) due to a reduction of BCAAs might play a crucial unrecognised factor in the etiology of depression and may evoke depressive symptomatology and lower energy metabolism in patients with major depression. In the future, mTor and its up- and downstream signalling partners might be important targets for the development of novel antidepressants. PMID:27490818

  8. Assessment of psychological pain in major depressive episodes.

    PubMed

    Mee, Steven; Bunney, Blynn G; Bunney, William E; Hetrick, William; Potkin, Steven G; Reist, Christopher

    2011-11-01

    Severe psychological or mental pain is defined as an experience of unbearable torment which can be associated with a psychiatric illness (e.g., major depressive disorder) or a tragic loss such as the death of a child. A brief self-rating scale (Mee-Bunney Psychological Pain Assessment Scale [MBPPAS]) was developed to assess the intensity of psychological pain. The scale was used to measure psychological pain in 73 major depressive episode (MDE) patients and 96 non-psychiatric controls. In addition to the MBPPAS, all subjects completed four additional instruments: Suicidal Behavior Questionnaire (SBQ), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), and the Brief Pain Inventory (BPI). Known-groups, content and convergent validity, and internal reliability of the scale were established. MDE and control subjects were ranked according to MBPPAS scores. A threshold was set at 32 representing 0.5 SD above the mean for MDEs. MDE subjects above the threshold of 32 had significantly higher SBQ scores than those below. A significant linear correlation between psychological pain and SBQ suicidality scores was observed. This is the first study to contrast psychological pain in controls and patients with MDE. Our results suggest that psychological pain is a useful and unique construct in patients with MDE that can be reliably assessed and may aid in the evaluation of suicidal risk. PMID:21831397

  9. Circuits regulating pleasure and happiness in major depression.

    PubMed

    Loonen, A J M; Ivanova, S A

    2016-02-01

    The introduction of selective serotonin reuptake inhibitors has gradually changed the borders of the major depression disease class. Anhedonia was considered a cardinal symptom of endogenous depression, but the potential of selective serotonin reuptake inhibitors to treat anxiety disorders has increased the relevance of stress-induced morbidity. This shift has led to an important heterogeneity of current major depressive disorder. The complexity can be disentangled by postulating the existence of two different but mutually interacting neuronal circuits regulating the intensity of anhedonia (lack of pleasure) and dysphoria (lack of happiness). These circuits are functionally dominated by partly closed limbic (regulating misery-fleeing behaviour) and extrapyramidal (regulating reward-seeking behaviour) cortico-striato-thalamo-cortical (CSTC) circuits. The re-entry circuits include the shell and core parts of the accumbens nucleus, respectively. Pleasure can be considered to result from finding relief from the hypermotivation to exhibit rewarding behaviour, and happiness from finding relief from negative or conflicting circumstances. Hyperactivity of the extrapyramidal CSTC circuit results in craving, whereas hyperactivity of the limbic system results in dysphoria. PMID:26826634

  10. Modelling cognitive affective biases in major depressive disorder using rodents.

    PubMed

    Hales, Claire A; Stuart, Sarah A; Anderson, Michael H; Robinson, Emma S J

    2014-10-01

    Major depressive disorder (MDD) affects more than 10% of the population, although our understanding of the underlying aetiology of the disease and how antidepressant drugs act to remediate symptoms is limited. Major obstacles include the lack of availability of good animal models that replicate aspects of the phenotype and tests to assay depression-like behaviour in non-human species. To date, research in rodents has been dominated by two types of assays designed to test for depression-like behaviour: behavioural despair tests, such as the forced swim test, and measures of anhedonia, such as the sucrose preference test. These tests have shown relatively good predictive validity in terms of antidepressant efficacy, but have limited translational validity. Recent developments in clinical research have revealed that cognitive affective biases (CABs) are a key feature of MDD. Through the development of neuropsychological tests to provide objective measures of CAB in humans, we have the opportunity to use 'reverse translation' to develop and evaluate whether similar methods are suitable for research into MDD using animals. The first example of this approach was reported in 2004 where rodents in a putative negative affective state were shown to exhibit pessimistic choices in a judgement bias task. Subsequent work in both judgement bias tests and a novel affective bias task suggest that these types of assay may provide translational methods for studying MDD using animals. This review considers recent work in this area and the pharmacological and translational validity of these new animal models of CABs. PMID:24467454

  11. Altered hippocampal morphology in unmedicated patients with major depressive illness.

    PubMed

    Bearden, Carrie E; Thompson, Paul M; Avedissian, Christina; Klunder, Andrea D; Nicoletti, Mark; Dierschke, Nicole; Brambilla, Paolo; Soares, Jair C

    2009-01-01

    Despite converging evidence that major depressive illness is associated with both memory impairment and hippocampal pathology, findings vary widely across studies and it is not known whether these changes are regionally specific. In the present study we acquired brain MRIs (magnetic resonance images) from 31 unmedicated patients with MDD (major depressive disorder; mean age 39.2+/-11.9 years; 77% female) and 31 demographically comparable controls. Three-dimensional parametric mesh models were created to examine localized alterations of hippocampal morphology. Although global volumes did not differ between groups, statistical mapping results revealed that in MDD patients, more severe depressive symptoms were associated with greater left hippocampal atrophy, particularly in CA1 (cornu ammonis 1) subfields and the subiculum. However, previous treatment with atypical antipsychotics was associated with a trend towards larger left hippocampal volume. Our findings suggest effects of illness severity on hippocampal size, as well as a possible effect of past history of atypical antipsychotic treatment, which may reflect prolonged neuroprotective effects. This possibility awaits confirmation in longitudinal studies. PMID:19843010

  12. Abnormal cerebellar volume in acute and remitted major depression.

    PubMed

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Hirjak, Dusan; Thomann, Philipp A; Wolf, Robert C

    2016-11-01

    Abnormal cortical volume is well-documented in patients with major depressive disorder (MDD), but cerebellar findings have been heterogeneous. It is unclear whether abnormal cerebellar structure relates to disease state or medication. In this study, using structural MRI, we investigated cerebellar volume in clinically acute (with and without psychotropic treatment) and remitted MDD patients. High-resolution structural MRI data at 3T were obtained from acute medicated (n=29), acute unmedicated (n=14) and remitted patients (n=16). Data from 29 healthy controls were used for comparison purposes. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Patients with an acute MDD episode showed increased volume of left cerebellar area IX, and this was true for both medicated and unmedicated individuals (p<0.05 cluster-corrected). Remitted patients exhibited bilaterally increased area IX volume. In remitted, but not in acutely ill patients, area IX volume was significantly associated with measures of depression severity, as assessed by the Hamilton Depression Rating Scale (HAMD). In addition, area IX volume in remitted patients was significantly related to the duration of antidepressant treatment. In acutely ill patients, no significant relationships were established using clinical variables, such as HAMD, illness or treatment duration and number of depressive episodes. The data suggest that cerebellar area IX, a non-motor region that belongs to a large-scale brain functional network with known relevance to core depressive symptom expression, exhibits abnormal volume in patients independent of clinical severity or medication. Thus, the data imply a possible trait marker of the disorder. However, given bilaterality and an association with clinical scores at least in remitted patients, the current findings raise the possibility that cerebellar volume may be reflective of successful treatment as well. PMID:27321187

  13. Revisiting the Serotonin Hypothesis: Implications for Major Depressive Disorders.

    PubMed

    Fakhoury, Marc

    2016-07-01

    Major depressive disorder (MDD) is a heritable neuropsychiatric disease associated with severe changes at cellular and molecular levels. Its diagnosis mainly relies on the characterization of a wide range of symptoms including changes in mood and behavior. Despite the availability of antidepressant drugs, 10 to 30 % of patients fail to respond after a single or multiple treatments, and the recurrence of depression among responsive patients is very high. Evidence from the past decades suggests that the brain neurotransmitter serotonin (5-HT) is incriminated in MDD, and that a dysfunction of 5-HT receptors may play a role in the genesis of this disease. The 5-HT membrane transporter protein (SERT), which helps regulate the serotonergic transmission, is also implicated in MDD and is one of the main targets of antidepressant therapy. Although a number of behavioral tests and animal models have been developed to study depression, little is known about the neurobiological bases of MDD. Understanding the role of the serotonergic pathway will significantly help improve our knowledge of the pathophysiology of depression and may open up avenues for the development of new antidepressant drugs. The overarching goal of this review is to present recent findings from studies examining the serotonergic pathway in MDD, with a focus on SERT and the serotonin 1A (5-HT1A), serotonin 1B (5-HT1B), and serotonin 2A (5-HT2A) receptors. This paper also describes some of the main molecules involved in the internalization of 5-HT receptors and illustrates the changes in 5-HT neurotransmission in knockout mice and animal model of depression. PMID:25823514

  14. Possible role of adrenomedullin and nitric oxide in major depression.

    PubMed

    Akpinar, Abdullah; Yaman, Gozde Bacik; Demirdas, Arif; Onal, Suleyman

    2013-10-01

    Adrenomedullin (ADM) and nitric oxide (NO) have been implicated in the pathogenesis of certain psychiatric disorders such as schizophrenia and bipolar disorder. ADM induces vasorelaxation by activating adenylate cyclase and stimulating the release of NO. These two molecules are known to influence cerebral activity. In this study, we aimed to examine the serum levels of ADM and NO in patients with major depression (MD). We enrolled 50 patients with MD and 50 healthy control subjects. The diagnosis of MD was established on the basis of a structured clinical interview using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The severity of depressive symptoms was evaluated using Hamilton's 17-item Depression Rating Scale. The mean serum levels of ADM and NO in patients with MD were significantly higher than those in healthy subjects (p=0.001, for both). The severity of psychomotor retardation in patients with MD was significantly correlated with the ADM (r=0.37, p=0.007) and NO levels (r=0.29, p=0.038). The patients with obvious psychomotor retardation had significantly higher levels of ADM and NO than did the patients with no psychomotor retardation (p=0.025, p=0.030). A significantly positive correlation was found between ADM and NO levels in patients with MD (r=0.79, p=0.001). Serum levels of ADM and NO levels were not correlated with the severity or duration of depression or depressive symptoms (except psychomotor retardation). In conclusion, our study indicates that serum levels of ADM and NO are elevated in patients with MD and that increased serum levels of ADM and NO may be associated with psychomotor retardation. The ADM-NO system may serve as a new target in the treatment of patients with MD and psychomotor retardation. PMID:23867466

  15. Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder

    PubMed Central

    Mittal, Pankaj Kumar; Swami, Mukesh Kumar

    2014-01-01

    Introduction. Major depressive disorder (MDD) and bipolar affective disorder (BAD) are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group) were included in the study. Patients were recruited in depressive phase (moderate to severe depression). Patients having age outside 18–45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT). Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P = 0.031) with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression. PMID:24744917

  16. Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression

    PubMed Central

    Karabatsiakis, A; Böck, C; Salinas-Manrique, J; Kolassa, S; Calzia, E; Dietrich, D E; Kolassa, I-T

    2014-01-01

    Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities. PMID:26126180

  17. Adjunctive Brexpiprazole: A Review in Major Depressive Disorder.

    PubMed

    McKeage, Kate

    2016-02-01

    Brexpiprazole (Rexulti(®)) is a serotonin-dopamine activity modulator, with a unique receptor binding profile and low intrinsic D2 activity suggestive of a lower potential than aripiprazole to cause activation-like adverse effects, such as akathisia. The drug was recently approved by the US FDA for adjunctive therapy with antidepressant treatment (ADT) in patients with major depressive disorder (MDD). In two phase III trials, adjunctive oral brexpiprazole 2 or 3 mg once daily was more effective than monotherapy with ADT in improving depressive symptoms in adults with MDD who demonstrated an incomplete response to previous treatment with ADT. Adjunctive brexpiprazole was generally well tolerated in clinical trials, which included treatment periods of up to 52 weeks. Results of ongoing trials should help position the drug in the treatment of MDD. In the meantime, brexpiprazole provides a valid option for patients with persistent symptoms despite standard antidepressant therapy. PMID:26849053

  18. From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression

    PubMed Central

    Slavich, George M.; Irwin, Michael R.

    2014-01-01

    Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation. PMID:24417575

  19. The Efficacy of Neurofeedback in Patients with Major Depressive Disorder: An Open Labeled Prospective Study.

    PubMed

    Cheon, Eun-Jin; Koo, Bon-Hoon; Choi, Joong-Hyun

    2016-03-01

    The purpose of this study was to evaluate the effect of neurofeedback on depressive symptoms and electrophysiological disturbances in patients with major depressive disorder. We recruited participants suffering from depression to evaluate efficacy of left prefrontal beta with alpha/theta training. An 8-week, prospective, open-label study was undertaken. Twenty participants were recruited. The treatment protocol was twice or three times a week training of beta at F3 with alpha/theta at Pz for 8 weeks. When every visit, patients were received beta training for 30 min, and then alpha/theta training for 30 min. Baseline, 4 and 8 week scores of; the Hamilton rating scale for Depression (HAM-D), the Hamilton rating scale for Anxiety (HAM-A), the Beck Depression Inventory (BDI)-II, the Beck Anxiety Inventory (BAI), Clinical global impression-severity (CGI-S), and pre- and post-treatment resting state EEGs were compared. Interhemispheric alpha power asymmetry (A score) was computed for homologous sites F3-F4. Pre- and post-training clinical assessments revealed significant improvements in HAM-D, HAM-A, BDI, and CGI-S scores. Cumulative response rates by HAM-D were 35.0 and 75.0 % at 4 and 8 weeks, respectively, corresponding cumulative remission rates by HAM-D were 15.0 and 55.0 %, respectively. No significant differences were found between pre- and post-treatment A score. Neurofeedback treatment could improve depressive symptoms significantly. In addition, anxiety symptoms and clinical illness severity decreased significantly after neurofeedback treatment. Despite its several limitations, such as, small sample size and lack of a control group, this study suggested neurofeedback has significant effects in patients with major depressive disorder. PMID:26392114

  20. 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

  1. GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression.

    PubMed

    Rajkowska, Grazyna; O'Dwyer, Gillian; Teleki, Zsofia; Stockmeier, Craig A; Miguel-Hidalgo, Jose Javier

    2007-02-01

    Post-mortem morphometric studies report reductions in the average density and size of cortical neurons in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (ORB) in major depressive disorder (MDD). The contribution of specific neuronal phenotypes to this general pathology in depression is still unclear. Post-mortem sections from the dlPFC and ORB regions of 14 subjects with MDD and 11 controls were immunostained to visualize calbindin-immunoreactive (CB-IR) and parvalbumin-immunoreactive (PV-IR) presumptive GABAergic neurons. A three-dimensional cell counting probe was used to assess the cell packing density and size of CB-IR neurons in layers II+IIIa and PV-IR neurons in layers III-VI. The density of CB-IR neurons was significantly reduced by 50% in depression in the dlPFC and there was a trend toward reduction in the ORB. The size of CB-IR somata was significantly decreased (18%) in depression in the dlPFC with a trend toward reduction in the ORB. In contrast, there was no difference in the density of PV-IR neurons between the depressed and control groups in the dlPFC. The size of PV-IR neuronal soma was unchanged in depressed compared to control subjects in either dlPFC or ORB. In depression, subpopulations of GABAergic neurons may be affected differently in dlPFC and ORB. A significant reduction in the density and size of GABAergic interneurons immunoreactive for calcium binding proteins was found predominantly in the dlPFC region. These cellular changes are consistent with recent neuroimaging studies revealing a reduction in the cortical levels of GABA in depression. PMID:17063153

  2. Animal models of major depression and their clinical implications.

    PubMed

    Czéh, Boldizsár; Fuchs, Eberhard; Wiborg, Ove; Simon, Mária

    2016-01-01

    Major depressive disorder is a common, complex, and potentially life-threatening mental disorder that imposes a severe social and economic burden worldwide. Over the years, numerous animal models have been established to elucidate pathophysiology that underlies depression and to test novel antidepressant treatment strategies. Despite these substantial efforts, the animal models available currently are of limited utility for these purposes, probably because none of the models mimics this complex disorder fully. It is presumable that psychiatric illnesses, such as affective disorders, are related to the complexity of the human brain. Here, we summarize the animal models that are used most commonly for depression, and discuss their advantages and limitations. We discuss genetic models, including the recently developed optogenetic tools and the stress models, such as the social stress, chronic mild stress, learned helplessness, and early-life stress paradigms. Moreover, we summarize briefly the olfactory bulbectomy model, as well as models that are based on pharmacological manipulations and disruption of the circadian rhythm. Finally, we highlight common misinterpretations and often-neglected important issues in this field. PMID:25891248

  3. How Did Everyone Get Diagnosed with Major Depressive Disorder?

    PubMed

    Horwitz, Allan V

    2015-01-01

    Psychiatric diagnoses often reflect a matrix of sociological factors associated with professional prestige, economic forces, and cultural fashions. Diagnostic systems conceptualize the same underlying psychosocial problems in very different ways during various time periods. Since the publication of the third edition of the Diagnostic and Statistical Manual (DSM-III) in 1980, psychological distress resulting from social circumstances that previously was viewed as a general problem of nerves, neuroses, and anxiety was transformed into the specific diagnosis of major depressive disorder. Several factors, including the contrasting ways in which DSM-III defined anxiety and depression, the necessity of using explicit diagnoses to obtain professional legitimacy and reimbursement for services, and the marketing practices of the pharmaceutical industry, account for why depression replaced anxiety as the diagnosis most suitable for treated mental health conditions. Beneath the changing veneer of psychiatric labels, however, lies the same mélange of psychic ills that resist the precise labels current diagnostic fashions strive to impose upon them. PMID:26657685

  4. Olfactory bulb volume predicts therapeutic outcome in major depression disorder.

    PubMed

    Negoias, Simona; Hummel, Thomas; Symmank, Anja; Schellong, Julia; Joraschky, Peter; Croy, Ilona

    2016-06-01

    The volume of the olfactory bulb (OB) is strongly reduced in patients with major depressive disorder (MDD) and this group exhibits markedly decreased olfactory function. It has been suggested that olfactory input is important for maintaining balance in limbic neurocircuits. The aim of our study was to investigate whether reduced OB volume is associated with response to therapy in MDD. Twenty-four inpatients (all women, age 21-49 years, mean 38 ± 10 years SD) with MDD and 36 healthy controls (all women, age 20-52 years, mean 36 ± 10 years SD) underwent structural MRI. OB volume was compared between responders (N = 13) and non-responders (N = 11) to psychotherapy. Retest of OB volume was performed about 6 months after the end of therapy in nine of the patients. Therapy responders exhibited no significant difference in OB volume compared to healthy controls. However, average OB volume of non-responders was 23 % smaller compared to responders (p = .0011). Furthermore, OB volume was correlated with the change of depression severity (r = .46, p = .024). Volume of the OB did not change in the course of therapy. OB volume may be a biological vulnerability factor for the occurrence and/or maintenance of depression, at least in women. PMID:25977168

  5. Desvenlafaxine in the treatment of major depressive disorder.

    PubMed

    Pae, Chi-Un

    2011-12-01

    Desvenlafaxine (DESV) is a newer antidepressant, which inhibits serotonin-norepinephrine reuptake neurotransmission, similarly to venlafaxine, milnacipran and duloxetine. It was approved in February 2008 by the FDA for the treatment of major depressive disorder (MDD), based on well-controlled and adequately powered, large clinical trials demonstrating efficacy and safety for patients with MDD. Currently available data show that DESV has proven efficacy, acceptable safety and tolerability profiles, convenient once-daily dosing and minimal impact on the cytochrome P450 enzyme system in patients with MDD. This mini-review summarizes the clinical data and practical use of DESV under this approved indication. PMID:22098230

  6. Dynamic Resting-State Functional Connectivity in Major Depression.

    PubMed

    Kaiser, Roselinde H; Whitfield-Gabrieli, Susan; Dillon, Daniel G; Goer, Franziska; Beltzer, Miranda; Minkel, Jared; Smoski, Moria; Dichter, Gabriel; Pizzagalli, Diego A

    2016-06-01

    Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking. PMID:26632990

  7. Patient-reported functioning in major depressive disorder

    PubMed Central

    IsHak, Waguih William; James, David M.; Mirocha, James; Youssef, Haidy; Tobia, Gabriel; Pi, Sarah; Collison, Katherine L.; Cohen, Robert M.

    2016-01-01

    Objectives: Compared with the general population, patients with major depressive disorder (MDD) report substantial deficits in their functioning that often go beyond the clinical resolution of depressive symptoms. This study examines the impact of MDD and its treatment on functioning. Methods: From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult outpatients with MDD at entry and exit points of each level of antidepressant treatment and again 12 months post treatment. Functioning was measured using the Work and Social Adjustment Scale (WSAS). Results: The results show that only 7% of patients with MDD reported within-normal functioning before treatment. The proportion of patients achieving within-normal functioning (WSAS) scores significantly increased after treatment. However, the majority of patients (>60%) were still in the abnormal range on functioning at exit. Although remitted patients had greater improvements compared with nonremitters, a moderate proportion of remitted patients continued to experience ongoing deficits in functioning after treatment (20–40%). Follow-up data show that the proportions of patients experiencing normal scores for functioning after 12 months significantly decreased from the end of treatment to the follow-up phase, from 60.1% to 49% (p < 0.0001), a finding that was particularly significant in nonremitters. Limitations of this study include the reliance on self-report of functioning and the lack of information on patients who dropped out. Conclusion: This study points to the importance of functional outcomes of MDD treatment as well as the need to develop personalized interventions to improve functioning in MDD. PMID:27347363

  8. The association between suicide risk and self-esteem in Japanese university students with major depressive episodes of major depressive disorder

    PubMed Central

    Mitsui, Nobuyuki; Asakura, Satoshi; Shimizu, Yusuke; Fujii, Yutaka; Toyomaki, Atsuhito; Kako, Yuki; Tanaka, Teruaki; Kitagawa, Nobuki; Inoue, Takeshi; Kusumi, Ichiro

    2014-01-01

    Background The suicide risk among young adults is related to multiple factors; therefore, it is difficult to predict and prevent suicidal behavior. Aim We conducted the present study to reveal the most important factors relating to suicidal ideation in Japanese university students with major depressive episodes (MDEs) of major depressive disorder (MDD). Methods The subjects were 30 Japanese university students who had MDEs of MDD, and were aged between 18 and 26 years old. They were divided into two groups – without suicide risk group (n=15), and with suicide risk group (n=15) – based on the results of the Mini-International Neuropsychiatric Interview. Additionally, healthy controls were recruited from the same population (n=15). All subjects completed the self-assessment scales including the Beck Depression Inventory 2nd edition (BDI-II), the Beck Hopelessness Scale (BHS), Rosenberg’s Self-Esteem Scale (RSES), and SF-36v2™ (The Medical Outcomes Study 36-item short-form health survey version 2), and they were all administered a battery of neuropsychological tests. Results The RSES score of the suicide risk group was significantly lower than the RSES score of the without suicide risk group, whereas the BDI-II score and the BHS score were not significantly different between the two groups. The mean social functioning score on the SF-36v2 of the with suicide risk group was significantly lower than that of the without suicide risk group. Conclusion The individual’s self-esteem and social functioning may play an important role in suicide risk among young adults with MDEs of MDD. PMID:24868158

  9. Kappa Opioids, Salvinorin A and Major Depressive Disorder

    PubMed Central

    Taylor, George T.; Manzella, Francesca

    2016-01-01

    Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research. PMID:26903446

  10. Psychosocial Functioning in Youths at High Risk to Develop Major Depressive Disorder.

    ERIC Educational Resources Information Center

    Birmaher, Boris; Bridge, Jeffrey A.; Williamson, Douglas E.; Brent, David A.; Dahl, Ronald E.; Axelson, David A.; Dorn, Lorah D.; Ryan, Neal D.

    2004-01-01

    Objective: To compare the psychosocial functioning of children and adolescents at high risk of major depressive disorder with youths with acute major depressive disorder and healthy controls. Method: High-risk (n = 57), major depressive disorder (n = 71), and healthy control (n = 48) youths and their families were recruited from 1987 to 1996 and…

  11. A Study of the Predictive Validity of the Children's Depression Inventory for Major Depression Disorder in Puerto Rican Adolescents

    ERIC Educational Resources Information Center

    Rivera-Medina, Carmen L.; Bernal, Guillermo; Rossello, Jeannette; Cumba-Aviles, Eduardo

    2010-01-01

    This study aims to evaluate the predictive validity of the Children's Depression Inventory items for major depression disorder (MDD) in an outpatient clinic sample of Puerto Rican adolescents. The sample consisted of 130 adolescents, 13 to 18 years old. The five most frequent symptoms of the Children's Depression Inventory that best predict the…

  12. The Prevalence and Diagnostic Validity of Short-Duration Hypomanic Episodes and Major Depressive Episodes.

    PubMed

    Miller, Shefali; Dennehy, Ellen B; Suppes, Trisha

    2016-03-01

    Current diagnostic criteria for a hypomanic episode, as outlined in both the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and DSM-5), require a minimum duration of four consecutive days of symptoms of mood elevation. The 4-day criterion for duration of hypomania has been challenged as arbitrary and lacking empirical support, with many arguing that shorter-duration hypomanic episodes are highly prevalent and that those experiencing these episodes are clinically more similar to patients with bipolar disorder than to those with unipolar major depressive disorder. We review the current evidence regarding the prevalence, diagnostic validity, and longitudinal illness correlates of shorter-duration hypomanic episodes and summarize the arguments for and against broadening the diagnostic criteria for hypomania to include shorter-duration variants. Accumulating findings suggest that patients with major depressive episodes and shorter-duration hypomanic episodes represent a complex clinical phenotype, perhaps best conceptualized as being on the continuum between those with unipolar depressive episodes alone and those with DSM-5-defined bipolar II disorder. Further investigation is warranted, ideally involving large prospective, controlled studies, to elucidate the diagnostic and treatment implications of depression with shorter-duration hypomanic episodes. PMID:26830885

  13. Facial recognition of happiness among older adults with active and remitted major depression.

    PubMed

    Shiroma, Paulo R; Thuras, Paul; Johns, Brian; Lim, Kelvin O

    2016-09-30

    Biased emotion processing in depression might be a trait characteristic independent of mood improvement and a vulnerable factor to develop further depressive episodes. This phenomenon of among older adults with depression has not been adequately examined. In a 2-year cross-sectional study, 59 older patients with either active or remitted major depression, or never-depressed, completed a facial emotion recognition task (FERT) to probe perceptual bias of happiness. The results showed that depressed patients, compared with never depressed subjects, had a significant lower sensitivity to identify happiness particularly at moderate intensity of facial stimuli. Patients in remission from a previous major depressive episode but with none or minimal symptoms had similar sensitivity rate to identify happy facial expressions as compared to patients with an active depressive episode. Further studies would be necessary to confirm whether recognition of happy expression reflects a persistent perceptual bias of major depression in older adults. PMID:27428081

  14. Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression

    PubMed Central

    Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Guevara, Sara; Machado-Vieira, Rodrigo; Richards, Erica M.; Brutsche, Nancy E.; Nolan, Neal M.; Zarate, Carlos A.

    2015-01-01

    Objective The N-methyl-D-aspartate receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD) and bipolar depression. Clinical predictors may identify those more likely to benefit from ketamine within clinically-heterogeneous populations. Method Treatment-resistant inpatients with DSM-IV-TR-diagnosed MDD or bipolar I/II depression currently experiencing a moderate-to-severe major depressive episode were enrolled between November 2004 and March 2013. All subjects received a single subanesthetic (0.5mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230-minute post-infusion time point (N=108), at Day 1 (N=82), and at Day 7 (N=71). Univariate Pearson correlations were performed for each variable with change-from-baseline in the 17-item Hamilton Depression Rating Scale (HDRS). Multivariate linear regression was then conducted for statistically significant predictors (p<0.05, two-tailed). Results Higher body mass index (BMI) correlated with greater HDRS improvement at 230 minutes and at Day 1 (standardized β=−0.30, p=0.004), but not at Day 7 (standardized β=−0.18, p=0.10). Family history of an alcohol use disorder in a first-degree relative was associated with greater HDRS improvement at Day 1 (standardized β=−0.37, p=0.001) and Day 7 (standardized β=−0.41, p<0.001). No prior history of suicide attempt(s) was associated with greater improvement only at Day 7 (standardized β=0.28, p=0.01). The overall statistical model explained 13, 23, and 36 percent of HDRS percent change variance at 230 minutes, Day 1, and Day 7, respectively. Conclusion Despite its post-hoc nature, the study identified several clinical correlates of ketamine's rapid and durable antidepressant effects. Further investigation of these relationships is critical for individualized treatment of depression. PMID:24922494

  15. Psychometric Properties of the Beck Depression Inventory-II (BDI-II) among Community-Dwelling Older Adults

    ERIC Educational Resources Information Center

    Segal, Daniel L.; Coolidge, Frederick L.; Cahill, Brian S.; O'Riley, Alisa A.

    2008-01-01

    The psychometric properties of the Beck Depression Inventory-II (BDI-II) as a self-administered screening tool for depressive symptoms were examined in a sample of community-dwelling older and younger adults. Participants completed the BDI-II, the Center for Epidemiologic Studies Depression Scale, the Coolidge Axis II Inventory, the Perceived…

  16. Peripheral biomarkers in animal models of major depressive disorder.

    PubMed

    Carboni, Lucia

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets. PMID:24167347

  17. Folates and S-adenosylmethionine for major depressive disorder.

    PubMed

    Papakostas, George I; Cassiello, Clair F; Iovieno, Nadia

    2012-07-01

    Interest in nonpharmaceutical supplements for treating major depressive disorder (MDD) has increased significantly, both among patients and among clinicians during the past decades. Despite the large array of antidepressants (ADs) available, many patients continue to experience relatively modest response and remission rates, in addition to a burden of side effects that can hinder treatment compliance and acceptability. In this article, we review the literature on folates and S-adenosylmethionine (SAMe), 2 natural compounds linked in the 1-carbon cycle metabolic pathway, for which substantial evidence supports their involvement in mood disorders. Background information, efficacy data, proposed mechanisms of action, and side effects are reviewed. Based on existing data, supplementation with SAMe, as well as with various formulations of folates, appears to be efficacious and well tolerated in reducing depressive symptoms. Compared with other forms of folates, 5-methyltetrahydrofolate (L-methylfolate or 5-MTHF) may represent a preferable treatment option for MDD given its greater bioavailability in patients with a genetic polymorphism, and the lower risk of specific side effects associated with folic acid. Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium. PMID:22762295

  18. [Electroconvulsive therapy for major depression in borderline personality disorder].

    PubMed

    Gescher, D M; Malevani, J

    2012-03-01

    Depressive disorder is a serious and frequent complication in borderline personality disorder (BPD), however, its severity tends to be neglected particularly if symptoms are short-lived or inconsistent as is common in patients with BPD. Yet the high frequency in these patients requires especially rapid and effective therapy to reduce the risks of vital endangerment, chronification and psychosocial impairment. Efficient crisis intervention is essential for continuity of the disease-specific multimodal therapy enabling lasting remission and social and vocational rehabilitation in BPD. In particular with regard to the high incidence of poor or failed pharmacological responses in patients with BPD, electroconvulsive therapy (ECT) is of significant relevance among antidepressant treatment options. Despite the wide consensus on its efficacy, there are only few selected trials on ECT for major depression (MD) in BPD. This review summarises the published original studies on this issue, and critically scrutinises indication, benefits and risks of ECT for MD in BPD. It contributes to a focused, discriminating view on ECT and thus enables an optimised patient-oriented, efficient indication for MD in BPD. PMID:21678232

  19. Cognition as a target in major depression: new developments.

    PubMed

    Solé, Brisa; Jiménez, Esther; Martinez-Aran, Anabel; Vieta, Eduard

    2015-02-01

    Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric illness often accompanied of cognitive dysfunction which may persist even when patients achieve clinical remission. Currently, cognitive deficits emerge as a potential target because they compromise the functional outcome of depressed patients. The aim of this study was to review data for several potential pharmacological treatments targeting cognition in MDD, resulting from monotherapy or adjunctive treatment. An extensive and systematic Pubmed/Medline search of the published literature until March 2014 was conducted using a variety of search term to find relevant articles. Bibliographies of retrieved papers were further examined for publications of interest. Searches were limited to articles available in English language. We describe studies using modafinil, lisdexamfetamine, ketamine, lanicemine, memantine, galantamine, donepezil, vortioxetine, intranasal oxytocin, omega-3, s-adenosyl-methionine, scopolamine and erythropoietin. From these articles, we determined that there are a number of promising new therapies, pharmacological agents or complementary medicines, but data are just emerging. Drugs and therapies targeting cognitive dysfunction in MDD should prove effective in improving specific cognitive domains and functioning, while ruling out pseudospecificity. PMID:25640673

  20. Vortioxetine: a review of its use in major depressive disorder.

    PubMed

    Garnock-Jones, Karly P

    2014-09-01

    Vortioxetine (Brintellix(®)) is a serotonin (5-HT) transporter inhibitor that also acts on several 5-HT receptors, such as the 5-HT3 and 5-HT1A receptors. It is approved in the US and the EU for the treatment of adult patients with major depressive disorder (MDD); this article reviews the pharmacological properties of oral vortioxetine and its clinical efficacy and tolerability in these patients. Vortioxetine is generally efficacious in patients with MDD in acute treatment trials (including elderly patients), in a relapse-prevention trial, and in open-label extension trials. It is associated with improved cognitive function in patients with MDD; this does not occur solely via improvement in depressive symptom severity. It is well tolerated, but is associated with significantly increased sexual dysfunction at the highest dosage; however, vortioxetine was shown to improve previous-treatment-emergent sexual dysfunction in patients with well-treated MDD to a greater degree than escitalopram. Vortioxetine extends the available treatment options for patients with MDD, and further investigation into its comparative efficacy versus other antidepressants will allow for more accurate placement among these treatment options. PMID:25145538

  1. The 5-HT1A receptor in Major Depressive Disorder.

    PubMed

    Kaufman, Joshua; DeLorenzo, Christine; Choudhury, Sunia; Parsey, Ramin V

    2016-03-01

    Major Depressive Disorder (MDD) is a highly prevalent psychiatric diagnosis that is associated with a high degree of morbidity and mortality. This debilitating disorder is currently one of the leading causes of disability nationwide and is predicted to be the leading cause of disease burden by the year 2030. A large body of previous research has theorized that serotonergic dysfunction, specifically of the serotonin (5-HT) 1A receptor, plays a key role in the development of MDD. The purpose of this review is to describe the evolution of our current understanding of the serotonin 1A (5-HT1A) receptor and its role in the pathophysiology MDD through the discussion of animal, post-mortem, positron emission tomography (PET), pharmacologic and genetic studies. PMID:26851834

  2. Review: Magnetic Resonance Spectroscopy Studies of Pediatric Major Depressive Disorder

    PubMed Central

    Kondo, Douglas G.; Hellem, Tracy L.; Sung, Young-Hoon; Kim, Namkug; Jeong, Eun-Kee; DelMastro, Kristen K.; Shi, Xianfeng; Renshaw, Perry F.

    2011-01-01

    Introduction. This paper focuses on the application of Magnetic Resonance Spectroscopy (MRS) to the study of Major Depressive Disorder (MDD) in children and adolescents. Method. A literature search using the National Institutes of Health's PubMed database was conducted to identify indexed peer-reviewed MRS studies in pediatric patients with MDD. Results. The literature search yielded 18 articles reporting original MRS data in pediatric MDD. Neurochemical alterations in Choline, Glutamate, and N-Acetyl Aspartate are associated with pediatric MDD, suggesting pathophysiologic continuity with adult MDD. Conclusions. The MRS literature in pediatric MDD is modest but growing. In studies that are methodologically comparable, the results have been consistent. Because it offers a noninvasive and repeatable measurement of relevant in vivo brain chemistry, MRS has the potential to provide insights into the pathophysiology of MDD as well as the mediators and moderators of treatment response. PMID:21197097

  3. Support Tool in the Diagnosis of Major Depressive Disorder

    NASA Astrophysics Data System (ADS)

    Nunes, Luciano Comin; Pinheiro, Plácido Rogério; Pequeno, Tarcísio Cavalcante; Pinheiro, Mirian Calíope Dantas

    Major Depressive Disorder have been responsible for millions of professionals temporary removal, and even permanent, from diverse fields of activities around the world, generating damage to social, financial, productive systems and social security, and especially damage to the image of the individual and his family that these disorders produce in individuals who are patients, characteristics that make them stigmatized and discriminated into their society, making difficult their return to the production system. The lack of early diagnosis has provided reactive and late measures, only when the professional suffering psychological disorder is already showing signs of incapacity for working and social relationships. This article aims to assist in the decision making to establish early diagnosis of these types of psychological disorders. It presents a proposal for a hybrid model composed of expert system structured methodologies for decision support (Multi-Criteria Decision Analysis - MCDA) and representations of knowledge structured in logical rules of production and probabilities (Artificial Intelligence - AI).

  4. Antidepressants and their effect on cognition in major depressive disorder.

    PubMed

    Papakostas, George I

    2015-08-01

    Cognitive functioning is a symptom of major depressive disorder (MDD) that deserves particular attention by clinicians and researchers. Despite the fact that cognitive dysfunction represents a symptom of MDD as well as a functional outcome measure, cognition has been insufficiently investigated in antidepressant trials. While, until recently, few placebo-controlled trials have measured cognition in MDD, those examples which did have consisted of older adults. Of agents tested thus far in placebo-controlled trials (citalopram, duloxetine, vortioxetine), only the latter has been studied in patients aged 18-65, and only the latter has been shown to be superior to placebo in improving measures of executive functioning and to do so across adult age groups. Both duloxetine and vortioxetine appear to result in greater improvements than placebo in immediate and delayed memory. Clinicians who wish to improve the psychosocial recovery of patients with MDD should be familiar with studies of new options for treatment. PMID:26335095

  5. Different patterns of cortical excitability in major depression and vascular depression: a transcranial magnetic stimulation study

    PubMed Central

    2013-01-01

    Background Clinical and functional studies consider major depression (MD) and vascular depression (VD) as different neurobiological processes. Hypoexcitability of the left frontal cortex to transcranial magnetic stimulation (TMS) is frequently reported in MD, whereas little is known about the effects of TMS in VD. Thus, we aimed to assess and compare motor cortex excitability in patients with VD and MD. Methods Eleven VD patients, 11 recurrent drug-resistant MD patients, and 11 healthy controls underwent clinical, neuropsychological and neuroimaging evaluations in addition to bilateral resting motor threshold, cortical silent period, and paired-pulse TMS curves of intracortical excitability. All patients continued on psychotropic drugs, which were unchanged throughout the study. Results Scores on one of the tests evaluating frontal lobe abilities (Stroop Color-Word interference test) were worse in patients compared with controls. The resting motor threshold in patients with MD was significantly higher in the left hemisphere compared with the right (p < 0.05), and compared with the VD patients and controls. The cortical silent period was bilaterally prolonged in MD patients compared with VD patients and controls, with a statistically significant difference in the left hemisphere (p < 0.01). No differences were observed in the paired-pulse curves between patients and controls. Conclusions This study showed distinctive patterns of motor cortex excitability between late-onset depression with subcortical vascular disease and early-onset recurrent drug resistant MD. The data provide a TMS model of the different processes underlying VD and MD. Additionally, our results support the “Vascular depression hypothesis” at the neurophysiological level, and confirm the inter-hemispheric asymmetry to TMS in patients with MD. We were unable to support previous findings of impaired intracortical inhibitory mechanisms to TMS in patients with MD, although a drug

  6. 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

  7. Depression as Measured by the Beck Depression Inventory-II among Injecting Drug Users

    ERIC Educational Resources Information Center

    Johnson, Mark E.; Neal, David B.; Brems, Christiane; Fisher, Dennis G.

    2006-01-01

    This study conducts a confirmatory factor analysis of the Beck Depression Inventory-II (BDI-II) with a sample of 598 individuals who reported recent injecting drug use. Findings indicate that out of four models tested, the best model for this sample is a three-factor solution (somatic, affective, and cognitive) previously reported by Buckley,…

  8. Cognitive-Behavioral Therapy of Panic Disorder with Secondary Major Depression: A Preliminary Investigation.

    ERIC Educational Resources Information Center

    Laberge, Benoit; And Others

    1993-01-01

    Investigated extent to which cognitive-behavioral therapy can be used successfully in treatment of secondary depressed panic patients. Findings from eight panic patients with major depression and seven panic patients without major depression showed that cognitive-behavioral therapy was significantly superior to information-based therapy in…

  9. Major depression in mothers predict reduced ventral striatum activation in adolescent female offspring with and without depression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder. However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for major depressive ...

  10. Temporal cortex dopamine D2/3 receptor binding in major depression.

    PubMed

    Lehto, Soili M; Kuikka, Jyrki; Tolmunen, Tommi; Hintikka, Jukka; Viinamäki, Heimo; Vanninen, Ritva; Haatainen, Kaisa; Koivumaa-Honkanen, Heli; Honkalampi, Kirsi; Tiihonen, Jari

    2008-06-01

    The aim of this study was to assess the dopamine function of the temporal cortex in major depressive disorder using [(123)I]epidepride to image D(2/3) receptor binding sites. Ten major depressives and 10 healthy controls were selected from a general population sample for single-photon emission computed tomography imaging. Among the major depressives there was a strong bilateral correlation between the scores on the 21-item Hamilton Depression Rating Scale and D(2/3) receptor binding. Dopaminergic abnormalities may be present in the temporal cortices of major depressives. PMID:18588596

  11. Cross-cultural examination of measurement invariance of the Beck Depression Inventory-II.

    PubMed

    Dere, Jessica; Watters, Carolyn A; Yu, Stephanie Chee-Min; Bagby, R Michael; Ryder, Andrew G; Harkness, Kate L

    2015-03-01

    Given substantial rates of major depressive disorder among college and university students, as well as the growing cultural diversity on many campuses, establishing the cross-cultural validity of relevant assessment tools is important. In the current investigation, we examined the Beck Depression Inventory-Second Edition (BDI-II; Beck, Steer, & Brown, 1996) among Chinese-heritage (n = 933) and European-heritage (n = 933) undergraduates in North America. The investigation integrated 3 distinct lines of inquiry: (a) the literature on cultural variation in depressive symptom reporting between people of Chinese and Western heritage; (b) recent developments regarding the factor structure of the BDI-II; and (c) the application of advanced statistical techniques to the issue of cross-cultural measurement invariance. A bifactor model was found to represent the optimal factor structure of the BDI-II. Multigroup confirmatory factor analysis showed that the BDI-II had strong measurement invariance across both culture and gender. In group comparisons with latent and observed variables, Chinese-heritage students scored higher than European-heritage students on cognitive symptoms of depression. This finding deviates from the commonly held view that those of Chinese heritage somatize depression. These findings hold implications for the study and use of the BDI-II, highlight the value of advanced statistical techniques such as multigroup confirmatory factor analysis, and offer methodological lessons for cross-cultural psychopathology research more broadly. PMID:25314096

  12. Subtypes of major depression: latent class analysis in depressed Han Chinese women

    PubMed Central

    Li, Y.; Aggen, S.; Shi, S.; Gao, J.; Li, Y.; Tao, M.; Zhang, K.; Wang, X.; Gao, C.; Yang, L.; Liu, Y.; Li, K.; Shi, J.; Wang, G.; Liu, L.; Zhang, J.; Du, B.; Jiang, G.; Shen, J.; Zhang, Z.; Liang, W.; Sun, J.; Hu, J.; Liu, T.; Wang, X.; Miao, G.; Meng, H.; Li, Y.; Hu, C.; Li, Y.; Huang, G.; Li, G.; Ha, B.; Deng, H.; Mei, Q.; Zhong, H.; Gao, S.; Sang, H.; Zhang, Y.; Fang, X.; Yu, F.; Yang, D.; Liu, T.; Chen, Y.; Hong, X.; Wu, W.; Chen, G.; Cai, M.; Song, Y.; Pan, J.; Dong, J.; Pan, R.; Zhang, W.; Shen, Z.; Liu, Z.; Gu, D.; Wang, X.; Liu, X.; Zhang, Q.; Flint, J.; Kendler, K. S.

    2014-01-01

    Background Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally? Method Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ≥30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus. Results Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n=27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct. Conclusions MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences. PMID:25065911

  13. Evaluation of opioid modulation in major depressive disorder.

    PubMed

    Ehrich, Elliot; Turncliff, Ryan; Du, Yangchun; Leigh-Pemberton, Richard; Fernandez, Emilio; Jones, Reese; Fava, Maurizio

    2015-05-01

    Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ-opioid partial agonist, buprenorphine (BUP), and a potent μ-opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent 1-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments, and self-reported questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist-antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders. PMID:25518754

  14. Evaluation of Opioid Modulation in Major Depressive Disorder

    PubMed Central

    Ehrich, Elliot; Turncliff, Ryan; Du, Yangchun; Leigh-Pemberton, Richard; Fernandez, Emilio; Jones, Reese; Fava, Maurizio

    2015-01-01

    Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ-opioid partial agonist, buprenorphine (BUP), and a potent μ-opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent 1-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments, and self-reported questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist–antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders. PMID:25518754

  15. Increased Amygdala Response to Shame in Remitted Major Depressive Disorder

    PubMed Central

    Pulcu, Erdem; Lythe, Karen; Elliott, Rebecca; Green, Sophie; Moll, Jorge; Deakin, John F. W.; Zahn, Roland

    2014-01-01

    Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD), and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one’s own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8). This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15). Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission. PMID:24497992

  16. Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder.

    PubMed

    Salvadore, Giacomo; Nugent, Allison C; Lemaitre, Herve; Luckenbaugh, David A; Tinsley, Ruth; Cannon, Dara M; Neumeister, Alexander; Zarate, Carlos A; Drevets, Wayne C

    2011-02-14

    Previous neuromorphometric investigations of major depressive disorder (MDD) have reported abnormalities in gray matter in several regions, although the results have been inconsistent across studies. Some discrepancies in the results across studies may reflect design limitations such as small sample sizes, whereas others may reflect biological variability that potentially manifests as differences in clinical course. For example, it remains unclear whether the abnormalities found in persistently depressed MDD subjects extend to or persist in patients who experience prolonged remission. The aim of the present study was to investigate gray matter (GM) differences in unmedicated, currently-depressed participants (dMDD) and unmedicated, currently-remitted (rMDD) participants with MDD compared to healthy controls (HC). The GM density and volume were compared across groups using voxel-based morphometry, a quantitative neuroanatomical technique, and high-resolution MRI images from 107 HC, 58 dMDD and 27 rMDD subjects. Relative to the HC group the dMDD group had reduced GM in the dorsal anterolateral (DALPFC), the dorsomedial (DMPFC) and the ventrolateral prefrontal cortex (VLPFC). Relative to the rMDD group the dMDD group showed reduced GM in the DALPFC, the VLPFC, the anterior cingulate cortex (ACC), the precuneus and the inferior parietal lobule. No regions were identified in which the rMDD group showed significantly lower GM compared to the HC group after p-values were corrected for the number of comparisons performed. In unmedicated patients in the depressed phase of MDD, we found evidence of morphometric abnormalities in DALPFC and in medial prefrontal cortical regions belonging to the visceromotor network. These findings, along with the absence of GM abnormalities in the remitted sample imply a possible link between greater GM tissue and better clinical outcome. Consistent with other neuroimaging and post-mortem neuropathological studies of MDD, we also found

  17. Epigenetic differences in monozygotic twins discordant for major depressive disorder.

    PubMed

    Malki, K; Koritskaya, E; Harris, F; Bryson, K; Herbster, M; Tosto, M G

    2016-01-01

    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

  18. 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

  19. Reduced detection of positive expressions in major depression.

    PubMed

    Milders, Maarten; Bell, Stephen; Boyd, Emily; Thomson, Lewis; Mutha, Ravindra; Hay, Steven; Gopala, Anitha

    2016-06-30

    In patients with depression, negative biases have been reported in various cognitive domains, but few studies have examined whether even detection is affected, i.e. are depressed patients more likely to detect the presence of negative stimuli? This study compared detection of sad and happy faces in patients (n=17) and healthy participants (n=18) using an attentional blink task. Patients with depression detected significantly fewer happy faces than matched healthy participants, but for sad faces the group difference was non-significant. The results suggest that depression may affect the detection of positive stimuli. PMID:27138819

  20. 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

  1. Frequency-dependent alterations in regional homogeneity in major depression.

    PubMed

    Xue, Song; Wang, Xu; Wang, Wanqian; Liu, Jia; Qiu, Jiang

    2016-06-01

    Previous studies using resting-state functional magnetic resonance imaging (fMRI) have found abnormal spontaneous neural activity in patients with major depressive disorder (MDD). Yet, the frequency-dependent neural activity in MDD is largely unknown. Here, we used resting-state fMRI and regional homogeneity (ReHo) methods to investigate spontaneous neural activity in specific frequency bands of 31 MDD patients and 31 age-, gender- and education-matched healthy controls. We examined spontaneous neural activity in three frequency bands: slow-4 (0.027-0.073Hz), slow-5 (0.010-0.027Hz), and the typical band (0.01-0.08Hz). Compared to controls, MDD patients showed increased ReHo in the middle frontal gyrus (MFG) and decreased ReHo in the fusiform and postcentral gyrus at the typical band. Importantly, MDD patients showed increased ReHo in the middle occipital gyrus (MOG) and decreased ReHo in the anterior cingulate cortex (ACC), inferior frontal gyrus (IFG), superior frontal gyrus (SFG) and the bilateral thalamus in the slow-4 band, while they showed increased ReHo in the medial prefrontal cortex (mPFC) in the slow-5 band. Our results suggest that the abnormality of ReHo in MDD is associated with the frequency band and that future studies should take frequency band effect into account when examining spontaneous neural activity. PMID:26968135

  2. Meta-analyses of genetic studies on major depressive disorder.

    PubMed

    López-León, S; Janssens, A C J W; González-Zuloeta Ladd, A M; Del-Favero, J; Claes, S J; Oostra, B A; van Duijn, C M

    2008-08-01

    The genetic basis of major depressive disorder (MDD) has been investigated extensively, but the identification of MDD genes has been hampered by conflicting results from underpowered studies. We review all MDD case-control genetic association studies published before June 2007 and perform meta-analyses for polymorphisms that had been investigated in at least three studies. The study selection and data extraction were performed in duplicate by two independent investigators. The 183 papers that met our criteria studied 393 polymorphisms in 102 genes. Twenty-two polymorphisms (6%) were investigated in at least three studies. Seven polymorphisms had been evaluated in previous meta-analyses, 5 of these had new data available. Hence, we performed meta-analyses for 20 polymorphisms in 18 genes. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistically significant associations were found for the APOE varepsilon2 (OR, 0.51), GNB3 825T (OR, 1.38), MTHFR 677T (OR, 1.20), SLC6A4 44 bp Ins/Del S (OR, 1.11) alleles and the SLC6A3 40 bpVNTR 9/10 genotype (OR, 2.06). To date, there is statistically significant evidence for six MDD susceptibility genes (APOE, DRD4, GNB3, MTHFR, SLC6A3 and SLC6A4). PMID:17938638

  3. Perceived parenting and risk for major depression in Chinese women

    PubMed Central

    Gao, J.; Li, Y.; Cai, Y.; Chen, J.; Shen, Y.; Ni, S.; Wei, Y.; Qiu, Y.; Zhu, X.; Liu, Y.; Lu, C.; Chen, C.; Niu, Q.; Tang, C.; Yang, Y.; Wang, Q.; Cui, W.; Xia, J.; Liu, T.; Zhang, J.; Zhao, B.; Guo, Z.; Pan, J.; Chen, H.; Luo, Y.; Sun, L.; Xiao, X.; Chen, Q.; Zhao, X.; He, F.; Lv, L.; Guo, L.; Liu, L.; Li, H.; Shi, S.; Flint, J.; Kendler, K. S.; Tao, M.

    2012-01-01

    Background In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China? Method Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview. Results Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD. Conclusions Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD. PMID:21943491

  4. Nonlinear analysis of EEG in major depression with fractal dimensions.

    PubMed

    Akar, Saime A; Kara, Sadik; Agambayev, Sumeyra; Bilgic, Vedat

    2015-08-01

    Major depressive disorder (MDD) is a psychiatric mood disorder characterized by cognitive and functional impairments in attention, concentration, learning and memory. In order to investigate and understand its underlying neural activities and pathophysiology, EEG methodologies can be used. In this study, we estimated the nonlinearity features of EEG in MDD patients to assess the dynamical properties underlying the frontal and parietal brain activity. EEG data were obtained from 16 patients and 15 matched healthy controls. A wavelet-chaos methodology was used for data analysis. First, EEGs of subjects were decomposed into 5 EEG sub-bands by discrete wavelet transform. Then, both the Katz's and Higuchi's fractal dimensions (KFD and HFD) were calculated as complexity measures for full-band and sub-bands EEGs. Last, two-way analyses of variances were used to test EEG complexity differences on each fractality measures. As a result, a significantly increased complexity was found in both parietal and frontal regions of MDD patients. This significantly increased complexity was observed not only in full-band activity but also in beta and gamma sub-bands of EEG. The findings of the present study indicate the possibility of using the wavelet-chaos methodology to discriminate the EEGs of MDD patients from healthy controls. PMID:26738004

  5. cGMP Signaling, Phosphodiesterases and Major Depressive Disorder

    PubMed Central

    Reierson, Gillian W; Guo, Shuyu; Mastronardi, Claudio; Licinio, Julio; Wong, Ma-Li

    2011-01-01

    Deficits in neuroplasticity are hypothesized to underlie the pathophysiology of major depressive disorder (MDD): the effectiveness of antidepressants is thought to be related to the normalization of disrupted synaptic transmission and neurogenesis. The cyclic adenosine monophosphate (cAMP) signaling cascade has received considerable attention for its role in neuroplasticity and MDD. However components of a closely related pathway, the cyclic guanosine monophosphate (cGMP) have been studied with much lower intensity, even though this signaling transduction cascade is also expressed in the brain and the activity of this pathway has been implicated in learning and memory processes. Cyclic GMP acts as a second messenger; it amplifies signals received at postsynaptic receptors and activates downstream effector molecules resulting in gene expression changes and neuronal responses. Phosphodiesterase (PDE) enzymes degrade cGMP into 5’GMP and therefore they are involved in the regulation of intracellular levels of cGMP. Here we review a growing body of evidence suggesting that the cGMP signaling cascade warrants further investigation for its involvement in MDD and antidepressant action. PMID:22654729

  6. Managing major depressive disorder through the use of adjunct therapies.

    PubMed

    Katzman, Martin A

    2014-12-01

    Although many treatments for Major Depressive Disorder (MDD) exist, only half of all patients respond to initial trial of pharmacotherapy and only a third will achieve remission with that trial. First-line therapies for the management of MDD include psychotherapy or pharmacotherapy, alone or in combination. Given the disappointing rates of response and remission to initial therapy, clinicians are looking for methods to improve the management of MDD, such as through the use of adjunct therapies. The first article in this series, by Katzman and Chokka, discusses gaps in the treatment of MDD and proposes measures to change and strengthen future practice guidelines. Epstein et al. summarize the findings of clinical studies, systematic analyses, and reviews of trials supporting the use of adjunct therapy for the treatment of MDD. Velehorschi et al. review emerging research identifying common pathophysiological processes between MDD and three of its comorbidities. Lastly, Cameron and Habert highlight the challenges that primary care physicians face in the management of MDD. Ultimately, the goal of treatment is to not only relieve symptoms of MDD, but achieve sustained remission. This supplement was written to address the issues of less than ideal outcomes and approaches to enhancing response and remission rates. PMID:25539870

  7. Surface vulnerability of cerebral cortex to major depressive disorder.

    PubMed

    Peng, Daihui; Shi, Feng; Li, Gang; Fralick, Drew; Shen, Ting; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang; Fang, Yiru

    2015-01-01

    Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process. PMID:25793287

  8. Antidepressants versus placebo in major depression: an overview.

    PubMed

    Khan, Arif; Brown, Walter A

    2015-10-01

    Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or non-profit agencies. This narrowing of the drug-placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM-III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant-placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive. PMID:26407778

  9. Surface Vulnerability of Cerebral Cortex to Major Depressive Disorder

    PubMed Central

    Li, Gang; Fralick, Drew; Shen, Ting; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang; Fang, Yiru

    2015-01-01

    Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process. PMID:25793287

  10. Antidepressants versus placebo in major depression: an overview

    PubMed Central

    Khan, Arif; Brown, Walter A

    2015-01-01

    Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or non-profit agencies. This narrowing of the drug-placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM-III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant-placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive. PMID:26407778

  11. Cellular Changes in the Postmortem Hippocampus in Major Depression

    PubMed Central

    Stockmeier, Craig A.; Mahajan, Gouri J.; Konick, Lisa C.; Overholser, James C.; Jurjus, George J.; Meltzer, Herbert Y.; Uylings, Harry B.M.; Friedman, Lee; Rajkowska, Grazyna

    2010-01-01

    Background Imaging studies report that hippocampal volume is decreased in major depressive disorder (MDD). A cellular basis for reduced hippocampal volume in MDD has not been identified. Methods Sections of right hippocampus were collected in 19 subjects with MDD and 21 normal control subjects. The density of pyramidal neurons, dentate granule cell neurons, glia, and the size of the neuronal somal area were measured in systematic, randomly placed three-dimensional optical disector counting boxes. Results In MDD, cryostat-cut hippocampal sections shrink in depth a significant 18% greater amount than in control subjects. The density of granule cells and glia in the dentate gyrus and pyramidal neurons and glia in all cornv ammonis (CA)/hippocampal subfields is significantly increased by 30% –35% in MDD. The average soma size of pyramidal neurons is significantly decreased in MDD. Conclusion In MDD, the packing density of glia, pyramidal neurons, and granule cell neurons is significantly increased in all hippocampal subfields and the dentate gyrus, and pyramidal neuron soma size is significantly decreased as well. It is suggested that a significant reduction in neuropil in MDD may account for decreased hippocampal volume detected by neuroimaging. In addition, differential shrinkage of frozen sections of the hippocampus suggests differential water content in hippocampus in MDD. PMID:15522247

  12. Targeting the Glutamatergic System to Treat Major Depressive Disorder

    PubMed Central

    Mathews, Daniel C.; Henter, Ioline D.; Zarate, Carlos A.

    2012-01-01

    Major depressive disorder (MDD) is a severe, debilitating medical illness that affects millions of individuals worldwide. The young age of onset and chronicity of the disorder has a significant impact on the long-term disability that affected individuals face. Most existing treatments have focused on the ‘monoamine hypothesis’ for rational design of compounds. However, patients continue to experience low remission rates, residual subsyndromal symptoms, relapses and overall functional impairment. In this context, growing evidence suggests that the glutamatergic system is uniquely central to the neurobiology and treatment of MDD. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of MDD, and discuss the efficacy of glutamatergic agents as novel therapeutics. Preliminary clinical evidence has been promising, particularly with regard to the N-methyl-D-aspartate (NMDA) antagonist ketamine as a ‘proof-of-concept’ agent. The review also highlights potential molecular and inflammatory mechanisms that may contribute to the rapid antidepressant response seen with ketamine. Because existing pharmacological treatments for MDD are often insufficient for many patients, the next generation of treatments needs to be more effective, rapid acting and better tolerated than currently available medications. There is extant evidence that the glutamatergic system holds considerable promise for developing the next generation of novel and mechanistically distinct agents for the treatment of MDD. PMID:22731961

  13. Leptin depresses food intake in great tits (Parus major).

    PubMed

    Lõhmus, Mare; Sundström, L Fredrik; El Halawani, Mohammed; Silverin, Bengt

    2003-03-01

    Food availability for wild organisms typically varies both in time and space, requiring a mechanism that regulates the storage of excess energy and makes it possible to use stores during energy shortfall. Leptin, a protein hormone encoded by an obesity gene, has been suggested to be the signal mediator for this flux of energy. In a controlled laboratory experiment on caged great tits (Parus major) we evaluated the effect of leptin on food intake and behaviour. Experimental birds were given an intramuscular injection of 10 microg leptin dissolved in phosphate buffered saline (PBS), while the control birds were injected with PBS only at 09:00 h after a night's fasting. Within the first 20 min after injections we observed a significant difference in food intake between groups: control birds initially fed at higher rates compared to leptin treated birds. The cumulative food intake suggested that the effect of leptin disappeared after approximately 40-50 min post-injections. Similar results have previously been found in domesticated chickens. To our knowledge, this is the first study to show that leptin depresses food intake in wild birds. PMID:12620247

  14. Pharmacogenetics in major depression: a comprehensive meta-analysis.

    PubMed

    Niitsu, Tomihisa; Fabbri, Chiara; Bentini, Francesco; Serretti, Alessandro

    2013-08-01

    A number of candidate gene studies focused on major depression (MD) and antidepressant (AD) efficacy have been carried out, but results mainly remain inconclusive. We performed a comprehensive meta-analysis of published candidate gene studies focused on AD efficacy in MD to evaluate the cumulative evidence. A random-effect model was applied to study the polymorphisms with genotypic counts available from at least three independent studies. On the base of previous evidence, the analysis was stratified by ethnicity (Caucasian, Asian, and other/mixed), and AD class (SSRIs and mixed/other ADs). Genotypic data were available for 16 polymorphisms in 11 genes. After the exclusion of 5-HTTLPR in SLC6A4 included in another recent meta-analysis, 15 polymorphisms in 11 genes were included in the present meta-analysis (BDNF rs6265, SLC6A4 STin2, HTR1A rs6295, HTR2A rs6311, rs6313 and rs7997012, HTR6 rs1805054, TPH1 rs1800532, SLC6A2 rs5569, COMT rs4680, GNB3 rs5443, FKBP5 rs1360780 and rs3800373, and ABCB1 rs1045642 and rs2032582). Our results suggested that BDNF rs6265 (Val66Met) heterozygous genotype was associated with better SSRIs response compared to the homozygous genotypes, particularly in Asians (OR=1.53, 95%CI 1.12-2.07, p=0.007). SLC6A4 STin2, HTR2A rs6311 and rs7997012, GNB3 rs5443, FKBP5 rs1360780 and rs3800373, and ABCB1 rs2032582 showed associations with AD efficacy, but these results were highly dependent on one or two single studies. In conclusion, our findings suggested the BDNF Val66Met as the best single candidate involved in AD response, with a selective effect on SSRI treatment. Our overall results supported no major effect of any single gene variant on AD efficacy. PMID:23733030

  15. Implicit Cognition and the Maintenance and Treatment of Major Depression

    ERIC Educational Resources Information Center

    Friedman, Michael A.; Whisman, Mark A.

    2004-01-01

    Although extensive research has identified the role of consciously expressed cognition in the onset and maintenance of depression, much less work has directly examined the role of nonconscious, automatic, implicit cognition biases and depression. Further, whereas there is evidence of changes in self-report measures of cognition following cognitive…

  16. Adolescents with Major Depression Demonstrate Increased Amygdala Activation

    ERIC Educational Resources Information Center

    Yang, Tony T.; Simmons, Alan N.; Matthews, Scott C.; Tapert, Susan F.; Frank, Guido K.; Max, Jeffrey E.; Bischoff-Grethe, Amanda; Lansing, Amy E.; Brown, Gregory; Strigo, Irina A.; Wu, Jing; Paulus, Martin P.

    2010-01-01

    Objective: Functional neuroimaging studies have led to a significantly deeper understanding of the underlying neural correlates and the development of several mature models of depression in adults. In contrast, our current understanding of the underlying neural substrates of adolescent depression is very limited. Although numerous studies have…

  17. Using Imagery Rescripting to Treat Major Depression: Theory and Practice

    ERIC Educational Resources Information Center

    Wheatley, Jon; Hackmann, Ann

    2011-01-01

    This paper considers the role that intrusive memories may play in maintaining depression and the rationale for using imagery rescripting in order to target these memories. Potential mechanisms of change underlying imagery rescripting are discussed. The relationship between depressive rumination and memories is considered, as well as potential…

  18. [Factorial analysis of the Hamilton depression scale, II].

    PubMed

    Dreyfus, J F; Guelfi, J D; Ruschel, S; Blanchard, C; Pichot, P

    1981-04-01

    A factorial analysis (principal components with Varimax rotation) was performed on 85 ratings of the Hamilton Depression Rating Scale obtained in 1979-1980 on inpatients with a major depressive illness. Using a replicable statistical technique, 4 factors were obtained. These factors do not overlap with those obtain on a similar sample with a similar technique nor with those obtained by other authors. It thus appears that there is no such thing as a factorial structure of this scale. PMID:7305179

  19. Dysregulation of visual motion inhibition in major depression.

    PubMed

    Norton, Daniel J; McBain, Ryan K; Pizzagalli, Diego A; Cronin-Golomb, Alice; Chen, Yue

    2016-06-30

    Individuals with depression show depleted concentrations of the inhibitory neurotransmitter GABA in occipital (visual) cortex, predicting weakened inhibition within their visual systems. Yet, visual inhibition in depression remains largely unexplored. To fill this gap, we examined the inhibitory process of center-surround suppression (CSS) of visual motion in depressed individuals. Perceptual performance in discriminating the direction of motion was measured as a function of stimulus presentation time and contrast in depressed individuals (n=27) and controls (n=22). CSS was operationalized as the accuracy difference between conditions using large (7.5°) and small (1.5°) grating stimuli. Both depressed and control participants displayed the expected advantage in accuracy for small stimuli at high contrast. A significant interaction emerged between subject group, contrast level and presentation time, indicating that alterations of CSS in depression were modulated by stimulus conditions. At high contrast, depressed individuals showed significantly greater CSS than controls at the 66ms presentation time (where the effect peaked in both groups). The results' specificity and dependence on stimulus features such as contrast, size and presentation time suggest that they arise from changes in early visual processing, and are not the results of a generalized deficit or cognitive bias. PMID:27111216

  20. A Genetic Susceptibility Mechanism for Major Depression: Combinations of polymorphisms Defined the Risk of Major Depression and Subpopulations.

    PubMed

    Wang, Yanfang; Sun, Ning; Li, Suping; Du, Qiaorong; Xu, Yong; Liu, Zhifeng; Zhang, Kerang

    2015-06-01

    Major Depression (MD) is a highly inherited psychiatric disorder. The norepinephrine transporter (NET) gene plays important role in pathophysiology of MD. This study attempted to examine the relationship between polymorphisms of NET gene and MD. Patients with MD and healthy controls were recruited and subgrouped. The T-182C and G1287A polymorphisms of NET gene were genotyped by direct sequencing. The genotypic and allelic frequencies were compared using the Pearson χ2 analysis. The linkage disequilibrium was analyzed using the UNPHASED program. Significant differences in genotypic and allelic frequencies of T-182C polymorphism were observed between MD subgroups and controls. When referenced by TT genotype, the OR value increased gradient from TC to CC genotype; when referenced by T allele, the odds ratio value of C allele also increased. Compared with those having both -182 T/T and 1287 G/G genotypes, in patients with MD, early-onset MD, and MD with suicide concept group, the -182 C/C and 1287 G/A combinatorial genotype has significant risk; yet in patients with MD family history, the -182 C/C and 1287 A/A combinatorial genotype has significant risk. Different combinations of T-182C and the G1287A polymorphisms of NET gene might increase morbidity risk of MD subpopulations. PMID:26061302

  1. Prevalence of Incompletely Penetrant Huntington’s Disease Alleles Among Individuals With Major Depressive Disorder

    PubMed Central

    Perlis, Roy H.; Smoller, Jordan W.; Mysore, Jayalakshmi; Sun, Mei; Gillis, Tammy; Purcell, Shaun; Rietschel, Marcella; Nöthen, Markus M.; Witt, Stephanie; Maier, Wolfgang; Iosifescu, Dan V.; Sullivan, Patrick; Rush, A. John; Fava, Maurizio; Breiter, Hans; Macdonald, Marcy; Gusella, James

    2011-01-01

    Objective Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington’s disease may have higher levels of depressive symptoms than healthy comparison populations. However, the prevalence of HTT CAG repeat expansions among individuals diagnosed with major depressive disorder has not been established. Method This was a case-control genetic association study of HTT CAG allele size in two discovery cohorts of individuals with major depressive disorder and comparison subjects without major depression as well as a replication cohort of individuals with major depression and comparison subjects without major depression. Results CAG repeat lengths of 36 or greater were observed in six of 3,054 chromosomes from individuals with major depression, compared with none of 4,155 chromosomes from comparison subjects. In a third cohort, one expanded allele was observed among 1,202 chromosomes in the major depression group, compared with none of 2,678 chromosomes in comparison subjects. No clear pattern of clinical features was shared among individuals with the expanded repeats. Conclusions In clinical populations of individuals diagnosed with major depression, approximately 3 in 1,000 carried expanded HTT CAG alleles. PMID:20360314

  2. The association of major depressive episode and personality traits in patients with fibromyalgia

    PubMed Central

    de Melo Santos, Danyella; Lage, Laís Verderame; Jabur, Eleonora Kehl; Kaziyama, Helena Hideko Seguchi; Iosifescu, Dan V; de Lucia, Mara Cristina Souza; Fráguas, Renério

    2011-01-01

    INTRODUCTION: Personality traits have been associated with primary depression. However, it is not known whether this association takes place in the case of depression comorbid with fibromyalgia. OBJECTIVE: The authors investigated the association between a current major depressive episode and temperament traits (e.g., harm avoidance). METHOD: A sample of 69 adult female patients with fibromyalgia was assessed with the Temperament and Character Inventory. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview severity of depressive symptomatology with the Beck Depression Inventory, and anxiety symptomatology with the IDATE-state and pain intensity with a visual analog scale. RESULTS: A current major depressive episode was diagnosed in 28 (40.5%) of the patients. They presented higher levels of harm avoidance and lower levels of cooperativeness and self-directedness compared with non-depressed patients, which is consistent with the Temperament and Character Inventory profile of subjects with primary depression. However, in contrast to previous results in primary depression, no association between a major depressive episode and self-transcendence was found. CONCLUSIONS: The results highlight specific features of depression in fibromyalgia subjects and may prove important for enhancing the diagnosis and prognosis of depression in fibromyalgia patients. PMID:21808861

  3. Anatomical and functional brain abnormalities in unmedicated major depressive disorder

    PubMed Central

    Yang, Xiao; Ma, Xiaojuan; Li, Mingli; Liu, Ye; Zhang, Jian; Huang, Bin; Zhao, Liansheng; Deng, Wei; Li, Tao; Ma, Xiaohong

    2015-01-01

    Background Using magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (rsfMRI) to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD). Patients and methods Fifty patients with MDD and 50 matched healthy control participants free of psychotropic medication underwent high-resolution structural and rsfMRI scanning. Optimized diffeomorphic anatomical registration through exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used to find potential differences in gray-matter volume (GMV) and regional homogeneity (ReHo) between the two groups. A Pearson correlation model was used to analyze associations of morphometric and functional changes with clinical symptoms. Results Compared to healthy controls, patients with MDD showed significant GMV increase in the left posterior cingulate gyrus and GMV decrease in the left lingual gyrus (P<0.001, uncorrected). In ReHo analysis, values were significantly increased in the left precuneus and decreased in the left putamen (P<0.001, uncorrected) in patients with MDD compared to healthy controls. There was no overlap between anatomical and functional changes. Linear correlation suggested no significant correlation between mean GMV values within regions with anatomical abnormality and ReHo values in regions with functional abnormality in the patient group. These changes were not significantly correlated with symptom severity. Conclusion Our study suggests a dissociation pattern of brain regions with anatomical and functional alterations in unmedicated patients with MDD, especially with regard to GMV and ReHo. PMID:26425096

  4. Descriptive Epidemiology of Major Depressive Disorder in Canada in 2012

    PubMed Central

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

    2015-01-01

    Objective: 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). Method: 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. Results: 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. Conclusions: 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. PMID:25886546

  5. Treatment-resistant major depressive disorder and assisted dying.

    PubMed

    Schuklenk, Udo; van de Vathorst, Suzanne

    2015-08-01

    Competent patients suffering from treatment-resistant depressive disorder should be treated no different in the context of assisted dying to other patients suffering from chronic conditions that render their lives permanently not worth living to them. Jurisdictions that are considering, or that have, decriminalised assisted dying are discriminating unfairly against patients suffering from treatment-resistant depression if they exclude such patients from the class of citizens entitled to receive assistance in dying. PMID:25935906

  6. On the Factor Structure of the Beck Depression Inventory-II: G Is the Key

    ERIC Educational Resources Information Center

    Brouwer, Danny; Meijer, Rob R.; Zevalkink, Jolien

    2013-01-01

    The Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) is intended to measure severity of depression, and because items represent a broad range of depressive symptoms, some multidimensionality exists. In recent factor-analytic studies, there has been a debate about whether the BDI-II can be considered as one scale or whether…

  7. The Factor Structure of the Beck Depression Inventory-II: An Evaluation

    ERIC Educational Resources Information Center

    Vanheule, Stijn; Desmet, Mattias; Groenvynck, Hans; Rosseel, Yves; Fontaine, Johnny

    2008-01-01

    The Beck Depression Inventory-II (BDI-II) is a frequently used scale for measuring depressive severity. BDI-II data (404 clinical; 695 nonclinical adults) were analyzed by means of confirmatory factor analysis to test whether the factor structure model with a somatic-affective and cognitive component of depression, formulated by Beck and…

  8. Confirmatory Factor Analysis of the Beck Depression Inventory-II in Bariatric Surgery Candidates

    ERIC Educational Resources Information Center

    Hall, Brian J.; Hood, Megan M.; Nackers, Lisa M.; Azarbad, Leila; Ivan, Iulia; Corsica, Joyce

    2013-01-01

    Screening for depression is an integral part of psychological evaluations conducted prior to bariatric surgery. The Beck Depression Inventory-II (BDI-II) is the most commonly used measure of depression in these treatment evaluations. The reliability and validity of the BDI-II has not yet been evaluated within bariatric surgery-seeking samples,…

  9. Maintenance pharmacotherapy for recurrent major depressive disorder: 5-year follow-up study.

    PubMed

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

    2008-08-01

    Practice guidelines endorse maintenance antidepressant treatment for recurrent major depressive disorder. In the Vantaa Depression Study, we followed 218 psychiatric patients with major depressive disorder for up to 5 years with a life-chart. Of these patients, 86 (39.4%) had more than three lifetime episodes and an indication for maintenance pharmacotherapy. However, of these, only 57% received treatment and only for 16% of the time indicated. Good adherence to pharmacotherapy in the acute phase independently predicted maintenance treatment. The tertiary preventive impact of maintenance treatment may remain limited, as many patients with major depressive disorder either do not receive it, or receive it for too short a period. PMID:18670005

  10. Subthreshold Hypomanic Symptoms in Progression From Unipolar Major Depression to Bipolar Disorder

    PubMed Central

    Fiedorowicz, Jess G.; Endicott, Jean; Leon, Andrew C.; Solomon, David A.; Keller, Martin B.; Coryell, William H.

    2011-01-01

    Objective We determined if subthreshold hypomanic symptoms predicted new onset mania or hypomania. Method We identified 550 individuals followed for at least one year in the National Institute of Mental Health Collaborative Depression Study with a diagnosis of major depression at intake. All participants were screened at baseline for a total of five manic symptoms: elevated mood, decreased need for sleep, high energy, increased goal-directed activity, and grandiosity. Participants were followed prospectively for a mean of 17.5 and up to 31 years. Longitudinal Interval Follow-up Examinations monitored course of illness and identified any hypomania or mania. The association of subthreshold hypomanic symptoms at baseline with subsequent hypomania or mania was determined in survival analyses using Cox Proportional-Hazards Regression. Results With a cumulative probability of one-in-four on survival analysis, 19.6% (N=108) of the sample experienced hypomania or mania, resulting in revision of diagnoses for 12.2% to bipolar II and 7.5% to bipolar I disorder. The number of subthreshold hypomanic symptoms, psychosis, and age of onset predicted progression to bipolar disorder. Less need for sleep, unusual energy, and increased goal-directed activities were specifically implicated. Conclusions Symptoms of hypomania, even when of low intensity, were very frequently associated with subsequent progression to bipolar disorder, although the majority of patients who converted did not have any symptoms of hypomania at baseline. Therefore, continued monitoring for the possibility of progression to bipolar disorder over the long-term course of major depressive disorder is necessary. PMID:21078709

  11. Selected Executive Skills in Adolescents with Recent First Episode Major Depression

    ERIC Educational Resources Information Center

    Kyte, Zoe A.; Goodyer, Ian M.; Sahakian, Barbara J.

    2005-01-01

    Background: To investigate whether recent first episode major depression in adolescence is characterised by selected executive difficulties in attentional flexibility, behavioural inhibition and decision-making. Methods: Selected executive functions were compared in adolescents with recent (past year) first episode major depression (n = 30) and…

  12. Racial/Ethnic Differences in Mental Health Service Use among Adolescents with Major Depression

    ERIC Educational Resources Information Center

    Cummings, Janet R.; Druss, Benjamin G.

    2011-01-01

    Objective: Little is known about racial/ethnic differences in the receipt of treatment for major depression in adolescents. This study examined differences in mental health service use in non-Hispanic white, black, Hispanic, and Asian adolescents who experienced an episode of major depression. Method: Five years of data (2004-2008) were pooled…

  13. A Pilot Study of Adjunctive Family Psychoeducation in Adolescent Major Depression: Feasibility and Treatment Effect

    ERIC Educational Resources Information Center

    Sanford, Mark; Boyle, Michael; McCleary, Lynn; Miller, Jennifer; Steele, Margaret; Duku, Eric; Offord, David

    2006-01-01

    Objective: To obtain preliminary evidence of the feasibility and effectiveness of adjunctive family psychoeducation in adolescent major depressive disorder. Method: Participants were from outpatient clinics in Hamilton and London, Ontario. Over 24 months, 41 adolescents ages 13 through 18 years meeting major depressive disorder criteria were…

  14. Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial

    PubMed Central

    Mao, Jun J.; Xie, Sharon X.; Zee, Jarcy; Soeller, Irene; Li, Qing S.; Rockwell, Kenneth; Amsterdam, Jay D.

    2015-01-01

    Background We performed a proof of concept trial to evaluate relative safety and efficacy of Rhodiola rosea (R. rosea) versus sertraline for mild to moderate major depressive disorder. Hypothesis We hypothesize that R. rosea would have similar therapeutic effects as sertraline but with less adverse events. Study Design Phase II randomized placebo controlled clinical trial Methods 57 subjects were randomized to 12 weeks of standardized R. rosea extract, sertraline, or placebo. Changes over time in Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression Change (CGI/C) scores among groups were examined using mixed-effects models. Results Modest, albeit statistically non-significant, reductions were observed for HAM-D, BDI, and CGI/C scores for all treatment conditions with no significant difference between groups (p=0.79, p=0.28, and p=0.17, respectively). The decline in HAM-D scores was greater for sertraline (−8.2, 95% confidence interval [CI], −12.7 to −3.6) versus R. rosea (−5.1, 95% CI: −8.8 to −1.3) and placebo (−4.6, 95% CI: −8.6 to −0.6). While the odds of improving (versus placebo) were greater for sertraline (1.90 [0.44–8.20]; odds ratio [95% CI]) than R. rosea (1.39 [0.38–5.04]), more subjects on sertraline reported adverse events (63.2%) than R. rosea (30.0%) or placebo (16.7%) (p=0.012). Conclusions Although R. rosea produced less antidepressant effect versus sertraline, it also resulted in significantly fewer adverse events and was better tolerated. These findings suggest that R. rosea, although less effective than sertraline, may possess a more favorable risk to benefit ratio for individuals with mild to moderate depression. PMID:25837277

  15. 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

  16. A systematic approach to pharmacotherapy for geriatric major depression.

    PubMed

    Mulsant, Benoit H; Blumberger, Daniel M; Ismail, Zahinoor; Rabheru, Kiran; Rapoport, Mark J

    2014-08-01

    The broadening use of antidepressants among older Americans has not been associated with a notable decrease in the burden of geriatric depression. This article, based on a selective review of the literature, explores several explanations for this paradox. The authors propose that the effectiveness of antidepressants depends in large part on the way they are used. Evidence supports that antidepressant pharmacotherapy leads to better outcomes when guided by a treatment algorithm as opposed to attempting to individualize treatment. Several published guidelines and pharmacotherapy algorithms developed for the treatment of geriatric depression are reviewed, and an updated algorithm proposed. PMID:25037293

  17. Regulation of major histocompatibility complex class II genes

    PubMed Central

    Choi, Nancy M.; Majumder, Parimal; Boss, Jeremy M.

    2010-01-01

    Summary The major histocompatibility complex class II (MHC-II) genes are regulated at the level of transcription. Recent studies have shown that chromatin modification is critical for efficient transcription of these genes, and a number of chromatin modifying complexes recruited to MHC-II genes have been described. The MHC-II genes are segregated from each other by a series of chromatin elements, termed MHC-II insulators. Interactions between MHC-insulators and the promoters of MHC-II genes are mediated by the insulator factor CCCTC-binding protein and are critical for efficient expression. This regulatory mechanism provides a novel view of how the entire MHC-II locus is assembled architecturally and can be coordinately controlled. PMID:20970972

  18. Personality, Stressful Life Events, and Treatment Response in Major Depression

    ERIC Educational Resources Information Center

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  19. Objective Sleep in Pediatric Anxiety Disorders and Major Depressive Disorder

    ERIC Educational Resources Information Center

    Forbes, Erika E.; Bertocci, Michele A.; Gregory, Alice M.; Ryan, Neal D.; Axelson, David A.; Birmaher, Boris; Dahl, Ronald E.

    2008-01-01

    A study to examine sleep problems encountered in anxiety and depressive disorders among children and adolescents is conducted. Results indicated subjective and objective sleep problems in children and adolescents with anxiety disorders and need to be kept in mind when treating young anxious people.

  20. Clarifying the causal relationship in women between childhood sexual abuse and lifetime major depression

    PubMed Central

    Kendler, K. S.; Aggen, S. H.

    2013-01-01

    Background Childhood sexual abuse (CSA) is strongly associated with risk for major depression (MD) but the degree to which this association is causal remains uncertain. Method We applied structural equation modeling using the Mplus program to 1493 longitudinally assessed female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Results Our model included (i) retrospective self- and co-twin reports on CSA, (ii) major potentially confounding covariates, (iii) assessment of lifetime history of MD at two separate interviews, and (iv) mood-congruent recall (implemented by allowing current depressive symptoms to predict reporting of CSA). In a model with only measurement error, CSA explained 9.6% of MD. Including four key covariates reduced the variance explained to 5.3%, with the largest effects found for parental loss and low parental warmth. Adding the effect of mood-congruent recall to a final well-fitting model reduced the percentage of variance explained in lifetime MD (LTMD) by CSA to 4.4%. In this model, current depressive symptoms significantly predicted recall of CSA. Conclusions In a model correcting for measurement error, confounding and the impact of mood-congruent recall, CSA remains substantially associated with the risk for LTMD in women. These findings strongly suggest, but do not prove, that this association is causal, and are consistent with previous results in this sample using a co-twin control design, but also indicate that more than half of the uncorrected CSA–MD association is probably not causal. Traumatic life experiences contribute substantially to the risk for LTMD. PMID:23942036

  1. T helper 17 cells may drive neuroprogression in major depressive disorder: Proposal of an integrative model.

    PubMed

    Slyepchenko, Anastasiya; Maes, Michael; Köhler, Cristiano A; Anderson, George; Quevedo, João; Alves, Gilberto S; Berk, Michael; Fernandes, Brisa S; Carvalho, André F

    2016-05-01

    The exact pathophysiology of major depressive disorder (MDD) remains elusive. The monoamine theory, which hypothesizes that MDD emerges as a result of dysfunctional serotonergic, dopaminergic and noradrenergic pathways, has guided the therapy of this illness for several decades. More recently, the involvement of activated immune, oxidative and nitrosative stress pathways and of decreased levels of neurotrophic factors has provided emerging insights regarding the pathophysiology of MDD, leading to integrated theories emphasizing the complex interplay of these mechanisms that could lead to neuroprogression. In this review, we propose an integrative model suggesting that T helper 17 (Th17) cells play a pivotal role in the pathophysiology of MDD through (i) microglial activation, (ii) interactions with oxidative and nitrosative stress, (iii) increases of autoantibody production and the propensity for autoimmunity, (iv) disruption of the blood-brain barrier, and (v) dysregulation of the gut mucosa and microbiota. The clinical and research implications of this model are discussed. PMID:26898639

  2. Perceived Weight, Not Obesity, Increases Risk for Major Depression Among Adolescents

    PubMed Central

    Roberts, Robert E.; Duong, Hao T.

    2013-01-01

    This study examined the association between major depression, obesity and body image among adolescents. Methods: Participants were 4,175 youths 11–17 years of age sampled from the community who were interviewed using the Diagnostic Interview Schedule for Children and Adolescents, Version IV, completed a self-report questionnaire, and had their weight and height measured. There were 2 measures of body image: perceived weight and body satisfaction. Obesity was associated with increased risk of depression, with no controls for covariates. However, when the association was examined in models which included weight, major depression, and body image measures and covariates, there was no association between major depression and body weight, nor between body satisfaction and major depression. Perceived overweight was strongly and independently associated with body weight (O.R. = 2.62). We found no independent association between major depression and body weight. If there is an etiologic link between major depression and body weight among adolescents, it most likely operates through processes involving components of body image. Future research should focus on the role of depression and body image in the etiology of obesity. PMID:23643102

  3. Major Depressive Disorder and Dysthymia at the Intersection of Nativity and Racial-Ethnic Origins.

    PubMed

    Szaflarski, Magdalena; Cubbins, Lisa A; Bauldry, Shawn; Meganathan, Karthikeyan; Klepinger, Daniel H; Somoza, Eugene

    2016-08-01

    Immigrants often have lower rates of depression than US-natives, but longitudinal assessments across multiple racial-ethnic groups are limited. This study examined the rates of prevalent, acquired, and persisting major depression and dysthymia by nativity and racial-ethnic origin while considering levels of acculturation, stress, and social ties. Data from the National Epidemiologic Survey on Alcohol and Related Conditions were used to model prevalence and 3-year incidence/persistence of major depression and dysthymia (DSM-IV diagnoses) using logistic regression. Substantive factors were assessed using standardized measures. The rates of major depression were lower for most immigrants, but differences were noted by race-ethnicity and outcome. Furthermore, immigrants had higher prevalence but not incidence of dysthymia. The associations between substantive factors and outcomes were mixed. This study describes and begins to explain immigrant trajectories of major depression and dysthymia over a 3-year period. The continuing research challenges and future directions are discussed. PMID:26438660

  4. Identification of depressed patient types in the community and their treatment needs: findings from the DEPRES II (Depression Research in European Society II) survey. DEPRES Steering Committee.

    PubMed

    Tylee, A; Gastpar, M; Lépine, J P; Mendlewicz, J

    1999-05-01

    DEPRES II (Depression Research in European Society II), the first in-depth, pan-European survey of depression in the community, provided an opportunity to identify depressed patient types and their treatment needs. Cluster analysis applied to data generated from DEPRES II interviews revealed six depressed patient types with clearly differentiated profiles. The patient type with moderately impaired depression has episodic depression and minimal disability. By contrast, severe depression associated with anxiety presents with chronic symptoms, including anxiety and panic, and causes considerable disruption to normal life and employment. Depression associated with chronic physical problems and depression associated with social problems are characterized by chronic physical illness and relationship or financial difficulties, respectively, and sufferers are pessimistic about recovery. Depression associated with sleep problems is associated with symptoms of tiredness and broken or inadequate sleep, and is commonly caused by stress. Tiredness is also a principal symptom of depression associated with tiredness or fatigue, but sufferers' ability to sleep is unaffected. All patient types would benefit from antidepressant therapy. The depressed patient types identified from the DEPRES II data make intuitive sense, but now need to be tested for face validity in the primary care setting. PMID:10435768

  5. Optimizing Scripted Dialogues for an e-Health Intervention for Suicidal Veterans with Major Depression.

    PubMed

    Kasckow, J; Zickmund, S; Rotondi, A; Welch, A; Gurklis, J; Chinman, M; Fox, L; Haas, G L

    2015-07-01

    Suicide is a health concern among Veterans with depression. We had previously reported on scripted dialogues adapted for an e-health system that engages at-risk veterans with schizophrenia. Here we report a further adaptation of the dialogues for Veterans with depression. Usability was assessed with nine outpatients with a history of major depression and suicidality. We noted that participants preferred greater specificity in the wording of questions. Topics that elicited an emotional response dealt with questions on suicide, social isolation and family relationships. Based on feedback, dialogues were revised for patients with depression. We also compared responses between those with depression and those with schizophrenia who were previously tested. The two groups shared similar themes. Also, individuals with a history of major depression had less trouble with vocabulary comprehension but were less willing to answer more questions daily. PMID:25342076

  6. Role of Peripheral Vascular Resistance for the Association Between Major Depression and Cardiovascular Disease

    PubMed Central

    Bouzinova, Elena V.; Wiborg, Ove; Aalkjaer, Christian

    2015-01-01

    Abstract: Major depression and cardiovascular diseases are 2 of the most prevalent health problems in Western society, and an association between them is generally accepted. Although the specific mechanism behind this comorbidity remains to be elucidated, it is clear that it has a complex multifactorial character including a number of neuronal, humoral, immune, and circulatory pathways. Depression-associated cardiovascular abnormalities associate with cardiac dysfunctions and with changes in peripheral resistance. Although cardiac dysfunction in association with depression has been studied in detail, little attention was given to structural and functional changes in resistance arteries responsible for blood pressure control and tissue perfusion. This review discusses recent achievements in studies of depression-associated abnormalities in resistance arteries in humans and animal experimental models. The changes in arterial structure, contractile and relaxing functions associated with depression symptoms are discussed, and the role of these abnormalities for the pathology of major depression and cardiovascular diseases are suggested. PMID:25469807

  7. Treatment of nonpsychotic major depression during pregnancy: patient safety and challenges

    PubMed Central

    Epstein, Richard A; Moore, Katherine M; Bobo, William V

    2014-01-01

    In pregnant women with major depression, the overarching goal of treatment is to achieve or maintain maternal euthymia, thus limiting both maternal and fetal exposure to the harmful effects of untreated or incompletely treated depression. However, the absence of uniformly effective therapies with guaranteed obstetric and fetal safety makes the treatment of major depression during pregnancy among the most formidable of clinical challenges. Clinicians and patients are still faced with conflicting data and expert opinion regarding the reproductive safety of antidepressants in pregnancy, as well as large gaps in our understanding of the effectiveness of most antidepressants and nonpharmacological alternatives for treating antenatal depression. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated maternal depression during pregnancy, the effectiveness of interventions for maternal depression during pregnancy, and potential obstetric, fetal, and neonatal risks associated with antenatal antidepressant use. PMID:25258558

  8. The influence of anhedonia on feedback negativity in major depressive disorder.

    PubMed

    Liu, Wen-hua; Wang, Ling-zhi; Shang, He-rui; Shen, Yue; Li, Zhi; Cheung, Eric F C; Chan, Raymond C K

    2014-01-01

    Anhedonia is associated with reward-processing deficits of the dopamine system, which may increase the risk of depression. Nevertheless, few previous studies have examined the influence of hedonic tone on event-related potential (ERP) measures of reward processing in major depressive disorder. A simple gambling task was used to elicit feedback negativity (FN), an ERP component elicited by feedback indicating gain versus loss, in 27 patients with major depression and 27 healthy participants. We found that participants with depression were characterized by reduced FN responses, especially towards monetary gains, but not losses, compared with healthy individuals. In addition, the amplitude of FN to gain feedback in participants with depression was related to anhedonia severity and depressive symptoms. These findings indicate an association between low hedonic capacity and reduction in FN. As a neural measure of reward sensitivity, FN may be generated in part by reward-related activity. PMID:24316199

  9. The high prevalence of "soft" bipolar (II) features in atypical depression.

    PubMed

    Perugi, G; Akiskal, H S; Lattanzi, L; Cecconi, D; Mastrocinque, C; Patronelli, A; Vignoli, S; Bemi, E

    1998-01-01

    Seventy-two percent of 86 major depressive patients with atypical features as defined by the DSM-IV and evaluated systematically were found to meet our criteria for bipolar II and related "soft" bipolar disorders; nearly 60% had antecedent cyclothymic or hyperthymic temperaments. The family history for bipolar disorder validated these clinical findings. Even if we limit the diagnosis of bipolar II to the official DSM-IV threshold of 4 days of hypomania, 32.6% of atypical depressives in our sample would meet this conservative threshold, a rate that is three times higher than the estimates of bipolarity among atypical depressives in the literature. By definition, mood reactivity was present in all patients, while interpersonal sensitivity occurred in 94%. Lifetime comorbidity rates were as follows: social phobia 30%, body dysmorphic disorder 42%, obsessive-compulsive disorder 20%, and panic disorder (agoraphobia) 64%. Both cluster A (anxious personality) and cluster B (e.g., borderline and histrionic) personality disorders were highly prevalent. These data suggest that the "atypicality" of depression is favored by affective temperamental dysregulation and anxiety comorbidity, clinically manifesting in a mood disorder subtype that is preponderantly in the realm of bipolar II. In the present sample, only 28% were strictly unipolar and characterized by avoidant and social phobic features, without histrionic traits. PMID:9515190

  10. Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

    PubMed Central

    2014-01-01

    Background Although genetic variation is believed to contribute to an individual’s susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder. Results Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Conclusions Our results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease. PMID:24694013

  11. [Major depression in the child: validation of the syndrome and pharmacologic treatment].

    PubMed

    Goulet, J

    1989-02-01

    The concept of childhood depression has been the object of controversies over many years. Recent developments have permitted rapid progress in many areas of research. The author offers an update on the validity of the diagnosis of major depression in childhood and on pharmacological treatment. He then attempts to delineate the uses and limitations of this therapeutic approach. In the latter part, practical advice on the use of drugs in childhood depression is given. PMID:2647269

  12. Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study

    PubMed Central

    2016-01-01

    Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ2 test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry. PMID:27051248

  13. Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study.

    PubMed

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

    2016-04-01

    Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ(2) test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry. PMID:27051248

  14. Depression Impairs Learning, whereas the Selective Serotonin Reuptake Inhibitor, Paroxetine, Impairs Generalization in Patients with Major Depressive Disorder

    PubMed Central

    Herzallah, Mohammad M.; Moustafa, Ahmed A.; Natsheh, Joman Y.; Danoun, Omar A.; Simon, Jessica R.; Tayem, Yasin I.; Sehwail, Mahmud A.; Amleh, Ivona; Bannoura, Issam; Petrides, Georgios; Myers, Catherine E.; Gluck, Mark A.

    2013-01-01

    To better understand how medication status and task demands affect cognition in Major Depressive Disorder (MDD), we evaluated medication-naïve patients with MDD, medicated patients with MDD receiving the Selective Serotonin Reuptake Inhibitors (SSRI) paroxetine, and healthy controls. All three groups were administered a computer-based cognitive task with two phases, an initial phase in which a sequence is learned through reward-based feedback (which our prior studies suggest is striatal-dependent), followed by a generalization phase that involves a change in the context where learned rules are to be applied (which our prior studies suggest is hippocampal-region dependent). Medication-naïve MDD patients were slow to learn the initial sequence but were normal on subsequent generalization of that learning. In contrast, medicated patients learned the initial sequence normally, but were impaired at the generalization phase. We argue that these data suggest (i) an MDD-related impairment in striatal-dependent sequence learning which can be remediated by SSRIs and (ii) an SSRI-induced impairment in hippocampal-dependent generalization of past learning to novel contexts, not otherwise seen in the medication-naïve MDD group. Thus, SSRIs might have a beneficial effect on striatal function required for sequence learning, but a detrimental effect on the hippocampus and other medial temporal lobe structures critical for generalization. PMID:23953023

  15. Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty.

    PubMed

    Satterthwaite, T D; Cook, P A; Bruce, S E; Conway, C; Mikkelsen, E; Satchell, E; Vandekar, S N; Durbin, T; Shinohara, R T; Sheline, Y I

    2016-07-01

    Depressive symptoms are common in multiple psychiatric disorders and are frequent sequelae of trauma. A dimensional conceptualization of depression suggests that symptoms should be associated with a continuum of deficits in specific neural circuits. However, most prior investigations of abnormalities in functional connectivity have typically focused on a single diagnostic category using hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female participants from three diagnostic groups (healthy controls, n=17; major depression, n=38; and post-traumatic stress disorder, n=50), we examine the dimensional relationship between resting-state functional dysconnectivity and severity of depressive symptoms across diagnostic categories using a data-driven analysis (multivariate distance-based matrix regression). This connectome-wide analysis identified foci of dysconnectivity associated with depression severity in the bilateral amygdala. Follow-up seed analyses using subject-specific amygdala segmentations revealed that depression severity was associated with amygdalo-frontal hypo-connectivity in a network of regions including bilateral dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In contrast, anxiety was associated with elevated connectivity between the amygdala and the ventromedial prefrontal cortex. Taken together, these results emphasize the centrality of the amygdala in the pathophysiology of depressive symptoms, and suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a critical neurobiological feature across clinical diagnostic categories. PMID:26416545

  16. Affective temperaments play an important role in the relationship between childhood abuse and depressive symptoms in major depressive disorder.

    PubMed

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

    2016-02-28

    Previous studies have shown that various factors, such as genetic and environmental factors, contribute to the development of major depressive disorder (MDD). The aim of this study is to clarify how multiple factors, including affective temperaments, childhood abuse and adult life events, are involved in the severity of depressive symptoms in MDD. A total of 98 participants with MDD were studied using the following self-administered questionnaire surveys: Patient Health Questionnaire-9 measuring the severity of depressive symptoms; Life Experiences Survey (LES) measuring negative and positive adult life events; Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A) measuring affective temperaments; and the Child Abuse and Trauma Scale (CATS) measuring childhood abuse. The data were analyzed using single and multiple regression analyses and structural equation modeling (SEM). The neglect score reported by CATS indirectly predicted the severity of depressive symptoms through affective temperaments measured by TEMPS-A in SEM. Four temperaments (depressive, cyclothymic, irritable, and anxious) directly predicted the severity of depressive symptoms. The negative change in the LES score also directly predicted severity. This study suggests that childhood abuse, especially neglect, indirectly increases the severity of depressive symptoms through increased scores of affective temperaments in MDD. PMID:26708440

  17. Effects of Intensive Short-Term Dynamic Psychotherapy on Depressive Symptoms and Executive Functioning in Major Depression.

    PubMed

    Ajilchi, Bita; Nejati, Vahid; Town, Joel M; Wilson, Ryan; Abbass, Allan

    2016-07-01

    This study examined the efficacy of intensive short-term dynamic psychotherapy (ISTDP) on depressive symptoms and executive functioning in patients with major depression. We examined pretest, posttest, and follow-up depression scores as well as pretest-posttest executive functioning scores between 16 participants receiving ISTDP and 16 allocated to wait-list control. Participants in each group were matched according to age, sex, and educational level. Mixed-models analyses demonstrated significant interaction effects of group and time on depression scores when the group ISTDP was compared with the wait-list control group; participants receiving ISTDP had significantly reduced depression severity both after treatment and at follow-up. Next, a series of hierarchical regression models demonstrated modest improvements on most tests of executive functioning in participants receiving ISTDP. Depressed patients receiving ISTDP show a sustained reduction in depression severity after treatment and after 12-month follow-up and improvements in executive functioning after treatment compared with a wait-list control. PMID:27065106

  18. Criterion Validity, Severity Cut Scores, and Test-Retest Reliability of the Beck Depression Inventory-II in a University Counseling Center Sample

    ERIC Educational Resources Information Center

    Sprinkle, Stephen D.; Lurie, Daphne; Insko, Stephanie L.; Atkinson, George; Jones, George L.; Logan, Arthur R.; Bissada, Nancy N.

    2002-01-01

    The criterion validity of the Beck Depression Inventory-II (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996) was investigated by pairing blind BDI-II administrations with the major depressive episode portion of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I; M. B. First, R. L. Spitzer, M. Gibbon, & J. B. W. Williams,…

  19. Science Motivation Questionnaire II: Validation with Science Majors and Nonscience Majors

    ERIC Educational Resources Information Center

    Glynn, Shawn M.; Brickman, Peggy; Armstrong, Norris; Taasoobshirazi, Gita

    2011-01-01

    From the perspective of social cognitive theory, the motivation of students to learn science in college courses was examined. The students--367 science majors and 313 nonscience majors--responded to the Science Motivation Questionnaire II, which assessed five motivation components: intrinsic motivation, self-determination, self-efficacy, career…

  20. Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder

    PubMed Central

    Kugel, Harald; Krug, Axel; Schöning, Sonja; Ohrmann, Patricia; Uhlmann, Christina; Postert, Christian; Suslow, Thomas; Heindel, Walter; Arolt, Volker; Kircher, Tilo; Dannlowski, Udo

    2014-01-01

    Background Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder. Methods For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes. Results Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala. Conclusions The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy. PMID:25051163

  1. Altered White Matter Microstructure in Adolescents with Major Depression: A Preliminary Study

    ERIC Educational Resources Information Center

    Cullen, Kathryn R.; Klimes-Dougan, Bonnie; Muetzel, Ryan; Mueller, Bryon A.; Camchong, Jazmin; Houri, Alaa; Kurma, Sanjiv; Lim, Kelvin O.

    2010-01-01

    Objective: Major depressive disorder (MDD) occurs frequently in adolescents, but the neurobiology of depression in youth is poorly understood. Structural neuroimaging studies in both adult and pediatric populations have implicated frontolimbic neural networks in the pathophysiology of MDD. Diffusion tensor imaging (DTI), which measures white…

  2. Recovery from Major Depressive Disorder among Female Adolescents: A Prospective Test of the Scar Hypothesis

    ERIC Educational Resources Information Center

    Beevers, Christopher G.; Rohde, Paul; Stice, Eric; Nolen-Hoeksema, Susan

    2007-01-01

    This study examined the psychosocial consequences of experiencing major depressive disorder (MDD). In a 7-year longitudinal study of 496 female adolescents, the authors identified 49 girls who experienced their first episode of MDD and then recovered. They were compared with a randomly selected group of 98 never depressed participants on 13…

  3. Correlates of Psychological Distress and Major Depressive Disorder among African American Men

    ERIC Educational Resources Information Center

    Lincoln, Karen D.; Taylor, Robert Joseph; Watkins, Daphne C.; Chatters, Linda M.

    2011-01-01

    This study examines the demographic correlates of depressive symptoms, serious psychological distress (SPD), and major depressive disorder (MDD; 12-month and lifetime prevalence) among a national sample of African American men. Analysis of the National Survey of American Life (NSAL) data set provides first-time substantiation of important…

  4. Psychosocial Treatments for Major Depression and Dysthymia in Older Adults: A Review of the Research Literature

    ERIC Educational Resources Information Center

    Zalaquett, Carlos P.; Stens, Andrea N.

    2006-01-01

    Older adults represent a growing segment of the population with the highest suicide rate and an increasing need of counseling services for major depression and dysthymia. The present study examined the literature with the purpose of identifying research addressing psychosocial treatments of depression in later life. A summary of treatments…

  5. Fluoxetine, Smoking, and History of Major Depression: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Spring, Bonnie; Doran, Neal; Pagoto, Sherry; McChargue, Dennis; Cook, Jessica Werth; Bailey, Katherine; Crayton, John; Hedeker, Donald

    2007-01-01

    The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine…

  6. Relationship of Premenstrual Syndrome and Premenstrual Dysphoric Disorder with Major Depression: Relevance to Clinical Practice

    PubMed Central

    Padhy, Susanta Kumar; Sarkar, Sidharth; Beherre, Prakash B.; Rathi, Rajesh; Panigrahi, Mahima; Patil, Pradeep Sriram

    2015-01-01

    Background: Premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD) and depressive disorder are fairly common; symptoms do overlap, often under-identified and under-emphasized, particularly in rural India. Objective: The objective was to assess the occurrence of PMS and PMDD in a sample of students and staff of a nursing college and to find their correlation with depression. Materials and Methods: A prospective cohort study; Tertiary Care Hospital in Rural India (Wardha, Maharashtra); 118 female nursing students or staff aged between 18 and 40 years, who were likely to stay within the institution for the study period. The participants were rated on Penn daily symptom report prospectively for a period of 3-month. Those who scored positive were applied diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV TR) criteria for PMDD; and were applied primary care evaluation of mental disorders depression screening followed by DSM-IV TR criteria for depression. Severity of depression was measured using Hamilton Depression Rating Scale. Results: Main outcome measures were frequency and severity of depression in individuals with PMS and PMDD and their clinical and sociodemographic correlation. The age range of the sample was 18-37 years. Some PMS symptoms were observed in 67%; diagnosis of PMDD in 10%; depressive symptoms in 28% of the sample. 46.4% of those with depressive symptoms had major depression. The diagnosis of major depression was significantly associated with the severity of PMS symptoms as well as the presence of PMDD. Conclusion: Premenstrual syndrome is present in a substantial proportion of young females. Concurrent depression is increased by the severity of PMS symptoms and the presence of PMDD. Gynecologist needs to screen such subjects for depression and refer to mental-health professional early, in routine clinical practice. PMID:25969600

  7. Self-compassion as an emotion regulation strategy in major depressive disorder.

    PubMed

    Diedrich, Alice; Grant, Michaela; Hofmann, Stefan G; Hiller, Wolfgang; Berking, Matthias

    2014-07-01

    Cognitive reappraisal and acceptance are two presumably adaptive emotion regulation strategies in depression. More recently, self-compassion has been discussed as another potentially effective strategy for coping with depression. In the present study, we compared the effectiveness of self-compassion with a waiting condition, reappraisal, and acceptance in a clinically depressed sample, and tested the hypothesis that the intensity of depressed mood would moderate the differential efficacy of these strategies. In an experimental design, we induced depressed mood at four points in time in 48 participants meeting criteria for major depressive disorder. After each mood induction, participants were instructed to wait, reappraise the situation, accept their negative emotions, or employ self-compassion to regulate their depressed mood. Self-ratings of depressed mood were assessed before and after each mood induction and regulation phase. Results showed that the reduction of depressed mood was significantly greater in the self-compassion condition than in the waiting condition. No significant differences were observed between the self-compassion and the reappraisal condition, and between the self-compassion and the acceptance condition in patients' mood ratings. However, the intensity of self-rated depressed mood at baseline was found to moderate the comparative effectiveness of self-compassion and reappraisal with a trend of self-compassion being more effective than reappraisal in high depressed mood at baseline. These findings support the use of self-compassion as another adaptive emotion regulation strategy for patients with major depressive disorder, especially for those suffering from high levels of depressed mood. PMID:24929927

  8. Major depressive disorder: mechanism-based prescribing for personalized medicine

    PubMed Central

    Saltiel, Philip F; Silvershein, Daniel I

    2015-01-01

    Individual patients with depression present with unique symptom clusters – before, during, and even after treatment. The prevalence of persistent, unresolved symptoms and their contribution to patient functioning and disease progression emphasize the importance of finding the right treatment choice at the onset and the utility of switching medications based on suboptimal responses. Our primary goal as clinicians is to improve patient function and quality of life. In fact, feelings of well-being and the return to premorbid levels of functioning are frequently rated by patients as being more important than symptom relief. However, functional improvements often lag behind resolution of mood, attributed in large part to persistent and functionally impairing symptoms – namely, fatigue, sleep/wake disturbance, and cognitive dysfunction. Thus, patient outcomes can be optimized by deconstructing each patient’s depressive profile to its component symptoms and specifically targeting those domains that differentially limit patient function. This article will provide an evidence-based framework within which clinicians may tailor pharmacotherapy to patient symptomatology for improved treatment outcomes. PMID:25848287

  9. Outcome trajectories and mediation in psychotherapeutic treatments of major depression.

    PubMed

    Klug, Günther; Zimmermann, Johannes; Huber, Dorothea

    2016-04-01

    Trajectories and mediators of change were investigated in a process-outcome study. Patients were allocated at random to psychoanalytic therapy (PA) or psychodynamic therapy (PD), and later to cognitive-behavioral therapy (CBT). Measurement points were at pre-treatment, during ongoing treatment, at post-treatment, and during a three-year follow-up. Outcome trajectories were assessed using the Beck Depression Inventory (BDI; Hautzinger et al. 1994), the Symptom Checklist 90 Revised Version (SCL-90-R; Franke 1995), and the Inventory of Interpersonal Problems (IIP; Horowitz, Strauss, and Kordy 2000). Therapeutic alliance and introject were tested as mediators, assessed using the Helping Alliance Questionnaire (HAQ; Bassler, Potratz, and Krauthauser 1995) and INTREX, introject surface (Tress 1993). Multilevel modeling was applied to estimate outcome trajectories and to test for mediation. Symptoms decreased in early and ongoing treatment in all treatment groups. After the end of treatment, depressive and general psychiatric symptoms continued to decrease in significantly greater degree in the PA group than in the PD and CBT cohorts. During early treatment, interpersonal problems decreased significantly more in those allocated to PD than in the PA and CBT groups. During ongoing treatment, improvement in interpersonal problems was significantly higher in the PA group than in the others and, compared to CBT, continued to increase significantly after termination. Mediational analyses revealed that neither introject affiliation nor therapeutic alliance mediated differential treatment effects. PMID:27151999

  10. Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

    PubMed Central

    Wolkowitz, Owen M.; Mellon, Synthia H.; Epel, Elissa S.; Lin, Jue; Dhabhar, Firdaus S.; Su, Yali; Reus, Victor I.; Rosser, Rebecca; Burke, Heather M.; Kupferman, Eve; Compagnone, Mariana; Nelson, J. Craig; Blackburn, Elizabeth H.

    2011-01-01

    Background Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation. Methodology Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex. Principal Findings The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05). Conclusions These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is

  11. Predictors of first lifetime episodes of major depression in midlife women

    PubMed Central

    Bromberger, J. T.; Kravitz, H. M.; Matthews, K.; Youk, A.; Brown, C.; Feng, W.

    2010-01-01

    Background Little is known about factors that predict first lifetime episodes of major depression in middle-aged women. It is not known whether health-related factors and life stress pose more or less of a risk to the onset of clinical depression than does the menopausal transition. Method The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to assess diagnoses of lifetime, annual and current major depression in a community-based sample of premenopausal or early perimenopausal African American and White women. Menstrual cycle characteristics, psychosocial and health-related factors, and blood samples for assay of reproductive hormones were obtained annually. Two hundred and sixty-six women without a history of major depression at baseline constituted the cohort for the current analyses. Results Over 7 years of follow-up, 42 (15.8%) women met criteria for a diagnosis of major depression. Frequent vasomotor symptoms (VMS; hot flashes and/or night sweats) (HR 2.14, p=0.03) were a significant predictor of major depression in univariate analyses. After simultaneous adjustment for multiple predictors in Cox proportional hazards analyses, frequent VMS were no longer significant; lifetime history of an anxiety disorder (HR 2.20, p=0.02) and role limitations due to physical health (HR 1.88, p=0.07) at baseline and a very stressful life event (HR 2.25, p=0.04) prior to depression onset predicted a first episode of major depression. Conclusions Both earlier (e.g. history of anxiety disorders) and more proximal factors (e.g. life stress) may be more important than VMS in contributing to a first episode of major depression during midlife. PMID:18377672

  12. Self-Referential Processing, Rumination, and Cortical Midline Structures in Major Depression

    PubMed Central

    Nejad, Ayna Baladi; Fossati, Philippe; Lemogne, Cédric

    2013-01-01

    Major depression is associated with a bias toward negative emotional processing and increased self-focus, i.e., the process by which one engages in self-referential processing. The increased self-focus in depression is suggested to be of a persistent, repetitive and self-critical nature, and is conceptualized as ruminative brooding. The role of the medial prefrontal cortex in self-referential processing has been previously emphasized in acute major depression. There is increasing evidence that self-referential processing as well as the cortical midline structures play a major role in the development, course, and treatment response of major depressive disorder. However, the links between self-referential processing, rumination, and the cortical midline structures in depression are still poorly understood. Here, we reviewed brain imaging studies in depressed patients and healthy subjects that have examined these links. Self-referential processing in major depression seems associated with abnormally increased activity of the anterior cortical midline structures. Abnormal interactions between the lateralized task-positive network, and the midline cortical structures of the default mode network, as well as the emotional response network, may underlie the pervasiveness of ruminative brooding. Furthermore, targeting this maladaptive form of rumination and its underlying neural correlates may be key for effective treatment. PMID:24124416

  13. Neural correlates of self-perceptions in adolescents with major depressive disorder.

    PubMed

    Bradley, Kailyn A L; Colcombe, Stan; Henderson, Sarah E; Alonso, Carmen M; Milham, Michael P; Gabbay, Vilma

    2016-06-01

    Alteration in self-perception is a salient feature in major depression. Hyperactivity of anterior cortical midline regions has been implicated in this phenomenon in depressed adults. Here, we extend this work to depressed adolescents during a developmental time when neuronal circuitry underlying the sense of self matures by using task-based functional magnetic resonance imaging (fMRI) and connectivity analyses. Twenty-three depressed adolescents and 18 healthy controls (HC) viewed positive and negative trait words in a scanner and judged whether each word described them ('self' condition) or was a good trait to have ('general' condition). Self-perception scores were based on participants' endorsements of positive and negative traits during the fMRI task. Depressed adolescents exhibited more negative self-perceptions than HC. Both groups activated cortical midline regions in response to self-judgments compared to general-judgments. However, depressed adolescents recruited the posterior cingulate cortex/precuneus more for positive self-judgments. Additionally, local connectivity of the dorsal medial prefrontal cortex was reduced during self-reflection in depressed adolescents. Our findings highlight differences in self-referential processing network function between depressed and healthy adolescents and support the need for further investigation of brain mechanisms associated with the self, as they may be paramount to understanding the etiology and development of major depressive disorder. PMID:26943454

  14. Pharmacology Update on Chronic Obstructive Pulmonary Disease, Rheumatoid Arthritis, and Major Depression.

    PubMed

    Weatherspoon, Deborah; Weatherspoon, Christopher A; Abbott, Brianna

    2015-12-01

    This article presents a brief review and summarizes current therapies for the treatment of chronic obstructive pulmonary disease, major depression, and rheumatoid arthritis. One new pharmaceutical agent is highlighted for each of the topics. PMID:26596663

  15. Sex differences of salivary cortisol secretion in patients with major depression.

    PubMed

    Hinkelmann, Kim; Botzenhardt, Johannes; Muhtz, Christoph; Agorastos, Agorastos; Wiedemann, Klaus; Kellner, Michael; Otte, Christian

    2012-01-01

    Depression is associated with increased cortisol secretion and occurs more often in women than in men. Thus, it has been hypothesized that differences in cortisol secretion might, in part, be responsible for the greater risk of developing depression in women. However, only few studies have examined sex differences in baseline cortisol secretion in depressed patients and healthy controls. We examined sex effects on cortisol secretion in 52 medication-free patients with major depression (37 women, 15 men, mean ± SD age 35 ± 11 years, Hamilton Depression Scale mean score 27 ± 5) and 50 healthy age- and sex-matched control subjects. Salivary cortisol concentrations were measured at 8:00, 12:00, 16:00, and 22:00 h. Repeated measures analysis of covariance revealed a group × sex interaction (p = 0.05). Post hoc tests revealed higher cortisol concentrations in depressed compared to healthy men [F(1;29) = 7.5, p = 0.01]. No differences were found between depressed and non-depressed women. Our results do not support the hypothesis that differences in cortisol secretion between depressed and non-depressed subjects are more pronounced in women than in men. Study characteristics and methods as well as sex-specific confounding variables such as menstrual cycle, menopause and the use of oral contraceptives may account for inconclusive results across studies. PMID:21790344

  16. Brain Activity in Adolescent Major Depressive Disorder Before and After Fluoxetine Treatment

    PubMed Central

    Tao, Rongrong; Calley, Clifford S.; Hart, John; Mayes, Taryn L.; Nakonezny, Paul A.; Lu, Hanzhang; Kennard, Betsy D.; Tamminga, Carol A.; Emslie, Graham J.

    2014-01-01

    Objective Major depression in adolescents is a significant public health concern because of its frequency and severity. To examine the neurobiological basis of depression in this population, the authors studied functional activation characteristics of the brain before and after antidepressant treatment in antidepressant-naive depressed adolescents and healthy comparison subjects. Method Depressed (N=19) and healthy (N=21) adolescents, ages 11 to 18 years, underwent functional MRI assessment while viewing fearful and neutral facial expressions at baseline and again 8 weeks later. The depressed adolescents received 8 weeks of open-label fluoxetine treatment after their baseline scan. Results Voxel-wise whole brain analyses showed that depressed youths have exaggerated brain activation compared with healthy comparison subjects in multiple regions, including the frontal, temporal, and limbic cortices. The 8 weeks of fluoxetine treatment normalized most of these regions of hyperactivity in the depressed group. Region-of-interest analyses of the areas involved in emotion processing indicated that before treatment, depressed youths had significantly greater activations to fearful relative to neutral facial expressions than did healthy comparison subjects in the amygdala, orbitofrontal cortex, and subgenual anterior cingulate cortex bilaterally. Fluoxetine treatment decreased activations in all three regions, as compared with the repeat scans of healthy comparison subjects. Conclusions While effective treatments are available, the impact of depression and its treatment on the brain in adolescents is understudied. This study confirms increases in brain activation in untreated depressed adolescents and demonstrates reductions in these aberrant activations with treatment. PMID:22267183

  17. Unexplained Painful Physical Symptoms in Patients with Major Depressive Disorder: Prevalence, Pathophysiology and Management.

    PubMed

    Jaracz, Jan; Gattner, Karolina; Jaracz, Krystyna; Górna, Krystyna

    2016-04-01

    Patients with major depression often report pain. In this article, we review the current literature regarding the prevalence and consequences, as well as the pathophysiology, of unexplained painful physical symptoms (UPPS) in patients with major depressive disorder (MDD). UPPS are experienced by approximately two-thirds of depressed patients. The presence of UPPS makes a correct diagnosis of depression more difficult. Moreover, UPPS are a predictor of a poor response to treatment and a more chronic course of depression. Pain, in the course of depression, also has a negative impact on functioning and quality of life. Frequent comorbidity of depression and UPPS has inspired the formulation of an hypothesis regarding a shared neurobiological mechanism of both conditions. Evidence from neuroimaging studies has shown that frontal-limbic dysfunction in depression may explain abnormal pain processing, leading to the presence of UPPS. Increased levels of proinflamatory cytokines and substance P in patients with MDD may also clarify the pathophysiology of UPPS. Finally, dysfunction of the descending serotonergic and noradrenergic pathways that normally suppress ascending sensations has been proposed as a core mechanism of UPPS. Psychological factors such as catastrophizing also play a role in both depression and chronic pain. Therefore, pharmacological treatment and/or cognitive therapy are recommended in the treatment of depression with UPPS. Some data suggest that serotonin and noradrenaline reuptake inhibitors (SNRIs) are more effective than selective serotonin reuptake inhibitors (SSRIs) in the alleviation of depression and UPPS. However, the pooled analysis of eight randomised clinical trials showed similar efficacy of duloxetine (an SNRI) and paroxetine (an SSRI) in reducing UPPS in depression. Further integrative studies examining genetic factors (e.g. polymorphisms of genes for interleukins, serotonin transporter and receptors), molecular factors (e.g. cytokines

  18. Does family history of depression predict major depression in midlife women? Study of Women's Health Across the Nation Mental Health Study (SWAN MHS).

    PubMed

    Colvin, Alicia; Richardson, Gale A; Cyranowski, Jill M; Youk, Ada; Bromberger, Joyce T

    2014-08-01

    This study aims to determine whether family history of depression predicts major depression in midlife women independent of psychosocial and health profiles at midlife. Participants were 303 African American and Caucasian women (42-52 years at baseline) recruited into the Study of Women's Health Across the Nation (SWAN) and the Women's Mental Health Study (MHS) in Pittsburgh. Major depression was assessed annually with the Structured Clinical Interview for DSM-IV. Family mental health history was collected at the ninth or tenth follow-up. Multivariable logistic regression was used to determine whether family history of depression predicted major depression in midlife, adjusting for covariates. The odds of experiencing major depression during the study were three times greater for those with a family history than for those without a family history (OR = 3.22, 95% CI = 1.95-5.31). Family history predicted depression (OR = 2.67, 95% CI = 1.50-4.78) after adjusting for lifetime history of depression, age, trait anxiety, chronic medical conditions, and stressful life events. In analyses stratified by lifetime history of depression, family history significantly predicted depression only among women with a lifetime history of depression. Family history of depression predicts major depression in midlife women generally, but particularly in those with a lifetime history of depression prior to midlife. PMID:24952069

  19. Does Family History of Depression Predict Major Depression in Midlife Women? Study of Women’s Health Across the Nation Mental Health Study (SWAN MHS)

    PubMed Central

    Colvin, Alicia; Richardson, Gale A.; Cyranowski, Jill M.; Youk, Ada; Bromberger, Joyce T.

    2014-01-01

    Purpose To determine whether family history of depression predicts major depression in midlife women independent of psychosocial and health profiles at midlife. Methods Participants were 303 African American and Caucasian women (42–52 years at baseline) recruited into the Study of Women’s Health Across the Nation (SWAN) and the Women’s Mental Health Study (MHS) in Pittsburgh. Major depression was assessed annually with the Structured Clinical Interview for DSM-IV. Family mental health history was collected at the 9th or 10th follow-up. Multivariable logistic regression was used to determine whether family history of depression predicted major depression in midlife, adjusting for covariates. Results The odds of experiencing major depression during the study were three times greater for those with a family history than for those without a family history (OR=3.22, 95% CI=1.95- 5.31). Family history predicted depression (OR=2.67, 95% CI=1.50–4.78) after adjusting for lifetime history of depression, age, trait anxiety, chronic medical conditions, and stressful life events. In analyses stratified by lifetime history of depression, family history significantly predicted depression only among women with a lifetime history of depression. Conclusions Family history of depression predicts major depression in midlife women generally, but particularly in those with a lifetime history of depression prior to midlife. PMID:24952069

  20. New generation multi-modal antidepressants: focus on vortioxetine for major depressive disorder

    PubMed Central

    Katona, Cornelius L; Katona, Cara P

    2014-01-01

    Vortioxetine is a novel antidepressant with effects on multiple 5-HT receptors and on the serotonin transporter. This paper reviews preclinical and clinical evidence regarding its mechanism of action, its tolerability, and its efficacy in treating major depression. Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators. There may be a clinically meaningful advantage in terms of tolerability. PMID:24570588

  1. Pro- and anti-inflammatory cytokines, but not CRP, are inversely correlated with severity and symptoms of major depression.

    PubMed

    Schmidt, Frank M; Schröder, Thomas; Kirkby, Kenneth C; Sander, Christian; Suslow, Thomas; Holdt, Lesca M; Teupser, Daniel; Hegerl, Ulrich; Himmerich, Hubertus

    2016-05-30

    To clarify findings of elevated cytokine levels in major depression (MD), this study aimed to investigate the relationship between serum levels of cytokines, symptoms of MD and antidepressant treatment outcome. At baseline (T0) and 4 weeks following initiation of antidepressant treatment (T1), levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), CRP and depression ratings HAMD-17 and BDI-II were assessed in 30 patients with MD and 30 age-and sex-matched controls. At T0, in the patient group, cytokines, but not CRP, negatively correlated with individual BDI-II-items, factors and severities and showed both negative and positive correlations with HAMD-17 items. At T1 and within the controls, no such relationships were observed. At T0 and T1, levels of both pro- and anti-inflammatory cytokines were significantly higher in treatment responders (ΔHAMD-17T0-T1≥50%,n=15) compared to non-responders. When controlled for baseline BDI, differences between groups were only found significant for IL-2 at T0. The results suggest cytokines are not generally pro-depressive but rather relate to more specific regulation of symptoms and severities in MD. Together with the association between cytokines and treatment responder status, these data support cytokines as a promising but still controversial biomarker of depression. PMID:27137966

  2. Validation of the face-name pairs task in major depression: impaired recall but not recognition.

    PubMed

    Smith, Kimberley J; Mullally, Sinead; McLoughlin, Declan; O'Mara, Shane

    2014-01-01

    Major depression can be associated with neurocognitive deficits which are believed in part to be related to medial temporal lobe pathology. The purpose of this study was to investigate this impairment using a hippocampal-dependent neuropsychological task. The face-name pairs task was used to assess associative memory functioning in 19 patients with major depression. When compared to age-sex-and-education matched controls, patients with depression showed impaired learning, delayed cued-recall, and delayed free-recall. However, they also showed preserved recognition of the verbal and nonverbal components of this task. Results indicate that the face-name pairs task is sensitive to neurocognitive deficits in major depression. PMID:24575068

  3. Suicidal risk factors of recurrent major depression in Han Chinese women.

    PubMed

    Zhu, Yuzhang; Zhang, Hongni; Shi, Shenxun; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; 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 Seedman; Flint, Jonathan; Liu, Ying

    2013-01-01

    The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD). Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized anxiety disorder (GAD), social phobia, and animal phobia was seen in suicidal patients. The present findings indicate that specific factors act to increase the likelihood of suicide in MD. Our results may help improve the clinical assessment of suicide risk in depressed patients, especially for women. PMID:24312196

  4. Cognitive conflicts in major depression: Between desired change and personal coherence

    PubMed Central

    Feixas, Guillem; Montesano, Adrián; Compañ, Victoria; Salla, Marta; Dada, Gloria; Pucurull, Olga; Trujillo, Adriana; Paz, Clara; Muñoz, Dámaris; Gasol, Miquel; Saúl, Luis Ángel; Lana, Fernando; Bros, Ignasi; Ribeiro, Eugenia; Winter, David; Carrera-Fernández, María Jesús; Guàrdia, Joan

    2014-01-01

    Objectives The notion of intrapsychic conflict has been present in psychopathology for more than a century within different theoretical orientations. However, internal conflicts have not received enough empirical attention, nor has their importance in depression been fully elaborated. This study is based on the notion of cognitive conflict, understood as implicative dilemma (ID), and on a new way of identifying these conflicts by means of the Repertory Grid Technique. Our aim was to explore the relevance of cognitive conflicts among depressive patients. Design Comparison between persons with a diagnosis of major depressive disorder and community controls. Methods A total of 161 patients with major depression and 110 non-depressed participants were assessed for presence of IDs and level of symptom severity. The content of these cognitive conflicts was also analysed. Results Repertory grid analysis indicated conflict (presence of ID/s) in a greater proportion of depressive patients than in controls. Taking only those grids with conflict, the average number of IDs per person was higher in the depression group. In addition, participants with cognitive conflicts displayed higher symptom severity. Within the clinical sample, patients with IDs presented lower levels of global functioning and a more frequent history of suicide attempts. Conclusions Cognitive conflicts were more prevalent in depressive patients and were associated with clinical severity. Conflict assessment at pre-therapy could aid in treatment planning to fit patient characteristics. Practitioner points Internal conflicts have been postulated in clinical psychology for a long time but there is little evidence about its relevance due to the lack of methods to measure them. We developed a method for identifying conflicts using the Repertory Grid Technique. Depressive patients have higher presence and number of conflicts than controls. Conflicts (implicative dilemmas) can be a new target for intervention in

  5. Substance Use and Depression Symptomatology: Measurement Invariance of the Beck Depression Inventory (BDI-II) among Non-Users and Frequent-Users of Alcohol, Nicotine and Cannabis

    PubMed Central

    Moore, Ashlee A.; Neale, Michael C.; Silberg, Judy L.; Verhulst, Brad

    2016-01-01

    Depression is a highly heterogeneous condition, and identifying how symptoms present in various groups may greatly increase our understanding of its etiology. Importantly, Major Depressive Disorder is strongly linked with Substance Use Disorders, which may ameliorate or exacerbate specific depression symptoms. It is therefore quite plausible that depression may present with different symptom profiles depending on an individual’s substance use status. Given these observations, it is important to examine the underlying construct of depression in groups of substance users compared to non-users. In this study we use a non-clinical sample to examine the measurement structure of the Beck Depression Inventory (BDI-II) in non-users and frequent-users of various substances. Specifically, measurement invariance was examined across those who do vs. do not use alcohol, nicotine, and cannabis. Results indicate strict factorial invariance across non-users and frequent-users of alcohol and cannabis, and metric invariance across non-users and frequent-users of nicotine. This implies that the factor structure of the BDI-II is similar across all substance use groups PMID:27046165

  6. Substance Use and Depression Symptomatology: Measurement Invariance of the Beck Depression Inventory (BDI-II) among Non-Users and Frequent-Users of Alcohol, Nicotine and Cannabis.

    PubMed

    Moore, Ashlee A; Neale, Michael C; Silberg, Judy L; Verhulst, Brad

    2016-01-01

    Depression is a highly heterogeneous condition, and identifying how symptoms present in various groups may greatly increase our understanding of its etiology. Importantly, Major Depressive Disorder is strongly linked with Substance Use Disorders, which may ameliorate or exacerbate specific depression symptoms. It is therefore quite plausible that depression may present with different symptom profiles depending on an individual's substance use status. Given these observations, it is important to examine the underlying construct of depression in groups of substance users compared to non-users. In this study we use a non-clinical sample to examine the measurement structure of the Beck Depression Inventory (BDI-II) in non-users and frequent-users of various substances. Specifically, measurement invariance was examined across those who do vs. do not use alcohol, nicotine, and cannabis. Results indicate strict factorial invariance across non-users and frequent-users of alcohol and cannabis, and metric invariance across non-users and frequent-users of nicotine. This implies that the factor structure of the BDI-II is similar across all substance use groups. PMID:27046165

  7. Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

    PubMed

    Fang, Peng; Zeng, Ling-Li; Shen, Hui; Wang, Lubin; Li, Baojuan; Liu, Li; Hu, Dewen

    2012-01-01

    Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001) of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease. PMID:23049910

  8. Major depressive disorder predicts cardiac events in patients with coronary artery disease.

    PubMed

    Carney, R M; Rich, M W; Freedland, K E; Saini, J; teVelde, A; Simeone, C; Clark, K

    1988-01-01

    Fifty-two patients undergoing cardiac catheterization and subsequently found to have significant coronary artery disease (CAD) were given structured psychiatric interviews before catheterization. Nine of these patients met criteria for major depressive disorder. All 52 patients were contacted 12 months after catheterization, and the occurrence of myocardial infarction, angioplasty, coronary bypass surgery and death was determined. Results of the study show that major depressive disorder was the best predictor of these major cardiac events during the 12 months following catheterization. The predictive effect was independent of the severity of CAD, left ventricular ejection fraction, and the presence of smoking. Furthermore, with the exception of smoking, there were no statistically significant differences between those patients with major depressive disorder and the remaining patients on any variable studied. The possible mechanisms relating major depressive disorder to subsequent cardiac events are discussed. It is concluded that major depressive disorder is an important independent risk factor for the occurrence of major cardiac events in patients with CAD. PMID:2976950

  9. Symptoms of Major Depression in a Sample of Fathers of Infants: Sociodemographic Correlates and Links to Father Involvement

    ERIC Educational Resources Information Center

    Bronte-Tinkew, Jacinta; Moore, Kristin A.; Matthews, Gregory; Carrano, Jennifer

    2007-01-01

    Depression has been extensively studied for mothers but not for fathers. This study examines the sociodemographic correlates of symptoms of depression and how depression is associated with father involvement using the Composite International Diagnostic Interview-Short Form (CIDI-SF) for major depression. The study uses a sample of 2,139 resident…

  10. Nitric Oxide-Related Biological Pathways in Patients with Major Depression

    PubMed Central

    Baranyi, Andreas; Amouzadeh-Ghadikolai, Omid; Rothenhäusler, Hans-Bernd; Theokas, Simon; Robier, Christoph; Baranyi, Maria; Koppitz, Michael; Reicht, Gerhard; Hlade, Peter; Meinitzer, Andreas

    2015-01-01

    Background Major depression is a well-known risk factor for cardiovascular diseases and increased mortality following myocardial infarction. However, biomarkers of depression and increased cardiovascular risk are still missing. The aim of this prospective study was to evaluate, whether nitric-oxide (NO) related factors for endothelial dysfunction, such as global arginine bioavailability, arginase activity, L-arginine/ADMA ratio and the arginine metabolites asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) might be biomarkers for depression-induced cardiovascular risk. Methods In 71 in-patients with major depression and 48 healthy controls the Global Arginine Bioavailability Ratio (GABR), arginase activity (arginine/ornithine ratio), the L-arginine/ADMA ratio, ADMA, and SDMA were determined by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at baseline at the time of in-patient admittance and at the time of hospital discharge. Results The ADMA concentrations in patients with major depression were significantly elevated and the SDMA concentrations were significantly decreased in comparison with the healthy controls. Even after a first improvement of depression, ADMA and SDMA levels remained nearly unchanged. In addition, after a first improvement of depression at the time of hospital discharge, a significant decrease in arginase activity, an increased L-arginine/ADMA ratio and a trend for increased global arginine bioavailability were observed. Conclusions Our study results are evidence that in patients with major depression ADMA and SDMA might be biomarkers to indicate an increased cardiovascular threat due to depression-triggered NO reduction. GABR, the L-arginine/ADMA ratio and arginase activity might be indicators of therapy success and increased NO production after remission. PMID:26581044

  11. Brain SPECT guided repetitive transcranial magnetic stimulation (rTMS) in treatment resistant major depressive disorder.

    PubMed

    Jha, Shailesh; Chadda, Rakesh K; Kumar, Nand; Bal, C S

    2016-06-01

    Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential treatment in treatment resistant major depressive disorder (MDD). However, there is no consensus about the exact site of stimulation for rTMS. Single-photon emission computed tomography (SPECT) offers a potential technique in deciding the site of stimulation. The present study was conducted to assess the difference in outcome of brain SPECT assisted rTMS versus standard protocol of twenty sessions of high frequency rTMS as add on treatment in 20 patients with treatment resistant MDD, given over a period of 4 weeks. Thirteen subjects (group I) received high frequency rTMS over an area of hypoperfusion in the prefrontal cortex, as identified on SPECT, whereas 7 subjects (group II) were administered rTMS in the left dorsoslateral prefrontal cortex (DLPFC) area. Improvement was monitored using standardized instruments. Patients in the group I showed a significantly better response compared to those in the group II. In group I, 46% of the subjects were responders on MADRS, 38% on BDI and 77% on CGI. The parallel figures of responders in Group II were 0% on MADRS, 14% on BDI and 43% on CGI. There were no remitters in the study. No significant untoward side effects were noticed. The study had limitations of a small sample size and non-controlled design, and all the subjects were also receiving the standard antidepressant therapy. Administration of rTMS over brain SPECT specified area of hypoperfusion may have a better clinical outcome compared to the standard protocol. PMID:27208445

  12. Is Ursa Major II the Progenitor of the Orphan Stream?

    SciTech Connect

    Fellhauer, M.; Evans, N.W.; Belokurov, V.; Zucker, D.B.; Yanny, B.; Wilkinson, M.I.; Gilmore, G.; Irwin, M.J.; Bramich, D.M.; Vidrih, S.; Hewett, Paul C.; /Cambridge U., Inst. of Astron. /Michigan State U.

    2006-11-01

    Prominent in the ''Field of Streams''--the Sloan Digital Sky Survey map of substructure in the Galactic halo--is an ''Orphan Stream'' without obvious progenitor. In this numerical study, we show a possible connection between the newly found dwarf satellite Ursa Major II (UMa II) and the Orphan Stream. We provide numerical simulations of the disruption of UMa II that match the observational data on the position, distance and morphology of the Orphan Stream. We predict the radial velocity of UMa II as -100kms{sup -1}, as well as the existence of strong velocity gradients along the Orphan Stream. The velocity dispersion of UMa II is expected to be high, though this can be caused both by a high dark matter content or by the presence of unbound stars in a disrupted remnant. However, the existence of a gradient in the mean radial velocity across UMa II provides a clear-cut distinction between these possibilities. The simulations support the idea that some of the anomalous, young halo globular clusters like Palomar 1 or Arp 2 or Ruprecht 106 may be physically associated with the Orphan Stream.

  13. Hydrogeochemical evolution of inland lakes’ water: A study of major element geochemistry in the Wadi El Raiyan depression, Egypt

    PubMed Central

    Mohamed, Essam A.; El-Kammar, Ahmed M.; Yehia, Mohamed M.; Abu Salem, Hend S.

    2015-01-01

    Wadi El Raiyan is a great depression located southwest of Cairo in the Western Desert of Egypt. Lake Qarun, located north of the study area, is a closed basin with a high evaporation rate. The source of water in the lake is agricultural and municipal drainage from the El Faiyum province. In 1973, Wadi El Raiyan was connected with the agricultural wastewater drainage system of the Faiyum province and received water that exceeded the capacity of Lake Qarun. Two hydrogeological regimes have been established in the area: (i) higher cultivated land and (ii) lower Wadi El Raiyan depression lakes. The agricultural drainage water of the cultivated land has been collected in one main drain (El Wadi Drain) and directed toward the Wadi El Raiyan depression, forming two lakes at different elevations (upper and lower). In the summer of 2012, the major chemical components were studied using data from 36 stations distributed over both hydrogeological regimes in addition to one water sample collected from Bahr Youssef, the main source of freshwater for the Faiyum province. Chemical analyses were made collaboratively. The major ion geochemical evolution of the drainage water recharging the El Raiyan depression was examined. Geochemically, the Bahr Youssef sample is considered the starting point in the geochemical evolution of the studied surface water. In the cultivated area, major-ion chemistry is generally influenced by chemical weathering of rocks and minerals that are associated with anthropogenic inputs, as well as diffuse urban and/or agricultural drainage. In the depression lakes, the water chemistry generally exhibits an evaporation-dependent evolutionary trend that is further modified by cation exchange and precipitation of carbonate minerals. PMID:26644942

  14. Structural Asymmetry of Dorsolateral Prefrontal Cortex Correlates with Depressive Symptoms: Evidence from Healthy Individuals and Patients with Major Depressive Disorder.

    PubMed

    Liu, Wei; Mao, Yu; Wei, Dongtao; Yang, Junyi; Du, Xue; Xie, Peng; Qiu, Jiang

    2016-06-01

    In this study, we investigated the role of structural asymmetry of the dorsolateral prefrontal cortex (DLPFC) in the continuum of depression from healthy individuals to patients. Structural magnetic resonance imaging was performed in 70 patients with major depressive disorder (MDD), 49 matched controls, and 349 healthy university students to calculate structural asymmetry indexes of the DLPFC. First-episode, treatment-naive MDD patients showed a relatively lower asymmetry index than healthy controls, and their asymmetry index was negatively correlated with the depressive symptoms. This abnormality was normalized by antidepressants in medicated MDD patients. Furthermore, the asymmetry index was negatively correlated with the depressive symptoms in university students; this was replicated at two time points in a subgroup of students, suggesting good test-retest reliability. Our findings are consistent with previous studies that support the imbalance hypothesis of MDD and suggest a potential structural basis underlying the functional asymmetry of the DLPFC in depression. In future, the structural index of the DLPFC may become a potential biomarker to evaluate individuals' risk for the onset of MDD. PMID:27015663

  15. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms.

    PubMed

    Owens, Matthew; Herbert, Joe; Jones, Peter B; Sahakian, Barbara J; Wilkinson, Paul O; Dunn, Valerie J; Croudace, Timothy J; Goodyer, Ian M

    2014-03-01

    Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys. PMID:24550453

  16. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms

    PubMed Central

    Owens, Matthew; Herbert, Joe; Jones, Peter B.; Sahakian, Barbara J.; Wilkinson, Paul O.; Dunn, Valerie J.; Croudace, Timothy J.; Goodyer, Ian M.

    2014-01-01

    Major depressive disorder (MD) is a debilitating public mental health problem with severe societal and personal costs attached. Around one in six people will suffer from this complex disorder at some point in their lives, which has shown considerable etiological and clinical heterogeneity. Overall there remain no validated biomarkers in the youth population at large that can aid the detection of at-risk groups for depression in general and for boys and young men in particular. Using repeated measurements of two well-known correlates of MD (self-reported current depressive symptoms and early-morning cortisol), we undertook a population-based investigation to ascertain subtypes of adolescents that represent separate longitudinal phenotypes. Subsequently, we tested for differential risks for MD and other mental illnesses and cognitive differences between subtypes. Through the use of latent class analysis, we revealed a high-risk subtype (17% of the sample) demarcated by both high depressive symptoms and elevated cortisol levels. Membership of this class of individuals was associated with increased levels of impaired autobiographical memory recall in both sexes and the greatest likelihood of experiencing MD in boys only. These previously unidentified findings demonstrate at the population level a class of adolescents with a common physiological biomarker specifically for MD in boys and for a mnemonic vulnerability in both sexes. We suggest that the biobehavioral combination of high depressive symptoms and elevated morning cortisol is particularly hazardous for adolescent boys. PMID:24550453

  17. Cancer Patients with Major Depressive Disorder: Testing a Biobehavioral/Cognitive Behavior Intervention

    ERIC Educational Resources Information Center

    Brothers, Brittany M.; Yang, Hae-Chung; Strunk, Daniel R.; Andersen, Barbara L.

    2011-01-01

    Objective: In this Phase II trial, we evaluated a novel psychological treatment for depressed patients coping with the stresses of cancer. Effectiveness of a combined biobehavioral intervention (BBI) and cognitive behavior therapy (CBT) was studied. Method: Participants were 36 cancer survivors (mean age = 49 years; 88% Caucasian; 92% female)…

  18. The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review.

    PubMed

    Bruno, Antonio; Morabito, Paolo; Spina, Edoardo; Muscatello, Maria Rosaria

    2016-01-01

    Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for once-daily administration, thereby improving patient adherence. This agent differs from other available SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials (one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of MDD in relation to currently available antidepressants including other SNRIs. PMID:26572745

  19. The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review

    PubMed Central

    Bruno, Antonio; Morabito, Paolo; Spina, Edoardo; Muscatello, Maria Rosaria

    2016-01-01

    Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for once-daily administration, thereby improving patient adherence. This agent differs from other available SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials (one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of MDD in relation to currently available antidepressants including other SNRIs. PMID:26572745

  20. Relapse Prevention in Major Depressive Disorder: Mindfulness-Based Cognitive Therapy Versus an Active Control Condition

    PubMed Central

    Shallcross, Amanda J.; Gross, James J.; Visvanathan, Pallavi D.; Kumar, Niketa; Palfrey, Amy; Ford, Brett Q.; Dimidjian, Sona; Shirk, Stephen; Holm-Denoma, Jill; Goode, Kari M.; Cox, Erica; Chaplin, William; Mauss, Iris B.

    2015-01-01

    Objective We evaluated the comparative effectiveness of Mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. Method Ninety-two participants in remission from Major Depressive Disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for non-specific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. Results Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (group x time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction post-intervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. Conclusions MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID:26371618

  1. Usefulness of LDAEP to Predict Tolerability to SSRIs in Major Depressive Disorder: A Case Report

    PubMed Central

    Lee, Seung-Hwan; Park, Eun Jin

    2012-01-01

    We report here a patient with major depressive disorder who experienced severe adverse effects after the administration of SSRIs (serotonin selective reuptake inhibitors) without improvement of his depressive symptoms. These adverse effects disappeared and his depressive symptoms improved after discontinuation of the SSRIs and the administration of tianeptine. The patient exhibited a low value for the loudness dependent of auditory evoked potentials (LDAEP) -0.14 at baseline, which means that his central serotonergic neurotransmission was already highly active. We assumed that it was this high serotonergic activity that rendered him unresponsive to SSRIs, and brought on him the adverse effects, and that the tianeptine was effective due to the lack of serotonin reuptake inhibitory action. Thus, we suggest that LDAEP can be used to predict an individual patient's tolerability and clinical response to SSRIs in major depression. PMID:22396689

  2. Usefulness of LDAEP to predict tolerability to SSRIs in major depressive disorder: a case report.

    PubMed

    Park, Young-Min; Lee, Seung-Hwan; Park, Eun Jin

    2012-03-01

    We report here a patient with major depressive disorder who experienced severe adverse effects after the administration of SSRIs (serotonin selective reuptake inhibitors) without improvement of his depressive symptoms. These adverse effects disappeared and his depressive symptoms improved after discontinuation of the SSRIs and the administration of tianeptine. The patient exhibited a low value for the loudness dependent of auditory evoked potentials (LDAEP) -0.14 at baseline, which means that his central serotonergic neurotransmission was already highly active. We assumed that it was this high serotonergic activity that rendered him unresponsive to SSRIs, and brought on him the adverse effects, and that the tianeptine was effective due to the lack of serotonin reuptake inhibitory action. Thus, we suggest that LDAEP can be used to predict an individual patient's tolerability and clinical response to SSRIs in major depression. PMID:22396689

  3. Milnacipran in panic disorder with agoraphobia and major depressive disorder: a case report.

    PubMed

    Chen, Mu-Hong; Liou, Ying-Jay

    2011-01-01

    A 51-year-old woman had panic disorder with agoraphobia and major depressive disorder sequentially. The aforementioned symptoms subsided significantly after treatment with milnacipran, 125 mg, administered daily for 2 months. However, panic attacks with agoraphobia were noted frequently when she tapered down milnacipran to 50 mg daily. She consequently experienced depression that gradually increased in degree, with poor energy, poor sleep, thoughts of helplessness, and ideas of death. After administration of a daily dose of 125 mg of milnacipran for 1 month, her panic attacks with agoraphobia and depressed mood were again alleviated. The present report shows significant effects of milnacipran on the comorbidity of panic disorder with agoraphobia and major depressive disorder. PMID:21926486

  4. Incident Major Depressive Episodes increase the severity and risk of apathy in HIV infection

    PubMed Central

    Kamat, Rujvi; Cattie, Jordan E.; Marcotte, Thomas D.; Woods, Steven Paul; Franklin, Donald R.; Corkran, Stephanie H.; Ellis, Ronald J.; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Apathy and depression are inter-related yet separable and prevalent neuropsychiatric disturbances in persons infected with HIV. In the present study of 225 HIV+ persons, we investigated the role of an incident depressive episode in changes in apathy. Participants completed the apathy subscale of the Frontal Systems Behavior Scale during a detailed neuropsychiatric and neuromedical evaluation at visit 1 and again at approximately a 14 month follow-up. The Composite International Diagnostic Interview was used to obtain diagnoses of a new major depressive disorder. At their follow-up visit, participants were classified into four groups depending on their visit 1 elevation in apathy and new major depressive episode (MDE) status. Apathetic participants at baseline with a new MDE (n=23) were at risk for continued, clinically elevated apathy at follow-up, although severity of symptoms did not increase. Of the 144 participants without clinically elevated apathy at visit 1, those who developed a new MDE (n=16) had greater apathy symptomatology at follow-up than those without MDE. These findings suggest that HIV+ individuals, who do not as yet present with elevated apathy, may be at greater risk of elevated psychiatric distress should they experience a new/recurrent depressive episode. Thus, in the context of previous findings, it appears that although apathy and depression are separable constructs, they interact such that a new depressive episode is a risk factor for incident apathy. PMID:25679203

  5. Paroxetine Treatment in Children and Adolescents with Major Depressive Disorder: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    ERIC Educational Resources Information Center

    Emslie, Graham J.; Wagner, Karen Dineen; Kutcher, Stan; Krulewicz, Stan; Fong, Regan; Carpenter, David J.; Lipschitz, Alan; Machin, Andrea; Wilkinson, Christel

    2006-01-01

    Objective: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. Method: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating…

  6. Theory of mind ability predicts prognosis of outpatients with major depressive disorder.

    PubMed

    Yamada, Kazuo; Inoue, Yumiko; Kanba, Shigenobu

    2015-12-15

    A theory of mind (ToM) deficit in patients with major depressive episodes is associated with difficulty in social adjustment, and thus may indicate a poorer prognosis. We investigated the association between ToM deficits and the outcome in patients who had recovered from major depressive episodes. We evaluated ToM abilities of 100 patients with major depressive disorder during a period of remission. The patients were followed up for one year and their outcomes observed. After one year, patients who had a ToM deficit according to a second-order false belief question relapsed significantly more frequently than did patients who did not have a deficit (Fisher's exact test P<0.0001; relative risk (RR)=8.286; CI 2.608, 26.324). Significant differences between these two groups were shown in scores of the Global Assessment of Functioning Scale (P<0.0001). Our results suggest that a ToM deficit after symptom remission in patients with major depressive disorder predicts a higher relapse rate and lower social function one year after recovering from a major depressive episode. PMID:26477953

  7. Partner violence and major depression in women: a community study of Chinese Americans.

    PubMed

    Hicks, Madelyn Hsiao-Rei; Li, Zhonghe

    2003-11-01

    This cross-sectional, retrospective study used epidemiological and anthropological methods toward two aims: 1) to examine associations between partner violence and major depression in a community probability sample of women and 2) to provide new data on partner violence in Chinese Americans. In this study, 181 Chinese American women were interviewed, with 178 completing structured sections on CIDI 2.1 major depression and on partner violence history. Results indicate that a history of partner violence is associated with significantly higher rates of lifetime, 12-month, and current major depression in this community population. This effect is specific and independent of other factors. Partner violence also has a dose-response relationship with the severity of major depression episodes, increasing risk for severe and moderate episodes. The strength and specificity of this association, its dose-response effect, and its commonality across different populations suggest a possible causal role for partner violence needing further investigation in research on major depression in women. PMID:14614339

  8. Cohesin regulates major histocompatibility complex class II genes through interactions with MHC-II insulators1

    PubMed Central

    Majumder, Parimal; Boss, Jeremy M.

    2011-01-01

    Cohesin is a multiprotein ringed complex that is most well known for its role in stabilizing the association of sister chromatids between S phase and M. More recently cohesin was found to be associated with transcriptional insulators, elements that are associated with the organization of chromatin into regulatory domains. The human major histocompatibility complex class II (MHC-II) locuscontains ten intergenic elements, termed MHC-II insulators, which bind the transcriptional insulator protein CCCTC transcription factor (CTCF). MHC-II insulators interact with each other forming a base architecture of discrete loops and potential regulatory domains. When MHC-II genes are expressed, their proximal promoter regulatory regions reorganize to the foci established by the interacting MHC-II insulators. MHC-II insulators also bind cohesin, but the functional role of cohesin in regulating this system is not known. Here we show that the binding of cohesin to MHC-II insulators occurred irrespective of MHC-II expression but was required for optimal expression of the HLA-DR and HLA-DQ genes. In a DNA dependent manner, cohesin subunits interacted with CTCF and the MHC-II specific transcription factors RFX and CIITA. Intriguingly, cohesin subunits were important for DNA looping interactions between the HLA-DRA promoter region and a 5’ MHC-II insulator but were not required for interactions between the MHC-II insulators themselves. This latter observation introduces cohesin as a regulator of MHC-II expression by initiating or stabilizing MHC-II promoter regulatory element interactions with the MHC-II insulator elements; events which are required for maximal MHC-II transcription. PMID:21911605

  9. Resting-State Connectivity Predictors of Response to Psychotherapy in Major Depressive Disorder

    PubMed Central

    Crowther, Andrew; Smoski, Moria J; Minkel, Jared; Moore, Tyler; Gibbs, Devin; Petty, Chris; Bizzell, Josh; Schiller, Crystal Edler; Sideris, John; Carl, Hannah; Dichter, Gabriel S

    2015-01-01

    Despite the heterogeneous symptom presentation and complex etiology of major depressive disorder (MDD), functional neuroimaging studies have shown with remarkable consistency that dysfunction in mesocorticolimbic brain systems are central to the disorder. Relatively less research has focused on the identification of biological markers of response to antidepressant treatment that would serve to improve the personalized delivery of empirically supported antidepressant interventions. In the present study, we investigated whether resting-state functional brain connectivity (rs-fcMRI) predicted response to Behavioral Activation Treatment for Depression, an empirically validated psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20 matched nondepressed controls completed rs-fcMRI scans after which the MDD group received an average of 12 sessions of psychotherapy. The mean change in Beck Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically meaningful response. Resting-state neuroimaging data were analyzed with a seed-based approach to investigate functional connectivity with four canonical resting-state networks: the default mode network, the dorsal attention network, the executive control network, and the salience network. At baseline, the MDD group was characterized by relative hyperconnectivity of multiple regions with precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity of the precuneus with the left middle temporal gyrus and connectivity of the dACC with the parahippocampal gyrus predicted the magnitude of pretreatment MDD symptoms. Hierarchical linear modeling revealed that response to psychotherapy in the MDD group was predicted by pretreatment

  10. 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

  11. Reducing the Burden of Difficult-to-Treat Major Depressive Disorder: Revisiting Monoamine Oxidase Inhibitor Therapy

    PubMed Central

    2013-01-01

    Objective: Difficult-to-treat depression (eg, depression with atypical or anxious symptoms, treatment-resistant depression, or depression with frequent recurrence) is a challenging real-world health issue. This critical review of the literature focuses on monoamine oxidase inhibitor (MAOI) therapy and difficult-to-treat forms of depression. Data Sources: A PubMed literature search was performed in November 2012 and refreshed through January 2013 with no date restrictions using key search terms including MAO inhibitor therapy or MAOI and depression and anxiety, atypical, treatment-resistant, recurrent, relapse, or refractory. Study Selection: Articles were selected to summarize the current needs in difficult-to-treat depression as well as the use of MAOI therapies in this area. Results: Two strategies have fallen out of favor in the care of patients with major depressive disorder. The first is the use of MAOI therapy and the second is the proactive recognition of difficult-to-treat depression that may not respond as well to more frequently used antidepressants. The infrequent use of MAOIs stems from the perception that other oral therapies for depression are safer and easier to use than oral MAOIs; however, transdermal delivery is one potential strategy to improve the safety of this class of agents. Although food-related interactions with transdermal delivery of MAOI therapy can be lessened, clinicians still need to be vigilant for drug-drug interactions and serotonin syndrome. Conclusions: Clinicians should consider MAOIs for patients who have had several unsuccessful trials of antidepressants. Guidelines generally reserve MAOIs as third- and fourth-line treatments due to concerns over safety and tolerability; however, transdermal delivery of an MAOI may allay some of the safety and tolerability concerns. Patients should be provided education about MAOIs and their risks. PMID:24511450

  12. Characterizing major depression phenotypes by presence and type of psychomotor disturbance in adolescents and young adults.

    PubMed

    Leventhal, Adam M; Pettit, Jeremy W; Lewinsohn, Peter M

    2008-01-01

    Major depressive disorder (MDD) is phenomenologically heterogeneous, which has prompted investigation of intermediate MDD phenotypes based on specific key symptoms. Presence and type of psychomotor disturbance may be an important psychopathologic feature that differentiates clinically distinct forms of juvenile MDD. This study examined the phenotypic status of three putative MDD phenotypes in a community sample of 941 youths: (1) agitated depression (MDD with psychomotor agitation), (2) retarded depression (MDD with psychomotor retardation), and (3) agitated-retarded depression (MDD with psychomotor agitation and retardation within an episode). Hasler et al.'s [2004: Neuropsychopharmacology 29:1765-1781] criteria of specificity (degree of association with relevant symptoms and conditions related to the disease of interest versus other psychiatric conditions), stability (degree of stability over time), and heritability (degree of familial aggregation with relevant conditions) were used to evaluate the phenotypic significance of these subtypes. Results were suggestive that agitated depression was a relatively specific phenotypic syndrome characterized by irritability, arousal, physical complaints, and vulnerability to anxiety disorders and alcohol dependence; low stability across depressive episodes; and low heritability. Agitated-retarded depression was relatively specific and characterized by increased severity, recurrence, vegetative symptoms, suicidal ideation, social impairment, endogeneity, and vulnerability to anxiety disorders and bulimia; low stability across episodes; and modest heritability. Although retarded depression was associated with some specific distinguishing characteristics, most associations were explained by the increased severity of this phenotype. Retarded depression evidenced little stability or heritability. These findings offer partial support of the phenotypic status of agitated and agitated-retarded depression in youths. PMID:17385727

  13. Longitudinal Stability of the Beck Depression Inventory II: A Latent Trait-State-Occasion Model

    ERIC Educational Resources Information Center

    Wu, Pei-Chen

    2016-01-01

    In a six-wave longitudinal study with two cohorts (660 adolescents and 630 young adults), this study investigated the longitudinal stability of the Beck Depression Inventory II (BDI-II) using the Trait-State-Occasion (TSO) model. The results revealed that the full TSO model was the best fitting representation of the depression measured by the…

  14. Measurement Invariance and Latent Mean Differences of the Beck Depression Inventory II across Gender Groups

    ERIC Educational Resources Information Center

    Wu, Pei-Chen

    2010-01-01

    This study examined measurement invariance (i.e., configural invariance, metric invariance, scalar invariance) of the Chinese version of Beck Depression Inventory II (BDI-II-C) across college males and females and compared gender differences on depression at the latent factor mean level. Two samples composed of 402 male college students and 595…

  15. The efficacy of vortioxetine for the treatment of major depressive disorder.

    PubMed

    Dhir, Ashish; Sarvaiya, Jayrajsinh

    2014-12-01

    Vortioxetine (Lu AA21004; Brintellix(®)) has received approval from various international regulatory agencies for the treatment of major depression. The drug molecule has a multimodal mechanism of action that projects it as a unique molecule for the treatment of major depression. These mechanisms include property to inhibit serotonin reuptake via inhibiting serotonin transporters and acting on multiple serotonin receptor subtypes. Vortioxetine is an agonist of 5-HT1A, a partial agonist of 5-HT1B and an antagonist of 5-HT1D, 5-HT3 and 5-HT7 serotoninergic receptors. The molecule has been found to be effective and well-tolerable to be administered in humans for the treatment of major depression. Precautions should be exercised when vortioxetine is prescribed with cytochrome P450 inducers and inhibitors. This review attempts to compile the efficacy profile of vortioxetine in different clinical trials and the results are compared with other standard antidepressants. PMID:25418918

  16. Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

    PubMed Central

    Karling, Pontus; Wikgren, Mikael; Adolfsson, Rolf; Norrback, Karl-Fredrik

    2016-01-01

    Background/Aims Gastrointestinal symptoms and hypothalamus-pituitary-adrenal (HPA) axis dysfunction are frequently observed in patients with major depression. The primary aim of the study was to investigate the relationship between HPA-axis function and self-perceived functional gastrointestinal symptoms in major depression. Methods Patients with major depression (n = 73) and controls representative of the general population (n = 146) underwent a weight-adjusted very low dose dexamethasone suppression test (DST). Patients and controls completed the gastrointestinal symptom rating scale-iritable bowel syndrome (GSRS-IBS) and the hospital anxiety depression scale. Medical records of the patients were screened over a ten year period for functional gastrointestinal disorder and pain conditions. Results Patients with high GSRS-IBS scores (above median) exhibited HPA-axis hypersuppression more often than controls (defined by the lowest 10% cutoff of the post-DST cortisol values among controls, adjusted OR 7.25, CI 1.97–26.7) whereas patients with low GSRS-IBS scores did not differ from controls concerning their post-DST cortisol values. Patients who had consulted primary care for functional gastrointestinal disorder (P = 0.039), lumbago (P = 0.006) and chronic multifocal pain (P = 0.057) also exhibited an increased frequency of hypersuppression. Conclusions HPA-axis hypersuppression is associated with functional gastrointestinal symptoms in patients with major depression. PMID:26507800

  17. Gender Abuse and Major Depression Among Transgender Women: A Prospective Study of Vulnerability and Resilience

    PubMed Central

    Bockting, Walter; Rosenblum, Andrew; Hwahng, Sel; Mason, Mona; Macri, Monica; Becker, Jeffrey

    2014-01-01

    Objectives. We examined the social and interpersonal context of gender abuse and its effects on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depression among transgender women. Methods. We conducted a 3-year prospective study (2004–2007) among 230 transgender women aged 19 to 59 years from the New York City Metropolitan Area. Statistical techniques included generalized estimating equations (logistic regression). Results. We observed significant associations of psychological and physical gender abuse with major depression during follow-up. New or persistent experiences of both types of abuse were associated with 4- to 7-fold increases in the likelihood of incident major depression. Employment, transgender presentation, sex work, and hormone therapy correlated across time with psychological abuse; the latter 2 variables correlated with physical abuse. The association of psychological abuse with depression was stronger among younger than among older transgender women. Conclusions. Psychological and physical gender abuse is endemic in this population and may result from occupational success and attempts to affirm gender identity. Both types of abuse have serious mental health consequences in the form of major depression. Older transgender women have apparently developed some degree of resilience to psychological gender abuse. PMID:24328655

  18. The role of the kynurenine pathway in suicidality in adolescent major depressive disorder

    PubMed Central

    Bradley, Kailyn A. L.; Case, Julia A. C.; Khan, Omar; Ricart, Thomas; Hanna, Amira; Alonso, Carmen M.; Gabbay, Vilma

    2015-01-01

    The neuroimmunological kynurenine pathway (KP) has been implicated in major depressive disorder (MDD) in adults and adolescents, most recently in suicidality in adults. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins. Here, we examined the KP in 20 suicidal depressed adolescents—composed of past attempters and those who expressed active suicidal intent—30 non-suicidal depressed youth, and 22 healthy controls (HC). Plasma levels of TRP, KYN, 3-hydroxyanthranilic acid, and KYN/TRP (index of IDO) were assessed. Suicidal adolescents showed decreased TRP and elevated KYN/TRP compared to both non-suicidal depressed adolescents and HC. Findings became more significantly pronounced when excluding medicated participants, wherein there was also a significant positive correlation between KYN/TRP and suicidality. Finally, although depressed adolescents with a history of suicide attempt differed from acutely suicidal adolescents with respect to disease severity, anhedonia, and suicidality, the groups did not differ in KP measures. Our findings suggest a possible specific role of the KP in suicidality in depressed adolescents, while illustrating the clinical phenomenon that depressed adolescents with a history of suicide attempt are similar to acutely suicidal youth and are at increased risk for completion of suicide. PMID:25865484

  19. The role of the kynurenine pathway in suicidality in adolescent major depressive disorder.

    PubMed

    Bradley, Kailyn A L; Case, Julia A C; Khan, Omar; Ricart, Thomas; Hanna, Amira; Alonso, Carmen M; Gabbay, Vilma

    2015-06-30

    The neuroimmunological kynurenine pathway (KP) has been implicated in major depressive disorder (MDD) in adults and adolescents, most recently in suicidality in adults. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins. Here, we examined the KP in 20 suicidal depressed adolescents-composed of past attempters and those who expressed active suicidal intent-30 non-suicidal depressed youth, and 22 healthy controls (HC). Plasma levels of TRP, KYN, 3-hydroxyanthranilic acid (3-HAA), and KYN/TRP (index of IDO) were assessed. Suicidal adolescents showed decreased TRP and elevated KYN/TRP compared to both non-suicidal depressed adolescents and HC. Findings became more significantly pronounced when excluding medicated participants, wherein there was also a significant positive correlation between KYN/TRP and suicidality. Finally, although depressed adolescents with a history of suicide attempt differed from acutely suicidal adolescents with respect to disease severity, anhedonia, and suicidality, the groups did not differ in KP measures. Our findings suggest a possible specific role of the KP in suicidality in depressed adolescents, while illustrating the clinical phenomenon that depressed adolescents with a history of suicide attempt are similar to acutely suicidal youth and are at increased risk for completion of suicide. PMID:25865484

  20. Influence of gender and hemispheric lateralization on heat pain perception in major depression.

    PubMed

    Bär, K J; Greiner, W; Letsch, A; Köbele, R; Sauer, H

    2003-01-01

    Increased incidence of clinical pain complaints from patients with major depression, as well as increased experimental pain thresholds have been reported. The basis of this phenomenon remains unclear, as well as its relation to medication, clinical recovery, gender and lateralization of hemispheric function. We aimed to further elucidate heat pain perception in depression applying a testing battery including assessment (on both arms) of warmth perception, heat pain perception and heat pain tolerance, and the jaw opening reflex (duration of ES2 component) as a putative indicator of descending pain inhibition. The battery was applied to 20 patients and 20 age- and sex-matched controls. Patients were assessed: on admission (acutely depressed, off-medication), few days after admission (depressed, on medication), and after clinical recovery (mostly on medication), and controls at corresponding intervals. Significant elevated heat pain thresholds were found off and on medication in the acute stage (mainly in women) and after recovery on the right arm only. Elevated heat pain tolerance (on the right arm only) was seen in medicated patients in the acute and recovered stage. Significant prolongation of ES2 duration was only found in acutely depressed patients off medication. While confirming hypalgesia to heat pain in major depression, our findings demonstrate a close relation to gender and strong influence of lateralization after recovery. Altered pain processing at brain stem level might only partially be responsible for the observed finding. PMID:12765857

  1. Food for thought: understanding the value, variety and usage of management algorithms for major depressive disorder.

    PubMed

    Katzman, Martin A; Anand, Leena; Furtado, Melissa; Chokka, Pratap

    2014-12-01

    By 2020, depression is projected to be among the most important contributors to the global burden of disease. A plethora of data confirms that despite the availability of effective therapies, major depressive disorder continues to exact an enormous toll; this, in part, is due to difficulties reaching complete remission, as well as the specific associated costs of both the disorder's morbidity and mortality. The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. The use of management algorithms has been shown to improve treatment outcomes in major depressive disorder and may be less costly than "usual care" practices. Nevertheless, many patients with depression remain untreated. As well, even those who are treated often continue to experience suboptimal quality of life. As such, the treatment algorithms in this article may improve outcomes for patients suffering with depression. This paper introduces some of the principal reasons underlying these treatment gaps and examines measures or recommendations that might be changed or strengthened in future practice guidelines to bridge them. PMID:25539872

  2. Genome-wide linkage on chromosome 10q26 for a dimensional scale of major depression.

    PubMed

    Knowles, Emma E M; Kent, Jack W; McKay, D Reese; Sprooten, Emma; Mathias, Samuel R; Curran, Joanne E; Carless, Melanie A; de Almeida, Marcio A A; Harald, H H Goring; Dyer, Tom D; Olvera, Rene L; Fox, Peter T; Duggirala, Ravi; Almasy, Laura; Blangero, John; Glahn, David C

    2016-02-01

    Major depressive disorder (MDD) is a common and potentially life-threatening mood disorder. Identifying genetic markers for depression might provide reliable indicators of depression risk, which would, in turn, substantially improve detection, enabling earlier and more effective treatment. The aim of this study was to identify rare variants for depression, modeled as a continuous trait, using linkage and post-hoc association analysis. The sample comprised 1221 Mexican-American individuals from extended pedigrees. A single dimensional scale of MDD was derived using confirmatory factor analysis applied to all items from the Past Major Depressive Episode section of the Mini-International Neuropsychiatric Interview. Scores on this scale of depression were subjected to linkage analysis followed by QTL region-specific association analysis. Linkage analysis revealed a single genome-wide significant QTL (LOD=3.43) on 10q26.13, QTL-specific association analysis conducted in the entire sample revealed a suggestive variant within an intron of the gene LHPP (rs11245316, p=7.8×10(-04); LD-adjusted Bonferroni-corrected p=8.6×10(-05)). This region of the genome has previously been implicated in the etiology of MDD; the present study extends our understanding of the involvement of this region by highlighting a putative gene of interest (LHPP). PMID:26655122

  3. The validity of major depression with atypical features based on a community study.

    PubMed

    Horwath, E; Johnson, J; Weissman, M M; Hornig, C D

    1992-10-01

    This article reports on evidence for the validity of major depression (MDD) with atypical features (defined as overeating and oversleeping) as a distinct subtype based on cross-sectional and 1-year prospective data from the Epidemiologic Catchment Area study. MDD with atypical features, when compared to MDD without atypical features, was associated with a younger age of onset, more psychomotor slowing, and more comorbid panic disorder, drug abuse or dependence, and somatization disorder. These differences could not be explained by differences in demographic characteristics or by symptom severity. This study, based on a community sample, found that major depression with atypical features may constitute a distinct subtype. PMID:1447429

  4. Collaborative care regarding major depressed patients: A review of guidelines and current practices.

    PubMed

    Van den Broeck, Kris; Remmen, Roy; Vanmeerbeek, Marc; Destoop, Marianne; Dom, Geert

    2016-08-01

    Major Depressive Disorder (MDD) is a severe and common mental disorder. A growing body of evidence suggests that stepped and/or collaborative care treatment models have several advantages for severely depressed patients and caretakers. However, despite the availability of these treatment strategies and guidance initiatives, many depressive patients are solely treated by the general practitioner (GP), and collaborative care is not common. In this paper, we review a selected set of international guidelines to inventory the best strategies for GPs and secondary mental health care providers to collaborate when treating depressed patients. Additionally, we systematically searched the literature, listing potential ways of cooperation, and potentially supporting tools. We conclude that the prevailing guidelines only include few and rather vague directions regarding the cooperation between GPs and specialised mental health practitioners. Inspiring recent studies, however, suggest that relatively little efforts may result in effective collaborative care and a broader implementation of the guidelines in general. PMID:27136418

  5. Self-report symptoms that predict major depression in patients with prominent physical symptoms.

    PubMed

    Abbey, S E; Toner, B B; Garfinkel, P E; Kennedy, S H; Kaplan, A S

    1990-01-01

    The diagnosis of depression in patients presenting with both depressive and physical symptoms is potentially confounded and problematic. The present study of 271 patients with four types of illness all with prominent physical symptoms--end-stage renal disease (n = 99), irritable bowel syndrome (n = 21), post-infectious neuromyasthenia (n = 25) and eating disorders (n = 126)--investigates if there are a group of symptoms on the Beck Depression Inventory (BDI) which predict the diagnosis of major depressive episode (MDE) made using the Diagnostic Interview Schedule (DIS). Discriminant function analysis of BDI responses yielded a four item function--self-hate, indecisiveness, loss of appetite and suicidal thoughts--which maximally discriminated between patients with and without a current MDE and correctly classified 75 percent of subjects. PMID:2265887

  6. A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

    PubMed Central

    Lapidus, Kyle A.B.; Levitch, Cara F.; Perez, Andrew M.; Brallier, Jess W.; Parides, Michael K.; Soleimani, Laili; Feder, Adriana; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.

    2014-01-01

    Background The N-methyl-d-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Methods Twenty patients with major depression were randomized and 18 completed two treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution in a randomized, double-blind, crossover study. The primary efficacy outcome measure was change in depression severity 24 hours following ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Results Patients showed significant improvement in depressive symptoms at 24 hours following ketamine compared to placebo [t=4.39, p<0.001; estimated mean MADRS score difference of 7.6 ± 3.7 (95% CI: 3.9 – 11.3)]. Eight of 18 patients (44%) met response criteria 24 hours following ketamine administration, compared to 1 of 18 (6%) following placebo (p=0.033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. Conclusions This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression. Trial Registration clinicaltrials.gov identifier NCT01304147 PMID:24821196

  7. Disparities in detection and treatment history among mothers with major depression in Los Angeles

    PubMed Central

    Lara-Cinisomo, Sandraluz; Griffin, Beth Ann; Daugherty, Lindsay

    2009-01-01

    Objective This study's goal was to determine disparities in detection and treatment histories among a group of racial and ethnically diverse mothers with major depression. Methods Our sample included 276 racially and ethnically diverse mothers who participated in the Los Angeles Family and Neighborhood Survey (L.A.FANS) and who were classified with major depression based on the Comprehensive International Diagnostic Interview -Short Form (CIDI-SF). We used logistic regression to assess the association between demographic factors and previous detection with major depression, mental health specialty use, and the use of a primary care physician among these women. The demographic factors examined included race and ethnicity, immigration status, marital status, education, income, body mass index (BMI), maternal age, number of children, children's ages, history of emotional problems, and history of diabetes. Results Results indicated that 69 percent of mothers had not been previously detected with major depression nor had they sought mental health treatment in the 12 months prior to the interview. The odds of having been previously detected with major depression were significantly higher among white and single mothers, as well as among mothers with higher BMIs and those with a history of emotional problems. Non-immigrant mothers without emotional problems had higher odds of having seen a mental health specialist in the 12 months prior to the interview compared to immigrant mothers without emotional problems; no differences in mental health treatment were found between non-immigrant and immigrant mothers with emotional problems. Finally, African-American mothers and those with a history of diabetes had significantly higher odds of seeing a primary care physician compared to Hispanic mothers and those with no history of diabetes, respectively. Conclusion Our analyses of a population of depressed mothers living in Los Angeles highlight the need for detection and treatment

  8. Season of birth, clinical manifestations and Dexamethasone Suppression Test in unipolar major depression

    PubMed Central

    Fountoulakis, Konstantinos N; Iacovides, Apostolos; Karamouzis, Michael; Kaprinis, George S; Ierodiakonou, Charalambos

    2007-01-01

    Background Reports in the literature suggest that the season of birth might constitute a risk factor for the development of a major psychiatric disorder, possibly because of the effect environmental factors have during the second trimester of gestation. The aim of the current paper was to study the possible relationship of the season of birth and current clinical symptoms in unipolar major depression. Methods The study sample included 45 DSM-IV major depressive patients and 90 matched controls. The SCAN v. 2.0, Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) were used to assess symptomatology, and the 1 mg Dexamethasone Suppression Test (DST) was used to subcategorize patients. Results Depressed patients as a whole did not show differences in birth season from controls. However, those patients born during the spring manifested higher HDRS while those born during the summer manifested the lowest HAS scores. DST non-suppressors were almost exclusively (90%) likely to be born during autumn and winter. No effect from the season of birth was found concerning the current severity of suicidal ideation or attempts. Discussion The current study is the first in this area of research using modern and rigid diagnostic methodology and a biological marker (DST) to categorize patients. Its disadvantages are the lack of data concerning DST in controls and a relatively small size of patient sample. The results confirm the effect of seasonality of birth on patients suffering from specific types of depression. PMID:17683542

  9. Mirtazapine in the treatment of adolescents with major depression: an open-label, multicenter pilot study.

    PubMed

    Haapasalo-Pesu, Kirsi-Maria; Vuola, Tapani; Lahelma, Liisa; Marttunen, Mauri

    2004-01-01

    This multicenter, open-label study with a duration of 85 days was performed to evaluate the antidepressant efficacy and safety of mirtazapine (dose range, 30-45 mg) in 12-18-year-old adolescents diagnosed with major depression. Twenty-four (24) patients (15 female patients and 9 male patients) meeting the DSM-IV criteria for major depression and the Hamilton Rating Scale for Depression (HAM-D-17) score of 18 at baseline were enrolled in the study. The primary outcome measures were HAM-D-17, Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) scales. Any changes in symptoms of anxiety were measured using the Hamilton Anxiety Rating Scale (HAM-A). The average age of the 23 subjects, who were eligible for analysis, was 16.3 years (standard deviation (SD) 6.11, median 17.3). The mean daily dose of mirtazapine was 32.9 mg. Mirtazapine showed a marked efficacy on all rating scales and was well tolerated. Mirtazapine had a beneficial effect on sleep. A rapid onset of sleep and pattern of action was seen. No dropouts due to adverse events were recorded. The most common treatment-emergent adverse events were tiredness, increased appetite, and dizziness. The results of this study suggest that mirtazapine may be an effective treatment for major depression in adolescents. PMID:15319015

  10. Health Related Quality of Life, Depression, Anxiety and Stress in Patients with Beta-Thalassemia Major

    PubMed Central

    Adib-Hajbaghery, M; Ahmadi, M; S, Poormansouri

    2015-01-01

    Background Awareness of factors associated with quality of life (QOL) in patients with beta-Thalassemia major (β-TM) is necessary to develop clinical programs in order to improve social support and QOL in β-TM patients. This study aimed to examine QoL, depression, anxiety, and stress in β-TM patients in Ahvaz, Iran. Materials and Methods A cross-sectional study was conducted on173 β-TM patients aged ≥12 years (12-18=55, ≥19=118). Subjects were selected using a census method. Data collection instrument consisted of three parts including: demographic questions, SF-36 questionnaire and depression, anxiety, and stress scale (DAS-21). Results The participants obtained a mean score of 64.38±18.20 for QOL, 6.4±5.1 for depression, 4.8±3.9 for anxiety, and 7.3±4.9 for stress. Significant relationship was found between QOL and employment (P=0.02) and education level (P<0.001). Patients in the age group of 12-18 years old had higher mean scores in the majority of QoL dimensions than those aged ≤19. The mean scores of depression, anxiety, and stress were higher in patients aged ≤19. No significant correlation was observed between QOL and depression, anxiety, stress scores, and other demographic variables. Moreover, a significant inverse correlation was found between QOL and depression (P<0.001,r= -0.62), anxiety (P<0.001,r= -0.55), and stress scores (P<0.001, r= -0.5) . Conclusion This study showed that β-TM patients experienced a considerable decrease both in their overall QoL and in its dimensions. A majority of the β-TM patients were also suffered from mild to severe depression, anxiety, and stress. PMID:26985352

  11. Levels of serum immunomodulators and alterations with electroconvulsive therapy in treatment-resistant major depression

    PubMed Central

    Zincir, Serkan; Öztürk, Pelin; Bilgen, Ali Emrah; İzci, Filiz; Yükselir, Cihad

    2016-01-01

    Studies in recent years have indicated that neuroimmunological events and immune activation may have a place in the etiology of depression. It has been suggested from data that there is a causal relationship between activation of the immune system and excessive release of proinflammatory cytokines, such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and the etiology of depression. Although the mechanism of action of electroconvulsive therapy (ECT) is unclear, there is evidence that it can reduce cytokines and immune system changes. In our study, we aimed to determine how levels of serum immunomodulators were affected by ECT in major depression patients. This study was conducted on 50 patients with treatment-resistant major depression. The data of the patients were compared with 30 healthy individuals with similar demographic characteristics. A clinical response occurred in the patients and at the end of therapy, IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels were measured. The disease severity was assessed with the 17-item Hamilton Depression Rating Scale. Data analysis was performed using SPSS Version 15. Significant differences were determined between the patients with major depression and control group with respect to basal serum IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels. ECT treatment was shown to reduce these differences. ECT may cause significant changes in the activity of the immune system. The consideration of the relationship between the immune endocrine neurotransmitter systems could contribute to new theories regarding the mechanism of antidepressant treatment and biology of depression. PMID:27366071

  12. Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder

    PubMed Central

    Nishida, Masaki; Nakashima, Yusaku; Nishikawa, Toru

    2016-01-01

    Introduction Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process. Methods Healthy control participants (n=17) and patients medicated for major depressive disorder (n=11) were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand) paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement). Participants’ brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs). Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5–16 Hz) and slow-frequency spindle activity (10.5–12.5 Hz). Result Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups. Conclusion Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep. PMID

  13. Levels of serum immunomodulators and alterations with electroconvulsive therapy in treatment-resistant major depression.

    PubMed

    Zincir, Serkan; Öztürk, Pelin; Bilgen, Ali Emrah; İzci, Filiz; Yükselir, Cihad

    2016-01-01

    Studies in recent years have indicated that neuroimmunological events and immune activation may have a place in the etiology of depression. It has been suggested from data that there is a causal relationship between activation of the immune system and excessive release of proinflammatory cytokines, such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and the etiology of depression. Although the mechanism of action of electroconvulsive therapy (ECT) is unclear, there is evidence that it can reduce cytokines and immune system changes. In our study, we aimed to determine how levels of serum immunomodulators were affected by ECT in major depression patients. This study was conducted on 50 patients with treatment-resistant major depression. The data of the patients were compared with 30 healthy individuals with similar demographic characteristics. A clinical response occurred in the patients and at the end of therapy, IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels were measured. The disease severity was assessed with the 17-item Hamilton Depression Rating Scale. Data analysis was performed using SPSS Version 15. Significant differences were determined between the patients with major depression and control group with respect to basal serum IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels. ECT treatment was shown to reduce these differences. ECT may cause significant changes in the activity of the immune system. The consideration of the relationship between the immune endocrine neurotransmitter systems could contribute to new theories regarding the mechanism of antidepressant treatment and biology of depression. PMID:27366071

  14. Discriminating Risk and Resilience Endophenotypes From Lifetime Illness Effects in Familial Major Depressive Disorder

    PubMed Central

    Peterson, Bradley S.; Wang, Zhishun; Horga, Guillermo; Warner, Virginia; Rutherford, Bret; Klahr, Kristin W.; Graniello, Barbara; Wickramaratne, Priya; Garcia, Felix; Yu, Shan; Hao, Xuejun; Adams, Phillip B.; Qian, Ming; Liu, Jun; Gerber, Andrew; Weissman, Myrna M.

    2014-01-01

    IMPORTANCE The neural systems that confer risk or vulnerability for developing familial depression, and those that protect against or confer resilience to becoming ill, can be disentangled from the effects of prior illness by comparing brain imaging measures in previously ill and never ill persons who have either a high or low familial risk for depression. OBJECTIVE To distinguish risk and resilience endophenotypes for major depression from the effects of prior lifetime illness. DESIGN, SETTING, AND PARTICIPANTS We used functional magnetic resonance imaging to measure and compare brain function during performance of an attentional, self-regulatory task across a large sample of multigenerational families ascertained specifically to be at either high or low risk for developing major depression. Study procedures were performed in a university setting. A total of 143 community participants were followed up prospectively for more than 20 years in a university setting. The sample was enriched with persons who were at higher or lower familial risk for developing depression based on being biological offspring of either a clinical sample of persons with major depression or a community control sample of persons with no discernible lifetime illness. MAIN OUTCOMES AND MEASURES Task-related change in blood oxygen level–dependent functional magnetic resonance imaging signal. RESULTS A risk endophenotype included greater activation of cortical attention circuits. A resilience endophenotype included greater activation of the dorsal anterior cingulate cortex. The effects of prior lifetime illness were common to both risk groups and included greater deactivation of default-mode circuits. CONCLUSIONS AND RELEVANCE These findings identify neural systems that increase risk for depression, those that protect from illness, and those that endure following illness onset, and they suggest circuits to target for developing novel preventive and therapeutic interventions. PMID:24369340

  15. Diagnosing major depressive disorder IV: relationship between number of symptoms and the diagnosis of disorder.

    PubMed

    Zimmerman, Mark; McGlinchey, Joseph B; Young, Diane; Chelminski, Iwona

    2006-06-01

    The symptom inclusion criteria for DSM-IV major depressive disorder (MDD) consist of a list of nine characteristic features of depression, at least five of which must be present. Two of the criteria for MDD, low mood and loss of interest or pleasure, are accorded greater importance than the remaining seven criteria in that one of these two features is required for the diagnosis. The implicit assumption underlying this organization of the criteria is that some individuals might meet five of the nine criteria without experiencing low mood or loss of interest or pleasure and thus be inappropriately diagnosed with major depression. We are not aware of any studies that have examined this assumption. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined how many psychiatric outpatients meet five of the nine DSM-IV criteria for MDD without simultaneously experiencing either low mood or loss of interest or pleasure. If this pattern is rare or does not exist, then the method of counting criteria to diagnose major depression could be simplified to a straightforward five out of nine. Twenty-seven (1.5%) patients reported five or more criteria in the absence of low mood or loss of interest or pleasure. More than half (N = 16) of these 27 patients were diagnosed with MDD or bipolar disorder, depressed type, in partial remission (N = 14), bipolar disorder mixed type (N = 1), or bipolar disorder not otherwise specified (N = 1). Six of the remaining 11 patients were diagnosed with depressive disorder not otherwise specified. Thus, few patients who met five or more of the MDD criteria were not diagnosed with a depressive disorder. This suggests that the diagnostic criteria for MDD can be simplified to a straightforward symptom count without reference to the necessity of low mood or loss of interest or pleasure. PMID:16772864

  16. Development of a Korean Version of the Perceived Deficits Questionnaire-Depression for Patients with Major Depressive Disorder

    PubMed Central

    Kim, Jae-Min; Hong, Jin-Pyo; Kim, Sang-Dae; Kang, Hee-Ju; Lee, Yong-Sung

    2016-01-01

    Objective Cognitive symptoms are an important component of depression and the Perceived Deficits Questionnaire-Depression is one of only a few instruments available for the subjective assessment of cognitive dysfunction in depression. Thus, the present study aimed to validate a Korean version of the PDQ-D (K-PDQ-D) using patients with major depressive disorder (MDD). Methods This study included 128 MDD patients who were assessed at study entry and 86 of these patients were then completed 12 weeks of antidepressant monotherapy. All subjects were assessed with the K-PDQ-D, the Montgomery-Asberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), the EuroQol-5 dimensions questionnaire (EQ-5D), and the number of sick leave days taken in the previous week. The internal consistency, Guttman’s split-half and test-retest reliabilities, factorial analyses, and concurrent and predictive validities of the K-PDQ-D were investigated. Results The K-PDQ-D exhibited excellent internal consistency and reliabilities, and was composed of four factors with high coefficients of determination. The concurrent validity analyses revealed that the K-PDQ-D scores were significantly correlated with the MADRS, SDS, and EQ-5D scores and the number of sick leave days taken. The K-PDQ-D scores at study entry significantly predicted changes in sick leave days and EQ-5D score from study entry to the 12-week endpoint. Conclusion The newly developed K-PDQ-D is a reliable and valid instrument for the evaluation of subjective cognitive symptoms in MDD patients. The K-PDQ-D may assist in the gathering of unique information regarding subjective cognitive complaints, which is important for the comprehensive evaluation of patients with MDD. PMID:26792037

  17. The promise of biomarkers in diagnosing major depression in primary care: the present and future.

    PubMed

    Redei, Eva E; Mehta, Neha S

    2015-08-01

    Major depressive disorder (MDD) is the most prevalent psychiatric disorder, but it can be underdiagnosed or misdiagnosed. Most people with depression are seen in primary care settings, where there are limited resources to diagnose and treat the patient. There is a lack of clinically validated objective laboratory-based diagnostic tests to diagnose MDD; however, it is clear that these tests could greatly improve the correct and timely diagnosis. This review aims to give a cross-sectional view of current efforts of DNA methylomic, transcriptomic, and proteomic approaches to identify biomarkers. We outline our view of the biomarker developmental steps from discovery to clinical application. We then propose that better cooperation will lead us closer to the common goal of identifying biological biomarkers for major depression. "The important thing is not to stop questioning. Curiosity has its own reason for existing." Albert Einstein. PMID:26081681

  18. The process of major depressive disorder (MDD) in women referred to the health centers

    PubMed Central

    Rahmati-Khameneh, Souraj; Mehrabi, Tayebeh; Izadi-Dehnavi, Maryam; Zargham-Boroujeni, Ali

    2011-01-01

    BACKGROUND: Major depressive disorder is one of the most widespread psychological problems in the world. The feelings of a person who is affected by this condition is boring. This article aimed to shed light on the experiences of women with major depressive disorder. METHODS: A qualitative approach with thematic analysis design has been used to describe the studied phenomenon as experienced by the participants. RESULTS: Analysis of 92 codes from 12 interviewed participants brought about 4 main themes including loss, inappropriate marital life, cognitive errors, and economic condition. CONCLUSIONS: This study revealed main concerns of the participants through their life and suggested that psychotherapists should be more sensitive to these aspects of their depress patients’ experiences. PMID:22224114

  19. ITIH family genes confer risk to schizophrenia and major depressive disorder in the Han Chinese population.

    PubMed

    He, Kuanjun; Wang, Qingzhong; Chen, Jianhua; Li, Tao; Li, Zhiqiang; Li, Wenjin; Wen, Zujia; Qiang, Yu; Wang, Meng; Shen, Jiawei; Song, Zhijian; Ji, Jue; Feng, Guoyin; Qi, Shuguang; Lin, He; Shi, Yongyong; Cheng, Zaohuo

    2014-06-01

    As a major extracellular matrix component, ITIHs played an important role in inflammation and carcinogenesis. Several genome-wide association studies have reported that some positive signals which were derived from the tight linkage disequilibrium region on chromosome 3p21 were associated with both schizophrenia and bipolar disorders in the Caucasian population. To further investigate whether this genomic region is also a susceptibility locus of schizophrenia and major depressive disorder in the Han Chinese population, we conducted this study by recruiting 1235 schizophrenia patients, 1045 major depressive disorder patients and 1235 healthy control subjects in the Han Chinese samples for a case-control study. We genotyped seven SNPs within this region using TaqMan® technology. We found that rs2710322 was significantly associated with schizophrenia (adjusted P(allele) = 0.0018, adjusted P(genotype) = 0.006, OR [95% CI] = 1.278 [1.117-1.462]) while rs1042779 was weakly associated with schizophrenia (adjusted P(allele) = 0.048, OR [95% CI] = 1.164 [1.040-1.303]) and major depressive disorder (adjusted P(allele) = 0.042, OR [95% CI] = 1.178 [1.047-1.326]); it was also our finding that rs3821831 was positively associated with major depressive disorder (adjusted P(allele) = 0.003, adjusted P(genotype) = 0.006, OR [95% CI] = 1.426 [1.156-1.760]). Furthermore, no haplotype was found to be associated with schizophrenia and major depressive disorder. Via the association analysis which combines the schizophrenia and major depressive disorder cases, we also notice that rs1042779 and rs3821831 were significantly associated with combined cases (rs1042779: adjusted P(allele) = 0.012, adjusted P(genotype) = 0.018, OR [95% CI] = 1.171 [1.060-1.292]; rs3821831:adjusted P(genotype) = 0.012, OR [95% CI] = 1.193 [1.010-1.410]). Our results revealed that the shared genetic risk factors of both schizophrenia and major depressive disorder exist in ITIH family genes in the Han Chinese

  20. 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. PMID:22063648

  1. Dimensions of Adolescent Alcohol Involvement as Predictors of Young-Adult Major Depression*

    PubMed Central

    Mason, W. Alex; Kosterman, Rick; Haggerty, Kevin P.; Hawkins, J. David; Redmond, Cleve; Spoth, Richard L.; Shin, Chungyeol

    2010-01-01

    Objective Adolescent alcohol involvement may increase risk for young-adult depression; however, findings are mixed and important questions remain unanswered. Because alcohol involvement among teens is multidimensional, this study examined the extent to which four different adolescent alcohol dimensions (i.e., frequency of alcohol use, quantity of consumption, frequency of heavy episodic drinking, and frequency of problem use) were predictive of young-adult major depressive disorder (MDD). Method Participants in this prospective longitudinal study, which extended from age 11 to age 22, were 429 rural teens (including 222 girls) and their families. Self-reports of each dimension of adolescent alcohol involvement were obtained at ages 16 and 18. Depression diagnoses were obtained at age 22, using a structured interview. Analyses included adolescent depressed mood, measured via self-report at ages 16 and 18. Data were analyzed using confirmatory factor analysis and structural equation modeling. Results The multidimensional nature of adolescent alcohol involvement was best represented by a first-order problem-use factor and a second-order alcohol-intake factor comprised of quantity, frequency, and heavy drinking. After controlling for gender and depressed mood, adolescent problem use, but not alcohol intake, was a significant positive predictor of young-adult MDD. Conclusions Findings help clarify the link between alcohol involvement and depression and suggest that harm-reduction strategies may help prevent later mood disorders. PMID:18299769

  2. Sleep disturbances: core symptoms of major depressive disorder rather than associated or comorbid disorders.

    PubMed

    Mendlewicz, Julien

    2009-01-01

    Depression is increasingly prevalent in Western countries. It has severe consequences and is associated with increased rates of disability, morbidity, and mortality. Despite numerous therapeutic options, a great number of depressed patients do not achieve full remission. In addition, despite good short-term outcomes, long-term therapeutic results remain disappointing and associated with a poor prognosis, raising significant concern in terms of public health. Impaired sleep - especially insomnia - may be at least partly responsible for this problem. Very close relationships between major depressive disorder (MDD) and sleep disorders have been observed. In particular, residual symptoms of sleep disturbance in a remitted patient may predict a relapse of the disease. However, most currently available antidepressants do not always take into consideration the sleep disturbances of depressed patients; some agents long used in clinical practice even appear to worsen them by their sleep-inhibiting properties. But some other new medications were shown to relieve early sleep disturbance in addition to alleviating other depression-related symptoms. This positive impact should promote compliance with medication and psychological treatments, and increase daytime performance and overall functioning. Complete remission of MDD appears therefore to depend on the relief of sleep disturbances, a core symptom of MDD that should be taken into consideration and treated early in depressed patients. PMID:19921968

  3. Patient-reported outcomes before and after treatment of major depressive disorder.

    PubMed

    IsHak, Waguih William; Mirocha, James; Pi, Sarah; Tobia, Gabriel; Becker, Bret; Peselow, Eric D; Cohen, Robert M

    2014-06-01

    Patient reported outcomes (PROs) of quality of life (QoL), functioning, and depressive symptom severity are important in assessing the burden of illness of major depressive disorder (MDD) and to evaluate the impact of treatment. We sought to provide a detailed analysis of PROs before and after treatment of MDD from the large Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. This analysis examines PROs before and after treatment in the second level of STAR*D. The complete data on QoL, functioning, and depressive symptom severity, were analyzed for each STAR*D level 2 treatment. PROs of QoL, functioning, and depressive symptom severity showed substantial impairments after failing a selective serotonin reuptake inhibitor trial using citalopram (level 1). The seven therapeutic options in level 2 had positive statistically (P values) and clinically (Cohen's standardized differences [Cohen's d]) significant impact on QoL, functioning, depressive symptom severity, and reduction in calculated burden of illness. There were no statistically significant differences between the interventions. However, a substantial proportion of patients still suffered from patient-reported QoL and functioning impairment after treatment, an effect that was more pronounced in nonremitters. PROs are crucial in understanding the impact of MDD and in examining the effects of treatment interventions, both in research and clinical settings. PMID:25152656

  4. Multichannel weighted speech classification system for prediction of major depression in adolescents.

    PubMed

    Ooi, Kuan Ee Brian; Lech, Margaret; Allen, Nicholas B

    2013-02-01

    Early identification of adolescents at high imminent risk for clinical depression could significantly reduce the burden of the disease. This study demonstrated that acoustic speech analysis and classification can be used to determine early signs of major depression in adolescents, up to two years before they meet clinical diagnostic criteria for the full-blown disorder. Individual contributions of four different types of acoustic parameters [prosodic, glottal, Teager's energy operator (TEO), and spectral] to depression-related changes of speech characteristics were examined. A new computational methodology for the early prediction of depression in adolescents was developed and tested. The novel aspect of this methodology is in the introduction of multichannel classification with a weighted decision procedure. It was observed that single-channel classification was effective in predicting depression with a desirable specificity-to-sensitivity ratio and accuracy higher than chance level only when using glottal or prosodic features. The best prediction performance was achieved with the new multichannel method, which used four features (prosodic, glottal, TEO, and spectral). In the case of the person-based approach with two sets of weights, the new multichannel method provided a high accuracy level of 73% and the sensitivity-to-specificity ratio of 79%/67% for predicting future depression. PMID:23192475

  5. Common Genetic and Environmental Influences on Major Depressive Disorder and Conduct Disorder

    ERIC Educational Resources Information Center

    Subbarao, Anjali; Rhee, Soo Hyun; Young, Susan E.; Ehringer, Marissa A.; Corley, Robin P.; Hewitt, John K.

    2008-01-01

    The evidence for common genetic and environmental influences on conduct disorder (CD) and major depressive disorder (MDD) in adolescents was examined. A sample of 570 monozygotic twin pairs, 592 dizygotic twin pairs, and 426 non-twin siblings, aged 12-18 years, was recruited from the Colorado Twin Registry. For the past year data, there was a…

  6. Shared Genetic Influences on Negative Emotionality and Major Depression/Conduct Disorder Comorbidity

    ERIC Educational Resources Information Center

    Tackett, Jennifer L.; Waldman, Irwin D.; Van Hulle, Carol A.; Lahey, Benjamin B.

    2011-01-01

    Objective: To investigate whether genetic contributions to major depressive disorder and conduct disorder comorbidity are shared with genetic influences on negative emotionality. Method: Primary caregivers of 2,022 same- and opposite-sex twin pairs 6 to 18 years of age comprised a population-based sample. Participants were randomly selected across…

  7. Telephone-Based Physical Activity Counseling for Major Depression in People with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Bombardier, Charles H.; Ehde, Dawn M.; Gibbons, Laura E.; Wadhwani, Roini; Sullivan, Mark D.; Rosenberg, Dori E.; Kraft, George H.

    2013-01-01

    Objective: Physical activity represents a promising treatment for major depressive disorder (MDD) in people with multiple sclerosis (MS). We conducted a single-blind, two-arm randomized controlled trial comparing a 12-week physical activity counseling intervention delivered primarily by telephone (n = 44) to a wait-list control group (N = 48).…

  8. Effect of Major Depression on the Self-Image of Adolescent Boys and Girls.

    ERIC Educational Resources Information Center

    Korhonen, Veijo; Laukkanen, Eila; Peiponen, Sirkka; Lehtonen, Johannes; Viinamaki, Heimo

    2001-01-01

    Studied the specific impact of major depressive disorder (MDD) on the self-image of adolescent boys and girls seeking outpatient treatment. Compared 68 adolescents with MDD and 39 with no psychiatric illness. Self-image among MDD patients was in general poorer than in the comparison group. The effect of MDD was more negative for girls than boys,…

  9. 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 outset of…

  10. New Insights into the Comorbidity between ADHD and Major Depression in Adolescent and Young Adult Females

    ERIC Educational Resources Information Center

    Biederman, Joseph; Ball, Sarah W.; Monuteaux, Michael C.; Mick, Eric; Spencer, Thomas J.; McCreary, Michelle; Cote, Michelle; Faraone, Stephen V.

    2008-01-01

    The association between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD) in adolescent and young adult females is evaluated. Findings indicate that MD emerging in the context of ADHD is an impairing and severe comorbidity that needs to be considered further clinically and scientifically.

  11. Psychotherapy, Pharmacotherapy, and Their Combination for Adolescents with Major Depressive Disorder: A Meta-Analysis

    ERIC Educational Resources Information Center

    Singh, Nikita; Reece, John

    2014-01-01

    This meta-analysis aims to inform clinical practice of treatment strategies for adolescents with major depressive disorder (MDD). The efficacy of three empirically validated treatments was compared to determine the most effective treatment. These were: cognitive-behavioural therapy (CBT), selective serotonin reuptake inhibitor (SSRI)…

  12. Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

    2008-01-01

    The outcome of a sequential treatment strategy that included cognitive behavioral therapy (CBT) in the prevention of major depressive disorder relapse among 46 youths is examined. Results show that youths under the antidepressant medication management plus relapse prevention CBT treatment was at lower risk for relapse than those under the…

  13. Intergenerational Transmission of Internalizing Problems: Effects of Parental and Grandparental Major Depressive Disorder on Child Behavior

    ERIC Educational Resources Information Center

    Pettit, Jeremy W.; Olino, Thomas M.; Roberts, Robert E.; Seeley, John R.; Lewinsohn, Peter M.

    2008-01-01

    Effects of lifetime histories of grandparental (G1) and parental (G2) major depressive disorder (MDD) on children's (G3) internalizing problems were investigated among 267 G3 children (ages 2-18 years) who received Child Behavior Checklist (CBCL) ratings and had diagnostic data available on 267 biological G2 parents and 527 biological G1…

  14. 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…

  15. Assessing and Interpreting Personality Change and Continuity in Patients Treated for Major Depression

    ERIC Educational Resources Information Center

    De Fruyt, Filip; Van Leeuwen, Karla; Bagby, R. Michael; Rolland, Jean-Pierre; Rouillon, Frederic

    2006-01-01

    Structural, mean- and individual-level, differential, and positive personality continuity were examined in 599 patients treated for major depression assigned to 1 of 6 forms of a 6-month pharmacy-psychotherapy program. Covariation among traits from the Five Factor model remained invariant across treatment, and patients described themselves as…

  16. Face-Memory and Emotion: Associations with Major Depression in Children and Adolescents

    ERIC Educational Resources Information Center

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

    2004-01-01

    Background: 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…

  17. Major depressive disorder: a qualitative study on the experiences of Iranian patients.

    PubMed

    Amini, Kourosh; Negarandeh, Reza; Cheraghi, Mohammad Ali; Eftekhar, Mehrdad

    2013-09-01

    Major depressive disorder (MDD) is one the most common mental disorders; it affects about 5-10% of the world population. This study explores the experiences of people with major depressive disorder in Zanjan, Iran. In order to identify recurring themes and patterns in individuals' experiences of major depressive disorder, semi-structured interviews with 18 patients were recorded and transcribed verbatim. The transcripts were then analyzed based on conventional qualitative content analysis. Five main categories emerged. The first category was called emotional paralysis and included the subcategories feeling severely depressed; feeling anxious; feeling impatient and irritable; and having dyshedonia. The second category was disturbance of thinking and was comprised of the subcategories of preoccupation, instable spiritual beliefs, and guilt. Cognitive decline was the third identified category and was further divided into subcategories of frustration, unawareness of the disorder, negative evaluation, indecisiveness, and loss of focus and loss of memory. Another major category was physical illnesses with the subcategories of physical discomfort, sleep problems, appetite disturbance, facial changes, sexual dysfunction, and medical conditions. The final category was failure in life, which had failure in personal affairs, jeopardized interpersonal relations, and unstable work life as subcategories. These findings provide a base for further research in this area. They also have clinical relevance for health care providers working with patients with MDD. Related cultural issues also are discussed. PMID:24004363

  18. Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

    ERIC Educational Resources Information Center

    Correa-Fernandez, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

    2012-01-01

    Objective: Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method: Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple…

  19. Antisaccades as a follow-up tool in major depressive disorder therapies: a pilot study.

    PubMed

    Malsert, Jennifer; Guyader, Nathalie; Chauvin, Alan; Polosan, Mircea; Poulet, Emmanuel; Szekely, David; Bougerol, Thierry; Marendaz, Christian

    2012-12-30

    Eight patients with major depression, included in a double-blind study, performed an antisaccade task. Results suggested a link between antisaccade performances and clinical scale scores in patients who respond to therapy. Moreover, error rates may well predict response from day of inclusion, thus serving as a state-marker for mood disorders. PMID:22648007

  20. 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…

  1. Prevalence of "DSM-IV" Major Depression among Spanish University Students

    ERIC Educational Resources Information Center

    Vazquez, Fernando L.; Blanco, Vanessa

    2008-01-01

    Objective: The authors' purpose in this study was to estimate prevalence and correlates of "Diagnostic and Statistical Manual of Mental Disorders," 4th edition ("DSM-IV"), major depressive episodes (MDEs) among Spanish university students. Participants and Methods: In October and November 2004, interviewers administered a screening tool to a…

  2. Major Depression in a Small Group of Adults with Down Syndrome.

    ERIC Educational Resources Information Center

    Myers, Beverly A.; Pueschel, Siegfried M.

    1995-01-01

    The clinical histories and treatment of 9 individuals with Down syndrome and major depression are presented, as are clinical characteristics of an additional 13 individuals. Vegetative symptoms of disinterest, withdrawal, mutism, psychomotor retardation, decreased appetite, and insomnia were prominent. Preoccupations with suicide, death,…

  3. Childhood Maltreatment and Differential Treatment Response and Recurrence in Adult Major Depressive Disorder

    ERIC Educational Resources Information Center

    Harkness, Kate L.; Bagby, R. Michael; Kennedy, Sidney H.

    2012-01-01

    Objective: A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Method:…

  4. An Efficacy/effectiveness Study of Cognitive-Behavioral Treatment for Adolescents with Comorbid Major Depression and Conduct Disorder.

    ERIC Educational Resources Information Center

    Rohde, Paul; Clarke, Gregory N.; Mace, David E.; Jorgensen, Jenel S.; Seeley, John R.

    2004-01-01

    Objective: To evaluate effectiveness of the Adolescent Coping With Depression (CWD-A) course, a cognitive-behavioral group intervention for depressed adolescents with comorbid conduct disorder. Method: Between 1998 and 2001, 93 nonincarcerated adolescents (ages 13-17 years) meeting criteria for major depressive disorder and conduct disorder were…

  5. Biased Recognition of Facial Affect in Patients with Major Depressive Disorder Reflects Clinical State

    PubMed Central

    Münkler, Paula; Rothkirch, Marcus; Dalati, Yasmin; Schmack, Katharina; Sterzer, Philipp

    2015-01-01

    Cognitive theories of depression posit that perception is negatively biased in depressive disorder. Previous studies have provided empirical evidence for this notion, but left open the question whether the negative perceptual bias reflects a stable trait or the current depressive state. Here we investigated the stability of negatively biased perception over time. Emotion perception was examined in patients with major depressive disorder (MDD) and healthy control participants in two experiments. In the first experiment subjective biases in the recognition of facial emotional expressions were assessed. Participants were presented with faces that were morphed between sad and neutral and happy expressions and had to decide whether the face was sad or happy. The second experiment assessed automatic emotion processing by measuring the potency of emotional faces to gain access to awareness using interocular suppression. A follow-up investigation using the same tests was performed three months later. In the emotion recognition task, patients with major depression showed a shift in the criterion for the differentiation between sad and happy faces: In comparison to healthy controls, patients with MDD required a greater intensity of the happy expression to recognize a face as happy. After three months, this negative perceptual bias was reduced in comparison to the control group. The reduction in negative perceptual bias correlated with the reduction of depressive symptoms. In contrast to previous work, we found no evidence for preferential access to awareness of sad vs. happy faces. Taken together, our results indicate that MDD-related perceptual biases in emotion recognition reflect the current clinical state rather than a stable depressive trait. PMID:26039710

  6. Biased recognition of facial affect in patients with major depressive disorder reflects clinical state.

    PubMed

    Münkler, Paula; Rothkirch, Marcus; Dalati, Yasmin; Schmack, Katharina; Sterzer, Philipp

    2015-01-01

    Cognitive theories of depression posit that perception is negatively biased in depressive disorder. Previous studies have provided empirical evidence for this notion, but left open the question whether the negative perceptual bias reflects a stable trait or the current depressive state. Here we investigated the stability of negatively biased perception over time. Emotion perception was examined in patients with major depressive disorder (MDD) and healthy control participants in two experiments. In the first experiment subjective biases in the recognition of facial emotional expressions were assessed. Participants were presented with faces that were morphed between sad and neutral and happy expressions and had to decide whether the face was sad or happy. The second experiment assessed automatic emotion processing by measuring the potency of emotional faces to gain access to awareness using interocular suppression. A follow-up investigation using the same tests was performed three months later. In the emotion recognition task, patients with major depression showed a shift in the criterion for the differentiation between sad and happy faces: In comparison to healthy controls, patients with MDD required a greater intensity of the happy expression to recognize a face as happy. After three months, this negative perceptual bias was reduced in comparison to the control group. The reduction in negative perceptual bias correlated with the reduction of depressive symptoms. In contrast to previous work, we found no evidence for preferential access to awareness of sad vs. happy faces. Taken together, our results indicate that MDD-related perceptual biases in emotion recognition reflect the current clinical state rather than a stable depressive trait. PMID:26039710

  7. Contribution of diet and major depression to incidence of acute myocardial infarction (AMI)

    PubMed Central

    2010-01-01

    Background Despite significant improvements in the treatment of coronary heart disease (CHD), it is still a major cause of mortality and morbidity among the Iranian population. Epidemiological studies have documented that risk factors including smoking and the biochemical profile are responsible for the development of acute myocardial infarction (AMI). Psychological factors have been discussed as potential risk factors for coronary heart disease. Among emotional factors, depression correlates with coronary heart disease, particularly myocardial infarction. Methods This case-control study was conducted on 120 cases (69 males and 51 females) of acute myocardial infarction (AMI) and 120 controls, with a mean age of 62.48 ± 15.39 years. Cases and controls were matched by age, residence and sex. Results The results revealed that severe depression was independently associated with the risk of AMI (P = 0.025, OR = 2.6, 95% CI 1.1-5.8). The analysis of variables indicated that risk factors for developing depression were unmarried, low levels of polyunsaturated fatty acids (PUFAs), total dietary fiber (TDF) and carbohydrates. The levels of these dietary factors were lowest in severely depressed patients compared to those categorised as moderate or mild cases. Furthermore, severely depressed subjects were associated with higher levels of total cholesterol, high systolic blood pressure (SBP) and WHR. Age, income, a family history of coronary heart disease, education level, sex, employment and smoking were not associated with severe depression. Conclusion The present study demonstrated that severe depression symptoms are independent risk factors for AMI. Furthermore, severe depression was associated with an unhealthy diet and AMI risk factors. PMID:21087475

  8. Antagonist but not agonist labeling of serotonin-1A receptors is decreased in major depressive disorder

    PubMed Central

    Stockmeier, Craig A.; Howley, Eimear; Shi, Xiaochun; Sobanska, Anna; Clarke, Gerard; Friedman, Lee; Rajkowska, Grazyna

    2009-01-01

    Serotonin-1A receptors may play a role in the pathophysiology of depression and suicide. In postmortem brain tissue, agonist binding to serotonin-1A receptors is reportedly increased or unchanged in depression or suicide, while neuroimaging studies report a decrease in antagonist binding to these receptors in subjects with depression. In this study, both agonist and antagonist radioligand binding to serotonin-1A receptors were examined in postmortem orbitofrontal cortex from subjects with major depressive disorder (MDD). Brain tissue was collected at autopsy from 11 subjects with MDD and 11 age- and gender-matched normal control subjects. Two depressed subjects had a recent psychoactive substance use disorder. Six subjects with MDD had a prescription for an antidepressant drug in the last month of life, and, of these six, postmortem bloods from only two subjects tested positive for an antidepressant drug. There was no significant difference between cohorts for age, postmortem interval or tissue pH. The receptor agonist [3H]8-OH-DPAT or the antagonist [3H]MPPF were used to autoradiographically label serotonin-1A receptors in frozen sections from cytoarchitectonically-defined left rostral orbitofrontal cortex (area 47). There was no significant difference between depressed and control subjects in agonist binding to serotonin-1A receptors. However, antagonist binding was significantly decreased in outer layers of orbitofrontal cortex in MDD. This observation in postmortem tissue confirms reports using an antagonist radioligand in living subjects with depression. Decreased antagonist binding to serotonin-1A receptors in outer layers of orbitofrontal cortex suggests diminished receptor signaling and may be linked to corresponding neuronal changes detected previously in these depressed subjects. PMID:19215942

  9. Clinical Relevance of Vilazodone Treatment in Patients With Major Depressive Disorder: Categorical Improvement in Symptoms

    PubMed Central

    Culpepper, Larry; Mathews, Maju; Ghori, Razi; Edwards, John

    2014-01-01

    Objective: To assess clinically relevant symptom improvement in patients with major depressive disorder (MDD) receiving vilazodone by using the Montgomery-Asberg Depression Rating Scale (MADRS), a clinician-rated scale used to measure MDD symptom severity and improvement. Method: Pooled data from 2 positive, phase 3, 8-week, double-blind, randomized, placebo-controlled trials in patients with MDD were analyzed. Patients received vilazodone 40 mg/d or placebo; post hoc analyses were conducted on study completers. Depression symptom improvement was evaluated by analyzing the proportions of patients who shifted from the baseline MADRS single-item symptom severity category of ≥ 2 (mild to severe symptoms) to an end-of-study category < 2 (minimal to no symptoms) or from ≥ 4 (moderate to severe symptoms) to ≤ 2 (mild to no symptoms). The proportion of patients who shifted from anxious depression to no anxious depression was also analyzed. Results: The percentage of patients who completed these studies with severity category shift from baseline ≥ 2 to end of study < 2 was significantly higher for vilazodone versus placebo on all MADRS items (odds ratio [OR] range, 1.4–1.7, P < .05) except reduced appetite (OR = 1.3, P = .232). A significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from baseline ≥ 4 to end of study ≤ 2 on MADRS items of apparent sadness, reported sadness, inner tension, reduced sleep, and lassitude (OR range, 1.5–2.0, P < .05). Additionally, a significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from anxious depression at baseline to no anxious depression at end of study (OR = 1.5, P = .031). Conclusions: These results suggest that vilazodone treatment is associated with clinically relevant changes in depression symptoms in patients with MDD. Trial Registration: ClinicalTrials.gov identifiers: NCT00285376 and NCT00683592 PMID:24940525

  10. Mood-congruent amygdala responses to subliminally presented facial expressions in major depression: associations with anhedonia

    PubMed Central

    Stuhrmann, Anja; Dohm, Katharina; Kugel, Harald; Zwanzger, Peter; Redlich, Ronny; Grotegerd, Dominik; Rauch, Astrid Veronika; Arolt, Volker; Heindel, Walter; Suslow, Thomas; Zwitserlood, Pienie; Dannlowski, Udo

    2013-01-01

    Background Anhedonia has long been recognized as a key feature of major depressive disorders, but little is known about the association between hedonic symptoms and neurobiological processes in depressed patients. We investigated whether amygdala mood-congruent responses to emotional stimuli in depressed patients are correlated with anhedonic symptoms at automatic levels of processing. Methods We measured amygdala responsiveness to subliminally presented sad and happy facial expressions in depressed patients and matched healthy controls using functional magnetic resonance imaging. Amygdala responsiveness was compared between patients and healthy controls within a 2 (group) × 2 (emotion) design. In addition, we correlated patients’ amygdala responsiveness to sad and happy facial stimuli with self-report questionnaire measures of anhedonia. Results We included 35 patients and 35 controls in our study. As in previous studies, we observed a strong emotion × group interaction in the bilateral amygdala: depressed patients showed greater amygdala responses to sad than happy faces, whereas healthy controls responded more strongly to happy than sad faces. The lack of automatic right amygdala responsiveness to happy faces in depressed patients was associated with higher physical anhedonia scores. Limitations Almost all depressed patients were taking antidepressant medications. Conclusion We replicated our previous finding of depressed patients showing automatic amygdala mood-congruent biases in terms of enhanced reactivity to negative emotional stimuli and reduced activity to positive emotional stimuli. The altered amygdala processing of positive stimuli in patients was associated with anhedonia scores. The results indicate that reduced amygdala responsiveness to positive stimuli may contribute to an-hedonic symptoms due to reduced/inappropriate salience attribution to positive information at very early processing levels. PMID:23171695

  11. Increased frontal sleep slow wave activity in adolescents with major depression

    PubMed Central

    Tesler, Noemi; Gerstenberg, Miriam; Franscini, Maurizia; Jenni, Oskar G.; Walitza, Susanne; Huber, Reto

    2015-01-01

    Sleep slow wave activity (SWA), the major electrophysiological characteristic of deep sleep, mirrors both cortical restructuring and functioning. The incidence of Major Depressive Disorder (MDD) substantially rises during the vulnerable developmental phase of adolescence, where essential cortical restructuring is taking place. The goal of this study was to assess characteristics of SWA topography in adolescents with MDD, in order to assess abnormalities in both cortical restructuring and functioning on a local level. All night high-density EEG was recorded in 15 patients meeting DSM-5 criteria for MDD and 15 sex- and age-matched healthy controls. The actual symptom severity was assessed using the Children's Depression Rating Scale—Revised (CDRS-R). Topographical power maps were calculated based on the average SWA of the first non-rapid eye movement (NREM) sleep episode. Depressed adolescents exhibited significantly more SWA in a cluster of frontal electrodes compared to controls. SWA over frontal brain regions correlated positively with the CDRS-R subscore “morbid thoughts”. Self-reported sleep latency was significantly higher in depressed adolescents compared to controls whereas sleep architecture did not differ between the groups. Higher frontal SWA in depressed adolescents may represent a promising biomarker tracing cortical regions of intense use and/or restructuring. PMID:26870661

  12. Taurine concentration in human blood peripheral lymphocytes: major depression and treatment with the antidepressant mirtazapine.

    PubMed

    Lima, Lucimey; Obregón, Francisco; Urbina, Mary; Carreira, Isabel; Baccichet, Edith; Peña, Solisbella

    2003-01-01

    Major depression is a serious disease with various systemic effects, including dysfunction of the immune response. Taurine has been known to be related to certain modifications of the immune system. The aim of this study was to determine the taurine concentration in lymphocytes of patients with major depression and to evaluate the influence of the antidepressant treatment with mirtazapine for six weeks on the levels of taurine. Gamma-aminobutyric acid, aspartate, glutamate and glutamine were also determined. Taurine, aspartate and glutamine levels were increased in the lymphocytes of depressed patients before mirtazapine treatment compared to the control group, and were normalized after treatment. Gamma-aminobutyric acid and glutamate did not differ between patients and controls. There was a significant and positive correlation between the severity of the disorder, measured by the Hamilton Rating Scale, and the concentration of taurine in the lymphocytes of depressed patients before treatment. This correlation was not observed after treatment and neither was there a correlation observed for the other amino acids. The present observations could be an indication of the relevance of taurine as a protective agent in the lymphocytes of patients with severe depression, and could be the result of modifications of taurine transport or efflux processes. PMID:12908614

  13. Verbal Learning and Memory in Older Adults with Minor and Major Depression

    PubMed Central

    Mesholam-Gately, Raquelle I.; Giuliano, Anthony J.; Zillmer, Eric A.; Barakat, Lamia P.; Kumar, Anand; Gur, Ruben C.; McAndrew, Lisa M.; Bilker, Warren B.; Elderkin-Thompson, Virginia; Moberg, Paul J.

    2012-01-01

    Late-life minor depression (miD) is a prevalent but poorly understood illness. Verbal learning and memory profiles have commonly been used to characterize neuropsychiatric disorders. This study compared the performance of 27 older adults with miD on the California Verbal Learning Test (CVLT) with 26 age-matched individuals with Major Depressive Disorder (MDD) and 36 non-depressed controls. Results revealed that the miD group performed comparably with controls and significantly better than the MDD group on several CVLT indices. Moreover, cluster analysis revealed three distinct groups, consistent with theoretical representations of “normal,” “subcortical,” and “cortical” verbal learning and memory profiles. The majority of the miD group showed “normal” profiles (74%), whereas most individuals with MDD displayed “subcortical” profiles (54%). The findings suggest that depression in the elderly is a heterogeneous entity and that the CVLT may be a useful tool for characterizing learning and memory in late-onset depressive disorders. PMID:22189596

  14. Parallels between major depressive disorder and Alzheimer's disease: role of oxidative stress and genetic vulnerability.

    PubMed

    Rodrigues, Roberto; Petersen, Robert B; Perry, George

    2014-10-01

    The thesis of this review is that oxidative stress is the central factor in major depressive disorder (MDD) and Alzheimer's disease (AD). The major elements involved are inflammatory cytokines, the hypothalamic-pituitary axis, the hypothalamic-pituitary gonadal, and arginine vasopressin systems, which induce glucocorticoid and "oxidopamatergic" cascades when triggered by psychosocial stress, severe life-threatening events, and mental-affective and somatic diseases. In individuals with a genomic vulnerability to depression, these cascades may result in chronic depression-anxiety-stress spectra, resulting in MDD and other known depressive syndromes. In contrast, in subjects with genomic vulnerability to AD, oxidative stress-induced brain damage triggers specific antioxidant defenses, i.e., increased levels of amyloid-β (Aβ) and aggregation of hyper-phosphorylated tau, resulting in paired helical filaments and impaired functions related to the ApoEε4 isoform, leading to complex pathological cascades culminating in AD. Surprisingly, all the AD-associated molecular pathways mentioned in this review have been shown to be similar or analogous to those found in depression, including structural damage, i.e., hippocampal and frontal cortex atrophy. Other interacting molecular signals, i.e., GSK-3β, convergent survival factors (brain-derived neurotrophic factor and heat shock proteins), and transition redox metals are also mentioned to emphasize the vast array of intermediates that could interact via comparable mechanisms in both MDD and AD. PMID:24927694

  15. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials

    PubMed Central

    Hausenblas, Heather Ann; Saha, Debbie; Dubyak, Pamela Jean; Anton, Stephen Douglas

    2015-01-01

    BACKGROUND Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder (MDD). Of these, accumulating trials reveal positive effects of the spice saffron (Crocus sativus L.) for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA The criteria for study selection included the following: (1) adults (aged 18 and older) with symptoms of depression, (2) randomized controlled trial, (3) effects of saffron supplementation on depressive symptoms examined, and (4) study had either a placebo control or anti-depressant comparison group. DATA EXTRACTION AND ANALYSIS Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs. placebo control groups, and for the saffron supplementation vs. antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta-analysis 2 was used to analyze the data. RESULTS Based on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs. placebo control in treating depressive symptoms (M ES

  16. 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

  17. Gene expression and association analysis of LIM (PDLIM5) in major depression.

    PubMed

    Iga, Jun-ichi; Ueno, Shu-ichi; Yamauchi, Ken; Numata, Shusuke; Motoki, Ikuyo; Tayoshi, Sumiko; Kinouchi, Sawako; Ohta, Koshi; Song, Hongwei; Morita, Kyoko; Rokutan, Kazuhito; Tanabe, Hirotaka; Sano, Akira; Ohmori, Tetsuro

    2006-06-12

    LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling. Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology. We hypothesized that the expression of the LIM mRNA in the native peripheral leukocytes may be a good candidate for the biological marker for mood disorders. Twenty patients with major depression and age- and sex-matched control subjects were included in this expression study. The LIM mRNA levels in the peripheral leukocytes from drug-naive depressive patients were significantly lower than those from control subjects and increased significantly after 4-week paroxetine treatments, to almost the same level as controls'. Hamilton depressive scores (HAM-D) were improved about 50% after 4-week treatment but neither paroxetine concentrations nor the changes of HAM-D scores showed significant correlation with the change of the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers of LIM gene, which were reported to be associated with bipolar disorder in patients with major depression and control subjects (n=130, each), but there were no associations between these SNPs and major depression. Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant. PMID:16595163

  18. A Comparative Study of Efficacy and Safety of Agomelatine and Escitalopram in Major Depressive Disorder

    PubMed Central

    Nukala, Srikrishna; Palla, Jayasree; Nambaru, Lakshmana Rao; Kasturi, Satyanarayana Murthy

    2015-01-01

    Background Major depressive disorder (MDD) is a mental disorder characterized by episodes of depressed mood, loss of interest or pleasure, feeling of guilt or low self-esteem, loss of energy, altered sleep patterns and difficulty in concentration. Objective This study was carried out to compare the efficacy and safety of Agomelatine with Escitalopram in the treatment of major depressive disorder. Design and Setting This is a prospective study conducted at Outpatient Department of Psychiatry, GSL Medical College & General hospital, Rajahmundry, India. Materials and Methods Patients with newly diagnosed major depressive disorder (DSM-IV-TR) with minimum score of 20 in Hamilton depression rating scale were randomly assigned Agomelatine (25-50 mg/day) or Escitalopram (10-20 mg/day) for a period of 8 weeks. The main efficacy outcome considered was the mean change of HAM-D17 score from baseline to end of therapy. Secondary outcome measures were Clinical Global Impressions–improvement (CGI) and severity (CGI-S) rating scales. Statistical Analysis Student t-test was used for comparing the groups and chi-square test was used for assessing the qualitative variables. For all statistical analysis p<0.05 was considered statistically significant. Results The drugs under study effectively reduced depressive symptoms at all the time points. The percentage of responders at 8weeks (last post baseline value) was 65.38% with Agomelatine and 57.40% with Escitalopram. The difference between the drugs was statistically not significant in all evaluations (p>0.05). The mean CGI-S and CGI-I scores were decreased in both the groups (p<0.05) and there was no statistically significant difference between the groups at any assessment during the study period. Both the treatment groups showed favourable safety profile. Conclusion The study results supported that Agomelatine is therapeutically similar to Escitalopram in terms of antidepressant effect. PMID:26266196

  19. Factor structure and diagnostic validity of the Beck Depression Inventory-II with adult clinical inpatients: comparison to a gold-standard diagnostic interview.

    PubMed

    Subica, Andrew M; Fowler, J Christopher; Elhai, Jon D; Frueh, B Christopher; Sharp, Carla; Kelly, Erin L; Allen, Jon G

    2014-12-01

    Little is known about the psychometric properties and clinical utility of the Beck Depression Inventory-II (BDI-II) among adult clinical inpatients, a group at high risk for major depressive disorder (MDD). Data from 1,904 adult inpatients were analyzed using confirmatory factor analysis (CFA), Cronbach's alpha, and Pearson's correlations. Receiver operating characteristic (ROC) analyses evaluating MDD diagnostic performance were conducted with a subsample (n = 467) using a structured diagnostic interview for reference. CFA of 3 previous 2-factor oblique solutions, observed in adolescent and older adult inpatient clinical samples, and 3 corresponding bifactor solutions indicated that BDI-II common item variance was overwhelmingly accounted for by 1 general factor specified to all items, with minor additional variance contributed by 2 specific factors. Analyses revealed high internal consistency (Cronbach's α = .93) and significant (p < .01) intercorrelations between the BDI-II total scale and Behavior and Symptom Identification Scale-24's Depression/Functioning (r = .79) and Overall (r = .82) subscales. ROC analyses generated low area under the curve (.695; 95% confidence interval [.637, .752]) and cutoff scores with poor sensitivity/specificity balance. BDI-II use as a screening instrument for overall depressive symptomology was supported, but MDD diagnostic performance was suboptimal. Clinicians are advised to use the BDI-II to gauge severity of depression and measure clinical changes to depressive symptomology over time but to be mindful of the limitations of the BDI-II as a diagnostic tool for adult inpatients. PMID:24932646

  20. 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

  1. Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression

    PubMed Central

    Hieronymus, F; Emilsson, J F; Nilsson, S; Eriksson, E

    2016-01-01

    The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0–4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants. PMID:25917369

  2. Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression.

    PubMed

    Hieronymus, F; Emilsson, J F; Nilsson, S; Eriksson, E

    2016-04-01

    The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants. PMID:25917369

  3. A Primary Care Focus on the Treatment of Patients With Major Depressive Disorder

    PubMed Central

    Weihs, Karen; Wert, Jonathan M

    2011-01-01

    Major depressive disorder (MDD) is a common psychiatric illness affecting nearly 20% of adults in the United States at least once during their lifetime. MDD is frequently diagnosed and treated in the primary care setting. Management of the disease may be complicated by patients and family members feeling stigmatized by the diagnosis and not understanding that depression is a treatable medical illness, which, in turn, fosters low rates of adherence to medication schedules. Incomplete or delayed response to treatment, adverse events associated with antidepressants, and medical or psychiatric comorbidities also interfere with optimal depression management. This paper presents an overview of diagnostic and treatment guidelines for MDD and focuses on challenges encountered by primary care physicians. The role of antidepressant medications, psychotherapy, and nonpharmacologic interventions for the treatment of patients with MDD is described, and factors influencing treatment selection, such as adverse event profiles and patient characteristics are examined. PMID:21642822

  4. Attentional Biases and the Persistence of Sad Mood in Major Depressive Disorder

    PubMed Central

    Clasen, Peter C.; Wells, Tony T.; Ellis, Alissa J.; Beevers, Christopher G.

    2013-01-01

    This study examined whether attentional biases for emotional information are associated with impaired mood recovery following a sad mood induction among individuals with and without major depressive disorder (MDD). Attentional biases were assessed with an exogenous cuing task using emotional facial expressions as cues among adults with (n = 48) and without (n = 224) current MDD. Mood reactivity and recovery were measured following a sad mood induction. Mood reactivity strongly predicted mood recovery; however, this relationship was moderated by attentional biases for negative emotional stimuli. Biases for sad and fear stimuli were associated with diminished mood recovery following mood induction across the sample. However, biases for sad stimuli were associated with significantly greater impairments in mood recovery among individuals with MDD than healthy controls. Furthermore, within the MDD group, impaired mood recovery was positively associated with depression severity. These results suggest that attentional biases maintain depression, in part, by facilitating the persistence of sad mood. PMID:22867117

  5. Resting-state functional connectivity in major depressive disorder: A review.

    PubMed

    Mulders, Peter C; van Eijndhoven, Philip F; Schene, Aart H; Beckmann, Christian F; Tendolkar, Indira

    2015-09-01

    Major depressive disorder (MDD) affects multiple large-scale functional networks in the brain, which has initiated a large number of studies on resting-state functional connectivity in depression. We review these recent studies using either seed-based correlation or independent component analysis and propose a model that incorporates changes in functional connectivity within current hypotheses of network-dysfunction in MDD. Although findings differ between studies, consistent findings include: (1) increased connectivity within the anterior default mode network, (2) increased connectivity between the salience network and the anterior default mode network, (3) changed connectivity between the anterior and posterior default mode network and (4) decreased connectivity between the posterior default mode network and the central executive network. These findings correspond to the current understanding of depression as a network-based disorder. PMID:26234819

  6. Improvement in Self-reported Quality of Life with Cognitive Therapy for Recurrent Major Depressive Disorder

    PubMed Central

    Jha, Manish Kumar; Minhajuddin, Abu; Thase, Michael E.; Jarrett, Robin B.

    2014-01-01

    Background Major Depressive Disorder is common, often recurrent and/or chronic. Theoretically, assessing quality of life (QoL) in addition to the current practice of assessing depressive symptoms has the potential to offer a more comprehensive evaluation of the effects of treatment interventions and course of illness. Methods Before and after acute-phase cognitive therapy (CT), 492 patients from Continuation Phase Cognitive Therapy Relapse Prevention trial (Jarrett et al., 2013, Jarrett and Thase, 2010) completed the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Inventory of Depressive Symptomatology Self-report (IDS-SR) & Beck Depression Inventory (BDI); clinicians completed Hamilton Rating Scale for Depression-17-items. Repeated measures analysis of variance evaluated the improvement in QoL before/after CT and measured the effect sizes. Change analyses to assess clinical significance (Hageman and Arrindell, 1999) were conducted. Results At the end of acute-phase CT, a repeated measure analysis of variance produced a statistically significant increase in Q-LES-Q scores with effect sizes of 0.48 - 1.3; 76.9 - 91.4% patients reported clinically significant improvement. Yet, only 11 - 38.2% QoL scores normalized. An analysis of covariance showed that change in depression severity (covariates=IDS-SR, BDI) completely accounted for the improvement in Q-LES-Q scores. Limitations There were only two time points of observation; clinically significant change analyses lacked matched normal controls; and generalizability is constrained by sampling characteristics. Conclusions: Quality of life improves significantly in patients with recurrent MDD after CT; however, this improvement is completely accounted for by change in depression severity. Normalization of QoL in all patients may require targeted, additional, and/or longer treatment. PMID:25082112

  7. Cognitive and Neural Aspects of Information Processing in Major Depressive Disorder: An Integrative Perspective

    PubMed Central

    Foland-Ross, Lara C.; Gotlib, Ian H.

    2012-01-01

    Researchers using experimental paradigms to examine cognitive processes have demonstrated that Major Depressive Disorder (MDD) is associated not with a general deficit in cognitive functioning, but instead with more specific anomalies in the processing of negatively valenced material. Indeed, cognitive theories of depression posit that negative biases in the processing of information play a critical role in influencing the onset, maintenance, and recurrence of depressive episodes. In this paper we review findings from behavioral studies documenting that MDD is associated with specific difficulties in attentional disengagement from negatively valenced material, with tendencies to interpret information in a negative manner, with deficits in cognitive control in the processing of negative material, and with enhanced memory for negative material. To gain a better understanding of the neurobiological basis of these abnormalities, we also examine findings from functional neuroimaging studies of depression and show that dysfunction in neural systems that subserve emotion processing, inhibition, and attention may underlie and contribute to the deficits in cognition that have been documented in depressed individuals. Finally, we briefly review evidence from studies of children who are at high familial risk for depression that indicates that abnormalities in cognition and neural function are observable before the onset of MDD and, consequently, may represent a risk factor for the development of this disorder. By integrating research from cognitive and neural investigations of depression, we can gain a more comprehensive understanding not only of how cognitive and biological factors interact to affect the onset, maintenance, and course of MDD, but also of how such research can aid in the development of targeted strategies for the prevention and treatment of this debilitating disorder. PMID:23162521

  8. Effects of levomilnacipran ER on fatigue symptoms associated with major depressive disorder.

    PubMed

    Freeman, Marlene P; Fava, Maurizio; Gommoll, Carl; Chen, Changzheng; Greenberg, William M; Ruth, Adam

    2016-03-01

    The aim of this study was to evaluate the effects of levomilnacipran extended-release (ER) on depression-related fatigue in adults with major depressive disorder. Post-hoc analyses of five phase III trials were carried out, with evaluation of fatigue symptoms based on score changes in four items: Montgomery-Åsberg Depression Rating Scale (MADRS) item 7 (lassitude), and 17-item Hamilton Depression Rating Scale (HAMD17) items 7 (work/activities), 8 (retardation), and 13 (somatic symptoms). Symptom remission was analyzed on the basis of score shifts from baseline to end of treatment: MADRS item 7 and HAMD17 item 7 (from ≥2 to ≤1); HAMD17 items 8 and 13 (from ≥1 to 0). The mean change in MADRS total score was analyzed in patients with low and high fatigue (MADRS item 7 baseline score <4 and ≥4, respectively). Patients receiving levomilnacipran ER had significantly greater mean improvements and symptom remission (no/minimal residual fatigue) on all fatigue-related items: lassitude (35 vs. 28%), work/activities (43 vs. 35%), retardation (46 vs. 39%), somatic symptoms (26 vs. 18%; all Ps<0.01 versus placebo). The mean change in MADRS total score was significantly greater with levomilnacipran ER versus placebo in both low (least squares mean difference=-2.8, P=0.0018) and high (least squares mean difference=-3.1, P<0.0001) fatigue subgroups. Levomilnacipran ER treatment was effective in reducing depression-related fatigue in adult patients with major depressive disorder and was associated with remission of fatigue symptoms. PMID:26584326

  9. Effects of levomilnacipran ER on fatigue symptoms associated with major depressive disorder

    PubMed Central

    Fava, Maurizio; Gommoll, Carl; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2016-01-01

    The aim of this study was to evaluate the effects of levomilnacipran extended-release (ER) on depression-related fatigue in adults with major depressive disorder. Post-hoc analyses of five phase III trials were carried out, with evaluation of fatigue symptoms based on score changes in four items: Montgomery–Åsberg Depression Rating Scale (MADRS) item 7 (lassitude), and 17-item Hamilton Depression Rating Scale (HAMD17) items 7 (work/activities), 8 (retardation), and 13 (somatic symptoms). Symptom remission was analyzed on the basis of score shifts from baseline to end of treatment: MADRS item 7 and HAMD17 item 7 (from ≥2 to ≤1); HAMD17 items 8 and 13 (from ≥1 to 0). The mean change in MADRS total score was analyzed in patients with low and high fatigue (MADRS item 7 baseline score <4 and ≥4, respectively). Patients receiving levomilnacipran ER had significantly greater mean improvements and symptom remission (no/minimal residual fatigue) on all fatigue-related items: lassitude (35 vs. 28%), work/activities (43 vs. 35%), retardation (46 vs. 39%), somatic symptoms (26 vs. 18%; all Ps<0.01 versus placebo). The mean change in MADRS total score was significantly greater with levomilnacipran ER versus placebo in both low (least squares mean difference=−2.8, P=0.0018) and high (least squares mean difference=−3.1, P<0.0001) fatigue subgroups. Levomilnacipran ER treatment was effective in reducing depression-related fatigue in adult patients with major depressive disorder and was associated with remission of fatigue symptoms. PMID:26584326

  10. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder

    PubMed Central

    Perlis, Roy

    2013-01-01

    Background Early identification of depressed individuals at high risk for treatment-resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Methods Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by, or readily amenable to, self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacologic treatment trial from those not reaching remission despite two trials. Results A logistic regression model achieved an area under the receiver operating characteristic curve (AUC) exceeding 0.71 in training, testing and validation cohorts, and maintained good calibration across cohorts. Performance of three alternative models using machine learning approaches–a naïve Bayes classifier and a support vector machine, and a random forest model – was less consistent. Similar performance was observed between more and less severe depression, males and females, and primary versus specialty care sites. A web-based calculator was developed which implements this tool and provides graphical estimates of risk. Conclusion Risk for treatment-resistance among outpatients with major depressive disorder can be estimated using a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. Registration Sequential Treatment Alternatives to Relieve Depression (STAR*D); NCT00021528; www.star-d.org PMID:23380715

  11. White matter integrity in major depressive disorder: Implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms.

    PubMed

    Tatham, Erica L; Ramasubbu, Rajamannar; Gaxiola-Valdez, Ismael; Cortese, Filomeno; Clark, Darren; Goodyear, Bradley; Foster, Jane; Hall, Geoffrey B

    2016-07-30

    This study examined the impact of childhood neglect, serotonin transporter (5-HTTLPR) and brain derived neurotrophic factor (BDNF) polymorphisms on white matter (WM) integrity in major depressive disorder (MDD) using diffusion tensor imaging (DTI). Fifty-five medication-free MDD patients and 18 controls underwent diffusion tensor imaging scanning, genotyping and completed the Childhood Trauma Questionnaire. Tract based spatial statistics (TBSS) findings revealed reduced fractional anisotropy (FA) in the MDD group in the anterior internal capsule. 5-HTTLPR-S'L' heterozygotes in the MDD group exhibited reduced FA in the internal capsule relative to S'S' and reduced FA in corona radiata compared to L'L'. Probabilistic tractography revealed higher FA in the uncinate fasciculus (UF) for BDNF val/val genotype relative to met-carriers, particularly in individuals with high depression severity. High depression severity and experiences of childhood physical or emotional neglect predicted higher FA in the UF and superior longitudinal fasciculus. Reductions in FA were identified for subgroups of MDD patients who were 5-HTTLPR heterozygotes and BDNF-met carriers. An association between emotional/physical neglect and FA was observed in subjects with high depressive symptoms. Our findings suggest that WM connectivity within frontal and limbic regions are affected by depression and influenced by experiences of neglect and genetic risk factors. PMID:27261564

  12. Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

    PubMed Central

    Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

    2015-01-01

    Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

  13. Bupropion in the treatment of problematic online game play in patients with major depressive disorder.

    PubMed

    Han, Doug Hyun; Renshaw, Perry F

    2012-05-01

    As one of the problematic behaviors in patients with major depressive disorder (MDD), excessive online game play (EOP) has been reported in a number of recent studies. Bupropion has been evaluated as a potential treatment for MDD and substance dependence. We hypothesized that bupropion treatment would reduce the severity of EOP as well as depressive symptoms. Fifty male subjects with comorbid EOP and MDD were randomly assigned to bupropion + education for internet use (EDU) or placebo + EDU groups. The current study consisted in a 12-week, prospective, randomized, double-blind clinical trial, including an eight-week active treatment phase and a four-week post treatment follow-up period. During the active treatment period, Young Internet Addiction Scale (YIAS) scores and the mean time of online game playing in the bupropion group were greatly reduced compared with those of the placebo group. The Beck Depression Inventory (BDI) scores in the bupropion group were also greatly reduced compared with those of the placebo group. During the four-week post-treatment follow-up period, bupropion-associated reductions in online game play persisted, while depressive symptoms recurred. Conclusively, bupropion may improve depressive mood as well as reduce the severity of EOP in patients with comorbid MDD and online game addiction. PMID:21447539

  14. Habenula responses to potential and actual loss in major depression: preliminary evidence for lateralized dysfunction.

    PubMed

    Furman, Daniella J; Gotlib, Ian H

    2016-05-01

    The habenula has been implicated in predicting negative events and in responding to unexpected negative outcomes. Animal models of depression have supported the hypothesis that perturbations in habenula activity contribute to the pathophysiology of Major Depressive Disorder (MDD), a psychiatric illness characterized by abnormalities in responding to negative feedback and by pessimism in evaluating the likelihood of future events. No research to date, however, has examined human habenula responses to potential and experienced negative outcomes in MDD. In this study, depressed and healthy control participants performed a probabilistic guessing task for monetary rewards and penalties during high-resolution functional magnetic resonance imaging of the habenula. In healthy adults, we observed a pattern of habenula activation consistent with its hypothesized role in predicting future losses and responding to suboptimal outcomes. In contrast, in depressed participants the left habenula was not activated significantly during the prediction or experience of monetary penalty. Complementing this group difference, attenuated habenula activation to negative feedback in control participants was associated with levels of shame and rumination. The results of this study suggest that depressed individuals are characterized by dysfunction in a neural system involved in generating expectations and comparing expectations with objective outcomes. PMID:26884545

  15. Interpersonal impacts mediate the association between personality and treatment response in major depression.

    PubMed

    Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

    2016-07-01

    Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record PMID:27031606

  16. Serum cortisol and BDNF in patients with major depression-effect of yoga.

    PubMed

    Naveen, G H; Varambally, Shivarama; Thirthalli, Jagadisha; Rao, Mukund; Christopher, Rita; Gangadhar, B N

    2016-06-01

    Depression is associated with low serum Brain Derived Neurotrophic Factor (BDNF) and elevated levels of serum cortisol. Yoga practices have been associated with antidepressant effects, increase in serum BDNF, and reduction in serum cortisol. This study examined the association between serum BDNF and cortisol levels in drug-naïve patients with depression treated with antidepressants, yoga therapy, and both. Fifty-four drug-naïve consenting adult outpatients with Major Depression (32 males) received antidepressants only (n = 16), yoga therapy only (n = 19), or yoga with antidepressants (n = 19). Serum BDNF andcortisol levels were obtained before and after 3 months using a sandwich ELISA method. One-way ANOVA, Chi-square test, and Pearson's correlation tests were used for analysis. The groups were comparable at baseline on most parameters. Significant improvement in depression scores and serum BDNF levels, and reduction in serum cortisol in the yoga groups, have been described in previous reports. A significant negative correlation was observed between change in BDNF (pre-post) and cortisol (pre-post) levels in the yoga-only group (r = -0.59, p = 0.008). In conclusion, yoga may facilitate neuroplasticity through stress reduction in depressed patients. Further studies are needed to confirm the findings and delineate the pathways for these effects. PMID:27174729

  17. Typus melancholicus and the Temperament and Character Inventory personality dimensions in patients with major depression.

    PubMed

    Kimura, S; Sato, T; Takahashi, T; Narita, T; Hirano, S; Goto, M

    2000-04-01

    Although many clinical studies have been conducted to determine the etiological role and clinical implications of typus melancholicus for unipolar depression, maladaptive personality features in depressive patients have not been well described. This study explores typus melancholicus, as measured by the rigidity subscale of the Munich Personality Test, and maladaptive personality features, as measured by the Temperament and Character Inventory (TCI), in 131 remitted patients with DSM-IV major depression and 154 normal controls. The patients reported significantly higher scores on rigidity and harm avoidance and significantly lower scores on self-directedness and cooperativeness. Only 23.6% of the variance of the rigidity scale was explained by the variance of the seven TCI scales, in which only persistence was significantly correlated positively to rigidity. Cluster analysis identified four subgroups, two of which were characterized by a high rigidity score. One of these two subgroups showed no maladaptive personality features, as measured by the TCI, while the other showed high harm avoidance and low self-directedness. These results indicate that the personality of depressive patients is characterized not only by typus melancholicus but also by maladaptive personality features, that typus melancholicus is not well represented by any TCI scale, and that typus melancholicus and maladaptive personality features can coexist in some depressive patients. PMID:10803813

  18. Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

    PubMed Central

    Wiste, Anna; Robinson, Elise B; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C; Fitzmaurice, Garrett M; Rietschel, Marcella; Penninx, Brenda W; Smoller, Jordan W; Perlis, Roy H

    2014-01-01

    Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of this study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European–American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts. Results A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04). Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ≤ 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8–1.1%. However, analyses in two replication cohorts testing a five feature model did not support this association. Conclusions Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, results are at most inconclusive because of lack of replication. Replication efforts are challenged by different ascertainment and assessment strategies in the different cohorts

  19. Screening for Depression after Cardiac Events Using the Beck Depression Inventory-II and the Geriatric Depression Scale

    ERIC Educational Resources Information Center

    Low, Gail D.; Hubley, Anita M.

    2007-01-01

    Despite findings that depression is a risk factor for heart disease and for death following cardiac events and that depressed cardiac patients experience significantly reduced quality of life and are less likely to follow treatment regimens, depression is neither adequately identified nor treated in cardiac patients. Recent calls in the literature…

  20. Early Symptom Improvement as a Predictor of Response to Extended Release Quetiapine in Major Depressive Disorder

    PubMed Central

    McIntyre, Roger S.; Gorwood, Philip; Thase, Michael E.; Liss, Charlie; Desai, Dhaval; Chen, Ji; Bauer, Michael

    2015-01-01

    Abstract The aim of this post-hoc analysis was to determine whether early symptom improvement with extended release quetiapine (quetiapine XR) may predict treatment outcome in patients with major depressive disorder. Data were from 6, double-blind, placebo-controlled studies of quetiapine XR (2 fixed-dose and 2 flexible-dose monotherapy and 2 adjunct studies) in adult patients with major depressive disorder. Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity Score (CGI-S) were assessed at baseline, weeks 2, 4, and 6. Hamilton Rating Scale for Depression (HAM-D) was assessed at baseline and week 6. The MADRS improvement at week 2 (15%, 20%, 25%, 30%) was used to predict response and remission, based on MADRS (50% improvement; total score ≤ 12) or HAM-D (50% improvement; total score ≤ 7). The CGI-S improvement (1 point) at week 2 was used to predict final outcome (CGI-S score ≤ 2). The predictive value for early improvement with quetiapine XR was found to be “very strong” (Yule’s Q coefficient, a combined measure of sensitivity and specificity) using 30% MADRS improvement as the threshold. This was relatively comparable for response and remission and for fixed-dose, flexible-dose, and adjunct studies. This was also observed for placebo. Exceptions were: adjunct studies (where predictivity was lower for ongoing antidepressant/placebo), and for remission (predictivity for remission appeared lower than for response with placebo). In conclusion, outcome at week 6 with quetiapine XR for a major depressive episode could be predicted by 30% improvement after 2 weeks, a finding that could give doctors confidence to continue treatment and may facilitate adherence in patients. PMID:26474010

  1. Whole brain resting-state analysis reveals decreased functional connectivity in major depression.

    PubMed

    Veer, Ilya M; Beckmann, Christian F; van Tol, Marie-José; Ferrarini, Luca; Milles, Julien; Veltman, Dick J; Aleman, André; van Buchem, Mark A; van der Wee, Nic J; Rombouts, Serge A R B

    2010-01-01

    Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder. PMID:20941370

  2. The Phenomenology of Major Depression and the Representativeness and Nature of DSM Criteria.

    PubMed

    Kendler, Kenneth S

    2016-08-01

    How should DSM criteria relate to the disorders they are designed to assess? To address this question empirically, the author examines how well DSM-5 symptomatic criteria for major depression capture the descriptions of clinical depression in the post-Kraepelin Western psychiatric tradition as described in textbooks published between 1900 and 1960. Eighteen symptoms and signs of depression were described, 10 of which are covered by the DSM criteria for major depression or melancholia. For two symptoms (mood and cognitive content), DSM criteria are considerably narrower than those described in the textbooks. Five symptoms and signs (changes in volition/motivation, slowing of speech, anxiety, other physical symptoms, and depersonalization/derealization) are not present in the DSM criteria. Compared with the DSM criteria, these authors gave greater emphasis to cognitive, physical, and psychomotor changes, and less to neurovegetative symptoms. These results suggest that important features of major depression are not captured by DSM criteria. This is unproblematic as long as DSM criteria are understood to index rather than constitute psychiatric disorders. However, since DSM-III, our field has moved toward a reification of DSM that implicitly assumes that psychiatric disorders are actually just the DSM criteria. That is, we have taken an index of something for the thing itself. For example, good diagnostic criteria should be succinct and require minimal inference, but some critical clinical phenomena are subtle, difficult to assess, and experienced in widely varying ways. This conceptual error has contributed to the impoverishment of psychopathology and has affected our research, clinical work, and teaching in some undesirable ways. PMID:27138588

  3. Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics

    PubMed Central

    de Sousa, Rafael T.; Zanetti, Marcus V.; Brunoni, Andre R.; Machado-Vieira, Rodrigo

    2015-01-01

    Major depressive disorder (MDD) is associated with a significant burden and costs to the society. As remission of depressive symptoms is achieved in only one-third of the MDD patients after the first antidepressant trial, unsuccessful treatments contribute largely to the observed suffering and social costs of MDD. The present article provides a summary of the therapeutic strategies that have been tested for treatment-resistant depression (TRD). A computerized search on MedLine/PubMed database from 1975 to September 2014 was performed, using the keywords “treatment-resistant depression”, “major depressive disorder”, “adjunctive”, “refractory” and “augmentation”. From the 581 articles retrieved, two authors selected 79 papers. A manual searching further considered relevant articles of the reference lists. The evidence found supports adding or switching to another antidepressant from a different class is an effective strategy in more severe MDD after failure to an initial antidepressant trial. Also, in subjects resistant to two or more classes of antidepressants, some augmentation strategies and antidepressant combinations should be considered, although the overall response and remission rates are relatively low, except for fast acting glutamatergic modulators. The wide range of available treatments for TRD reflects the complexity of MDD, which does not underlie diverse key features of the disorder. Larger and well-designed studies applying dimensional approaches to measure efficacy and effectiveness are warranted. PMID:26467411

  4. Usefulness of the Spanish version of the mood disorder questionnaire for screening bipolar disorder in routine clinical practice in outpatients with major depression

    PubMed Central

    2008-01-01

    Background According to some studies, almost 40% of depressive patients – half of them previously undetected – are diagnosed of bipolar II disorder when systematically assessed for hypomania. Thus, instruments for bipolar disorder screening are needed. The Mood Disorder Questionnaire (MDQ) is a self-reported questionnaire validated in Spanish in stable patients with a previously known diagnosis. The purpose of this study is to evaluate in the daily clinical practice the usefulness of the Spanish version of the MDQ in depressive patients. Methods Patients (n = 87) meeting DSM-IV-TR criteria for a major depressive episode, not previously known as bipolar were included. The affective module of the Structured Clinical Interview (SCID) was used as gold standard. Results MDQ screened 24.1% of depressive patients as bipolar, vs. 12.6% according to SCID. For a cut-off point score of 7 positive answers, sensitivity was 72.7% (95% CI = 63.3 – 82.1) and specificity 82.9% (95% CI = 74.9–90.9). Likelihood ratio of positive and negative tests were 4,252 y 0,329 respectively. Limitations The small sample size reduced the power of the study to 62%. Conclusion Sensitivity and specificity of the MDQ were high for screening bipolar disorder in patients with major depression, and similar to the figures obtained in stable patients. This study confirms that MDQ is a useful instrument in the daily clinical assessment of depressive patients. PMID:18498637

  5. An Open Trial of a New Acceptance-Based Behavioral Treatment for Major Depression with Psychotic Features

    ERIC Educational Resources Information Center

    Gaudiano, Brandon A.; Nowlan, Kathryn; Brown, Lily A.; Epstein-Lubow, Gary; Miller, Ivan W.

    2013-01-01

    Research suggests that cognitive and behavioral therapies produce significant benefits over medications alone in the treatment of severe, nonpsychotic major depression or primary psychotic disorders such as schizophrenia. However, previous research has not demonstrated the efficacy of psychotherapy for major depression with psychotic features. In…

  6. Are women with major depression in pregnancy identifiable in population health data?

    PubMed Central

    2013-01-01

    Background Although record linkage of routinely collected health datasets is a valuable research resource, most datasets are established for administrative purposes and not for health outcomes research. In order for meaningful results to be extrapolated to specific populations, the limitations of the data and linkage methodology need to be investigated and clarified. It is the objective of this study to investigate the differences in ascertainment which may arise between a hospital admission dataset and a dispensing claims dataset, using major depression in pregnancy as an example. The safe use of antidepressants in pregnancy is an ongoing issue for clinicians with around 10% of pregnant women suffer from depression. As the birth admission will be the first admission to hospital during their pregnancy for most women, their use of antidepressants, or their depressive condition, may not be revealed to the attending hospital clinicians. This may result in adverse outcomes for the mother and infant. Methods Population-based de-identified data were provided from the Western Australian Data Linkage System linking the administrative health records of women with a delivery to related records from the Midwives’ Notification System, the Hospital Morbidity Data System and the national Pharmaceutical Benefits Scheme dataset. The women with depression during their pregnancy were ascertained in two ways: women with dispensing records relating to dispensed antidepressant medicines with an WHO ATC code to the 3rd level, pharmacological subgroup, ‘N06A Antidepressants’; and, women with any hospital admission during pregnancy, including the birth admission, if a comorbidity was recorded relating to depression. Results From 2002 to 2005, there were 96698 births in WA. At least one antidepressant was dispensed to 4485 (4.6%) pregnant women. There were 3010 (3.1%) women with a comorbidity related to depression recorded on their delivery admission, or other admission to hospital

  7. Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes

    PubMed Central

    Judd, Lewis L.; Schettler, Pamela J.; Akiskal, Hagop; Coryell, William; Fawcett, Jan; Fiedorowicz, Jess G.; Solomon, David A.; Keller, Martin B.

    2013-01-01

    Background There is increasing evidence that subsyndromal manic symptoms occur frequently during bipolar major depressive episodes (MDEs) and may be a subtle form of ‘depressive mixed state.’ This paper examines the prevalence and clinical characteristics of MDEs with subsyndromal manic symptoms. The specific effects of overt irritability and psychomotor agitation are examined. Methods Bipolar (type I or II) patients with an MDE at intake (N=142) were compared based on the presence or absence of concurrent subsyndromal manic symptoms. The groups were further subdivided by the presence of symptoms of overt irritability and/or psychomotor agitation. Results Subsyndromal manic symptoms during bipolar MDEs were highly prevalent (76.1%), and were associated with significantly increased severity of depression/dysphoria in the intake episode, longer episode duration, and more suicidal ideation and behavior (past, current, and during long-term follow-up). Overt irritability and psychomotor agitation were the most prevalent subsyndromal manic symptoms (co-occurring in 57% and 39% of MDEs, respectively), and accounted for most of the negative effects associated with subsyndromal manic symptoms. Limitations The findings need to be confirmed in larger samples, which also examine the relationship to adequate antidepressant and/or mood stabilizing treatment. Conclusions The presence of one or more subsyndromal manic symptoms appears to be the modal presentation of bipolar MDEs and a marker for a subtle form of bipolar mixed depressive state. In particular, patients with symptoms of overt irritability and/or psychomotor agitation should be monitored closely to avoid serious clinical outcomes such as longer affective episodes, exacerbation of manic symptoms syndromal mania, and heightened suicidality. PMID:22314261

  8. Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies.

    PubMed

    Shyn, S I; Shi, J; Kraft, J B; Potash, J B; Knowles, J A; Weissman, M M; Garriock, H A; Yokoyama, J S; McGrath, P J; Peters, E J; Scheftner, W A; Coryell, W; Lawson, W B; Jancic, D; Gejman, P V; Sanders, A R; Holmans, P; Slager, S L; Levinson, D F; Hamilton, S P

    2011-02-01

    We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression and the publicly available Genetic Association Information Network-MDD data set. These data sets, totaling 3957 cases and 3428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of 2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P=6.78 x 10⁻⁷), SP4 (P=7.68 x 10⁻⁷) and GRM7 (P=1.11 x 10⁻⁶). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. On the basis of previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD. PMID:20038947

  9. Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders

    PubMed Central

    Wang, Yun; Yang, Liu-Qing; Li, Shu; Zhou, Yuan

    2015-01-01

    Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modeling offers a new tool for investigating social-interaction impairments in neuropsychiatric disorders. This review first introduces three widely used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD. PMID:26441689

  10. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers.

    PubMed

    Lopresti, Adrian L; Maker, Garth L; Hood, Sean D; Drummond, Peter D

    2014-01-01

    Biomarkers are regularly used in medicine to provide objective indicators of normal biological processes, pathogenic processes or pharmacological responses to therapeutic interventions, and have proved invaluable in expanding our understanding and treatment of medical diseases. In the field of psychiatry, assessment and treatment has, however, primarily relied on patient interviews and questionnaires for diagnostic and treatment purposes. Biomarkers in psychiatry present a promising addition to advance the diagnosis, treatment and prevention of psychiatric diseases. This review provides a summary on the potential of peripheral biomarkers in major depression with a specific emphasis on those related to inflammatory/immune and oxidative stress/antioxidant defences. The complexities associated with biomarker assessment are reviewed specifically around their collection, analysis and interpretation. Focus is placed on the potential of peripheral biomarkers to aid diagnosis, predict treatment response, enhance treatment-matching, and prevent the onset or relapse of major depression. PMID:24104186

  11. Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy

    PubMed Central

    Zorumski, Charles F.; Nagele, Peter; Mennerick, Steven; Conway, Charles R.

    2015-01-01

    Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15–30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant. PMID:26696909

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  14. Rational Treatment Choices for Non-major Depressions in Primary Care

    PubMed Central

    Ackermann, Ronald T; Williams, John W

    2002-01-01

    OBJECTIVE This review synthesizes available evidence for managing clinically significant dysphoric symptoms encountered in primary care, when formal criteria for major depression or dysthymia are not met. Discussion is focused on premenstrual dysphoric disorder (PMDD) and minor depression because of their significant prevalence in the primary care setting and the lack of clear practice guidelines for addressing each illness. DESIGN English language literature from prior systematic reviews was supplemented by searching medline, embase, the Cochrane Controlled Trials Registry, the Agency for Healthcare Research and Quality National Guideline Clearinghouse, and bibliographies of selected papers. Studies addressing the natural history or treatment of minor depression or PMDD were selected for review. Data were abstracted by 1 of 2 independent reviewers and studies were synthesized qualitatively. RESULTS Five individual studies that compared antidepressant or psychological treatments to placebo in patients with minor depression suggest short-term improvements in depressive symptoms with paroxetine, problem-solving therapy, and cognitive behavioral therapy, but not with amitryptiline. Modest benefits on mental health function were reported with paroxetine and with problem-solving therapy, but only in patients with severe functional impairment at baseline. Twenty-four controlled trials were identified that compared antidepressant or psychological treatments to placebo in patients with premenstrual dysphoric disorder. Pooled results from a recent systematic review of 15 randomized controlled trials and one additional trial abstract provide strong evidence for a significantly greater improvement in physical and psychological symptoms with serotonin-selective reuptake inhibitor medications when compared with placebo. Individual trials also suggest significantly greater improvements in symptom scores with venlafaxine, but not with tricyclic antidepressants. CONCLUSIONS The

  15. ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review

    PubMed Central

    Appleton, Katherine M; Sallis, Hannah M; Perry, Rachel; Ness, Andrew R; Churchill, Rachel

    2016-01-01

    Objective To assess the effects of n-3 polyunsaturated fatty acids (n-3PUFAs; also known as ω-3 fatty acids) compared with comparator for major depressive disorder (MDD) in adults. Design Systematic review and meta-analyses. Data sources The Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Registers (CCDANCTR) and International Trial Registries searched to May 2015. CINAHL searched to September 2013. Trial selection Inclusion criteria: a randomised controlled trial (RCT); that provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and was conducted in adults with MDD. Outcomes Primary outcomes were depressive symptomology and adverse events. Results 20 trials encompassing 26 relevant studies were found. For n-3PUFAs versus placebo, n-3PUFA supplementation resulted in a small-to-modest benefit for depressive symptomology: SMD=−0.32 (95% CI −0.52 to −0.12; 25 studies, 1373 participants, very low-quality evidence), but this effect is unlikely to be clinically meaningful, is very imprecise and, based on funnel plot inspection, sensitivity analyses and comparison with large well-conducted trials, is likely to be biased. Considerable evidence of heterogeneity between studies was also found, and was not explained by subgroup or sensitivity analyses. Numbers of individuals experiencing adverse events were similar in intervention and placebo groups (OR=1.24, 95% CI 0.95 to 1.62; 19 studies, 1207 participants; very low-quality evidence). For n-3PUFAs versus antidepressants, no differences were found between treatments in depressive symptomology (MD=−0.70 (95% CI −5.88 to 4.48); 1 study, 40 participants, very low-quality evidence). Conclusions At present, we do not have sufficient evidence to determine the effects of n-3PUFAs as a treatment for MDD. Further research in the form of adequately powered RCTs is needed. PMID:26936905

  16. Walk on the Bright Side: Physical Activity and Affect in Major Depressive Disorder

    PubMed Central

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

    2014-01-01

    Although prescribed exercise has been found to improve affect and reduce levels of depression, we do not know how self-initiated everyday physical activity influences levels of positive affect (PA) and negative affect (NA) in depressed persons. Fifty-three individuals diagnosed with Major Depressive Disorder (MDD) and 53 never-depressed controls participated in a seven-day experience sampling study. Participants were prompted randomly eight times per day and answered questions about their physical activity and affective state. Over the week, the two groups of participants did not differ in average level of physical activity. As expected, participants with MDD reported lower average PA and higher average NA than did never-depressed controls. Both participants with MDD and controls reported higher levels of PA at prompts after physical activity than at prompts after inactive periods; moreover, for both groups of participants, PA increased from a prompt after an inactive period to a subsequent prompt at which activity was reported. Depressed participants in particular showed a dose-response effect of physical activity on affect: longer duration and/or higher intensity of physical activity increased their PA significantly more than did short duration and/or lower intensity physical activity. Physical activity did not influence NA in either group. In contrast to previous treatment studies that examined the effects of prescribed structured exercise, this investigation showed that self-initiated physical activity influences PA. These findings also underscore the importance of distinguishing between PA and NA to gain a more comprehensive understanding of the effects of physical activity on affect in MDD. PMID:21553939

  17. Early Improvements in Individual Symptoms to Predict Later Remission in Major Depressive Disorder Treated With Mirtazapine.

    PubMed

    Funaki, Kei; Nakajima, Shinichiro; Suzuki, Takefumi; Mimura, Masaru; Uchida, Hiroyuki

    2016-09-01

    Few studies, to our knowledge, have examined whether early improvements in individual, instead of overall, depressive symptoms predict remission in major depressive disorder (MDD). This post hoc analysis used data from 194 patients with MDD enrolled in a 6-week double-blind, placebo-controlled, randomized trial of mirtazapine, to identify improvements in specific individual depressive symptoms in the early phase that are associated with subsequent remission. Trajectories of individual depressive symptoms over 6 weeks were compared between remitters and nonremitters. Early improvement was defined as a ≥20% decrease in the Hamilton Rating Scale for Depression 17 items (HAM-D17) total score in weeks 1 and 2, and remission was defined as a HAM-D17 final score of ≤7. Reliability parameters were calculated for early improvements in predicting later remission. Whether improvement in each of the HAM-D17 symptoms in weeks 1 or 2 predicted remission was examined, using binary logistic regression analyses. As a result, improvements in weeks 1 and 2 were associated with sensitivity of 0.82 and 0.99 and specificity of 0.54 and 0.44, respectively, in predicting remission in week 6. Improvements in insomnia late (P = .04) and insight (P = .007) in week 1 and somatic symptoms general (P = .002) and insight (P = .04) in week 2 were associated with remission in week 6. In conclusion, early improvements in insight, insomnia late, and somatic symptoms general, as well as overall depressive symptoms, may serve as specific clinical indicators of subsequent remission in patients with MDD receiving mirtazapine. PMID:26813241

  18. Evolving Refractory Major Depressive Disorder Diagnostic and Treatment Paradigms: Toward Closed-Loop Therapeutics

    PubMed Central

    Ward, Matthew P.; Irazoqui, Pedro P.

    2010-01-01

    Current antidepressant therapies do not effectively control or cure depressive symptoms. Pharmaceutical therapies altogether fail to address an estimated 4 million Americans who suffer from a recurrent and severe treatment-resistant form of depression known as refractory major depressive disorder. Subjective diagnostic schemes, differing manifestations of the disorder, and antidepressant treatments with limited theoretical bases each contribute to the general lack of therapeutic efficacy and differing levels of treatment resistance in the refractory population. Stimulation-based therapies, such as vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation, are promising treatment alternatives for this treatment-resistant subset of patients, but are plagued with inconsistent reports of efficacy and variable side effects. Many of these problems stem from the unknown mechanisms of depressive disorder pathogenesis, which prevents the development of treatments that target the specific underlying causes of the disorder. Other problems likely arise due to the non-specific stimulation of various limbic and paralimbic structures in an open-loop configuration. This review critically assesses current literature on depressive disorder diagnostic methodologies, treatment schemes, and pathogenesis in order to emphasize the need for more stringent depressive disorder classifications, quantifiable biological markers that are suitable for objective diagnoses, and alternative closed-loop treatment options tailored to well-defined forms of the disorder. A closed-loop neurostimulation device design framework is proposed, utilizing symptom-linked biomarker abnormalities as control points for initiating and terminating a corrective electrical stimulus which is autonomously optimized for correcting the magnitude and direction of observed biomarker abnormality. PMID:20631824

  19. Anhedonia, but not Irritability, Is Associated with Illness Severity Outcomes in Adolescent Major Depression

    PubMed Central

    Johnson, Amy R.; Alonso, Carmen M.; Evans, Lori K.; Babb, James S.; Klein, Rachel G.

    2015-01-01

    Abstract Objectives: Unlike adult major depressive disorder (MDD) which requires anhedonia or depressed mood for diagnosis, adolescent MDD can be sufficiently diagnosed with irritability in the absence of the former symptoms. In addition, the current Diagnostic and Statistical Manual of Mental Disorders (DSM) schema does not account for the interindividual variability of symptom severity among depressed adolescents. This practice has contributed to the high heterogeneity and diagnostic complexity of adolescent MDD. Here, we sought to examine relationships between two core symptoms of adolescent MDD – irritability and anhedonia, assessed both quantitatively and categorically – and other clinical correlates among depressed adolescents. Methods: Ninety adolescents with MDD (51 females), ages 12–20, were enrolled. Anhedonia and irritability scores were quantified by summing related items on the Children's Depression Rating Scale-Revised and the Beck Depression Inventory. Extremes of score distribution were defined as high or low irritability/anhedonia subgroups. A significance level of p=0.01 was set to adjust for the five comparisons. Results: Despite all subjects exhibiting moderate to severe MDD, both irritability and anhedonia scores manifested a full and normally distributed severity range including the lowest values possible. However, only anhedonia severity was associated with more severe clinical outcomes, including greater overall illness severity (p<0.001), suicidality scores (p<0.001), episode duration (p=0.006), and number of MDD episodes (p=0.01). Similarly, only the high-anhedonia subgroup manifested more severe outcomes; specifically, greater illness severity (p<0.0001), number of MDD episodes (p=0.01), episode duration (p=0.01), and suicidality scores (p=0.0001). Conclusions: Our findings suggest the significance of anhedonia as a hallmark of adolescent MDD and the need to incorporate dimensional analyses. These data are preliminary, and future

  20. Persistent Ehrlichia chaffeensis infection occurs in the absence of functional major histocompatibility complex class II genes

    NASA Technical Reports Server (NTRS)

    Ganta, Roman Reddy; Wilkerson, Melinda J.; Cheng, Chuanmin; Rokey, Aaron M.; Chapes, Stephen K.

    2002-01-01

    Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. We investigated the impact of two genes that control macrophage and T-cell function on murine resistance to E. chaffeensis. Congenic pairs of wild-type and toll-like receptor 4 (tlr4)- or major histocompatibility complex class II (MHC-II)-deficient mice were used for these studies. Wild-type mice cleared the infection within 2 weeks, and the response included macrophage activation and the synthesis of E. chaffeensis-specific Th1-type immunoglobulin G response. The absence of a functional tlr4 gene depressed nitric oxide and interleukin 6 secretion by macrophages and resulted in short-term persistent infections for > or =30 days. In the absence of MHC-II alleles, E. chaffeensis infections persisted throughout the entire 3-month evaluation period. Together, these data suggest that macrophage activation and cell-mediated immunity, orchestrated by CD4(+) T cells, are critical for conferring resistance to E. chaffeensis.

  1. Influence of painful physical symptoms in the treatment of Japanese patients with melancholic major depressive disorder: A prospective cohort study.

    PubMed

    Sekine, Atsushi; Hozumi, Satoshi; Shimizu, Tetsuo

    2016-08-30

    The aim of this study was to clarify how painful physical symptoms affect treatment outcomes in patients with melancholic major depressive disorder. The subjects comprised 100 consecutive Japanese outpatients with melancholic major depressive disorder who visited our clinic from October 2011 to October 2014. All subjects were interviewed for Diagnostic and Statistical Manual of Mental Disorders Axis 2, 3, and 4 and family history of major depressive disorder, and then grouped according to the presence of painful physical symptoms. We evaluated painful physical symptoms at baseline and after 12, 24, and 36 weeks of treatment and scores on the 17-item Hamilton Rating Scale for Depression, compared major depressive disorder remission between groups, and assessed responsiveness to antidepressants. The group with painful physical symptoms had a significantly more positive family history of major depressive disorder. The major depressive disorder remission rate was high in both groups, and no significant differences were observed. However, a significant relationship between major depressive disorder and painful physical symptoms remission was observed in the group with painful physical symptoms. A significantly higher number of remitted patients with painful physical symptoms (N=61) were administered serotonin-noradrenaline reuptake inhibitors, with significantly more receiving duloxetine than milnacipran. PMID:27294798

  2. [A nursing experience of cognitive therapy with a major depression patient].

    PubMed

    Wang, Tsuei-Bin; Chen, Mei-Ting

    2005-02-01

    The increasing number of major depressive patients with negative thinking warrants that cognitive therapy be recommended to correct negative-automatic thinking and inculcate positive thinking as a way to face problems. The purpose of this paper was to describe the nursing experience and effectiveness of implementing individual cognitive therapy on a patient with major depression in an acute ward over a one-month period. Through observation, interviewing, and comprehensive nursing assessment, the patient's negative thinking toward herself and her problems was identified, and her thoughts of suicide emerged. The following three major health problems were identified: risk of suicide, disturbed sleep pattern and ineffective coping. The patient underwent homework training throughout the ten individual cognitive therapy sessions, and was expected to use positive thinking instead of automatic thinking. After the intervention, the patient's depressive mood, sleep quality, and coping ability were improved. In addition, the patient no longer talked of suicide and was able to show stable emotions, maintain a homework, and attend church activities on her own initiative after discharge. It is therefore, suggested that cognitive therapy can be an effective intervention for nurses planning to care for this group of people. PMID:15712063

  3. A critical appraisal of the selegiline transdermal system for major depressive disorder.

    PubMed

    Bied, Adam M; Kim, Jungjin; Schwartz, Thomas L

    2015-01-01

    The selegiline transdermal system (STS) is the first antidepressant transdermal medication approved by the US FDA for the treatment of major depressive disorder. Its unique antidepressant delivery system allows for steady release of selegiline over 24 h with minimal fluctuation in drug serum levels. It is able to deliver high enough central nervous system concentrations required for an antidepressant effect without substantially inhibiting Monoamine oxidase-A in the gastrointestinal and hepatic system, thereby reducing the risk of tyramine hypertensive crises especially at the lowest doses. Patient adherence theoretically could be improved due to ease of use and once-daily dosing when compared to oral counterparts' need for multiple daily doses. Clinical trials have established that doses between 6 and 12 mg over 24 h have been effective for major depressive disorder and tolerated among patients. Episodes of hypertensive crisis with STS have been minimally reported thus far. Overall, STS appears to be an effective agent for major depressive disorder when held to regulatory standards and post marketing analyses. This paper reviews the pharmacologic characteristics of STS and results of studies investigating its clinical efficacy and safety. PMID:26427518

  4. Predicting 6-week treatment response to escitalopram pharmacotherapy in late-life major depressive disorder

    PubMed Central

    Saghafi, Ramin; Brown, Charlotte; Butters, Meryl A.; Cyranowski, Jill; Dew, Mary Amanda; Frank, Ellen; Gildengers, Ariel; Karp, Jordan F.; Lenze, Eric J.; Lotrich, Francis; Martire, Lynn; Mazumdar, Sati; Miller, Mark D.; Mulsant, Benoit H.; Weber, Elizabeth; Whyte, Ellen; Morse, Jennifer; Stack, Jacqueline; Houck, Patricia R.; Bensasi, Salem; Reynolds, Charles F.

    2013-01-01

    SUMMARY Objective Approximately half of older patients treated for major depressive disorder (MDD) do not achieve symptomatic remission and functional recovery with first-line pharmacotherapy. This study aims to characterize sociodemographic, clinical, and neuropsychologic correlates of full, partial, and non-response to escitalopram monotherapy of unipolar MDD in later life. Methods One hundred and seventy-five patients aged 60 and older were assessed at baseline on demographic variables, depression severity, hopelessness, anxiety, cognitive functioning, co-existing medical illness burden, social support, and quality of life (disability). Subjects received 10 mg/d of open-label escitalopram and were divided into full (n =55; 31%), partial (n =75; 42.9%), and non-responder (n =45; 25.7%) groups based on Hamilton depression scores at week 6. Univariate followed by multivariate analyses tested for differences between the three groups. Results Non-responders to treatment were found to be more severely depressed and anxious at baseline than both full and partial responders, more disabled, and with lower self-esteem than full responders. In general partial responders resembled full responders more than they resembled non-responders. In multivariate models, more severe anxiety symptoms (both psychological and somatic) and lower self-esteem predicted worse response status at 6 weeks. Conclusion Among treatment-seeking elderly persons with MDD, higher anxiety symptoms and lower self-esteem predict poorer response after six weeks of escitalopram treatment. PMID:17486678

  5. Predictors of first lifetime onset of major depressive disorder in young adulthood.

    PubMed

    Klein, Daniel N; Glenn, Catherine R; Kosty, Derek B; Seeley, John R; Rohde, Paul; Lewinsohn, Peter M

    2013-02-01

    The first onset of major depressive disorder (MDD) most frequently occurs in young adulthood. However, few studies have examined predictors of first lifetime MDD during this high-risk period. The present study examined a broad range of demographic, clinical, and psychosocial variables as prospective predictors of first onset of MDD in a large community sample of young adults (N = 502) from the Oregon Adolescent Depression Project. Between ages 19-31, 35.3% of the sample had a first lifetime MDD episode. Female gender, familial loading of mood disorders, history of childhood sexual abuse, prior history of anxiety disorder, poor self-reported physical health, and subthreshold depressive symptoms significantly predicted MDD onset. In a multivariate model, female gender, familial loading of mood disorders, and subthreshold depression each contributed unique variance in predicting first lifetime MDD. This model had a moderate-to-large effect in predicting MDD onset. Gender did not moderate the other predictors, and the magnitude of the effects did not diminish over the course of the follow-up. These findings indicate that a number of risk factors significantly predict first lifetime MDD in young adulthood, and that simple multivariate risk models may be useful for identifying individuals at high risk for MDD. PMID:22889243

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

    PubMed Central

    2014-01-01

    Background This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Methods 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 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. Conclusions 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. PMID:24690413

  7. A review of electroencephalographic changes in diabetes mellitus in relation to major depressive disorder.

    PubMed

    Baskaran, Anusha; Milev, Roumen; McIntyre, Roger S

    2013-01-01

    A bidirectional relationship exists between diabetes mellitus (DM) and major depressive disorder (MDD), with depression commonly reported in both type 1 DM (T1DM) and type 2 DM (T2DM), and depressive symptoms associated with a higher incidence of diabetes. However, how the two conditions are pathologically connected is not completely understood. Similar neurophysiological abnormalities have been reported in both DM and MDD, including elevated electroencephalographic (EEG) activity in low-frequency slow waves and increased latency and/or reduced amplitude of event-related potentials. It is possible that this association reflects some common underlying pathology, and it has been proposed that diabetes may place patients at risk for depression through a biological mechanism linking the metabolic changes of DM to changes in the central nervous system. In this review we will discuss EEG abnormalities in DM, as well as the biological mechanisms underlying various EEG parameters, in order to evaluate whether or not a common EEG biosignature exists between DM and MDD. Identifying such commonalities could significantly inform the current understanding of the mechanisms that subserve the development of the two conditions. Moreover, this new insight may provide the basis for informing new drug discovery capable of mitigating and possibly even preventing both conditions. PMID:23355785

  8. Aberrant emotion networks in early major depressive disorder patients: an eigenvector centrality mapping study.

    PubMed

    Song, Z; Zhang, M; Huang, P

    2016-01-01

    Major depressive disorder (MDD) is a serious mental disorder that negatively affects the quality of life of many individuals, and is a heavy economic burden to society. In recent years it was thought that depression is a 'disconnection syndrome'. Disorganized brain activity and un-modulated emotion responses were considered the key neuropathologies underlying depression. In the present study, we investigated the alteration of whole brain network connectivity in 28 first-episode, drug-naive patients, using resting-state functional magnetic resonance imaging and a new analytical method called voxel-based eigenvector centrality mapping. We found that compared with normal controls, MDD patients had lower functional connectivity in the bilateral middle frontal gyrus, insula, hippocampus, amygdala and cerebellum, and higher functional connectivity in the medial prefrontal cortex. The functional connectivity strength at the right hippocampus (r=-0.413, P=0.032) and the right insula (r=-0.372, P=0.041) negatively correlated with the severity of the disease. We further examined coordination among these regions, and found that frontal-subcortical connection was reduced and insula-medial prefrontal cortex (mPFC) connection was increased. These results are consistent with previous hypotheses on the neural mechanism of MDD, and provide further evidence that emotion networks are already interrupted in early stages of depression. PMID:27219345

  9. Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

    PubMed Central

    Baek, Song-Eun; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Rho, Dae-Young; Kim, Do-Hoon; Huh, Sun

    2016-01-01

    Objective This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method. Methods Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later. Results There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups. Conclusion These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA. PMID:27081384

  10. Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder.

    PubMed

    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

    2015-07-01

    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

  11. Amygdala and dorsomedial hyperactivity to emotional faces in youth with remitted Major Depression.

    PubMed

    Jenkins, Lisanne M; Kassel, Michelle T; Gabriel, Laura B; Gowins, Jennifer R; Hymen, Erica A; Vergés, Alvaro; Calamia, Matthew; Crane, Natania A; Jacobs, Rachel H; Ajilore, Olusola; Welsh, Robert C; Drevets, Wayne C; Phillips, Mary L; Zubieta, Jon-Kar; Langenecker, Scott A

    2016-05-01

    We present neuroimaging markers of the remitted state of major depressive disorder (rMDD) during facial emotion perception in 84 individuals during fMRI. Participants comprised 47 individuals (aged 18-23) diagnosed with rMDD and 37 healthy controls (HCs). Participants classified emotional faces or animals (control condition) in the Facial Emotion Perception Test (FEPT) during fMRI. Behavioural performance on the FEPT did not differ significantly between groups. During fMRI, both groups demonstrated significant blood oxygen level-dependent (BOLD) activity in bilateral inferior frontal gyri for the faces minus animals (F-A) contrast. The rMDD group additionally showed BOLD activity during F-A in numerous regions, including the bilateral paracingulate gyri, middle temporal gyri and right amygdala. The rMDD group exhibited significantly greater activity than the HC group in regions including the bilateral middle temporal gyri and left superior frontal gyrus. Although the rMDD group did not manifest the behavioural performance deficits on facial emotion recognition tasks that have been observed in actively depressed individuals, the rMDD group nevertheless showed increased BOLD activity compared with never-depressed controls during F-A in multiple posterior brain regions, suggesting that persistent effects of illness or possible trait vulnerabilities may distinguish individuals with rMDD from never-depressed controls. PMID:26714574

  12. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent.

    PubMed

    Hyde, Craig L; Nagle, Michael W; Tian, Chao; Chen, Xing; Paciga, Sara A; Wendland, Jens R; Tung, Joyce Y; Hinds, David A; Perlis, Roy H; Winslow, Ashley R

    2016-09-01

    Despite strong evidence supporting the heritability of major depressive disorder (MDD), previous genome-wide studies were unable to identify risk loci among individuals of European descent. We used self-report data from 75,607 individuals reporting clinical diagnosis of depression and 231,747 individuals reporting no history of depression through 23andMe and carried out meta-analysis of these results with published MDD genome-wide association study results. We identified five independent variants from four regions associated with self-report of clinical diagnosis or treatment for depression. Loci with a P value <1.0 × 10(-5) in the meta-analysis were further analyzed in a replication data set (45,773 cases and 106,354 controls) from 23andMe. A total of 17 independent SNPs from 15 regions reached genome-wide significance after joint analysis over all three data sets. Some of these loci were also implicated in genome-wide association studies of related psychiatric traits. These studies provide evidence for large-scale consumer genomic data as a powerful and efficient complement to data collected from traditional means of ascertainment for neuropsychiatric disease genomics. PMID:27479909

  13. Impact of electroconvulsive therapy on magnetoencephalographic correlates of dysfunctional emotional processing in major depression.

    PubMed

    Zwanzger, Peter; Klahn, Anna Luisa; Arolt, Volker; Ruland, Tillmann; Zavorotnyy, Maxim; Sälzer, Johannes; Domschke, Katharina; Junghöfer, Markus

    2016-04-01

    In major depressive disorder (MDD), electrophysiological and imaging studies provide evidence for a reduced neural activity in parietal and dorsolateral prefrontal regions. In the present study, neural correlates and temporal dynamics of visual affective perception have been investigated in patients with unipolar depression in a pre/post treatment design using magnetoencephalography (MEG). Nineteen in-patients and 19 balanced healthy controls passed MEG measurement while passively viewing pleasant, unpleasant and neutral pictures. After a 4-week treatment with electroconvulsive therapy or 4-week waiting period without intervention respectively, 16 of these patients and their 16 corresponding controls participated in a second MEG measurement. Before treatment neural source estimations of magnetic fields evoked by the emotional scenes revealed a general bilateral parietal hypoactivation in depressed patients compared to controls predominately at early and mid-latency time intervals. Successful ECT treatment, as reflected by a decline in clinical scores (Hamilton Depression Scale; HAMD) led to a normalization of this distinct parietal hypoactivation. Effective treatment was also accompanied by relatively increased neural activation at right temporo-parietal regions. The present study indicates dysfunctional parietal information processing and attention processes towards emotional stimuli in MDD patients which can be returned to normal by ECT treatment. Since convergent neural hypoactivations and treatment effects have recently been shown in MDD patients before and after pharmacological therapy, this electrophysiological correlate might serve as a biomarker for objective treatment evaluation and thereby potentially advance treatment options and support the prediction of individual treatment responses. PMID:26922827

  14. Levomilnacipran extended-release: a review of its use in adult patients with major depressive disorder.

    PubMed

    Scott, Lesley J

    2014-11-01

    Oral levomilnacipran extended-release (ER) [Fetzima™], the more active enantiomer of milnacipran, is the most recent serotonin norepinephrine reuptake inhibitor to be approved in the USA for the treatment of adults with major depressive disorder (MDD). MDD is characterized by depression and impairment of cognitive, social and work functioning. Once-daily levomilnacipran ER 40-120 mg was an effective and generally well-tolerated treatment in adults with MDD participating in 8-week phase III trials and a 1-year extension study. After 8 weeks, levomilnacipran ER treatment was associated with significantly greater and clinically meaningful improvements in depressive symptoms than placebo treatment and, in general, higher Montgomery-Asberg Depression Rating Scale responder rates and greater improvements in functional outcomes than placebo. The efficacy of levomilnacipran ER was maintained during the extension study, with no new safety signals detected; ongoing postmarketing evidence should more fully define the long-term safety of levomilnacipran ER. In the absence of head-to-head clinical trials, the relative position of levomilnacipran ER to that of other antidepressants remains to be determined. In the meantime, it is a useful addition to pharmacological options for the treatment of adult patients with MDD. This article summarizes the clinical use of oral levomilnacipran ER in adults with MDD, and briefly reviews the pharmacological properties of levomilnacipran. PMID:25270036

  15. Dissociable Self Effects for Emotion Regulation: A Study of Chinese Major Depressive Outpatients

    PubMed Central

    Wang, Xiaoxia; Feng, Zhengzhi; Zhou, Daiquan; Lei, Xu; Liao, Tongquan; Zhang, Li; Ji, Bing; Li, Jing

    2014-01-01

    Reappraisal is an adaptive emotion regulation strategy while the role of self-perspective in reappraisal process of depressed patients is largely unknown in terms of goals (valence/arousal) and tactics (detachment/immersion). In this study, 12 depressed individuals and 15 controls were scanned with MRI during which they either attend naturally to emotional stimuli, or adopt detachment/immersion strategy. Behaviorally, no group differences in self-reported emotion regulation effectiveness were found. In addition, we observed that (1) patients were less able to downregulate amygdala activation with recruitment of more dorsal lateral prefrontal cortex (dlPFC) when adopting detachment strategy regardless of valence, and this preserved ability to regulate emotion was inversely associated with severity of symptoms; (2) patients had deficits in upregulating amygdala activation when adopting immersion strategy, with less inferior frontal gyrus (IFG) activation and strengthening coupling of dlPFC and ventral medial prefrontal cortex (vmPFC) with amygdala; (3) comparison between groups yielded that patients showed stronger vmPFC activation under either self-detached or self-immersed condition. In conclusion, impaired modulatory effects of amygdala in depressed patients are compensated with strengthening cognitive control resources, with dissociable effects for different self-perspectives in reappraisal. These results may help clarify the role of self-perspective underlying reappraisal in major depression. PMID:24804219

  16. 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

  17. Neuromodulation of Attentional Control in Major Depression: A Pilot DeepTMS Study

    PubMed Central

    Naim-Feil, Jodie; Bradshaw, John L.; Sheppard, Dianne M.; Rosenberg, Oded; Levkovitz, Yechiel; Fitzgerald, Paul B.; Isserles, Moshe; Zangen, Abraham

    2016-01-01

    While Major Depressive Disorder (MDD) is primarily characterized by mood disturbances, impaired attentional control is increasingly identified as a critical feature of depression. Deep transcranial magnetic stimulation (deepTMS), a noninvasive neuromodulatory technique, can modulate neural activity and induce neuroplasticity changes in brain regions recruited by attentional processes. This study examined whether acute and long-term high-frequency repetitive deepTMS to the dorsolateral prefrontal cortex (DLPFC) can attenuate attentional deficits associated with MDD. Twenty-one MDD patients and 26 matched control subjects (CS) were administered the Beck Depression Inventory and the Sustained Attention to Response Task (SART) at baseline. MDD patients were readministered the SART and depressive assessments following a single session (n = 21) and after 4 weeks (n = 13) of high-frequency (20 Hz) repetitive deepTMS applied to the DLPFC. To control for the practice effect, CS (n = 26) were readministered the SART a further two times. The MDD group exhibited deficits in sustained attention and cognitive inhibition. Both acute and long-term high-frequency repetitive frontal deepTMS ameliorated sustained attention deficits in the MDD group. Improvement after acute deepTMS was related to attentional recovery after long-term deepTMS. Longer-term improvement in sustained attention was not related to antidepressant effects of deepTMS treatment. PMID:26823985

  18. Opening toward life: Experiences of basic body awareness therapy in persons with major depression

    PubMed Central

    Danielsson, Louise; Rosberg, Susanne

    2015-01-01

    Although there is a vast amount of research on different strategies to alleviate depression, knowledge of movement-based treatments focusing on body awareness is sparse. This study explores the experiences of basic body awareness therapy (BBAT) in 15 persons diagnosed with major depression who participated in the treatment in a randomized clinical trial. Hermeneutic phenomenological methodology inspired the approach to interviews and data analysis. The participants’ experiences were essentially grasped as a process of enhanced existential openness, opening toward life, exceeding the tangible corporeal dimension to also involve emotional, temporal, and relational aspects of life. Five constituents of this meaning were described: vitality springing forth, grounding oneself, recognizing patterns in one's body, being acknowledged and allowed to be oneself, and grasping the vagueness. The process of enhanced perceptual openness challenges the numbness experienced in depression, which can provide hope for change, but it is connected to hard work and can be emotionally difficult to bear. Inspired by a phenomenological framework, the results of this study illuminate novel clinical and theoretical insight into the meaning of BBAT as an adjunctive approach in the treatment of depression. PMID:25956354

  19. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

    PubMed

    Cassano, Paolo; Petrie, Samuel R; Hamblin, Michael R; Henderson, Theodore A; Iosifescu, Dan V

    2016-07-01

    We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD. PMID:26989758

  20. Potentiation of quantitative electroencephalograms following prefrontal repetitive transcranial magnetic stimulation in patients with major depression.

    PubMed

    Noda, Yoshihiro; Nakamura, Motoaki; Saeki, Takashi; Inoue, Misa; Iwanari, Hideo; Kasai, Kiyoto

    2013-01-01

    The long-lasting effects of repetitive transcranial magnetic stimulation (rTMS) on electroencephalogram (EEG) activity are not clear. We aimed to investigate the cumulative rTMS effects on EEG and clinical outcomes in patients with major depression. Twenty-five patients with medication-resistant depression underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex. We measured resting EEG and spectrum-power before and after the rTMS course. Clinical efficacy was evaluated with the Hamilton's Depression Rating Scale (HAM-D) and Wisconsin Card Sorting Test (WCST). In an ANOVA model, including all prefrontal electrodes, post hoc analyses revealed significant time effects on the theta (F1,24 = 7.89, P = 0.010; +43%), delta (F1,24 = 6.58, P = 0.017; +26%), and alpha (F1,24 = 4.64, P = 0.042; 31%) bands without site specificity. Clinical correlations were observed between F4 alpha power increases and improvements in HAM-D retardation, F3 alpha power increases and improvements of the absolute changes in perseveration and error number on the WCST, and C3 and C4 theta power increases and improvements of the percent change in perseveration and error number on the WCST following rTMS. Consecutive prefrontal rTMS could induce long-lasting EEG potentiations beyond the aftereffects, resulting in improved cognitive and depressive symptoms. PMID:23827366

  1. Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation in patients with schizophrenia and major depression

    PubMed Central

    HADAŠOVÁ, EVA; FRANKE, GERD; ZSCHIESCHE, MICHAEL; ČEŠKOVÁ, EVA; ZELENKOVÁ, OLGA; SIEGMUND, WERNER

    1996-01-01

    Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation phenotypes were determined in 115 Czech drug-free in-patients with schizophrenia (n=64) or major depressive disorder (n=51). These data were compared with a control group of 321 healthy volunteers from the North-East German area of Greifswald. The distribution of debrisoquine hydroxylator phenotypes was almost identical in patients and healthy controls. Thus, there were 8.7% (95% CI 5.4–12.0%) of poor metabolizers (PM) among patients while 8.7% (95% CI 3.6–13.8%) PM among the control group. The prevalences of PM amongst patients with chronic schizophrenia and major depression were 10.9% (95% CI 4.5–21.3%) and 5.9 % (95% CI 1.24–16.3%), respectively (χ2 schizophrenics vs control=0.315, NS; χ2 depressive patients vs control=0.450, NS). However, within the group of EM patients there was a significant (P<0.01) shift towards higher debrisoquine metabolic ratios, reflecting a lower hydroxylation capacity in EM patients compared with EM healthy controls. The proportion of slow acetylators (SA) was 60.0% (95% CI 51.0–68.9%) in the entire group of psychiatric patients and 57.5% (95% CI 52.1–62.9%) in the control group (χ2 all patients vs control=0.195, NS). Furthermore, there were no significant differences in the prevalence of the SA phenotype between controls and schizophrenics or patients with major depression. Although the results of this modest study were negative, the presence of subtle differences in the metabolic capacity between psychiatric patients and a healthy population cannot be ruled out. PMID:8735687

  2. Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression.

    PubMed

    Davis, R; Whittington, R; Bryson, H M

    1997-04-01

    Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term clinical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline. The optimum therapeutic dosage of nefazodone appears to be between 300 and 600 mg/day. Limited long term data suggest that nefazodone is effective in preventing relapse of depression in patients treated for up to 1 year. Analyses of pooled clinical trial results indicate that nefazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo in patients with major depression. Short term tolerability data indicate that nefazodone has a lower incidence of adverse anticholinergic, antihistaminergic and adrenergic effects than imipramine. Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointestinal effects (nausea, diarrhoea, anorexia) and adverse effects on sexual function, but is associated with more dizziness, dry mouth, constipation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures, priapism or significant sleep disruption, and appears to be relatively safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 isoenzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of major depression. Nonetheless

  3. Agomelatine beyond Borders: Current Evidences of Its Efficacy in Disorders Other than Major Depression

    PubMed Central

    De Berardis, Domenico; Fornaro, Michele; Serroni, Nicola; Campanella, Daniela; Rapini, Gabriella; Olivieri, Luigi; Srinivasan, Venkataramanujam; Iasevoli, Felice; Tomasetti, Carmine; De Bartolomeis, Andrea; Valchera, Alessandro; Perna, Giampaolo; Mazza, Monica; Di Nicola, Marco; Martinotti, Giovanni; Di Giannantonio, Massimo

    2015-01-01

    Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine’s antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression. PMID:25569089

  4. Agomelatine beyond borders: current evidences of its efficacy in disorders other than major depression.

    PubMed

    De Berardis, Domenico; Fornaro, Michele; Serroni, Nicola; Campanella, Daniela; Rapini, Gabriella; Olivieri, Luigi; Srinivasan, Venkataramanujam; Iasevoli, Felice; Tomasetti, Carmine; De Bartolomeis, Andrea; Valchera, Alessandro; Perna, Giampaolo; Mazza, Monica; Di Nicola, Marco; Martinotti, Giovanni; Di Giannantonio, Massimo

    2015-01-01

    Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine's antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression. PMID:25569089

  5. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    PubMed Central

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P < .01). Depending on the SDS subscale, 48%–55% of levomilnacipran ER–treated patients with moderate-extreme impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial

  6. Risk factors for major depression during midlife among a community sample of women with and without prior major depression: are they the same or different?

    PubMed Central

    Bromberger, J. T.; Schott, L.; Kravitz, H. M.; Joffe, H.

    2015-01-01

    Background Women’s vulnerability for a first lifetime-onset of major depressive disorder (MDD) during midlife is substantial. It is unclear whether risk factors differ for first lifetime-onset and recurrent MDD. Identifying these risk factors can provide more focused depression screening and earlier intervention. This study aims to evaluate whether lifetime psychiatric and health histories, personality traits, menopausal status and factors that vary over time, e.g. symptoms, are independent risk factors for first-onset or recurrent MDD across 13 annual follow-ups. Method Four hundred and forty-three women, aged 42–52 years, enrolled in the Study of Women’s Health Across the Nation in Pittsburgh and participated in the Mental Health Study. Psychiatric interviews obtained information on lifetime psychiatric disorders at baseline and on occurrences of MDD episodes annually. Psychosocial and health-related data were collected annually. Cox multivariable analyses were conducted separately for women with and without a MDD history at baseline. Results Women without lifetime MDD at baseline had a lower risk of developing MDD during midlife than those with a prior MDD history (28% v. 59%) and their risk profiles differed. Health conditions prior to baseline and during followups perception of functioning (ps < 0.05) and vasomotor symptoms (VMS) (p = 0.08) were risk factors for first lifetime-onset MDD. Being peri- and post-menopausal, psychological symptoms and a prior anxiety disorder were predominant risk factors for MDD recurrence. Conclusions The menopausal transition warrants attention as a period of vulnerability to MDD recurrence, while health factors and VMS should be considered important risk factors for first lifetime-onset of MDD during midlife. PMID:25417760

  7. Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder.

    PubMed

    Bunney, B G; Li, J Z; Walsh, D M; Stein, R; Vawter, M P; Cartagena, P; Barchas, J D; Schatzberg, A F; Myers, R M; Watson, S J; Akil, H; Bunney, W E

    2015-02-01

    Conventional antidepressants require 2-8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small

  8. The Extended Functional Neuroanatomy of Emotional Processing Biases for Masked Faces in Major Depressive Disorder

    PubMed Central

    Victor, Teresa A.; Furey, Maura L.; Fromm, Stephen J.; Bellgowan, Patrick S. F.; Öhman, Arne; Drevets, Wayne C.

    2012-01-01

    Background Major depressive disorder (MDD) is associated with a mood-congruent processing bias in the amygdala toward face stimuli portraying sad expressions that is evident even when such stimuli are presented below the level of conscious awareness. The extended functional anatomical network that maintains this response bias has not been established, however. Aims To identify neural network differences in the hemodynamic response to implicitly presented facial expressions between depressed and healthy control participants. Method Unmedicated-depressed participants with MDD (n = 22) and healthy controls (HC; n = 25) underwent functional MRI as they viewed face stimuli showing sad, happy or neutral face expressions, presented using a backward masking design. The blood-oxygen-level dependent (BOLD) signal was measured to identify regions where the hemodynamic response to the emotionally valenced stimuli differed between groups. Results The MDD subjects showed greater BOLD responses than the controls to masked-sad versus masked-happy faces in the hippocampus, amygdala and anterior inferotemporal cortex. While viewing both masked-sad and masked-happy faces relative to masked-neutral faces, the depressed subjects showed greater hemodynamic responses than the controls in a network that included the medial and orbital prefrontal cortices and anterior temporal cortex. Conclusions Depressed and healthy participants showed distinct hemodynamic responses to masked-sad and masked-happy faces in neural circuits known to support the processing of emotionally valenced stimuli and to integrate the sensory and visceromotor aspects of emotional behavior. Altered function within these networks in MDD may establish and maintain illness-associated differences in the salience of sensory/social stimuli, such that attention is biased toward negative and away from positive stimuli. PMID:23056309

  9. Plasma CRP Levels in Premenopausal Women with Major Depression: A 12-Month Controlled Study

    PubMed Central

    Cizza, G.; Eskandari, F.; Coyle, M.; Krishnamurthy, P.; Wright, E. C.; Mistry, S.; Csako, G.

    2009-01-01

    C-reactive protein (CRP), an inflammatory marker of cardiovascular risk, is often elevated in major depressive disorder (MDD). The magnitude and consistency of this elevation have not been previously characterized in premenopausal women with MDD. The aim of the study was to prospectively assess plasma CRP levels, body composition, endocrine and metabolic parameters, and depressive status in premenopausal women with MDD (n = 77) and controls (n = 41), aged 21 to 45. Women were enrolled in a 12-month, controlled study of bone turnover, the P.O.W.E.R. (Premenopausal, Osteoporosis, Women, Alendronate, Depression) Study. Blood samples were taken at Baseline, Month 6, and Month 12. Most subjects with MDD were in clinical remission. These women tended to have consistently higher CRP levels than controls over 12 months (p = 0.077). BMI was positively related to log[CRP] in women with MDD only. Nine women with MDD had CRP levels greater than 10 mg/l, a value associated with a very high cardiovascular risk. This subset was obese and had significantly higher triglycerides, total cholesterol, LDL-cholesterol, fasting insulin, and HOMA-IR than the rest of women with MDD. The variations in CRP levels over time were high (intra- and inter-individual coefficients of variations of ∼30–50% and ∼70–140%, respectively). No control had CRP levels greater than 10 mg/l. Depression was associated with increased plasma CRP in women with MDD. The clinical significance of abnormal plasma CRP for cardiovascular risk needs to be assessed in large prospective studies of women with depression. PMID:19408214

  10. Venlafaxine, paroxetine and milnacipran for major depressive disorder: a pragmatic 24-week study.

    PubMed

    Chuang, Hui-Yu; Chang, Yun-Hsuan; Cheng, Ling-Yi; Wang, Yu-Shan; Chen, Shiou-Lan; Chen, Shih-Heng; Chu, Chun-Hsien; Lee, I Hui; Chen, Po See; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band

    2014-10-31

    Major depressive disorder (MDD), one of the most common psychiatric disorders in the world, is a serious, recurrent and chronic mental disorder, which is associated with significant psychosocial disability and economic burden. Until recently, short-term effectiveness of antidepressants has been measured in terms of patients' response to the medications in significantly reduced depressive symptoms. Remission, a long-term elimination of symptoms and the restoration of normal functioning, has become the primary outcome of therapy. In the current study, the efficacy of three frequently prescribed antidepressants, venlafaxine (75-225 mg/day), paroxetine (20 mg/day) and milnacipran (100 mg/day), used in treating 249 MDD patients with Hamilton Rating Scale of Depression (HRSD₁₇) scores higher than 16 was compared. Each patient was evaluated at week 0, 1, 2, 4, 8, 12, 16, 20 and 24 in a 24-week open-label study. Eighty-two patients took venlafaxine, 97 took paroxetine and 70 patients took milnacipran. No significant differences were found between the three groups in the response condition (HRSD₁₇ scores decreased more than 50%) after 24 weeks of follow-up. For remission, the paroxetine was the least efficacious medication than either the milnacipran (HRSD₁₇ ≤ 7) or the venlafaxine (HRSD₁₇ ≤ 5) by the last observation carried forward (LOCF) analysis. Our results suggest that the absence of depressive symptoms alone may not be an indicator for MDD remission, but the duration of absent depressive symptoms may be a better indicator. PMID:25241986

  11. Clinical Relevance of Disturbances of Sleep and Vigilance in Major Depressive Disorder: A Review

    PubMed Central

    Murck, Harald; Post, Anke

    2010-01-01

    Objective: The primary objective of this article is to provide a concise review of the clinical relevance of sleep and vigilance in major depressive disorder. Data Sources: PubMed was reviewed (1990–2009) and English-language articles were identified using the key words sleep and depression and sleep and antidepressants. Secondary searches included articles cited in sources identified by the primary search. Study Selection: The narrative review provides brief descriptions of the normal physiology of sleep and changes associated with depression, as well as the impact of various treatments on these processes. Data Synthesis: Although it has long been known that sleep disturbances are an important characteristic of depression, relatively few studies have been conducted with the newer-generation antidepressants. Neither of the most widely used classes of antidepressants, the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, have particularly beneficial effects on sleep and, among the medications that reliably improve sleep efficiency, including mirtazapine and the tricyclic antidepressants, problems with daytime sedation can offset therapeutic benefit. Despite relatively widespread use, trazodone has not been demonstrated to be an effective and safe hypnotic in patients taking other antidepressants. For many patients, ongoing concomitant treatment with benzodiazepines and related drugs is the preferred option, again without convincing empirical support of longer-term efficacy. Among newer and investigational antidepressants, agomelatine shows promise with respect to both overall safety and effects on insomnia, although possible negative effects on liver function warrant further study. Conclusions: Sleep disturbances are a significant aspect of depressive syndromes, and relief of insomnia remains an important unmet need in antidepressant therapeutics. Development of a well-tolerated antidepressant medication that rapidly

  12. Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder

    PubMed Central

    Bunney, BG; Li, JZ; Walsh, DM; Stein, R; Vawter, MP; Cartagena, P; Barchas, JD; Schatzberg, AF; Myers, RM; Watson, SJ; Akil, H; Bunney, WE

    2016-01-01

    Conventional antidepressants require 2–8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small

  13. The Current Situation on Major Depressive Disorder in China: Research on Mechanisms and Clinical Practice.

    PubMed

    Hou, Zhenghua; Jiang, Wenhao; Yin, Yingying; Zhang, Zhijun; Yuan, Yonggui

    2016-08-01

    Depression is the most disabling disorder worldwide that accounts for the highest proportion of global burden attributable to mental disorders. Major depressive disorder (MDD) is characterized by deep sadness, reduced energy, vegetative nervous system dysregulation, cognitive dysfunction, and even a high suicidal tendency. Although other treatment choices are available, antidepressant medication is the front-line treatment option for MDD. Regarding clinical efficacy, only ~50% of patients respond to frontline antidepressants, and <33% obtain remission. Currently, objective indexes to guide clinical decisions are still lacking. Furthermore, knowledge about the neurobiological mechanisms underlying discrepant antidepressant outcomes is still also fragmentary. In the present review, we discuss the current research progress and clinical opinions on MDD in China. PMID:27237579

  14. Associations of Gender, Smoking, and Stress with Transitions in Major Depression Diagnoses

    PubMed Central

    Verplaetse, Terril L.; Smith, Philip H.; Pittman, Brian P.; Mazure, Carolyn M.; McKee, Sherry A.

    2016-01-01

    Using data from the newly available U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 3; n = 36,309), we evaluated relationships among gender, cigarette smoking status (current, former, non-smoker), life event stress (0-1 vs. 2+ events), and their impact on transitions in major depression diagnosis (MDD; new vs. absent cases; ongoing vs. remit cases). Women who were both current and former cigarette smokers with more than two stressful events had higher rates of new MDD diagnosis compared to men who were current or former smokers with two or more stressful events. Current smoking and experiencing two or more stressful events increased the odds of having an ongoing MDD diagnosis, while being a former smoker decreased these odds. Results suggest that smoking and stress are markers for depression risk in women and should help guide clinical assessment as well as gender-difference research on the biological underpinnings of these conditions. PMID:27354839

  15. Targets of polyamine dysregulation in major depression and suicide: Activity-dependent feedback, excitability, and neurotransmission.

    PubMed

    Limon, Agenor; Mamdani, Firoza; Hjelm, Brooke E; Vawter, Marquis P; Sequeira, Adolfo

    2016-07-01

    Major depressive disorder (MDD) is a leading cause of disability worldwide characterized by altered neuronal activity in brain regions involved in the control of stress and emotion. Although multiple lines of evidence suggest that altered stress-coping mechanisms underlie the etiology of MDD, the homeostatic control of neuronal excitability in MDD at the molecular level is not well established. In this review, we examine past and current evidence implicating dysregulation of the polyamine system as a central factor in the homeostatic response to stress and the etiology of MDD. We discuss the cellular effects of abnormal metabolism of polyamines in the context of their role in sensing and modulation of neuronal, electrical, and synaptic activity. Finally, we discuss evidence supporting an allostatic model of depression based on a chronic elevation in polyamine levels resulting in self-sustained stress response mechanisms maintained by maladaptive homeostatic mechanisms. PMID:27108532

  16. Bipolar and Major Depressive Disorder: Neuroimaging the Developmental-Degenerative Divide

    PubMed Central

    Savitz, Jonathan; Drevets, Wayne C

    2010-01-01

    Both major depressive disorder and bipolar disorder are the subject of a voluminous imaging and genetics literature. Here, we attempt a comprehensive review of MRI and metabolic PET studies conducted to date on these two disorders, and interpret our findings from the perspective of developmental and degenerative models of illness. Elevated activity and volume loss of the hippocampus, orbital and ventral prefrontal cortex are recurrent themes in the literature. In contrast, dorsal aspects of the PFC tend to display hypometabolism. Ventriculomegaly and white matter hyperintensities are intimately associated with depression in elderly populations and likely have a vascular origin. Important confounding influences are medication, phenotypic and genetic heterogeneity, and technological limitations. We suggest that environmental stress and genetic risk variants interact with each other in a complex manner to alter neural circuitry and precipitate illness. Imaging genetic approaches hold out promise for advancing our understanding of affective illness. PMID:19428491

  17. Pathogenetic and therapeutic applications of microRNAs in major depressive disorder.

    PubMed

    Dwivedi, Yogesh

    2016-01-01

    As a class of noncoding RNAs, microRNAs (miRNAs) regulate gene expression by inhibiting translation of messenger RNAs. These miRNAs have been shown to play a critical role in higher brain functioning and actively participate in synaptic plasticity. Pre-clinical evidence demonstrates that expression of miRNAs is differentially altered during stress. On the other hand, depressed individuals show marked changes in miRNA expression in brain. MiRNAs are also target of antidepressants and electroconvulsive therapy. Moreover, these miRNAs are present in circulating blood and can be easily detected. Profiling of miRNAs in blood plasma/serum provides evidence that determination of miRNAs in blood can be used as possible diagnostic and therapeutic tool. In this review article, these aspects are critically reviewed and the role of miRNAs in possible etiopathogenesis and therapeutic implications in the context of major depressive disorder is discussed. PMID:25689819

  18. Exploring Sudden Gains in Behavioral Activation Therapy for Major Depressive Disorder

    PubMed Central

    Hunnicutt-Ferguson, Kallio; Hoxha, Denada; Gollan, Jackie

    2012-01-01

    Understanding the onset and course of sudden gains in treatment provides clinical information to the patient and clinician, and encourages clinicians to strive for these sudden clinical gains with their patients. This study characterizes the occurrence of sudden gains with Behavioral Activation (BA; Martell, Addis, & Jacobson, 2001), and the extent to which pre-treatment dysfunctional depressive thinking predicts sudden gains during treatment. We enrolled a sample of adults (n = 42) between ages 18–65 diagnosed with primary Major Depressive Disorder. All participants completed a 16-week course of BA, with clinical and self-report assessments at pre-, mid- and post-treatment. Results indicated that sudden gain and non-sudden gain participants showed differential improvement across treatment. No significant effects emerged for the dysfunctional cognitive style as a predictor of sudden gain status. Sudden gains may result from interaction of non-specific factors with the BA techniques implemented during early phases of therapy. PMID:22336434

  19. The Network Model of Depression as a Basis for New Therapeutic Strategies for Treating Major Depressive Disorder in Parkinson’s Disease

    PubMed Central

    D’Ostilio, Kevin; Garraux, Gaëtan

    2016-01-01

    The high prevalence of major depressive disorder in people with Parkinson’s disease (PD), its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with PD within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation (NIBS) using high frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes NIBS together with cognitive and behavioral interventions. PMID:27148016

  20. Major Depression During and After the Menopausal Transition: Study of Women’s Health Across the Nation (SWAN)

    PubMed Central

    Bromberger, Joyce T.; Kravitz, Howard M.; Chang, Yue-Fang; Cyranowski, Jill M.; Brown, Charlotte; Matthews, Karen A.

    2013-01-01

    Background It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to premenopause. Objectives To examine whether the odds of experiencing major depression were greater when women were perimenopausal or postmenopausal compared to when they were premenopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms, serum levels or changes in estradiol, follicular stimulating hormone, or testosterone and relevant confounders. Methods Participants included the 221 African American and Caucasian women, aged 42–52, who were premenopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Women’s Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual, and current major depression at baseline and annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones were obtained annually. Results Women were two to four times more likely to experience major depression episode when they were perimenopausal or early postmenopausal. Repeated measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, vasomotor symptoms and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study. Conclusions The risk of major depression is greater for women during and immediately after the menopausal transition than when they are premenopausal. PMID:21306662

  1. Effect of Cognitive Therapy With Antidepressant Medications vs Antidepressants Alone on the Rate of Recovery in Major Depressive Disorder

    PubMed Central

    Hollon, Steven D.; DeRubeis, Robert J.; Fawcett, Jan; Amsterdam, Jay D.; Shelton, Richard C.; Zajecka, John; Young, Paula R.; Gallop, Robert

    2015-01-01

    IMPORTANCE Antidepressant medication (ADM) is efficacious in the treatment of depression, but not all patients achieve remission and fewer still achieve recovery with ADM alone. OBJECTIVE To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in major depressive disorder (MDD). DESIGN, SETTING, AND PARTICIPANTS A total of 452 adult outpatients with chronic or recurrent MDD participated in a trial conducted in research clinics at 3 university medical centers in the United States. The patients were randomly assigned to ADM treatment alone or CT combined with ADM treatment. Treatment was continued for up to 42 months until recovery was achieved. INTERVENTIONS Antidepressant medication with or without CT. MAIN OUTCOMES AND MEASURES Blind evaluations of recovery with a modified version of the 17-item Hamilton Rating Scale for Depression and the Longitudinal Interval Follow-up Evaluation. RESULTS Combined treatment enhanced the rate of recovery vs treatment with ADM alone (72.6% vs 62.5%; t451 = 2.45; P = .01; hazard ratio [HR], 1.33; 95% CI, 1.06–1.68; number needed to treat [NNT], 10; 95% CI, 5–72). This effect was conditioned on interactions with severity (t451 = 1.97; P = .05; NNT, 5) and chronicity (χ2 = 7.46; P = .02; NNT, 6) such that the advantage for combined treatment was limited to patients with severe, nonchronic MDD (81.3% vs 51.7%; n = 146; t145 = 3.96; P = .001; HR, 2.34; 95% CI, 1.54–3.57; NNT, 3; 95% CI, 2–5). Fewer patients dropped out of combined treatment vs ADM treatment alone (18.9% vs 26.8%; t451 = −2.04; P = .04; HR, 0.66; 95% CI, 0.45–0.98). Remission rates did not differ significantly either as a main effect of treatment or as an interaction with severity or chronicity. Patients with comorbid Axis II disorders took longer to recover than did patients without comorbid Axis II disorders regardless of the condition (P = .01). Patients who received combined treatment reported fewer

  2. 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

  3. Blue Again: Perturbational Effects of Antidepressants Suggest Monoaminergic Homeostasis in Major Depression

    PubMed Central

    Andrews, Paul W.; Kornstein, Susan G.; Halberstadt, Lisa J.; Gardner, Charles O.; Neale, Michael C.

    2011-01-01

    Some evolutionary researchers have argued that current diagnostic criteria for major depressive disorder (MDD) may not accurately distinguish true instances of disorder from a normal, adaptive stress response. According to disorder advocates, neurochemicals like the monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) are dysregulated in major depression. Monoamines are normally under homeostatic control, so the monoamine disorder hypothesis implies a breakdown in homeostatic mechanisms. In contrast, adaptationist hypotheses propose that homeostatic mechanisms are properly functioning in most patients meeting current criteria for MDD. If the homeostatic mechanisms regulating monoamines are functioning properly in these patients, then oppositional tolerance should develop with prolonged antidepressant medication (ADM) therapy. Oppositional tolerance refers to the forces that develop when a homeostatic mechanism has been subject to prolonged pharmacological perturbation that attempt to bring the system back to equilibrium. When pharmacological intervention is discontinued, the oppositional forces cause monoamine levels to overshoot their equilibrium levels. Since depressive symptoms are under monoaminergic control, this overshoot should cause a resurgence of depressive symptoms that is proportional to the perturbational effect of the ADM. We test this prediction by conducting a meta-analysis of ADM discontinuation studies. We find that the risk of relapse after ADM discontinuation is positively associated with the degree to which ADMs enhance serotonin and norepinephrine in prefrontal cortex, after controlling for covariates. The results are consistent with oppositional tolerance, and provide no evidence of malfunction in the monoaminergic regulatory mechanisms in patients meeting current diagnostic criteria for MDD. We discuss the evolutionary and clinical implications of our findings. PMID:21779273

  4. Sleep State Instabilities in Major Depressive Disorder: Detection and Quantification with Electrocardiogram-based Cardiopulmonary Coupling Analysis

    PubMed Central

    Yang, Albert. C.; Yang, Cheng-Hung; Hong, Chen-Jee; Tsai, Shih-Jen; Kuo, Chung-Hsun; Peng, Chung-Kang; Mietus, Joseph E.; Goldberger, Ary L.; Thomas, Robert J.

    2010-01-01

    Sleep disruption is an important aspect of major depressive disorder but lacks an objective and inexpensive means of assessment. We evaluated the utility of electrocardiogram (ECG)-based cardiopulmonary coupling analysis to quantify physiologic sleep stability in patients with major depression. Relative to controls, unmedicated depressed patients had a reduction in high-frequency coupling, an index of stable sleep, an increase in low-frequency coupling, an index of unstable sleep, and an increase in very-low-frequency coupling, an index of wakefulness/REM sleep. The medicated depressed group showed a restoration of stable sleep to a level comparable with that of the control group. ECG-based cardiopulmonary coupling analysis may provide a simple, cost-efficient point-of-care method to quantify sleep quality/stability and to objectively evaluate the severity of insomnia in patients with major depression. PMID:20624250

  5. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma

    PubMed Central

    Nemeroff, Charles B.; Heim, Christine M.; Thase, Michael E.; Klein, Daniel N.; Rush, A. John; Schatzberg, Alan F.; Ninan, Philip T.; McCullough, James P.; Weiss, Paul M.; Dunner, David L.; Rothbaum, Barbara O.; Kornstein, Susan; Keitner, Gabor; Keller, Martin B.

    2003-01-01

    Major depressive disorder is associated with considerable morbidity, disability, and risk for suicide. Treatments for depression most commonly include antidepressants, psychotherapy, or the combination. Little is known about predictors of treatment response for depression. In this study, 681 patients with chronic forms of major depression were treated with an antidepressant (nefazodone), Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or the combination. Overall, the effects of the antidepressant alone and psychotherapy alone were equal and significantly less effective than combination treatment. Among those with a history of early childhood trauma (loss of parents at an early age, physical or sexual abuse, or neglect), psychotherapy alone was superior to antidepressant monotherapy. Moreover, the combination of psychotherapy and pharmacotherapy was only marginally superior to psychotherapy alone among the childhood abuse cohort. Our results suggest that psychotherapy may be an essential element in the treatment of patients with chronic forms of major depression and a history of childhood trauma. PMID:14615578

  6. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma.

    PubMed

    Nemeroff, Charles B; Heim, Christine M; Thase, Michael E; Klein, Daniel N; Rush, A John; Schatzberg, Alan F; Ninan, Philip T; McCullough, James P; Weiss, Paul M; Dunner, David L; Rothbaum, Barbara O; Kornstein, Susan; Keitner, Gabor; Keller, Martin B

    2003-11-25

    Major depressive disorder is associated with considerable morbidity, disability, and risk for suicide. Treatments for depression most commonly include antidepressants, psychotherapy, or the combination. Little is known about predictors of treatment response for depression. In this study, 681 patients with chronic forms of major depression were treated with an antidepressant (nefazodone), Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or the combination. Overall, the effects of the antidepressant alone and psychotherapy alone were equal and significantly less effective than combination treatment. Among those with a history of early childhood trauma (loss of parents at an early age, physical or sexual abuse, or neglect), psychotherapy alone was superior to antidepressant monotherapy. Moreover, the combination of psychotherapy and pharmacotherapy was only marginally superior to psychotherapy alone among the childhood abuse cohort. Our results suggest that psychotherapy may be an essential element in the treatment of patients with chronic forms of major depression and a history of childhood trauma. PMID:14615578

  7. Major Depressive Disorder Is Associated with Broad Impairments on Neuropsychological Measures of Executive Function: A Meta-Analysis and Review

    ERIC Educational Resources Information Center

    Snyder, Hannah R.

    2013-01-01

    Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. Although many studies have…

  8. Attachment and social adjustment: relationships to suicide attempt and major depressive episode in a prospective study

    PubMed Central

    Grunebaum, Michael F.; Galfalvy, Hanga C.; Mortenson, Lindsey Y.; Burke, Ainsley K.; Oquendo, Maria A.; Mann, J. John

    2009-01-01

    Objective To study two aspects of interpersonal function - attachment security and social adjustment – in relation to suicide attempt and major depressive episode (MDE) during naturalistic follow-up of up to one year after presentation with MDE. Method 136 adults who presented with a DSM-IV MDE completed the Adult Attachment Scale and the Social Adjustment Scale-Self Report at study entry. Based on follow-up interviews at three months and one year, we used survival analysis to investigate the relationship of scores on these measures with time to a suicide attempt and time to recurrent MDE. Results Less secure/more avoidant attachment predicted increased risk of suicide attempt during the 1-year follow-up (Wald χ2=9.14, df=1, p=.003, HR=1.16, 95% CI=1.05 to 1.27). Poorer social adjustment predicted increased risk of recurrent MDE (Wald χ2=6.95, df=1, p=.008, HR=2.36, 95% CI=1.25 to 4.46), and that in turn increased the risk of a suicide attempt (z=4.19, df=1, p<.001, HR=17.3, 95% CI=4.6 to 65.5). Conclusions Avoidant attachment in the setting of major depressive disorder is a potential therapeutic target to prevent suicidal behavior. Enhancing social adjustment may reduce relapse in major depressive disorder and thereby reduce risk of a suicide attempt. Study limitations include small sample size and use of a self-report attachment scale. PMID:19819021

  9. Beyond Symptomatic Improvement:Assessing Real-World Outcomes in Patients With Major Depressive Disorder

    PubMed Central

    Guico-Pabia, Christine J.

    2010-01-01

    Objective: To quantify the negative impact that major depressive disorder (MDD) has on quality of life, disability, and work, family, and overall psychosocial functioning. Available scales that assess these areas of impairment as they relate to patients with MDD are described. Data Sources: PubMed searches were conducted using the following terms: (MDD OR major depressive disorder) AND (absenteeism OR absente*); AND (quality of life OR QOL); AND (psychosocial function*); AND (presente* OR presenteeism); AND (health care cost* OR [health care] cost*); AND (health outcome*); AND (functional outcome*); AND (family life); AND (disabil* OR disability); AND (work function*); AND (unemployment OR unemploy*). The literature search was conducted in July 2008 and was restricted to English language articles. There were no limits set on the dates of the search. Study Selection: Two hundred twenty potential articles were identified. Among these studies, 48 presented primary data directly demonstrating the effect of MDD on quality of life, disability, and work, family, and overall psychosocial functioning. Data Extraction: Primary data were compiled from these studies and are summarily described. Available scales that assess quality of life, disability, and work, family, and overall psychosocial functioning are also described. Data Synthesis: MDD was found to be associated with significant disability and declines in functioning and quality of life. The Sheehan Disability Scale, the 36-item Short-Form Health Survey, and the Work Limitations Questionnaire were the most commonly used scales according to this review of the literature, but the majority of studies used direct and indirect disability measures, such as health care and other disability-related costs. Conclusions: In addition to assessing symptomatic outcomes, physicians should routinely assess their depressed patients on “real-world” outcomes. The development of a concise functional outcome measure specific to MDD is

  10. Copy Number Variation in Subjects with Major Depressive Disorder Who Attempted Suicide

    PubMed Central

    Perlis, Roy H.; Ruderfer, Douglas; Hamilton, Steven P.; Ernst, Carl

    2012-01-01

    Background Suicide is one of the top ten leading causes of death in North America and represents a major public health burden, partcularly for people with Major Depressive disorder (MD). Many studies have suggested that suicidal behavior runs in families, however, identification of genomic loci that drive this efffect remain to be identified. Methodology/Principal Findings Using subjects collected as part of STAR*D, we genotyped 189 subjects with MD with history of a suicide attempt and 1073 subjects with Major Depressive disorder that had never attempted suicide. Copy Number Variants (CNVs) were called in Birdsuite and analyzed in PLINK. We found a set of CNVs present in the suicide attempter group that were not present in in the non-attempter group including in SNTG2 and MACROD2 – two brain expressed genes previously linked to psychopathology; however, these results failed to reach genome-wide signifigance. Conclusions These data suggest potential CNVs to be investigated further in relation to suicide attempts in MD using large sample sizes. PMID:23029476

  11. Molecular basis of major psychiatric diseases such as schizophrenia and depression.

    PubMed

    Tohyama, Masaya; Miyata, Shingo; Hattori, Tsuyoshi; Shimizu, Shoko; Matsuzaki, Shinsuke

    2015-06-01

    Recently several potential susceptibility genes for major psychiatric disorders (schizophrenia and major depression) such as disrupted-in-schizophrenia 1(DISC1), dysbindin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been reported. DISC1 is involved in neural development directly via adhesion molecules or via its binding partners of DISC1 such as elongation protein ζ-1 (FEZ1), DISC1-binding zinc-finger protein (DBZ) and kendrin. PACAP also regulates neural development via stathmin 1 or via regulation of the DISC1-DBZ binding. Dysbindin is also involved in neural development by regulating centrosomal microtubule network formation. All such molecules examined to date are involved in neural development. Thus, these findings provide new molecular insights into the mechanisms of neural development and neuropsychiatric disorders. On the other hand, in addition to neurons, both DISC and DBZ have been detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 inhibits the differentiation of oligodendrocyte precursor cells into oligodendrocytes, while DBZ has a positive regulatory role in oligodendrocyte differentiation. Evidence suggesting that disturbance of oligodendrocyte development causes major depression is also described. PMID:25595671

  12. Predictors of Longitudinal Outcomes after Unstable Response to Acute Phase Cognitive Therapy for Major Depressive Disorder

    PubMed Central

    Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.; Jarrett, Robin B.

    2015-01-01

    After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT (C-CT), double-blinded fluoxetine or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT. PMID:25985046

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

    PubMed Central

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

    2016-01-01

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

  14. Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity

    PubMed Central

    Li, Li; Shelton, Richard Charles; Chassan, Rachel Ann; Hammond, John Charles; Gower, Barbara Ann; Garvey, Timothy W

    2016-01-01

    Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes. PMID:27274905

  15. Microstructural Abnormalities in Subcortical Reward Circuitry of Subjects with Major Depressive Disorder

    PubMed Central

    Blood, Anne J.; Iosifescu, Dan V.; Makris, Nikos; Perlis, Roy H.; Kennedy, David N.; Dougherty, Darin D.; Kim, Byoung Woo; Lee, Myung Joo; Wu, Shirley; Lee, Sang; Calhoun, Jesse; Hodge, Steven M.; Fava, Maurizio; Rosen, Bruce R.; Smoller, Jordan W.; Gasic, Gregory P.; Breiter, Hans C.

    2010-01-01

    Background Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB). Methodology/Principal Findings We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity. Conclusions/Significance These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression. PMID:21124764

  16. Prognostic value of imbalanced interhemispheric functional coordination in early therapeutic efficacy in major depressive disorder.

    PubMed

    Hou, Zhenghua; Song, Xiaopeng; Jiang, Wenhao; Yue, Yingying; Yin, Yingying; Zhang, Yuqun; Liu, Yijun; Yuan, Yonggui

    2016-09-30

    This study aims to explore the early response of antidepressant therapy by measuring the voxel-mirrored homotopic connectivity (VMHC) in major depressive disorder (MDD). Eighty-two MDD patients [n=42 treatment-responsive depression (RD) and n=40 non-responding depression (NRD)] and n=50 normal controls (NC) underwent clinical measures and a magnetic resonance imaging scan, and the VMHC values were calculated. Receiver operating characteristic (ROC) curve analysis was applied to determine the capability of altered VMHC to distinguish NRD. The NRD showed significantly decreased VMHC in bilateral precuneus (PCU) and inferior temporal gyrus (ITG), and increased VMHC in middle frontal gyrus (MFG) and caudate nucleus as compared to RD. When compared with NC, the NRD exhibited reduced VMHC in bilateral cerebellum anterior lobe, thalamus and postcentral gyrus. Moreover, VHMC in medial frontal gyrus, postcentral gyrus and precentral gyrus were significantly decreased in RD. Correlation analysis showed that reduced VMHC in PCU was negatively correlated with the baseline HAMD score of the NRD group. The ROC curve indicated that the combined changes of the three regional VMHC (PCU, ITG and MFG) could effectively identify NRD. The current study suggests that interhemispheric asynchrony may represents a novel neural trait underlying the prediction of early therapeutic outcome in MDD. PMID:27497214

  17. Blood transcriptomic markers for major depression: from animal models to clinical settings.

    PubMed

    Redei, Eva E; Mehta, Neha S

    2015-05-01

    Depression is a heterogeneous disorder and, similar to other spectrum disorders, its manifestation varies by age of onset, severity, comorbidity, treatment responsiveness, and other factors. A laboratory blood test based on specific biomarkers for major depressive disorder (MDD) and its subgroups could increase diagnostic accuracy and expedite the initiation of treatment. We identified candidate blood biomarkers by examining genome-wide expression differences in the blood of animal models representing both the genetic and environmental/stress etiologies of depression. Human orthologs of the resulting transcript panel were tested in pilot studies. Transcript abundance of 11 blood markers differentiated adolescent subjects with early-onset MDD from adolescents with no disorder (ND). A set of partly overlapping transcripts distinguished adolescent patients who had comorbid anxiety disorders from those with only MDD. In adults, blood levels of nine transcripts discerned subjects with MDD from ND controls. Even though cognitive behavioral therapy (CBT) resulted in remission of some patients, the levels of three transcripts consistently signaled prior MDD status. A coexpression network of transcripts seems to predict responsiveness to CBT. Thus, our approach can be developed into clinically valid diagnostic panels of blood transcripts for different manifestations of MDD, potentially reducing diagnostic heterogeneity and advancing individualized treatment strategies. PMID:25823952

  18. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients

    PubMed Central

    Woo, Young Sup; Rosenblat, Joshua D.; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S.

    2016-01-01

    Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. PMID:26792035

  19. Effects of the Serotonin Transporter Polymorphism and History of Major Depression on Overgeneral Autobiographical Memory

    PubMed Central

    Sumner, Jennifer A.; Vrshek-Schallhorn, Suzanne; Mineka, Susan; Zinbarg, Richard E.; Craske, Michelle G.; Redei, Eva E.; Wolitzky-Taylor, Kate; Adam, Emma K.

    2013-01-01

    Overgeneral autobiographical memory (OGM) is a key memory deficit in major depressive disorder (MDD). Much research has examined cognitive mechanisms underlying OGM, but little work has investigated potential neurobiological influences. There is preliminary evidence that a genetic serotonergic vulnerability coupled with depressive symptoms may be associated with other memory impairments, and experimental research suggests a role for serotonin in OGM. We investigated whether a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was associated with OGM in interaction with a lifetime history of MDD in 370 young adults in a longitudinal study of risk for emotional disorders. There was a significant interaction between 5-HTTLPR genotype and lifetime history of MDD in predicting OGM. Among S allele homozygotes, MDD history was associated with greater OGM, whereas no significant relationship between MDD history and OGM emerged among L carriers. Furthermore, there was evidence that a greater number of S alleles was associated with greater memory specificity in individuals without a history of MDD. Implications for understanding cognitive and biological risk for depression are discussed. PMID:24341893

  20. Effects of the serotonin transporter polymorphism and history of major depression on overgeneral autobiographical memory.

    PubMed

    Sumner, Jennifer A; Vrshek-Schallhorn, Suzanne; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G; Redei, Eva E; Wolitzky-Taylor, Kate; Adam, Emma K

    2014-01-01

    Overgeneral autobiographical memory (OGM) is a key memory deficit in major depressive disorder (MDD). Much research has examined cognitive mechanisms underlying OGM, but little work has investigated potential neurobiological influences. There is preliminary evidence that a genetic serotonergic vulnerability coupled with depressive symptoms may be associated with other memory impairments, and experimental research suggests a role for serotonin in OGM. We investigated whether a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was associated with OGM in interaction with a lifetime history of MDD in 370 young adults in a longitudinal study of risk for emotional disorders. There was a significant interaction between 5-HTTLPR genotype and lifetime history of MDD in predicting OGM. Among S allele homozygotes, MDD history was associated with greater OGM, whereas no significant relationship between MDD history and OGM emerged among L carriers. Furthermore, there was evidence that a greater number of S alleles were associated with greater memory specificity in individuals without a history of MDD. Implications for understanding cognitive and biological risk for depression are discussed. PMID:24341893

  1. Neurobiological effects of exercise on major depressive disorder: A systematic review.

    PubMed

    Schuch, Felipe Barreto; Deslandes, Andrea Camaz; Stubbs, Brendon; Gosmann, Natan Pereira; Silva, Cristiano Tschiedel Belem da; Fleck, Marcelo Pio de Almeida

    2016-02-01

    Exercise displays promise as an efficacious treatment for people with depression. However, no systematic review has evaluated the neurobiological effects of exercise among people with major depressive disorder (MDD). The aim of this article was to systematically review the acute and chronic biological responses to exercise in people with MDD. Two authors conducted searches using Medline (PubMed), EMBASE and PsycINFO. From the searches, twenty studies were included within the review, representing 1353 people with MDD. The results demonstrate that a single bout of exercise increases atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), copepetin and growth hormone among people with MDD. Exercise also potentially promotes long-term adaptations of copeptin, thiobarbituric acid reactive species (TBARS) and total mean frequency (TMF). However, there is limited evidence that exercise promotes adaptations on neurogenesis, inflammation biomarkers and brain structure. Associations between depressive symptoms improvement and hippocampus volume and IL-1β were found. Nevertheless, the paucity of studies and limitations presented within, precludes a more definitive conclusion of the underlying neurobiological explanation for the antidepressant effect of exercise in people with MDD. Further trials should utilize appropriate assessments of neurobiological markers in order to build upon the results of our review and further clarify the potential mechanisms associated with the antidepressant effects of exercise. PMID:26657969

  2. Taurine transporter in lymphocytes of patients with major depression treated with venlafaxine plus psychotherapy.

    PubMed

    Fazzino, Fili; Obregón, Francisco; Morles, Margarita; Rojas, Andrés; Arocha, Luis; Mata, Salvador; Lima, Lucimey

    2009-01-01

    The taurine transporter and taurine are present in lymphocytes, where taurine functions as an antioxidant and an anti-inflammatory agent. Taurine levels are elevated in lymphocytes of subjects with major depression, but returns to control levels after treatment with the antidepressant mirtazapine. Patients (40) were diagnosed using the Diagnostic and Statistical Manual IV of the American Psychiatric Association, and the severity of their condition was determined by the Hamilton Scale of Depression. One group of patients was treated with venlafaxine and the other with venlafaxine plus Neuro-Linguistic Programming. Lymphocytes were isolated from the peripheral blood by Ficoll/Hypaque. The coexistence of the taurine transporter with a subpopulation of CD4+ and CD8+ lymphocytes was measured by immunofluorescence. The levels of the pro-inflammatory, IL-2, and the anti-inflammatory, IL-4, cytokines were determined by ELISA while plasma amino acid levels were determined by HPLC. The percentage of CD4+ cells significantly decreased after both treatments, whereas the levels of CD8+ cells remained unchanged. The taurine transporter of CD4+ and CD8+ cells decreased after integrate treatment. No differences were found in the levels of IL-2 while IL-4 levels increased after integrate treatment. The observed effects of treatment on the taurine transporter and IL-4 content might modify lymphocyte activity during depression. PMID:19239152

  3. Genomewide Significant Linkage to Recurrent, Early-Onset Major Depressive Disorder on Chromosome 15q

    PubMed Central

    Holmans, Peter; Zubenko, George S.; Crowe, Raymond R.; DePaulo Jr., J. Raymond; Scheftner, William A.; Weissman, Myrna M.; Zubenko, Wendy N.; Boutelle, Sandra; Murphy-Eberenz, Kathleen; MacKinnon, Dean; McInnis, Melvin G.; Marta, Diana H.; Adams, Philip; Knowles, James A.; Gladis, Madeleine; Thomas, Jo; Chellis, Jennifer; Miller, Erin; Levinson, Douglas F.

    2004-01-01

    A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs (555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers (mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Zlr statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Zlr=4.14, equivalent LOD = 3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD. PMID:15108123

  4. Getting the balance right: Established and emerging therapies for major depressive disorders

    PubMed Central

    Perović, Bojana; Jovanović, Marija; Miljković, Branislava; Vezmar, Sandra

    2010-01-01

    Major depressive disorder (MDD) is a common and serious illness of our times, associated with monoamine deficiency in the brain. Moreover, increased levels of cortisol, possibly caused by stress, may be related to depression. In the treatment of MDD, the use of older antidepressants such as monoamine oxidase inhibitors and tricyclic antidepressants is decreasing rapidly, mainly due to their adverse effect profiles. In contrast, the use of serotonin reuptake inhibitors and newer antidepressants, which have dual modes of action such as inhibition of the serotonin and noradrenaline or dopamine reuptake, is increasing. Novel antidepressants have additive modes of action such as agomelatine, a potent agonist of melatonin receptors. Drugs in development for treatment of MDD include triple reuptake inhibitors, dual-acting serotonin reuptake inhibitors and histamine antagonists, and many more. Newer antidepressants have similar efficacy and in general good tolerability profiles. Nevertheless, compliance with treatment for MDD is poor and may contribute to treatment failure. Despite the broad spectrum of available antidepressants, there are still at least 30% of depressive patients who do not benefit from treatment. Therefore, new approaches in drug development are necessary and, according to current research developments, the future of antidepressant treatment may be promising. PMID:20856599

  5. White Matter Abnormalities in Major Depression: A Tract-Based Spatial Statistics and Rumination Study

    PubMed Central

    Lv, Xueyu; Zhou, Yuan; Hong, Yang; Li, Tao; Tong, Haibing; Wang, Xiaoling; Wang, Weidong; Jiang, Tianzi

    2012-01-01

    Increasing evidence indicates that major depressive disorder (MDD) is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has evaluated the relationship between white matter alterations and the ruminative state. In this study, we first explored the altered white matter using a tract-based spatial statistics (TBSS) method based on diffusion tensor imaging of 19 healthy and 16 depressive subjects. We then investigated correlations between the altered white matter microstructure in the identified altered regions and the severity of ruminations measured by the ruminative response scale. Our results demonstrated altered white matter microstructure in circuits connecting the prefrontal lobe, the parietal lobe and the limbic system (p<0.005, uncorrected), findings which support previous research. More importantly, the result also indicated that a greater alteration in the white matter is associated with a more ruminative state (p<0.05, Bonferroni corrected). The detected abnormalities in the white matter should be interpreted cautiously because of the small sample size in this study. This finding supports the psychometric significance of white matter deficits in MDD. PMID:22666366

  6. Prefrontal cortical response to emotional faces in individuals with major depressive disorder in remission

    PubMed Central

    Kerestes, Rebecca; Bhagwagar, Zubin; Nathan, Pradeep J.; Meda, Shashwath A.; Ladouceur, Cecile D.; Maloney, Kathleen; Matuskey, David; Ruf, Barbara; Saricicek, Aybala; Wang, Fei; Pearlson, Godfrey D.; Phillips, Mary L.; Blumberg, Hilary P.

    2013-01-01

    Abnormalities in the response of the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to negative emotional stimuli have been reported in acutely depressed patients. However, there is a paucity of studies conducted in unmedicated individuals with major depressive disorder in remission (rMDD) to assess whether these are trait abnormalities. To address this issue, 19 medication-free rMDD individuals and 20 healthy comparison (HC) participants were scanned using functional magnetic resonance imaging while performing an implicit emotion processing task in which they labeled the gender of faces depicting negative (fearful), positive (happy) and neutral facial expressions. The rMDD and HC groups were compared using a region-of-interest approach for two contrasts: fear vs. neutral and happy vs. neutral. Relative to HC, rMDD showed reduced activation in left OFC and DLPFC to fearful (vs. neutral) faces. Right DLPFC activation to fearful (vs. neutral) faces in the rMDD group showed a significant positive correlation with duration of euthymia. The findings support deficits in left OFC and DLPFC responses to negative emotional stimuli during euthymic periods of MDD, which may reflect trait markers of the illness or a ‘scar’ due to previous depression. Recovery may also be associated with compensatory increases in right DLPFC functioning. PMID:22595508

  7. Hippocampal Atrophy in Major Depression: a Function of Childhood Maltreatment Rather than Diagnosis?

    PubMed Central

    Opel, Nils; Redlich, Ronny; Zwanzger, Peter; Grotegerd, Dominik; Arolt, Volker; Heindel, Walter; Konrad, Carsten; Kugel, Harald; Dannlowski, Udo

    2014-01-01

    Reduced hippocampal volumes are probably the most frequently reported structural neuroimaging finding associated with major depressive disorder (MDD). However, it remains unclear whether altered hippocampal structure represents a risk factor for or a consequence of MDD. Reduced hippocampal volumes were consistently reported in subjects affected by childhood maltreatment. As the prevalence of childhood maltreatment is highly elevated in MDD populations, previous morphometric findings regarding hippocampal atrophy in MDD therefore might have been confounded by maltreatment experiences. The aim of this study was to differentiate the impact of childhood maltreatment from the influence of MDD diagnosis on hippocampal morphometry. Depressed patients (85) as well as 85 age- and sex-matched healthy controls underwent structural MRI. The Childhood Trauma Questionnaire was administered to estimate experiences of childhood maltreatment. Hippocampal volume and surface structure was examined by the use of two independent methods, automated segmentation (FSL-FIRST) and voxel-based morphometry (VBM8). In line with existing studies, MDD patients showed reduced hippocampal volumes, and childhood maltreatment was consistently associated with hippocampal volume loss in both, patients and healthy controls. However, no analysis revealed significant morphological differences between patients and controls if maltreatment experience was regressed out. Our results suggest that hippocampal alterations in MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients. PMID:24924799

  8. The road not taken: life experiences in monozygotic twin pairs discordant for major depression

    PubMed Central

    Kendler, KS; Halberstadt, LJ

    2012-01-01

    In an effort to understand how environmental experiences contribute to risk for major depression (MD), we conducted joint autobiographical interviews with 14 pairs of monozygotic twins (mean age 51.2) rigorously discordant for a lifetime history of MD. Twelve of the pairs could be sorted into four broad categories. In two pairs, discordance was associated with a single traumatic event occurring to the affected twin. In seven pairs, the well twin had one stable, long-term, successful romantic relationship, whereas the affected co-twin had romantic reversals one or more of which precipitated depressive episodes. These pairs varied in the degree to which the romantic problems seemed to arise from bad luck or poor choices. In one pair, occupational difficulties were strongly related to discordance in experiences with MD. In two pairs, several mechanisms seemed to be at work. Discordance in the quality of intimate love relationships was the most common etiological factor revealed by interview in these discordant pairs, with single dramatic events and occupational problems being considerably rarer. Even in this best of natural experiments, the causal interrelationship between personality, environment and depressive episodes was not always clear. Many pairs illustrated the protective effects of planfulness and the malignant effect of cumulative continuity where early difficulties in relationships shaped the subsequent life course. These results speak both to the importance of environmental influences on human well-being and psychopathology, and the complexity of the causal paths underlying their effects. PMID:22641178

  9. Hippocampal atrophy in major depression: a function of childhood maltreatment rather than diagnosis?

    PubMed

    Opel, Nils; Redlich, Ronny; Zwanzger, Peter; Grotegerd, Dominik; Arolt, Volker; Heindel, Walter; Konrad, Carsten; Kugel, Harald; Dannlowski, Udo

    2014-11-01

    Reduced hippocampal volumes are probably the most frequently reported structural neuroimaging finding associated with major depressive disorder (MDD). However, it remains unclear whether altered hippocampal structure represents a risk factor for or a consequence of MDD. Reduced hippocampal volumes were consistently reported in subjects affected by childhood maltreatment. As the prevalence of childhood maltreatment is highly elevated in MDD populations, previous morphometric findings regarding hippocampal atrophy in MDD therefore might have been confounded by maltreatment experiences. The aim of this study was to differentiate the impact of childhood maltreatment from the influence of MDD diagnosis on hippocampal morphometry. Depressed patients (85) as well as 85 age- and sex-matched healthy controls underwent structural MRI. The Childhood Trauma Questionnaire was administered to estimate experiences of childhood maltreatment. Hippocampal volume and surface structure was examined by the use of two independent methods, automated segmentation (FSL-FIRST) and voxel-based morphometry (VBM8). In line with existing studies, MDD patients showed reduced hippocampal volumes, and childhood maltreatment was consistently associated with hippocampal volume loss in both, patients and healthy controls. However, no analysis revealed significant morphological differences between patients and controls if maltreatment experience was regressed out. Our results suggest that hippocampal alterations in MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients. PMID:24924799

  10. Heart rate variability and treatment outcome in major depression: a pilot study.

    PubMed

    Jain, Felipe A; Cook, Ian A; Leuchter, Andrew F; Hunter, Aimee M; Davydov, Dmitry M; Ottaviani, Cristina; Tartter, Molly; Crump, Caroline; Shapiro, David

    2014-08-01

    Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N=26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N=16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R2>.43 and p<0.05 for both trials). Although vagal parasympathetic measures were correlated with antidepressant treatment outcome, their predictive power was not significant after adjusting for age and gender. In conclusion, baseline resting rVLF was associated with depression treatment outcome in two independent MDD treatment studies. These results should be interpreted with caution due to limited sample size, but a strength of this study is its validation of the rVLF predictor in an independent sample. rVLF merits prospective confirmation as a candidate biomarker. PMID:24769434

  11. Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression.

    PubMed

    Guilloux, Jean-Philippe; Bassi, Sabrina; Ding, Ying; Walsh, Chris; Turecki, Gustavo; Tseng, George; Cyranowski, Jill M; Sibille, Etienne

    2015-02-01

    Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales). PMID:25176167

  12. Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder

    PubMed Central

    Miyata, Shigeo; Kurachi, Masashi; Okano, Yoshiko; Sakurai, Noriko; Kobayashi, Ayumi; Harada, Kenichiro; Yamagata, Hirotaka; Matsuo, Koji; Takahashi, Keisuke; Narita, Kosuke; Fukuda, Masato; Ishizaki, Yasuki; Mikuni, Masahiko

    2016-01-01

    We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD. PMID:26926397

  13. Residual Symptoms Were Differentially Associated with Brain Function in Remitted Patients with Major Depressive Disorders

    PubMed Central

    Masai, Mieko; Pu, Shenghong; Yokoyama, Katsutoshi; Matsumura, Hiroshi; Yamanashi, Takehiko; Itakura, Masashi; Sugie, Takuya; Miura, Akihiko; Nagata, Izumi; Iwata, Masaaki; Kaneko, Koichi

    2016-01-01

    Background The desirable goals of the treatment of major depressive disorder (MDD) are considered both to achieve symptom remission and to help the patients be restored to their premorbid levels of functioning. Remission has often been defined clinically as a threshold using standardized scales. Such a definition, however, allows several residual symptoms to be present in the remitted state. The aim of this study was to examine the relationship between the levels of residual symptoms and social functioning and also the relationship between residual symptoms and brain function. Methods The subjects were 21 patients with MDD in remission, defined operationally using clinician-rated 17-item Hamilton Depression Scale. Depressive symptoms and social functioning were self-assessed with the Japanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D) and the Social Adaptation Self-evaluation Scale (SASS), respectively. Brain function was measured by the changes in concentration of oxy-hemoglobin ([oxy-Hb]) in the prefrontal and temporal cortices during verbal fluency task using near-infrared spectroscopy (NIRS). Results The mean CES-D total score was 18.0, s = 13.2, indicating that they have on average mild depression. Scores of CES-D total and those of its four factors showed a significantly negative correlation with the SASS total score. Among the four factors, “Interpersonal problems” factor showed the strongest correlation with it. CES-D total score and those of its three factors, “Depressed affect”, “Somatic and retarded activity” and “Positive affect”, showed significantly negative correlations with the mean [oxy-Hb] changes mainly in the left hemisphere, whereas “Interpersonal problems” factor showed a significantly positive correlation with the size of NIRS activation predominantly in right prefrontal regions. Conclusion Our results indicate that remitted patients with MDD possibly have residual symptoms which are most

  14. Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression.

    PubMed

    Chhetry, Binod Thapa; Hezghia, Adrienne; Miller, Jeffrey M; Lee, Seonjoo; Rubin-Falcone, Harry; Cooper, Thomas B; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

    2016-04-01

    White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity. PMID:26802812

  15. Lifetime History of Major Depression Predicts the Development of the Metabolic Syndrome in Middle-Aged Women

    PubMed Central

    Goldbacher, Edie M.; Bromberger, Joyce; Matthews, Karen A.

    2010-01-01

    Objective To prospectively examine the association of major depression with incidence of the metabolic syndrome in women. Methods Data were drawn from one of seven sites of the Study of Women’s Health Across the Nation (SWAN), a prospective cohort study of the menopausal transition. Participants were 429 (34.5% African-American) women. Major depression and comorbid diagnoses were assessed via the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders at baseline and seven annual follow-up evaluations. The metabolic syndrome was measured at baseline and each follow-up evaluation (except the second) based on National Cholesterol Education Program (NCEP) criteria. Results Longitudinal generalized estimating equations (GEE) models indicated that, in women who were free of the metabolic syndrome at baseline, a lifetime major depression history or current major depressive episode at baseline was significantly associated with the onset and presence of the metabolic syndrome during the follow-up (odds ratio = 1.82; 95% Confidence Interval (CI) = 1.06–3.14). Survival analyses showed that, in women who were free of the metabolic syndrome at baseline, a lifetime major depression history or current major depressive episode at baseline predicted increased risk of developing the metabolic syndrome during the follow-up (hazard ratio = 1.66; 95% CI = 0.99–3.75). Lifetime history of alcohol abuse or dependence predicted incident metabolic syndrome and attenuated the association between depression and the metabolic syndrome in both models. Conclusions This study documents that major depression is a significant predictor of the onset of the metabolic syndrome. Intervention studies targeting depression may prevent the development of the metabolic syndrome in women. PMID:19188528

  16. Genetic overlap between type 2 diabetes and major depressive disorder identified by bioinformatics analysis

    PubMed Central

    Ji, Hong-Fang; Zhuang, Qi-Shuai; Shen, Liang

    2016-01-01

    Our study investigated the shared genetic etiology underlying type 2 diabetes (T2D) and major depressive disorder (MDD) by analyzing large-scale genome wide association studies statistics. A total of 496 shared SNPs associated with both T2D and MDD were identified at p-value ≤ 1.0E-07. Functional enrichment analysis showed that the enriched pathways pertained to immune responses (Fc gamma R-mediated phagocytosis, T cell and B cell receptors signaling), cell signaling (MAPK, Wnt signaling), lipid metabolism, and cancer associated pathways. The findings will have potential implications for future interventional studies of the two diseases. PMID:27007159

  17. Children's view of a major depression affecting a parent in the family.

    PubMed

    Hedman Ahlström, Britt; Skärsäter, Ingela; Danielson, Ella

    2011-01-01

    This study aims to elucidate, from the children's perspective, the meaning for family life of a parent suffering a major depression disorder. Eight children and young adults were interviewed. Phenomenological-hermeneutic analysis generated two themes: (1) "Being a rescuing observer" with the subthemes, "Being attentive" and "Being considerate," and (2) "Being a frustrated observer" with the subthemes, "feeling discomfort" and "being out of it." Children's lives alternate between responsibility and loneliness as they wait for reciprocity in family life to return to normal. Children need support in order to manage their sense of responsibility and loneliness adequately. PMID:21859406

  18. Major depressive disorder in an adolescent with Turner syndrome: a case report.

    PubMed

    Mao, Shujiong; Sun, Liying; Li, Rong; Zhao, Zhengyan; Yang, Rongwang

    2016-05-01

    Turner syndrome (TS) is a chromosomal abnormality, of which the presence and impact of coexisting psychiatric morbidity has received little attention. The present report describes an adolescent with mosaic karyotype TS who had major depressive disorder with the predisposing cause of psychosocial burden, and relieved with the treatment of sertraline and complete remission with combined use of estradiol valerate. The report suggests us to pay more attention on the mood disorders in children with TS, especially in adolescents. For treatment aspect, medications for improving the puberty development and short stature should be added to in addition to antidepressants if they had mood disorders. PMID:26698832

  19. Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations

    PubMed Central

    Flory, Janine D.; Yehuda, Rachel

    2015-01-01

    Approximately half of people with post-traumatic stress disorder (PTSD) also suffer from Major Depressive Disorder (MDD). The current paper examines evidence for two explanations of this comorbidity. First, that the comorbidity reflects overlapping symptoms in the two disorders. Second, that the co-occurrence of PTSD and MDD is not an artifact, but represents a trauma-related phenotype, possibly a subtype of PTSD. Support for the latter explanation is inferred from literature that examines risk and biological correlates of PTSD and MDD, including molecular processes. Treatment implications of the comorbidity are considered. PMID:26246789

  20. Transcranial direct current stimulation for the treatment of major depressive disorder: a summary of preclinical, clinical and translational findings.

    PubMed

    Brunoni, Andre Russowsky; Ferrucci, Roberta; Fregni, Felipe; Boggio, Paulo Sergio; Priori, Alberto

    2012-10-01

    Major depressive disorder (MDD) is a common psychiatric illness, with 6-12% lifetime prevalence. It is also among the five most disabling diseases worldwide. Current pharmacological treatments, although relatively effective, present important side effects that lead to treatment discontinuation. Therefore, novel treatment options for MDD are needed. Here, we discuss the recent advancements of one new neuromodulatory technique--transcranial direct current stimulation (tDCS)--that has undergone intensive research over the past decade with promising results. tDCS is based on the application of weak, direct electric current over the scalp, leading to cortical hypo- or hyper-polarization according to the specified parameters. Recent studies have shown that tDCS is able to induce potent changes in cortical excitability as well as to elicit long-lasting changes in brain activity. Moreover, tDCS is a technique with a low rate of reported side effects, relatively easy to apply and less expensive than other neuromodulatory techniques--appealing characteristics for clinical use. In the past years, 4 of 6 phase II clinical trials and one recent meta-analysis have shown positive results in ameliorating depression symptoms. tDCS has some interesting, unique aspects such as noninvasiveness and low rate of adverse effects, being a putative substitutive/augmentative agent for antidepressant drugs, and low-cost and portability, making it suitable for use in clinical practice. Still, further phase II and phase III trials are needed as to better clarify tDCS role in the therapeutic arsenal of MDD. PMID:22651961

  1. Sociodemographic Correlates of Unipolar Major Depression among the Chinese Elderly in Klang Valley, Malaysia: An Epidemiological Study

    PubMed Central

    Verma, Rohit Kumar; Chakravarthy, Srikumar; Barua, Ankur

    2014-01-01

    Background. Depression, as one of the most disabling diseases around the world, had caught the global concern with its rising prevalence rate. There is a growing need of detecting depression, particularly in the old age population which is often left being overlooked. Methods. We conducted a cross-sectional community-based study which included 150 Chinese elderly aged 60 and above within Klang Valley area. We obtained the sociodemographic profiles and assessed the status of well-being, depression, and cognitive function of the participants with the help of instruments: WHO Five-Item Well-Being Index, Major (ICD-10) Depression Inventory, and 6-Item Cognitive Impairment Test. Results. We found that the prevalence of depression among the Chinese elderly within Klang Valley region was 10.7%. With multiple logistic regression, decision to consult doctor on depressed mood or memory problem and presence of cognitive impairment were shown to be significantly associated with unipolar major depression, whereas wellbeing status was also found to be statistically correlated with depression in univariate analysis. Conclusion. The prevalence of unipolar depression among Chinese elderly within Klang Valley, Malaysia presented that there was an increased trend compared to the previous studies. PMID:25544962

  2. Rare Copy Number Variation in Treatment-Resistant Major Depressive Disorder

    PubMed Central

    O’Dushlaine, Colm; Ripke, Stephan; Ruderfer, Douglas M.; Hamilton, Steven P.; Fava, Maurizio; Iosifescu, Dan V.; Kohane, Isaac S.; Churchill, Susanne E.; Castro, Victor M.; Clements, Caitlin C.; Blumenthal, Sarah R.; Murphy, Shawn N.; Smoller, Jordan W.; Perlis, Roy H.

    2014-01-01

    Background While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD). Methods We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial. Results CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100–200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction. Conclusions Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects. PMID:24529801

  3. Anxiety, depression and quality of life in patients with beta thalassemia major and their caregivers

    PubMed Central

    Yengil, Erhan; Acipayam, Can; Kokacya, Mehmet Hanifi; Kurhan, Faruk; Oktay, Gonul; Ozer, Cahit

    2014-01-01

    Mental health and health related quality of life is commonly affected in patients with chronic problems and their caregivers. In the present study, it was aimed to assess depression and anxiety in patients with beta thalassemia major (BTM) and in their caregivers; and to evaluate effects of these disorders on quality of life. The study was carried out in a district Hereditary Hemoglobinopathy Center and included 88 patients with BTM and 63 of their caregivers. All subjects were assessed using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Short Form-36 (SF-36) by a trained psychiatry resident via face-to-face interview. The BDI scores were 17 or above in 20.5% of the patients with BTM and 28.6% of their caregivers (P = 0.248). Of the patients with BTM, there were mild anxiety symptoms in 19.3%, while moderate and severe anxiety symptoms in 14.8% and 4.5%, respectively. Anxiety levels were similar between the patients with BTM and their caregivers (P = 0.878). It was found that BDI and BAI scores were negatively correlated to scores of physical health and mental health components of SF-36 in patients with BTM and their caregivers. In linear regression analysis, it was seen that depression affected physical and mental health of the patients with BTM and their caregivers regardless from anxiety. BTM leads an increase in the frequency of depression and anxiety in both patients and their caregivers, and affects negatively physical and mental components of quality of life. PMID:25232402

  4. Type-D Personality Can Predict Suicidality in Patients with Major Depressive Disorder

    PubMed Central

    Ko, Young-Hoon; Lee, Moon-Soo; Lee, Heon-Jeong; Kim, Leen

    2014-01-01

    Objective This study investigated the putative association between type-D personality and suicidality, including the history of suicide attempt and suicidal ideation in patients with major depressive disorder (MDD). Methods Eighty-six outpatients aged between 18 and 65 years with MDD were recruited for this study from Ilsan Paik Hospital. The cohort was stratified into two subgroups according to the presence of type-D personality and history of suicide attempt (yes vs. no). Depression severity was evaluated using the Hamilton Depression Rating Scale. The type-D Personality Scale-14 (DS-14), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Hamilton Anxiety Scale, and the Beck Scale for Suicidal Ideation (BSS) were also applied. Results The total BSS, BHS, and BIS scores were higher for the group with type-D personality than for the group without this personality (p=0.004, 0.01, and 0.003, respectively). In addition, the total scores for the BSS, BHS, and social inhibition (SI; subscale of DS-14) were higher for the group with a history of suicide attempt than for the group without this history (p=0.0000004, 0.003, and 0.033, respectively). There were positive correlations between the total DS-14 score and the total BSS, BHS, and BIS scores (r=0.413 and p=0.000077, r=0.404 and p=0.00012, and r=0.245 and p=0.024, respectively). Conclusion Depressed patients with type-D personality are more vulnerable to suicidality than those without type-D personality, even when the MDD severity is identical. In addition, the SI score was higher in patients with a history of suicide attempt than in those without this history. PMID:25110494

  5. Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder

    PubMed Central

    Leuchter, Andrew F.; Hunter, Aimee M.; Krantz, David E.; Cook, Ian A.

    2014-01-01

    Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness. PMID:25733956

  6. Antidepressant Response in Patients With Major Depression Exposed to NSAIDs: A Pharmacovigilance Study

    PubMed Central

    Gallagher, Patience J.; Castro, Victor; Fava, Maurizio; Weilburg, Jeffrey B.; Murphy, Shawn N.; Gainer, Vivian S.; Churchill, Susanne E.; Kohane, Isaac S.; Iosifescu, Dan V.; Smoller, Jordan W.; Perlis, Roy H.

    2013-01-01

    Objective It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system. Method Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed. Results NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21–2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables. Conclusions These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding. PMID:23032386

  7. Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder.

    PubMed

    Leuchter, Andrew F; Hunter, Aimee M; Krantz, David E; Cook, Ian A

    2014-12-01

    Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiolog