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  1. 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…

  2. 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.

  3. Major depression

    MedlinePlus

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

  4. 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, ...

  5. Major depressive disorder.

    PubMed

    Otte, Christian; Gold, Stefan M; Penninx, Brenda W; Pariante, Carmine M; Etkin, Amit; Fava, Maurizio; Mohr, David C; Schatzberg, Alan F

    2016-01-01

    Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multifactorial and its heritability is estimated to be approximately 35%. In addition, environmental factors, such as sexual, physical or emotional abuse during childhood, are strongly associated with the risk of developing MDD. No established mechanism can explain all aspects of the disease. However, MDD is associated with alterations in regional brain volumes, particularly the hippocampus, and with functional changes in brain circuits, such as the cognitive control network and the affective-salience network. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Management primarily comprises psychotherapy and pharmacological treatment. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. In this Primer, we provide an overview of the current evidence of MDD, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment. PMID:27629598

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

    PubMed

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

    2010-01-15

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

  7. [MAJOR DEPRESSION AND PERSONALIZED MEDICINE].

    PubMed

    Pitchot, W

    2015-01-01

    Depression is a major public health problem. According to the World Health Organization (OMS), depression is currently the second cause of disability in developing countries. Depression is also one of the most frequent mental illnesses. When treating depression, the main objective is to achieve complete remission and to prevent recurrence. Unfor-tunately, in clinical practice, this aim is particularly difficult to reach. Indeed, in clinical trials and in naturalistic studies, remission levels are rather low. The challenge is to individualize the treatment of depression taking account clinical specificities, but also advances in the field of biological and genetic research. Today, intense psychiatric research tries to discover biomarkers to predict treatment response. Because individuals are highly different from a biological, psychological and sociological point of view, more personalized therapeutic approaches are recommended. PMID:26285462

  8. Anomia in major depressive state.

    PubMed

    Georgieff, N; Dominey, P F; Michel, F; Marie-Cardine, M; Dalery, J

    1998-02-27

    Anomia, or word finding difficulty, is a frequent clinical symptom of the depressive state. This study investigates naming and lexicalization processes (or word production processes) in 11 depressive patients (major depressive state), through a picture naming task of 53 images corresponding to low frequency words. Depressives showed significantly more anomia and made more naming errors (semantically related substitution words) than control subjects. Tip-of-the-tongue (TOT) states, which correspond to an impairment at a later stage of phonological encoding with partial activation of phonological shape, remained rare in depressives despite the increase of lexicalization difficulties observed. Anomia observed in depressives could thus be related to an impairment at the early stage of lexicalization or word production processes (pre-phonological item selection and access, or storage of the semantic lexical item in Working Memory for further phonological encoding), without lexical-semantic disorganization. We discuss the relationship between such an elementary speech production disorder and cognitive impairments demonstrated in the depressive state (deficit of effortful and attentional processes, impairment in activation or initiation of cognitive processes and responses).

  9. 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…

  10. Emerging antidepressants to treat major depressive disorder.

    PubMed

    Block, Samantha G; Nemeroff, Charles B

    2014-12-01

    Depression is a common disorder with an annual risk of a depressive episode in the United States of 6.6%. Only 30-40% of patients remit with antidepressant monotherapy, leaving 60-70% of patients who do not optimally respond to therapy. Unremitted depressive patients are at increased risk for suicide. Considering the prevalence of treatment resistant depression and its consequences, treatment optimization is imperative. This review summarizes the latest treatment modalities for major depressive disorder including pharmacotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation and psychotherapy. Through advancements in research to better understand the pathophysiology of depression, advances in treatment will be realized.

  11. 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.

  12. The relationship of major depressive disorder to bipolar disorder: continuous or discontinuous?

    PubMed

    Benazzi, Franco

    2005-12-01

    Recent studies have questioned current diagnostic systems that split mood disorders into the independent categories of bipolar disorders and depressive disorders. The current classification of mood disorders runs against Kraepelin's unitary view of manic-depressive insanity (illness). The main findings of recent studies supporting a continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder are presented. The features supporting a continuity between bipolar II disorder and major depressive disorder currently are 1) depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support a splitting of mood disorders); 2) family history (major depressive disorder is the most common mood disorder in relatives of bipolar probands); 3) lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; 4) major depressive disorder with bipolar features such as depressive mixed states, young onset age, atypical features, bipolar family history, irritability, racing thoughts, and psychomotor agitation; 5) a high proportion of major depressive disorders shifting to bipolar disorders during long-term follow-up; 6) a high proportion of major depressive disorders with history of manic and hypomanic symptoms; 7) factors of hypomania present in major depressive disorder episodes; 8) recurrent course of major depressive disorder; and 9) depressive symptoms much more common than manic and hypomanic symptoms in the course of bipolar disorders.

  13. Hippocampal atrophy in recurrent major depression.

    PubMed Central

    Sheline, Y I; Wang, P W; Gado, M H; Csernansky, J G; Vannier, M W

    1996-01-01

    Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter > or = 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity. Images Fig. 1 Fig. 4 PMID:8632988

  14. 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…

  15. 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

  16. Depressive rumination alters cortisol decline in Major Depressive Disorder.

    PubMed

    LeMoult, Joelle; Joormann, Jutta

    2014-07-01

    Depressive rumination - a central characteristic of Major Depressive Disorder (MDD) - is a maladaptive emotion regulation strategy that prolongs sad mood and depressive episodes. Considerable research demonstrates the emotional and behavioral consequences of depressive rumination, yet few studies investigate its effect on neuroendocrine functioning. The current study examined the effect of an emotion regulation manipulation on the trajectory of cortisol concentrations among individuals with MDD and healthy controls (CTL). Sadness was induced via forced failure. Participants then were randomly assigned to a depressive rumination or distraction emotion regulation induction. MDDs in the rumination condition exhibited less cortisol decline compared to MDDs in the distraction condition and compared to CTLs in either condition. Findings suggest that depressive rumination alters the trajectory of cortisol secretion in MDD and may prolong cortisol production. Results thereby provide important insights into the interaction of biological and psychological factors through which distress contributes to MDD.

  17. Major depression: behavioral parameters of depression and recovery.

    PubMed

    Schelde, J T

    1998-03-01

    This paper reports on an ethological study of 11 depressed hospitalized subjects. Major depression and recovery are described in terms of general behavioral traits, i.e., behavior parameters. The hypothesis, that the primary behavioral feature of major depression is a reduction of social interaction and that secondary features are reduced self occupation and body mobility (posture flexibility) is tested. The behavioral patterns of depression and recovery are described and elucidated by 12 defined behavioral parameters, eight of which show significant changes between the first and the last hospital week. Findings from six of the parameters are consistent with the hypothesis and demonstrate social inhibition during depression; interactions between depression and nonverbal behavior are particularly striking. Findings also confirm that, during depression, self occupation and body mobility are reduced to a less significant degree than social inhibition. Possible relationships between findings and agitated forms of major depression are discussed. A final section examines findings in an evolutionary context and emphasizes their clinical implications. PMID:9521349

  18. 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…

  19. 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 ...

  20. 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.

  1. Advances in psychiatric epidemiology: rates and risks for major depression.

    PubMed Central

    Weissman, M M

    1987-01-01

    Over the last decade there has been a marked increase in information on the epidemiology of psychiatric disorders, particularly major depression, in adults living in the community and in families. The ability to conduct large epidemiologic studies of psychiatric disorders is due to improvements in diagnostic precision and reliability in psychiatry and to the development of systematic methods for collecting information on signs and symptoms to make diagnoses. Results from a recently completed epidemiologic survey of psychiatric disorders in five urban communities in the United States and from several large-scale family genetic studies suggest that major depression is a highly prevalent disorder. It occurs in adults and children, and there is evidence for an increased rate in younger people. The average age of first onset is in young adulthood. Most depressions are untreated. The firm risk factors for major depression include being female; young (born after World War II); separated/divorced or in an unhappy marriage; and having a family history of major depression. There is a two-to-threefold increased risk for major depression if there is a family history of the disorder. The relevance of these findings to clinical practice and public health is discussed. PMID:3826462

  2. Zebrafish models of major depressive disorders.

    PubMed

    Fonseka, Trehani M; Wen, Xiao-Yan; Foster, Jane A; Kennedy, Sidney H

    2016-01-01

    The zebrafish (Danio rerio) has emerged as a model species for translational research in various neuroscience areas, including depressive disorders. Because of their physiological (neuroanatomical, neuroendocrine, neurochemical) and genetic homology to mammals, robust phenotypes, and value in high-throughput genetic and chemical genetic screens, zebrafish are ideal for developing valid experimental models of major depression and discovering novel therapeutics. Behavioral testing approaches, such as approach-avoidance, cognitive, and social paradigms, are available in zebrafish and have utility in identifying depression-like indices in zebrafish in response to physiological, genetic, environmental, and/or psychopharmacological alterations. In addition, the high sensitivity of zebrafish to commonly prescribed psychotropic drugs supports the use of this model as an invaluable tool for pharmacological research and drug screening. This Review outlines the benefits of using the zebrafish model for depression studies and summarizes the current research in this field.

  3. Serum proteomic profiling of major depressive disorder

    PubMed Central

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

    2015-01-01

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

  4. Assessment of depression in medical patients: A systematic review of the utility of the Beck Depression Inventory-II

    PubMed Central

    Wang, Yuan-Pang; Gorenstein, Clarice

    2013-01-01

    To perform a systematic review of the utility of the Beck Depression Inventory for detecting depression in medical settings, this article focuses on the revised version of the scale (Beck Depression Inventory-II), which was reformulated according to the DSM-IV criteria for major depression. We examined relevant investigations with the Beck Depression Inventory-II for measuring depression in medical settings to provide guidelines for practicing clinicians. Considering the inclusion and exclusion criteria seventy articles were retained. Validation studies of the Beck Depression Inventory-II, in both primary care and hospital settings, were found for clinics of cardiology, neurology, obstetrics, brain injury, nephrology, chronic pain, chronic fatigue, oncology, and infectious disease. The Beck Depression Inventory-II showed high reliability and good correlation with measures of depression and anxiety. Its threshold for detecting depression varied according to the type of patients, suggesting the need for adjusted cut-off points. The somatic and cognitive-affective dimension described the latent structure of the instrument. The Beck Depression Inventory-II can be easily adapted in most clinical conditions for detecting major depression and recommending an appropriate intervention. Although this scale represents a sound path for detecting depression in patients with medical conditions, the clinician should seek evidence for how to interpret the score before using the Beck Depression Inventory-II to make clinical decisions. PMID:24141845

  5. Effects of mirtazapine on sleep polygraphic variables in major depression.

    PubMed

    Schittecatte, Michel; Dumont, Françoise; Machowski, Robert; Cornil, Catherine; Lavergne, Francis; Wilmotte, Jean

    2002-01-01

    Mirtazapine, a noradrenergic and specific serotonergic antidepressant(NaSSA), was administered on a flexible schedule in a sample of 17 drug-free patients meeting DSM-IV criteria for a major depressive episode. Sleep polygraphic recordings were performed before and during acute and chronic treatment. Severity of depression and subjective assessment of changes within different aspects of sleep were also evaluated. During the acute administration (first 2 days), mirtazapine significantly increased total sleep time, sleep efficiency, stage II, stage rapid eye movement and slow-wave sleep percentages, and decreased sleep latency and stage awake percentage. These effects persisted after 5 weeks of treatment. Subjectively, mirtazapine induced an improvement of sleep. This open, noncontrolled study suggests that mirtazapine ameliorates the sleep disturbances encountered in depressed patients both objectively and subjectively. PMID:12566938

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Current Issues in the Classification of Psychotic Major Depression

    PubMed Central

    Keller, Jennifer; Schatzberg, Alan F.; Maj, Mario

    2007-01-01

    Depression is one of the most common mental disorders worldwide. There are a number of depression subtypes, and there has been much debate about how to most accurately capture and organize the features and subtypes of major depression. We review the current state of categorizing unipolar major depression with psychotic features (psychotic major depression, PMD), including clinical, biological, and treatment aspects of the disorder. We then propose some improvements to the current unipolar major depression categorization system. Finally, we identify important issues in need of further research to help elucidate the subtype of unipolar PMD. PMID:17548842

  13. Cortical thickness differences between bipolar depression and major depressive disorder

    PubMed Central

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

    2014-01-01

    Objectives Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to differentiate BD and MDD could help clinicians avoid risks of treating BD with antidepressants without mood stabilizers. Methods Cortical thickness differences were assessed using magnetic resonance imaging in BD depressed patients (n = 18), MDD depressed patients (n = 56), and healthy volunteers (HVs) (n = 54). A general linear model identified clusters of cortical thickness difference between diagnostic groups. Results Compared to the HV group, the BD group had decreased cortical thickness in six regions, after controlling for age and sex, located within frontal and parietal lobes, and posterior cingulate cortex. Mean cortical thickness changes in clusters ranged from 7.6–9.6% (cluster wise p-values from 1.0 e−4 to 0.037). When compared to MDD, three clusters of lower cortical thickness in BD were identified that overlapped with clusters that differentiated the BD and HV groups. Mean cortical thickness changes in the clusters ranged from 7.5–8.2% (cluster wise p-values from 1.0 e−4 to 0.023). The difference in cortical thickness was more pronounced when the subgroup of subjects with bipolar I disorder (BD-I) was compared to the MDD group. Conclusions Cortical thickness patterns were distinct between BD and MDD. These results are a step toward developing an imaging test to differentiate the two disorders. PMID:24428430

  14. Desvenlafaxine succinate for major depressive disorder.

    PubMed

    Sproule, Beth A; Hazra, Monica; Pollock, Bruce G

    2008-07-01

    Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of venlafaxine. Desvenlafaxine succinate is now undergoing active evaluation for its therapeutic efficacy in a variety of disorders, including major depressive disorder, vasomotor symptoms associated with menopause, fibromyalgia and diabetic neuropathy. Desvenlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with similar activity to its parent compound venlafaxine, and little affinity for other brain targets, including muscarinic, cholinergic, histamine H(1) and alpha-adrenergic receptors. Desvenlafaxine has linear pharmacokinetics, low protein binding, a half-life of approximately 10 hours and is metabolized primarily via glucuronidation, and to a minor extent through CYP3A4. The desvenlafaxine succinate formulation appears to have good oral bioavailability. Clearance rates are reduced in the elderly, those with severe renal dysfunction and those with moderate to severe hepatic dysfunction, which may require dosage adjustments. Three published clinical trials have shown supportive but mixed results for the efficacy of desvenlafaxine in the treatment of major depressive disorder with daily doses ranging from 100 mg to 400 mg. One published clinical trial has shown mixed results for the efficacy of desvenlafaxine in the treatment of vasomotor symptoms associated with menopause with daily doses ranging from 50 mg to 200 mg. In these four clinical trials, desvenlafaxine was associated with several mild adverse effects, with the most common effect being nausea. Less common, but more serious, adverse effects reported in these trials included hypertension, QTc interval prolongation, exacerbation of ischemic cardiac disease, elevated lipids and elevated liver enzymes. The exact nature of these serious adverse effects, including the prevalence, clinical significance and potential risk factors, still needs to be fully elucidated. Desvenlafaxine has a low propensity for pharmacokinetic

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Hippocampal neuroplasticity in major depressive disorder.

    PubMed

    Malykhin, N V; Coupland, N J

    2015-11-19

    One of the most replicated findings has been that hippocampus volume is decreased in patients with major depressive disorder (MDD). Recent volumetric magnetic resonance imaging (MRI) studies suggest that localized differences in hippocampal volume may be more prominent than global differences. Preclinical and post-mortem studies in MDD indicated that different subfields of the hippocampus may respond differently to stress and may also have differential levels of plasticity in response to antidepressant treatment. Advances in high-field MRI allowed researchers to visualize and measure hippocampal subfield volumes in MDD patients in vivo. The results of these studies provide the first in vivo evidence that hippocampal volume reductions in MDD are specific to the cornu ammonis and dentate gyrus hippocampal subfields, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. In this review we discuss how recent advances in neuroimaging allow researchers to further understand hippocampal neuroplasticity in MDD and how it is related to antidepressant treatment, memory function, and disease progression.

  3. 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

  4. 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.

  5. 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…

  6. 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.

  7. 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

  8. Development and validation of the current concept of major depression.

    PubMed

    Maj, Mario

    2012-01-01

    The operational diagnostic criteria for major depression have remained more or less the same in the past 40 years. However, the threshold for the diagnosis fixed by operational definitions has been criticized for either being too high, excluding many depressive states which do not differ from currently defined major depression on several variables, or too low, so that the milder cases receiving the diagnosis do not respond to antidepressants better than to placebo. Furthermore, it has been stated that current operational criteria do not convey anymore the gestalt of the depressive syndrome, and that they lead to the inclusion under the heading of depression of several homeostatic responses to adverse life events. This paper reviews the development and validation of the current concept of major depression and identifies priorities for future research. PMID:22399134

  9. Social functioning in major depressive disorder.

    PubMed

    Kupferberg, Aleksandra; Bicks, Lucy; Hasler, Gregor

    2016-10-01

    Depression is associated with social risk factors, social impairments and poor social functioning. This paper gives an overview of these social aspects using the NIMH Research and Domain Criteria 'Systems for Social Processes' as a framework. In particular, it describes the bio-psycho-social interplay regarding impaired affiliation and attachment (social anhedonia, hyper-sensitivity to social rejection, competition avoidance, increased altruistic punishment), impaired social communication (impaired emotion recognition, diminished cooperativeness), impaired social perception (reduced empathy, theory-of-mind deficits) and their impact on social networks and the use of social media. It describes these dysfunctional social processes at the behavioural, neuroanatomical, neurochemical and genetic levels, and with respect to animal models of social stress. We discuss the diagnostic specificity of these social deficit constructs for depression and in relation to depression severity. Since social factors are importantly involved in the pathogenesis and the consequences of depression, such research will likely contribute to better diagnostic assessments and concepts, treatments and preventative strategies both at the diagnostic and transdiagnostic level. PMID:27395342

  10. Current understanding of the neurobiology of major depressive disorder.

    PubMed

    Chiriţă, Anca Livia; Gheorman, Victor; Bondari, Dan; Rogoveanu, Ion

    2015-01-01

    Depression is highly prevalent worldwide and associated with significant morbidity and mortality. Approximately 340 million people worldwide suffer from depression at any given time. Based on estimates from the World Health Organization (WHO), depression is responsible for the greatest proportion of burden associated with non-fatal health outcomes and accounts for approximately 12% total years lived with disability. Probably no single risk factor can be completely isolated in major depressive disorder (MDD), as interactions between many sources of vulnerability are the most likely explanation. Buttressing the identification of grief, demoralization, hopelessness and styles of psychological coping of the depressed patient are vital, ongoing scientific developments that flow from an increased understanding of this interplay amongst the immune system, endocrine system and brain. The rapidly accumulating body of neurobiological knowledge has catalyzed fundamental changes in how we conceptualize depressive symptoms and has important implications regarding the treatment and even prevention of depressive symptoms in patients.

  11. An IRT Analysis of the Symptoms of Major Depressive Disorder.

    PubMed

    Emmert-Aronson, Benjamin O; Brown, Timothy A

    2015-06-01

    This study examines the psychometric properties of a major depressive episode using a large sample (N = 2,907) of outpatients with mood and anxiety disorders. A two-parameter logistic model yielded item threshold and discrimination parameters. A two-group confirmatory factor analysis was used to evaluate gender bias. Item thresholds fell along a continuum with the core features of depressed mood and anhedonia, along with fatigue, endorsed at lower levels of depression, and change in appetite and suicidal ideation endorsed at more severe levels. Item discriminations were highest for depressed mood and anhedonia, and lowest for change in appetite and suicidal ideation. The data indicate that the symptoms of depression assess a range of severity, with varying precision in discriminating depression. No gender differences were observed. Three exploratory symptom sets were compared with the full symptom set for depression, offering quantitative evidence that can be used to modify the psychiatric classification system.

  12. 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

  13. 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

  14. 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

  15. Subcortical volumes differentiate Major Depressive Disorder, Bipolar Disorder, and remitted Major Depressive Disorder.

    PubMed

    Sacchet, Matthew D; Livermore, Emily E; Iglesias, Juan Eugenio; Glover, Gary H; Gotlib, Ian H

    2015-09-01

    Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps < 0.005). SVM distinguished MDD from BD with 59.5% accuracy. These findings indicate that mood disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.

  16. 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.

  17. 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

  18. 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

  19. Major depressive disorder in the African American population.

    PubMed

    Bailey, Rahn K; Patel, Milapkumar; Barker, Narviar C; Ali, Shahid; Jabeen, Shagufta

    2011-07-01

    Depression is a common mental disorder that presents with depressed mood. It can become chronic or recurrent and lead to substantial impairment in an individual's ability to function. At this level, it is identified as major depressive disorder (MDD). Depression and MDD occur across all racial and ethnic groups. Although many depressed patients are treated in primary care, depression in these settings has been underdetected and undertreated. African Americans, especially, who suffer from depression are frequently underdiagnosed and inadequately managed in primary care due to patient, physician, and treatment setting factors. Patient factors include being poor, uninsured, restrictive insurance policies, biological-genetic vulnerability, nonresponsiveness to traditional pharmacological interventions, and stigma (i.e., attitudes and perceptions of mental illness). Physician factors include diagnosis and assessment, physician characteristics, physician bias, and culture; and treatment setting factors include systemic variables such as lack of or poor access to health care, racism, environment, and patient management. African Americans are less likely to receive proper diagnosis and treatment, more likely to have depression for long periods of time, and more likely to suffer greater disability from depression. Understanding patient, physician, and treatment setting factors as contributing barriers that impede effective diagnosis and treatment of depression and MDD in African Americans is critical to effective patient management and discovery. Greater African American participation in clinical research trials also is needed to effectively improve, diagnose, and treat depression in African Americans. This article examines depression among African Americans in the context of gender, culture, and psychosocial determinants, and their engagement in clinical trials.

  20. 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

  1. 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

  2. Sleep-disordered breathing in major depressive disorder.

    PubMed

    Cheng, Philip; D Casement, Melynda; Chen, Chiau-Fang; Hoffmann, Robert F; Armitage, Roseanne; Deldin, Patricia J

    2013-08-01

    Individuals with major depressive disorder often experience obstructive sleep apnea. However, the relationship between depression and less severe sleep-disordered breathing is unclear. This study examined the rate of sleep-disordered breathing in depression after excluding those who had clinically significant sleep apnea (>5 apneas∙h⁻¹). Archival data collected between 1991 and 2005 were used to assess the prevalence of sleep-disordered breathing events in 60 (31 depressed; 29 healthy controls) unmedicated participants. Respiratory events were automatically detected using a program developed in-house measuring thermal nasal air-flow and chest pressure. Results show that even after excluding participants with clinically significant sleep-disordered breathing, individuals with depression continue to exhibit higher rates of sleep-disordered breathing compared with healthy controls (depressed group: apnea-hypopnea index mean = 0.524, SE = 0.105; healthy group: apnea-hypopnea index mean = 0.179, SE = 0.108). Exploratory analyses were also conducted to assess for rates of exclusion in depression studies due to sleep-disordered breathing. Study exclusion of sleep-disordered breathing was quantified based on self-report during telephone screening, and via first night polysomnography. Results from phone screening data reveal that individuals reporting depression were 5.86 times more likely to report a diagnosis of obstructive sleep apnea than presumptive control participants. Furthermore, all of the participants excluded for severe sleep-disordered breathing detected on the first night were participants with depression. These findings illustrate the importance of understanding the relationship between sleep-disordered breathing and depression, and suggest that screening and quantification of sleep-disordered breathing should be considered in depression research.

  3. 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

  4. 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.

  5. 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

  6. A controlled trial of amitriptyline and cianopramine in major depression.

    PubMed

    Mellsop, G W; Burgess, C D; Vijayasenan, M E

    1985-01-01

    The therapeutic efficacy and adverse effects of amitriptyline and cianopramine were compared in a double-blind, randomized, flexible-dose trial in 40 patients with major depressive episodes. The two drugs were equally effective in reducing scores on the Hamilton Psychiatric Rating Scale for Depression and on a global scale. Both drugs were associated with significant adverse effects. Fewer adverse effects were associated with cianopramine, however, which lacks antimuscarinic activity.

  7. 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

  8. Major depression induces oxidative stress and platelet hyperaggregability.

    PubMed

    Ormonde do Carmo, Monique B O; Mendes-Ribeiro, Antônio Cláudio; Matsuura, Cristiane; Pinto, Vivian L; Mury, Wanda V; Pinto, Nathalia O; Moss, Monique B; Ferraz, Marcos Rochedo; Brunini, Tatiana M C

    2015-02-01

    We have previously demonstrated an impairment of intraplatelet L-arginine-nitric oxide-cGMP pathway in major depression (MD) associated to platelet dysfunction. Here, we evaluated arginase pathway and phosphodiesterase 5 (PDE5) expression in platelets, systemic and intraplatelet oxidative status in untreated MD patients, and their effects on platelet aggregation. Blood samples were collected from 22 treatment naive MD patients (31 ± 2 yr) and 27 healthy subjects (33 ± 2 yr). MD patients presented with an activation of platelet arginase II, which competes with L-arginine for the production of nitric oxide (NO). An increase in protein carbonylation, overexpression of NADPH oxidase and PDE5, an enzyme that inactivates cGMP, was observed in platelets from MD patients compared to controls. In this context, platelet hyperaggregability was found in MD patients. On the other hand, antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase activities in serum and in platelets did not differ between groups. The increased activation of intraplatelet arginase and platelet aggregability, in addition to an overexpression of PDE5 and oxidative stress may contribute to alterations in L-arginine-NO-cGMP pathway and in platelet function, and consequently to the increased thrombotic risk in MD. PMID:25560770

  9. [Gap junctions: A new therapeutic target in major depressive disorder?].

    PubMed

    Sarrouilhe, D; Dejean, C

    2015-11-01

    Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder.

  10. 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…

  11. 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

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

    PubMed

    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

  13. Vilazodone in the treatment of major depressive disorder: efficacy across symptoms and severity of depression.

    PubMed

    Khan, Arif; Sambunaris, Angelo; Edwards, John; Ruth, Adam; Robinson, Donald S

    2014-03-01

    Vilazodone is a potent selective serotonin reuptake inhibitor and serotonin 1A receptor partial agonist approved for the treatment of major depressive disorder in adults. To assess the efficacy of vilazodone across a range of symptoms and severities of depression, data from two phase III, 8-week, randomized, double-blind, placebo-controlled trials were pooled for analysis. Overall improvement in depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Depression Rating Scale was statistically significant (P<0.05) for vilazodone treatment compared with placebo as early as Week 1 and continued throughout double-blind treatment. Vilazodone treatment compared with placebo showed significant improvement on all 10 individual MADRS symptom items at end of treatment (P<0.01). Rates of response and remission were significantly greater in the vilazodone group relative to the placebo group, with numbers needed to treat ranging from eight to nine for response and 12-17 for remission. Between-group treatment differences in MADRS and the other outcome measures were similar among all depression subgroups, with no consistent pattern associated with depression severity. These findings support the efficacy of vilazodone across a broad range of depressive symptoms and severities for the treatment of major depressive disorder.

  14. Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder.

    PubMed

    Berent, Dominika; Zboralski, Krzysztof; Orzechowska, Agata; Gałecki, Piotr

    2014-01-01

    The clinical implications of thyroid hormones in depression have been studied extensively and still remains disputable. Supplementation of thyroid hormones is considered to augment and accelerate antidepressant treatment. Studies on the role of thyroid hormones in depression deliver contradictory results. Here we assess theirs impact on depression severity and final clinical outcome in patients with major depression. Thyrotropin, free thyroxine (FT4), and free triiodothyronine (FT3) concentrations were measured with automated quantitative enzyme immunoassay. Depression severity and final clinical outcome were rated with 17-itemic Hamilton Rating Scale for Depression [HDRS(17)] and Clinical Global Impression Scales for severity and for improvement (CGIs, CGIi). FT3 and FT4 concentrations were significantly positively correlated with clinical improvement evaluated with CGIi (R = 0.38, P = 0.012; R = 0.33, P = 0.034, respectively). There was a significant correlation between FT4 concentrations and depression severity assessed in HDRS(17) (R = 0.31, P = 0.047). Male patients presented significantly higher FT3 serum levels (Z = 2.34, P = 0.018) and significantly greater clinical improvement (Z = 2.36, P = 0.018) when compared to female patients. We conclude that free thyroid hormones concentrations are associated with depression severity and have an impact on final clinical outcome. It can be more efficient to augment and accelerate the treatment of major depressive disorder with triiodothyronine instead of levothyroxine because of individual differences in thyroid hormones metabolism.

  15. Integrated management of major depression for people with cancer.

    PubMed

    Walker, Jane; Sharpe, Michael

    2014-12-01

    Major depression is an important complication of cancer. However, it is frequently inadequately treated. There are challenges both in identifying which cancer patients are depressed, and in ensuring that these patients receive effective treatment for their depression. Integration of depression management into cancer care has been advocated as a way to address these challenges. Such integrated approaches must include both the systematic identification of cases and the delivery of treatment. We describe here a system of depression care that includes both a screening programme to identify patients with depression and a linked treatment programme, based on the collaborative care model, called 'Depression Care for People with Cancer' (DCPC). The system of care was designed to be fully integrated with specialist cancer services and has been robustly evaluated in randomized trials. We describe how the system operates and explain why it is designed as it is. We also summarize the evidence for its effectiveness and cost-effectiveness and discuss its implementation in routine clinical practice.

  16. 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

  17. 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.

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. Fluvoxamine treatment of major depression associated with multiple sclerosis.

    PubMed

    Benedetti, Francesco; Campori, Euridice; Colombo, Cristina; Smeraldi, Enrico

    2004-01-01

    Fluvoxamine 200 mg was administered for 3 months to a group of 43 interferon beta-1b treated patients affected by major depression associated with multiple sclerosis. Despite a 16.3% attrition rate, 79% of patients achieved response. The drug was well tolerated.

  3. 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…

  4. 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

  5. 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

  6. 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…

  7. 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

  8. 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.

  9. 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

  10. 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

  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. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. [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

  19. 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

  20. Novel glutamatergic agents for major depressive disorder and bipolar disorder

    PubMed Central

    Machado-Vieira, Rodrigo; Ibrahim, Lobna; Henter, Ioline D.; Zarate, Carlos A.

    2011-01-01

    Mood disorders such as major depressive disorder (MDD) and bipolar disorder (BPD) are common, chronic, recurrent mental illnesses that affect the lives and functioning of millions of individuals worldwide. Growing evidence suggests that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of mood disorders as well as the efficacy of glutamatergic agents as novel therapeutics. PMID:21971560

  1. [THE THERAPUETIC USE OF TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION].

    PubMed

    Németh, Viola Luca; Csifcsák, Gábor; Kincses, Zsigmond Tamás; Janka, Zoltán; Must, Anita

    2016-03-30

    The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention. PMID:27188001

  2. 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

  3. 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

  4. 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

  5. Cognitive estimation in aged patients with major depressive disorder.

    PubMed

    Barabassy, Agota; Beinhoff, Ulrike; Riepe, Matthias W

    2010-03-30

    In everyday life, we often estimate rather than know. It was the goal of this study to assess the effect of depressed mood on cognitive estimation in old age. Cognitive estimation was performed in 44 subjects with major depressive disorder (MDD; DSM-IV) and 48 age-matched healthy subjects (HS). Severity of depressive symptoms was rated with the Montgomery-Asberg Depression Rating Scale (MADRS, mean=18.6+/-S.D. 4.85). Estimation tasks comprised the dimensions length (coin diameter), weight (pile of paper), quantity (number of marbles in a glass jar), and time (estimation of time it takes for a marble to roll down a marble track both before and after having observed it). Other than the procedure followed in previous tests on cognitive estimation, the tasks were performed by observing objects rather than pictures thereof. MDD patients overestimated time (before and after observation) and underestimated quantity. Cognitive estimation was not correlated to measures of frontal functioning or semantic knowledge. We conclude that MDD patients in old age are impaired to some extent in cognitive estimation and in the ability to correct themselves, deficits that are likely to affect the performance of everyday activities. PMID:20064666

  6. Hypothalamic-pituitary-gonadal axis in major depressive disorders.

    PubMed

    Undén, F; Ljunggren, J G; Beck-Friis, J; Kjellman, B F; Wetterberg, L

    1988-08-01

    The baseline LH, FSH and testosterone levels and the LH and FSH response to TRH-LHRH administration (delta LH, delta FSH) were investigated in 28 patients meeting the RDC criteria for an acute major depressive disorder, and in 20 healthy persons. Twenty-two patients were also reinvestigated in a state of complete or partial clinical remission. Cross-sectional and longitudinal comparisons were made between the groups divided according to sex and menopausal status. After mathematical correction for age differences, the depressed males with an abnormal DST response showed significantly (P less than 0.03) higher delta FSH in the acute state compared to the controls. No relation could be established between the HPG axis hormone levels and the nocturnal serum melatonin levels or the PRL or TSH response to TRH-LHRH administration. In the longitudinal part of the study, the depressed males with an abnormal DST response showed decreased (P less than 0.03) testosterone levels and increased delta FSH (n.s.) in the acute state compared to remission, in contrast to the males with a normal DST. The present results do not support a hypothesis regarding a stimulus-induced down-regulation of the pituitary LHRH receptors in our patients. The possible mechanisms by which HPA axis activation (as revealed by an abnormal DST response) could influence the HPG axis in depressed patients remain to be elucidated.

  7. Brain membrane lipids in major depression and anxiety disorders.

    PubMed

    Müller, Christian P; Reichel, Martin; Mühle, Christiane; Rhein, Cosima; Gulbins, Erich; Kornhuber, Johannes

    2015-08-01

    Major depression and anxiety disorders have high prevalence rates and are frequently comorbid. The neurobiological bases for these disorders are not fully understood, and available treatments are not always effective. Current models assume that dysfunctions in neuronal proteins and peptide activities are the primary causes of these disorders. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic throughput in neurons. Lipids may also leave the membrane as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Here we review how membrane lipids, which play roles in the membrane's function as a barrier and a signaling medium for classical transmitter signaling, contribute to depression and anxiety disorders and how this role may provide targets for lipid-based treatment approaches. Preclinical findings have suggested a crucial role for the membrane-forming n-3 polyunsaturated fatty acids, glycerolipids, glycerophospholipids, and sphingolipids in the induction of depression- and anxiety-related behaviors. These polyunsaturated fatty acids also offer new treatment options such as targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes. While clinical trials support this view, effective lipid-based therapies may need more individualized approaches. Altogether, accumulating evidence suggests a crucial role for membrane lipids in the pathogenesis of depression and anxiety disorders; these lipids could be exploited for improved prevention and treatment. This article is part of a Special Issue entitled Brain Lipids.

  8. 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

  9. 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

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

    PubMed

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

    2012-04-30

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

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

    PubMed

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

    2014-06-10

    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.

  12. 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.

  13. Evaluation of periodontitis in hospital outpatients with major depressive disorder

    PubMed Central

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

    2013-01-01

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

  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. 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.

  16. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression.

    PubMed

    Slavich, George M; Irwin, Michael R

    2014-05-01

    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.

  17. 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

  18. Moclobemide, imipramine and placebo in the treatment of major depression.

    PubMed

    Versiani, M; Nardi, A E; Mundim, F D; Alves, A; Schmid-Burgk, W

    1990-01-01

    Moclobemide was compared with imipramine and placebo in the treatment of major depressive episodes in 75 outpatients. The dosage of moclobemide (25 patients) was 300 mg daily for the first 5 days, after which it could be increased to 600 mg. Imipramine (25 patients) was given in a dosage starting with 33 mg and gradually increased to 100 mg/day in the first 5 days, after which it could be further increased; 25 patients received placebo. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression, the overall assessment of efficacy and the Zung Self-rating Scale, and clearly superior to placebo; there were no significant differences between the 2 active drugs. Moclobemide was better tolerated than imipramine, and was almost comparable to placebo in this respect.

  19. A critical review of pharmacotherapy for major depressive disorder.

    PubMed

    Dupuy, Jamie M; Ostacher, Michael J; Huffman, Jeffrey; Perlis, Roy H; Nierenberg, Andrew A

    2011-11-01

    Newer generation antidepressant drugs, with improvements in safety and tolerability, have replaced tricyclic antidepressants as first-line treatment of depressive illness. However, no single antidepressant drug from any class has distinguished itself as the obvious first-line treatment of major depression. The choice of therapy is driven primarily by patient choice, with informed consent for the risks of adverse effects. Cost has become an additional factor in this decision as several of the newer antidepressant drugs are now available in generic form. Several augmentation and drug-switching strategies have demonstrated benefit in refractory illness. While no single strategy distinguished itself as superior to the others, some have been more rigorously tested. Ongoing efforts at improving effectiveness, time to response, and tolerability have led to novel drug therapies. Efforts at characterizing predictors of treatment outcomes now include pharmacogenetic studies.

  20. Associations between chronotype, sleep quality, suicidality, and depressive symptoms in patients with major depression and healthy controls.

    PubMed

    Selvi, Yavuz; Aydin, Adem; Boysan, Murat; Atli, Abdullah; Agargun, Mehmed Yucel; Besiroglu, Lutfullah

    2010-10-01

    Research interest concerning associations between sleep characteristics and suicidality in psychopathology has been growing. However, possible linkages of suicidality to sleep characteristics in terms of sleep quality and chronotypes among depressive patients have not been well documented. In the current study, the authors investigated the possible effects of sleep quality and chronotype on the severity of depressive symptoms and suicide risk in patients with depressive disorder and healthy controls. The study was conducted on 80 patients clinically diagnosed with major depression and 80 healthy subjects who were demographically matched with the patient group. All participants completed a questionnaire package containing self-report measures, including the Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), Morningness-Eveningness Questionnaire (MEQ), and Suicide Ideation Scale (SIS), and subjects were interviewed with the suicidality section of the Mini-International Neuropsychiatric Interview (MINI). Results are as follows: (a) logistic regression analyses revealed that poor sleep quality and depression symptom severity significantly predicted onset of major depression; (b) morningness-type circadian rhythm may play as a significant relief factor after onset of major depression; (c) sleep variables of chronotype and sleep quality did not significantly predict suicide ideation after controlling for depressive symptoms in the major depression group; and (d) suicide ideation and poor sleep quality were antecedents of depression symptom severity in patients with major depression, and in healthy controls. Findings are discussed under the theoretical assumptions concerning possible relations between chronotype, sleep quality, depression, and suicidality. PMID:20969525

  1. 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

  2. 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

  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. Major depression during interferon-α treatment: vulnerability and prevention

    PubMed Central

    Lotrich, Francis E.

    2009-01-01

    Major Depressive Disorder (MDD) during interferons (IFN-α) treatment can occur within a few months of therapy, and shares many homologies with other forms of MDD, Most patients are resilient to the side effect ofinterferon-induced depression (IFN-MDD), but 15% to 40% are vulnerable. Several studies have employed antidepressants to prevent the incidence of an IFN-MDD episode, and the results suggest that prophylactic antidepressants may be specifically useful in those with pre-existing subthreshold depressive symptoms andlor a history of prior MDD episodes. Several other potential markers of vulnerability for IFN-MDD have been implicated in assessments of nondepressed patients before they start IFN-α These include poor sleep quality, premorbid elevations in inflammatory cytokines, genetic polymorphisms in the serotonin system, personality, and social support. The interplay of these factors strongly predicts who is at risk for IFN-MDD, and indicates several potentially modifiable targets for the personalized prevention of IFN-MDD, PMID:20135899

  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. Antidepressants in type II versus type I bipolar depression: A randomized discontinuation trial

    PubMed Central

    Vöhringer, Paul A.; Ostacher, Michael J.; El-Mallakh, Rif S.; Holtzman, Niki S.; Thommi, Sairah B.; Whitham, Elizabeth A.; Sullivan, Matthew C.; Baldassano, Claudia F.; Goodwin, Fredrick K.; Baldessarini, Ross J.; Ghaemi, S. Nassir

    2015-01-01

    Background We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among type-II over type-I bipolar disorder (BD) patients. Methods DSM-IV BD-I (n=21) and -II patients (n=49) in acute major depressive episodes were treated with ADs plus mood-stabilizers to euthymia sustained for two months, and then randomized openly to continue or discontinue ADs for up to three years. Outcomes were episode-recurrences and changes in standardized symptom-ratings. Results In follow-up averaging 1.64±0.98 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in type I than in type II bipolar depression (for type II, mean decrease in depressive episodes per year 0.21 ± 0.26 [CI:0.05, 0.37]; for type I: mean decrease 0.35 ± 0.15 [CI:0.30, 0.41]). Type II subjects continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than BD-I subjects. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission. Conclusions The findings do not confirm the hypothesis that long-term AD treatment in BP-II has better outcomes than in BD-I patients, except somewhat lower risk of manic/hypomanic episodes. PMID:26267418

  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. Modelling cognitive affective biases in major depressive disorder using rodents

    PubMed Central

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

    2014-01-01

    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. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24467454

  9. Italian neurologists' perception on cognitive symptoms in major depressive disorder.

    PubMed

    Neri, G; Serrati, C; Zolo, P; Cataldo, N; Ripellino, C

    2016-09-01

    The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians' perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists' perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists' socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients' functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists' perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.

  10. 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

  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. Effectiveness of Meta-Cognitive and Cognitive-Behavioral Therapy in Patients with Major Depressive Disorder

    PubMed Central

    Ashouri, Ahmad; Atef Vahid, Mohammad Kazem; Gharaee, Banafsheh; Rasoulian, Maryam

    2013-01-01

    Objective: The present study aimed to compare the effectiveness of metacognitive therapy (MCT) and cognitive-behavior therapy (CBT) in treating Iranian patients with major depressive disorder (MDD). Methods: Thirty three outpatients meeting DSM-IV-TR criteria for MDD without any other axis I and II disorders were randomly assigned to one of three treatment conditions, i.e. MCT, CBT and pharmacotherapy. The Beck Depression Inventory-II-Second Edition (BDI-II), Beck Anxiety Inventory (BAI), Ruminative Response Scale (RRS) and Dysfunctional Attitude Scale (DAS) were administered for pre-treatment, post-treatment and follow-up. Data were analyzed by repeated measures analysis of variance (ANOVA). Results: Based on repeated measures ANOVA, all the participants demonstrated improvement in depression, anxiety, dysfunctional attitude and ruminative response. Based on percentage results, all the patients in MCT and CBT groups showed significant improvement at post-treatment phase. Conclusions: MCT and CBT were more effective than pharmacotherapy alone In treatment of MDD. Declaration of interest: None. PMID:24644507

  13. 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,…

  14. 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

  15. 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

  16. Factor analysis of the Zung self-rating depression scale in a large sample of patients with major depressive disorder in primary care

    PubMed Central

    Romera, Irene; Delgado-Cohen, Helena; Perez, Teresa; Caballero, Luis; Gilaberte, Immaculada

    2008-01-01

    Background The aim of this study was to examine the symptomatic dimensions of depression in a large sample of patients with major depressive disorder (MDD) in the primary care (PC) setting by means of a factor analysis of the Zung self-rating depression scale (ZSDS). Methods A factor analysis was performed, based on the polychoric correlations matrix, between ZSDS items using promax oblique rotation in 1049 PC patients with a diagnosis of MDD (DSM-IV). Results A clinical interpretable four-factor solution consisting of a core depressive factor (I); a cognitive factor (II); an anxiety factor (III) and a somatic factor (IV) was extracted. These factors accounted for 36.9% of the variance on the ZSDS. The 4-factor structure was validated and high coefficients of congruence were obtained (0.98, 0.95, 0.92 and 0.87 for factors I, II, III and IV, respectively). The model seemed to fit the data well with fit indexes within recommended ranges (GFI = 0.9330, AGFI = 0.9112 and RMR = 0.0843). Conclusion Our findings suggest that depressive symptoms in patients with MDD in the PC setting cluster into four dimensions: core depressive, cognitive, anxiety and somatic, by means of a factor analysis of the ZSDS. Further research is needed to identify possible diagnostic, therapeutic or prognostic implications of the different depressive symptomatic profiles. PMID:18194524

  17. Personality traits in the differentiation of major depressive disorder and bipolar disorder during a depressive episode.

    PubMed

    Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos

    2016-02-28

    The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD.

  18. 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.

  19. Severity of depressive symptoms and accuracy of dietary reporting among obese women with major depressive disorder seeking weight loss treatment.

    PubMed

    Whited, Matthew C; Schneider, Kristin L; Appelhans, Bradley M; Ma, Yunsheng; Waring, Molly E; DeBiasse, Michele A; Busch, Andrew M; Oleski, Jessica L; Merriam, Philip A; Olendzki, Barbara C; Crawford, Sybil L; Ockene, Ira S; Lemon, Stephenie C; Pagoto, Sherry L

    2014-01-01

    An elevation in symptoms of depression has previously been associated with greater accuracy of reported dietary intake, however this association has not been investigated among individuals with a diagnosis of major depressive disorder. The purpose of this study was to investigate reporting accuracy of dietary intake among a group of women with major depressive disorder in order to determine if reporting accuracy is similarly associated with depressive symptoms among depressed women. Reporting accuracy of dietary intake was calculated based on three 24-hour phone-delivered dietary recalls from the baseline phase of a randomized trial of weight loss treatment for 161 obese women with major depressive disorder. Regression models indicated that higher severity of depressive symptoms was associated with greater reporting accuracy, even when controlling for other factors traditionally associated with reporting accuracy (coefficient  =  0.01 95% CI = 0.01 - 0.02). Seventeen percent of the sample was classified as low energy reporters. Reporting accuracy of dietary intake increases along with depressive symptoms, even among individuals with major depressive disorder. These results suggest that any study investigating associations between diet quality and depression should also include an index of reporting accuracy of dietary intake as accuracy varies with the severity of depressive symptoms.

  20. Augmentation treatment in major depressive disorder: focus on aripiprazole

    PubMed Central

    Nelson, J Craig; Pikalov, Andrei; Berman, Robert M

    2008-01-01

    Major depressive disorder (MDD) is a disabling psychiatric condition for which effective treatment remains an outstanding need. Antidepressants are currently the mainstay of treatment for depression; however, almost two-thirds of patients will fail to achieve remission with initial treatment. As a result, a range of augmentation and combination strategies have been used in order to improve outcomes for patients. Despite the popularity of these approaches, limited data from double-blind, randomized, placebo-controlled studies are available to allow clinicians to determine which are the most effective augmentation options or which patients are most likely to respond to which options. Recently, evidence has shown that adjunctive therapy with atypical antipsychotics has the potential for beneficial antidepressant effects in the absence of psychotic symptoms. In particular, aripiprazole has shown efficacy as an augmentation option with standard antidepressant therapy in two, large, randomized, double-blind studies. Based on these efficacy and safety data, aripiprazole was recently approved by the FDA as adjunctive therapy for MDD. The availability of this new treatment option should allow more patients with MDD to achieve remission and, ultimately, long-term, successful outcomes. PMID:19183784

  1. 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

  2. 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

  3. Intimate partner violence against adult women and its association with major depressive disorder, depressive symptoms and postpartum depression: a systematic review and meta-analysis.

    PubMed

    Beydoun, Hind A; Beydoun, May A; Kaufman, Jay S; Lo, Bruce; Zonderman, Alan B

    2012-09-01

    To date, few systematic reviews of observational studies have been conducted to comprehensively evaluate the co-morbidity of intimate partner violence (IPV) and specific depression outcomes in women. In this systematic review and meta-analysis, we summarize the extant literature and estimate the magnitude of the association between IPV and key depressive outcomes (elevated depressive symptoms, diagnosed major depressive disorder and postpartum depression). PubMed (January 1, 1980-December 31, 2010) searches of English-language observational studies were conducted. Most of the selected 37 studies had cross-sectional population-based designs, focused on elevated depressive symptoms and were conducted in the United States. Most studies suggested moderate or strong positive associations between IPV and depression. Our meta-analysis suggested two to three-fold increased risk of major depressive disorder and 1.5-2-fold increased risk of elevated depressive symptoms and postpartum depression among women exposed to intimate partner violence relative to non-exposed women. A sizable proportion (9%-28%) of major depressive disorder, elevated depressive symptoms, and postpartum depression can be attributed to lifetime exposure to IPV. In an effort to reduce the burden of depression, continued research is recommended for evaluating IPV preventive strategies.

  4. Gene-environment interactions in major depressive disorder.

    PubMed

    Klengel, Torsten; Binder, Elisabeth B

    2013-02-01

    Family, twin, and epidemiologic studies have suggested that both genes and environment are important risk factors for the development of major depressive disorder (MDD). In the absence of consistent and strong main genetic effects, numerous studies have supported gene-environment interactions in this disorder. While the impact of negative environmental factors, such as early life stress, traumatic experiences, and negative life events have been established as risk factors, they are not sufficient to predict MDD. This article will review evidence suggesting that genetic variants moderate the effects of adversities on the development of MDD, with a focus on the importance of careful characterization of the stressful life events as well as systemic and molecular mechanisms that potentially mediate these gene-environment interactions.

  5. 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).

  6. Molecular, Functional, and Structural Imaging of Major Depressive Disorder.

    PubMed

    Zhang, Kai; Zhu, Yunqi; Zhu, Yuankai; Wu, Shuang; Liu, Hao; Zhang, Wei; Xu, Caiyun; Zhang, Hong; Hayashi, Takuya; Tian, Mei

    2016-06-01

    Major depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD. PMID:27142698

  7. Desvenlafaxine succinate for the treatment of major depressive disorder.

    PubMed

    Lohoff, Falk W; Rickels, Karl

    2008-08-01

    Major depressive disorder (MDD) remains one of the most common psychiatric disorders with high morbidity and mortality. Effective treatment is limited and response/remission to antidepressant pharmacotherapy remains poor and unpredictable. The development of new antidepressants is thus of great importance to the field. Desvenlafaxine succinate (DVS) is the active metabolite of the serotonin and noradrenaline re-uptake inhibitor venlafaxine and was recently FDA approved for the treatment of MDD. DVS showed efficacy in clinical trials in MDD with doses ranging from 50 - 400 mg. Advantages compared to other antidepressants include once daily dosing at effective doses, no CYP450 metabolism and low drug-drug interactions. Concerns include side effect profile and moderate efficacy. DVS might be a useful addition to the arsenal of antidepressants available to the clinician. Additional studies, in particular head-to-head comparison to other antidepressants and long-term treatment studies, will be necessary to comprehensively evaluate DVS safety and efficacy for clinical practice.

  8. Characteristics of Depression as Assessed by the Diagnostic Assessment for the Severely Handicapped-II (DASH-II).

    ERIC Educational Resources Information Center

    Matson, Johnny L.; Rush, Karena S.; Hamilton, Martha; Anderson, Stephen J.; Bamburg, Jay W.; Baglio, Christopher S.; Kirkpatrick-Sanchez, Sharon; Williams, Don

    1999-01-01

    Fifty-seven individuals with severe mental retardation, including 18 with a diagnosis of depression, 19 with autism and 20 without emotional disorders, tested the validity of the Diagnostic Assessment for the Severely Handicapped II (DASH-II) depression subscale. Results found DASH-II to be a valid indicator of depression. (CR)

  9. 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

  10. 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 ...

  11. 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…

  12. Bias to negative emotions: a depression state-dependent marker in adolescent major depressive disorder.

    PubMed

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

    2012-06-30

    The aim of the current research was to examine for the first time the extent to which bias to negative emotions in an inhibitory control paradigm is a state or trait marker in major depressive disorder (MDD) in adolescents. We administered the affective go/no go task which measures the ability to switch attention to or away from positive or negative emotional stimuli to 40 adolescents with MDD (20 in acute episode (MDDa) and 20 in remission (MDDr)) and 17 healthy controls (HC). MDDa were significantly faster on the shift to negative target blocks as compared to shift to positive target blocks while HC and MDDr displayed the opposite pattern as measured by an "emotional bias index" (EBI=latency (shift to negative targets)-latency (shift to positive targets)). There was also a trend for an effect of group on commission errors, suggesting more impulsive responding by MDDa than both MDDr and HC independently of stimulus valence throughout the task. Negative bias was not associated with depression severity or medication status. In conclusion, bias to negative emotional stimuli appears to be present in the acute stage of MDD and absent in remission suggesting that it is a depression state-specific marker of MDD in adolescents. Latency emerges as a better proxy of negative bias than commission errors and accuracy on this inhibitory control task in adolescents with MDD.

  13. 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

  14. Tianeptine in combination with monoamine oxidase inhibitors for major depressive disorder.

    PubMed

    Tobe, Edward H

    2012-10-09

    Major depressive disorder may respond to monotherapy with monoamine oxidase inhibitors (MAOIs) or tianeptine. Literature search showed no reports of MAOIs combined with tianeptine. The method included was clinical case history. A 59-year-old woman had partial improvement of depression with the MAOI tranylcypromine combined with topiramate, trazodone and ziprasidone. The patient had further improvement of depression symptoms after addition of tianeptine. No adverse events were evident. The combination of MAIOs and tianeptine may be effective for refractory major depressive disorder.

  15. 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.

  16. 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

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

    PubMed Central

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

    2010-01-01

    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 was 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 evidence

  18. 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

  19. 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

  20. 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

  1. Abnormal temporal difference reward-learning signals in major depression.

    PubMed

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

    2008-08-01

    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 function in antidepressant unresponsive MDD. There is compelling evidence that dopamine neurons code a specific phasic (short duration) reward-learning signal, described by temporal difference (TD) theory. There is no current evidence for other neurons coding a TD reward-learning signal, although such evidence may be found in time. The neuronal substrates of the TD signal were not explored in this study. Phasic signals are believed to have quite different properties to tonic (long duration) signals. No studies have investigated phasic reward-learning signals in MDD. Therefore, adults with MDD receiving long-term antidepressant medication, and comparison controls both unmedicated and acutely medicated with the antidepressant citalopram, were scanned using fMRI during a reward-learning task. Three hypotheses were tested: first, patients with MDD have blunted TD reward-learning signals; second, controls given an antidepressant acutely have blunted TD reward-learning signals; third, the extent of alteration in TD signals in major depression correlates with illness severity ratings. The results supported the hypotheses. Patients with MDD had significantly reduced reward-learning signals in many non-brainstem regions: ventral striatum (VS), rostral and dorsal anterior cingulate, retrosplenial cortex (RC), midbrain and hippocampus. However, the TD signal was increased in the brainstem of patients. As predicted, acute antidepressant administration to controls was associated with a blunted TD signal, and the brainstem TD signal was not increased by acute citalopram administration. In a number of regions, the magnitude of the abnormal

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

    PubMed

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

    2016-06-14

    Although monozygotic (MZ) twins share the majority of their genetic makeup, they can be phenotypically discordant on several traits and diseases. DNA methylation is an epigenetic mechanism that can be influenced by genetic, environmental and stochastic events and may have an important impact on individual variability. In this study we explored epigenetic differences in peripheral blood samples in three MZ twin studies on major depressive disorder (MDD). Epigenetic data for twin pairs were collected as part of a previous study using 8.1-K-CpG microarrays tagging DNA modification in white blood cells from MZ twins discordant for MDD. Data originated from three geographical regions: UK, Australia and the Netherlands. Ninety-seven MZ pairs (194 individuals) discordant for MDD were included. Different methods to address non independently-and-identically distributed (non-i.i.d.) data were evaluated. Machine-learning methods with feature selection centered on support vector machine and random forest were used to build a classifier to predict cases and controls based on epivariations. The most informative variants were mapped to genes and carried forward for network analysis. A mixture approach using principal component analysis (PCA) and Bayes methods allowed to combine the three studies and to leverage the increased predictive power provided by the larger sample. A machine-learning algorithm with feature reduction classified affected from non-affected twins above chance levels in an independent training-testing design. Network analysis revealed gene networks centered on the PPAR-γ (NR1C3) and C-MYC gene hubs interacting through the AP-1 (c-Jun) transcription factor. PPAR-γ (NR1C3) is a drug target for pioglitazone, which has been shown to reduce depression symptoms in patients with MDD. Using a data-driven approach we were able to overcome challenges of non-i.i.d. data when combining epigenetic studies from MZ twins discordant for MDD. Individually, the studies yielded

  3. Abnormal temporal difference reward-learning signals in major depression.

    PubMed

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

    2008-08-01

    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 function in antidepressant unresponsive MDD. There is compelling evidence that dopamine neurons code a specific phasic (short duration) reward-learning signal, described by temporal difference (TD) theory. There is no current evidence for other neurons coding a TD reward-learning signal, although such evidence may be found in time. The neuronal substrates of the TD signal were not explored in this study. Phasic signals are believed to have quite different properties to tonic (long duration) signals. No studies have investigated phasic reward-learning signals in MDD. Therefore, adults with MDD receiving long-term antidepressant medication, and comparison controls both unmedicated and acutely medicated with the antidepressant citalopram, were scanned using fMRI during a reward-learning task. Three hypotheses were tested: first, patients with MDD have blunted TD reward-learning signals; second, controls given an antidepressant acutely have blunted TD reward-learning signals; third, the extent of alteration in TD signals in major depression correlates with illness severity ratings. The results supported the hypotheses. Patients with MDD had significantly reduced reward-learning signals in many non-brainstem regions: ventral striatum (VS), rostral and dorsal anterior cingulate, retrosplenial cortex (RC), midbrain and hippocampus. However, the TD signal was increased in the brainstem of patients. As predicted, acute antidepressant administration to controls was associated with a blunted TD signal, and the brainstem TD signal was not increased by acute citalopram administration. In a number of regions, the magnitude of the abnormal

  4. Recollection deficiencies in patients with major depressive disorder.

    PubMed

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

    2010-02-28

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

  5. The Beck Depression Inventory Second Edition (BDI-II): psychometric properties in Icelandic student and patient populations.

    PubMed

    Arnarson, Thornorethur Orn; Olason, Daníel Thorn; Smári, Jakob; Sigurethsson, Jón Friethrik

    2008-01-01

    The Beck Depression Inventory (BDI) is one of the most widely used self-report measures of depression in both research and clinical practice. The Beck Depression Inventory Second Edition (BDI-II) is the most recent version of the BDI. The objective of the present study was to assess the psychometric foundations of the Icelandic translation of the BDI-II, adding to its international knowledge base. Participants were in total 1454, 1206 students and 248 outpatient-clinic patients. All students completed the BDI-II and a subgroup (n=142) completed additional measures of anxiety and depression. The Mini-International Psychiatric Interview (MINI) and the BDI-II were administrated to the patients. Convergent and divergent validity of the BDI-II were supported. It discriminated satisfactorily between patients diagnosed and those not diagnosed with major depression. Confirmatory factor analyses revealed small differences between various factor models of the BDI-II, derived from previous studies. However, a model of three first-order factors (cognitive-affective-somatic) and one second-order factor (general depression) offered an acceptable description of the item covariance structure for the BDI-II in both samples. It is concluded that the psychometric properties of the Icelandic version of the BDI-II are supported in patient and student populations. PMID:18752106

  6. The predictive value of somatic and cognitive depressive symptoms for cytokine changes in patients with major depression

    PubMed Central

    Dannehl, Katharina; Rief, Winfried; Schwarz, Markus J; Hennings, Annika; Riemer, Sabine; Selberdinger, Verena; Stapf, Theresa; Euteneuer, Frank

    2014-01-01

    Context Elevated concentrations of proinflammatory cytokines have been hypothesized as an important factor in the pathophysiology of depression. Depression itself is considered to be a heterogeneous disorder. Current findings suggest that “cognitive” and “somatic” symptom dimensions are related to immune function in different ways. So far, little research has been done on the longitudinal aspects of inflammation in patients with major depression, especially with respect to different symptom dimensions of depression. Therefore, we investigated which aspects of depression may predict changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 over 4 weeks. Methods Forty-one patients with major depression diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and 45 healthy controls were enrolled. Serum measurements of TNF-alpha and IL-6 were conducted at baseline and 4 weeks later. Psychometric measures included the assessment of cognitive-affective depressive symptoms and somatic symptoms during the last 7 days as well as somatic symptoms during the last 2 years. Results Patients with depression showed increased levels of TNF-alpha (P<0.05) compared to healthy controls. Hierarchical regression analyses indicated that neither depressive nor somatic symptoms predict changes in proinflammatory cytokines in the whole sample of depressed patients. Moderation analyses and subsequent sex-stratified regression analyses indicated that higher somatoform symptoms during the last 2 years significantly predict an increase in TNF-alpha in women with major depression (P<0.05) but not in men. Exploratory analyses indicated that the stability of TNF-alpha and IL-6 (as indicated by intraclass correlation coefficients) over 4 weeks was high for TNF-alpha but lower for IL-6. Conclusion The present study demonstrated that a history of somatoform symptoms may be important for predicting future changes in TNF

  7. Depressive symptoms and major depressive disorder in patients affected by subclinical hypothyroidism: a cross-sectional study.

    PubMed

    Demartini, Benedetta; Ranieri, Rebecca; Masu, Annamaria; Selle, Valerio; Scarone, Silvio; Gambini, Orsola

    2014-08-01

    The relationship between subclinical hypothyroidism and depression is still controversial. Our objective was to compare the prevalence of depressive symptoms and major depressive disorder in a population of patients affected by subclinical hypothyroidism and a control group without thyroid disease. The authors enrolled 123 consecutive outpatients affected by subclinical hypothyroidism undergoing follow-up at the endocrinology department of San Paolo Hospital in Milan and 123 controls without thyroid disease under the charge of general physicians.All patients and controls underwent an evaluation by means of a psychiatric interview; Hamilton Rating Scale for Depression (HAM-D); Montgomery-Asberg Depression Rating Scale (MADRS); and serum thyroid stimulating hormone, free T4, and free T3 levels. Patients were also screened for thyroid peroxidase antibodies and thyroglobulin antibodies. Patients affected by subclinical hypothyroidism had a prevalence of depressive symptoms of 63.4% at HAM-D and 64.2% at MADRS; 22 patients (17.9%) had a diagnosis of depressive episode (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria). The control group had a prevalence of depressive symptoms of 27.6% at HAM-D and 29.3% at MADRS, and only seven controls had a diagnosis of depressive episode. The prevalence of depressive symptoms between these two groups was statistically different. This study underlines a strong association between subclinical hypothyroidism and depressive symptoms, which could have some important diagnostic and therapeutic implications in the clinical practice.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Mitochondrial Variants in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

    PubMed Central

    Rollins, Brandi; Martin, Maureen V.; Sequeira, P. Adolfo; Moon, Emily A.; Morgan, Ling Z.; Watson, Stanley J.; Schatzberg, Alan; Akil, Huda; Myers, Richard M.; Jones, Edward G.; Wallace, Douglas C.; Bunney, William E.; Vawter, Marquis P.

    2009-01-01

    Background Mitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in individuals with schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA) sequence have been reported in SZ and BD patients. Methodology/Principal Findings Dorsolateral prefrontal cortex (DLPFC) from a cohort of 77 SZ, BD, and MDD subjects and age-matched controls (C) was studied for mtDNA sequence variations and heteroplasmy levels using Affymetrix mtDNA resequencing arrays. Heteroplasmy levels by microarray were compared to levels obtained with SNaPshot and allele specific real-time PCR. This study examined the association between brain pH and mtDNA alleles. The microarray resequencing of mtDNA was 100% concordant with conventional sequencing results for 103 mtDNA variants. The rate of synonymous base pair substitutions in the coding regions of the mtDNA genome was 22% higher (p = 0.0017) in DLPFC of individuals with SZ compared to controls. The association of brain pH and super haplogroup (U, K, UK) was significant (p = 0.004) and independent of postmortem interval time. Conclusions Focusing on haplogroup and individual susceptibility factors in psychiatric disorders by considering mtDNA variants may lead to innovative treatments to improve mitochondrial health and brain function. PMID:19290059

  14. Monoamine oxidases in major depressive disorder and alcoholism.

    PubMed

    Duncan, Jeremy; Johnson, Shakevia; Ou, Xiao-Ming

    2012-06-01

    Monoamine oxidases play an integral role in brain function. Both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) regulate neurochemistry by degrading monoamine neurotransmitters (serotonin, dopamine, and norepinephrine). Any alteration in MAO levels can have devastating effects on the brain and behavior by lowering or raising neurotransmitter levels and producing toxic reactive oxygen species. In this review article, MAO is examined in terms of function and genetic organization, with special focus on recent discoveries related to the transcriptional regulation of MAO. In recent studies, transcriptional regulation involves a repressor protein, R1, for MAO-A and an activator protein, KLF11 (a Krüppel-like factor; also referred to as transforming growth factor-beta early inducible gene 2, TIEG2), for both MAO-A and MAO-B, by binding to Sp/KLF sites in the core promoters of MAO and regulating MAO gene expression. Furthermore, KLF11 may influence MAO-B expression and augment glyceraldehyde-3 phosphate dehydrogenase (GAPDH) to upregulate MAO-B transcription upon exposure to ethanol. Finally, we review recent progress in MAO research and highlight the roles that MAOs play in several psychiatric conditions, including chronic stress, major depressive disorder and alcohol dependence. Further research in this area is needed to better understand MAOs, their transcription factors and signaling pathways in psychiatric illnesses in order to develop new strategies for pharmacological advancement.

  15. 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

  16. 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…

  17. 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,…

  18. 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…

  19. 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…

  20. 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…

  1. Religious involvement and risk of major depression in a prospective nationwide study of African American adults.

    PubMed

    Ellison, Christopher G; Flannelly, Kevin J

    2009-08-01

    This study investigated the association between religious involvement and major depression in 607 African American adults, using longitudinal data from the National Survey of Black Americans. Logistic regression found that survey participants who reported receiving "a great deal" of guidance from religion in their day-to-day lives at Time 1 (1988-1989) were roughly half as likely (OR = 0.47, p < 0.01) to have major depression at Time 2 (1992), controlling for sociodemographic and psychological factors, and major depression at baseline. The odds of major depression were also lower for persons with high self-esteem (OR = 0.41, p < 0.01) and those who reported having satisfying relationships with friends and family members (OR = 0.51, p < 0.05) at baseline. No association was found between religious attendance or church support and major depression. The possible mechanisms through which religious involvement may protect against depression, especially among African Americans, are discussed.

  2. Problem Solving Therapy and Supportive Therapy in Older Adults with Major Depression and Executive Dysfunction: Effect on Disability

    PubMed Central

    Alexopoulos, George S.; Raue, Patrick J.; Kiosses, Dimitris N.; Mackin, R. Scott; Kanellopoulos, Dora; McCulloch, Charles; Areán, Patricia A.

    2010-01-01

    Context Older patients with depression and executive dysfunction represent a population with significant disability and high likelihood of failing pharmacotherapy. Objective To examine whether Problem Solving Therapy (PST) reduces disability more than Supportive Therapy (ST) in older patients with depression and executive dysfunction, and whether this effect is mediated by improvement in depressive symptoms. Design Randomized controlled trail, with participant recruitment from 12/02-11/07 and follow-up for 36 weeks. Setting Weill Cornell and University of California, San Francisco. Participants Adults (>59 years) with major depression and executive dysfunction. Intervention 12 sessions of either PST modified for older depressed adults with executive impairment, or ST. Main Outcome Measure Disability as quantified by the World Health Organization Assessment Schedule II (WHODAS II)-12 item form. Results 653 individuals were referred to this study, 221 of whom met criteria and were randomized to PST or ST. PST and ST led to comparable improvement of disability in the first 6 weeks of treatment, but a more prominent reduction in PST participants at weeks 9 and 12. The difference between PST and ST was greater in patients with greater cognitive impairment and higher number of previous episodes. Reduction in disability paralleled reduction in depressive symptoms. The therapeutic advantage of PST over ST in reducing depression was in part due to greater reduction of disability by PST. While disability increased during the 24 weeks following the end of treatment, the advantage of PST over ST-treated patients was retained. Conclusions This study suggests that PST is more effective than ST in reducing disability in older patients with major depression and executive dysfunction, and its benefits were retained after the end of treatment. The clinical value of this finding is that PST may be a treatment alternative in an older patient population likely to be resistant to

  3. Selective Hyper-responsiveness of the Interferon System in Major Depressive Disorders and Depression Induced by Interferon Therapy

    PubMed Central

    Hoyo-Becerra, Carolina; Erim, Yesim; Kis, Bernhard; Wang, Bo; Scherbaum, Norbert; Gerken, Guido

    2012-01-01

    Background Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood. Methods 50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed. Results IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients. Conclusions Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders. PMID:22701688

  4. Association between toll-like receptors expression and major depressive disorder.

    PubMed

    Hung, Yi-Yung; Kang, Hong-Yo; Huang, Kai-Wei; Huang, Tiao-Lai

    2014-12-15

    Accumulating evidences suggest that Toll-like receptors (TLRs) were involved in the pathophysiology of major depressive disorder. TLR4 was thought to be associated with major depressive disorder in animal model, but the others were still unknown. In order to examine TLR1-9 mRNA expression levels in peripheral blood and their relationships with the psychopathology of major depressive disorder, 30 patients with major depressive disorder were compared with 29 healthy controls. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess the severity of major depression. The mRNA expression levels of TLRs were examined in parallel with a housekeeping gene using real-time polymerase chain reaction (RT-PCR). Analysis of covariance with age and body mass index adjustment revealed a significantly higher expression of TLR3, 4, 5 and 7 mRNA but lower expression of TLR1 and 6 in patients with major depressive disorder as compared with healthy controls. Multiple linear regression analysis revealed that TLR4 was an independent risk factor relating to severity of major depression. These findings suggest that TLRs, especially TLR4, may be involved in the psychopathology of major depression.

  5. 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

  6. Altered choroid plexus gene expression in major depressive disorder

    PubMed Central

    Turner, Cortney A.; Thompson, Robert C.; Bunney, William E.; Schatzberg, Alan F.; Barchas, Jack D.; Myers, Richard M.; Akil, Huda; Watson, Stanley J.

    2014-01-01

    Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus (CP), the region that produces cerebrospinal fluid (CSF), in individuals with major depressive disorder (MDD). Genes that are expressed in the CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the CP at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled, and hybridized the cRNA to Illumina BeadChips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using BeadStudio software, we identified 169 transcripts differentially expressed (p < 0.05) between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ) pathway. Quantitative real-time PCR (qRT-PCR) confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the CP in MDD subjects that may lead to a disrupted blood-CSF-brain barrier. PMID:24795602

  7. Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications.

    PubMed

    Kudlow, P; Cha, D S; Carvalho, A F; McIntyre, R S

    2016-01-01

    Major depressive disorder (MDD) is a multi-factorial and heterogeneous disease. Robust evidence suggests that inflammation is involved in the pathogenesis of MDD for a subpopulation of individuals. However, it remains unclear what traits and/or states precede the onset of inflammation in this subpopulation of individuals with MDD. Several recent studies have implicated nitric oxide (NO) as a critical regulator of neuroinflammation, thus suggesting a possible role in the pathophysiology of MDD. The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for developing MDD in certain subpopulations may be mediated, in part, by inflammogenic trait and/or state variations in NO signaling pathways. We conducted a non-systematic literature search for English language studies via PubMed and Google Scholar, from 1985 to October 2014. Replicated evidence suggests that NO has contrasting effects in the central nervous system (CNS). Low concentrations of NO are neuroprotective and mediate physiological signaling whereas higher concentrations mediate neuroinflammatory actions and are neurotoxic. Certain polymorphisms in the neuronal nitric oxide synthase gene (NOS1) are associated MDD. Furthermore, state variations (e.g. decreased levels of essential co-factor, 5,6,7,8-tetrahydrobiopterin [BH4], enhanced microglial cell activity) in the NO signaling pathway are associated with an increased risk of developing MDD. Increased concentrations of NO enhance the production of reactive nitrogen species (RNS) and reactive oxygen species (ROS), which are associated with an increase in pro-inflammatory cytokines. Taken together, evidences suggest that abnormalities in NO signaling may constitute a trait-marker related to MDD pathophysiology, which could be explored for novel therapeutic targets. PMID:26812915

  8. Reduced Somatostatin in Subgenual Anterior Cingulate Cortex in Major Depression

    PubMed Central

    Tripp, Adam; Kota, Rama S.; Lewis, David A.; Sibille, Etienne

    2011-01-01

    Converging evidence suggests a central role for dysfunction of the subgenual anterior cingulate cortex (sgACC) in the pathophysiology of major depressive disorder (MDD). Underlying mechanisms may include altered GABAergic function. Expression of somatostatin (SST), an inhibitory neuropeptide localized to a subset of GABA neurons, has been shown to be lower in the dorsolateral prefrontal cortex of male MDD subjects. Here, to investigate whether alterations in SST may contribute to sgACC dysfunction in MDD, and whether the alterations display sex-specificity, we measured sgACC SST at the mRNA and precursor peptide levels in a large cohort of subjects with MDD. SST mRNA levels were analyzed by quantitative PCR (qPCR) in the postmortem sgACC from male (n=26) and female (n=25) subjects with MDD and sex-matched subjects with no psychiatric diagnosis (n=51). Prepro-SST protein levels were assessed in a subset of subjects (n=42 pairs) by semi-quantitative western blot. The mRNA expression of SST was significantly reduced by 38% in female subjects and by 27% in male subjects with MDD. The characteristic age-related decline in SST expression was observed in control (Pearson R=−0.357, p=0.005) but not MDD (R=−0.104, p=0.234) subjects, as low expression was detected across ages in MDD subjects. Protein expression was similarly reduced by 19% in both MDD groups, and findings were more robust in female (p=0.0056) than in males (p=0.0373) compared to respective controls. In conclusion, low SST represents a robust pathological finding in MDD. Specifically, alterations in SST signaling and/or SST-bearing GABA neurons may represent a critical pathophysiological entity that contributes to sgACC dysfunction and that matches the high female vulnerability to develop MDD. PMID:21232602

  9. Dietary patterns and anthropometric indices among Iranian women with major depressive disorder.

    PubMed

    Rashidkhani, Bahram; Pourghassem Gargari, Bahram; Ranjbar, Fatemeh; Zareiy, Sanaz; Kargarnovin, Zahra

    2013-11-30

    Major depression is a common mental disorder among women. A number of studies have demonstrated the association between some nutrients and food items with depression, but the studies on the association of dietary patterns with depression, especially in the Middle East, are rare. Further, the literature examining the relationship between anthropometric status and depression are inconsistent. In this study, 45 women with major depression and 90 patients with no mental disorder participated. We collected dietary intakes by a semi-quantitative food frequency questionnaire, and measured anthropometric indices (weight, height, waist and hip circumferences). Using factor analysis, two major dietary patterns were extracted: Healthy and Unhealthy. After adjusting for confounders, individuals who gained higher scores in healthy dietary pattern, had 84% lower odds of major depression; while the odds of major depression in participants who gained higher scores in unhealthy dietary pattern showed no significant association. No significant association was found between anthropometric indices and major depression. These results suggest that the healthy dietary pattern is significantly associated with lower odds of major depression in adult women. Further researches are needed to confirm these findings.

  10. 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

  11. The Network Model of Depression as a Basis for New Therapeutic Strategies for Treating Major Depressive Disorder in Parkinson's Disease.

    PubMed

    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.

  12. Evidence against mood-congruent attentional bias in Major Depressive Disorder.

    PubMed

    Cheng, Philip; Preston, Stephanie D; Jonides, John; Mohr, Alicia Hofelich; Thummala, Kirti; Casement, Melynda; Hsing, Courtney; Deldin, Patricia J

    2015-12-15

    Depression is consistently associated with biased retrieval and interpretation of affective stimuli, but evidence for depressive bias in earlier cognitive processing, such as attention, is mixed. In five separate experiments, individuals with depression (three experiments with clinically diagnosed major depression, two experiments with dysphoria measured via the Beck Depression Inventory) completed three tasks designed to elicit depressive biases in attention, including selective attention, attentional switching, and attentional inhibition. Selective attention was measured using a modified emotional Stroop task, while attentional switching and inhibition was examined via an emotional task-switching paradigm and an emotional counter task. Results across five different experiments indicate that individuals with depression perform comparably with healthy controls, providing corroboration that depression is not characterized by biases in attentional processes. PMID:26477954

  13. Evidence against mood-congruent attentional bias in Major Depressive Disorder.

    PubMed

    Cheng, Philip; Preston, Stephanie D; Jonides, John; Mohr, Alicia Hofelich; Thummala, Kirti; Casement, Melynda; Hsing, Courtney; Deldin, Patricia J

    2015-12-15

    Depression is consistently associated with biased retrieval and interpretation of affective stimuli, but evidence for depressive bias in earlier cognitive processing, such as attention, is mixed. In five separate experiments, individuals with depression (three experiments with clinically diagnosed major depression, two experiments with dysphoria measured via the Beck Depression Inventory) completed three tasks designed to elicit depressive biases in attention, including selective attention, attentional switching, and attentional inhibition. Selective attention was measured using a modified emotional Stroop task, while attentional switching and inhibition was examined via an emotional task-switching paradigm and an emotional counter task. Results across five different experiments indicate that individuals with depression perform comparably with healthy controls, providing corroboration that depression is not characterized by biases in attentional processes.

  14. Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

    PubMed

    Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

    2015-01-01

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder. PMID:26556285

  15. 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…

  16. Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

    PubMed

    Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

    2015-11-10

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

  17. 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…

  18. A Pilot Study of Culturally Adapted Cognitive Behavior Therapy for Hispanics with Major Depression

    ERIC Educational Resources Information Center

    Interian, Alejandro; Allen, Lesley A.; Gara, Michael A.; Escobar, Javier I.

    2008-01-01

    The purpose of this study was to evaluate a culturally adapted cognitive-behavioral treatment (CBT) for major depression among Hispanics in primary care. Cultural adaptations were applied based on a range of cultural considerations described in the literature. Fifteen Hispanic primary care patients with major depression were enrolled. All…

  19. 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…

  20. Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder

    PubMed Central

    Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

    2015-01-01

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13–18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder. PMID:26556285

  1. 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

  2. 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

  3. 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.

  4. A systematic approach to the pharmacotherapy of geriatric major depression

    PubMed Central

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

    2014-01-01

    SYNOPSIS While about 14% of older Americans are now taking an antidepressant, this broad use of antidepressants 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. First, we discuss and reject the possible explanations that antidepressants are not effective in the treatment of depression or that the results of randomized clinical trials are not applicable to the treatment of depression in “real-world” clinical settings. Instead, we propose that the efficacy of antidepressants depends in large part on the way they are used. We present evidence supporting that the use of antidepressant pharmacotherapy is associated with better outcomes when it is guided by a treatment algorithm (a “stepped care approach”) as opposed to an attempt to individualize treatment. We review published guidelines and pharmacotherapy algorithms that were developed for the treatment of geriatric depression. Finally, we propose an updated algorithm based on the authors’ interpretation of the available evidence. PMID:25037293

  5. The Role of Neurotrophins in Major Depressive Disorder.

    PubMed

    Jiang, Cheng; Salton, Stephen R

    2013-03-01

    Neurotrophins and other growth factors have been advanced as critical modulators of depressive behavior. Support for this model is based on analyses of knockout and transgenic mouse models, human genetic studies, and screens for gene products that are regulated by depressive behavior and/or antidepressants. Even subtle alteration in the regulated secretion of brain-derived neurotrophic factor (BDNF), for example, due to a single nucleotide polymorphism (SNP)-encoded Val-Met substitution in proBDNF that affects processing and sorting, impacts behavior and cognition. Alterations in growth factor expression result in changes in neurogenesis as well as structural changes in neuronal cytoarchitecture, including effects on dendritic length and spine density, in the hippocampus, nucleus accumbens, and prefrontal cortex. These changes have the potential to impact the plasticity and stability of synapses in the CNS, and the complex brain circuitry that regulates behavior. Here we review the role that neurotrophins play in the modulation of depressive behavior, and the downstream signaling targets they regulate that potentially mediate these behavioral pro-depressant and antidepressant effects. PMID:23691270

  6. 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.

  7. 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…

  8. The Role of Neurotrophins in Major Depressive Disorder

    PubMed Central

    Jiang, Cheng; Salton, Stephen R.

    2013-01-01

    Neurotrophins and other growth factors have been advanced as critical modulators of depressive behavior. Support for this model is based on analyses of knockout and transgenic mouse models, human genetic studies, and screens for gene products that are regulated by depressive behavior and/or antidepressants. Even subtle alteration in the regulated secretion of brain-derived neurotrophic factor (BDNF), for example, due to a single nucleotide polymorphism (SNP)-encoded Val-Met substitution in proBDNF that affects processing and sorting, impacts behavior and cognition. Alterations in growth factor expression result in changes in neurogenesis as well as structural changes in neuronal cytoarchitecture, including effects on dendritic length and spine density, in the hippocampus, nucleus accumbens, and prefrontal cortex. These changes have the potential to impact the plasticity and stability of synapses in the CNS, and the complex brain circuitry that regulates behavior. Here we review the role that neurotrophins play in the modulation of depressive behavior, and the downstream signaling targets they regulate that potentially mediate these behavioral pro-depressant and antidepressant effects. PMID:23691270

  9. 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

  10. Tianeptine in combination with monoamine oxidase inhibitors for major depressive disorder.

    PubMed

    Tobe, Edward H

    2012-01-01

    Major depressive disorder may respond to monotherapy with monoamine oxidase inhibitors (MAOIs) or tianeptine. Literature search showed no reports of MAOIs combined with tianeptine. The method included was clinical case history. A 59-year-old woman had partial improvement of depression with the MAOI tranylcypromine combined with topiramate, trazodone and ziprasidone. The patient had further improvement of depression symptoms after addition of tianeptine. No adverse events were evident. The combination of MAIOs and tianeptine may be effective for refractory major depressive disorder. PMID:23048001

  11. Perception of affective prosody in major depression: a link to executive functions?

    PubMed

    Uekermann, Jennifer; Abdel-Hamid, Mona; Lehmkämper, Caroline; Vollmoeller, Wolfgang; Daum, Irene

    2008-07-01

    Major depression is associated with impairments of executive functions and affect perception deficits, both being linked to dysfunction of fronto-subcortical networks. So far, little is known about the relationship between cognitive and affective deficits in major depression. In the present investigation, affect perception and executive functions were assessed in 29 patients with a diagnosis of major depression (Dep) and 29 healthy controls (HC). Both groups were comparable on IQ, age, and gender distribution. Depressed patients showed deficits of perception of affective prosody, which were significantly related to inhibition, set shifting, and working memory. Our findings suggest a significant association between cognitive deficits and affect perception impairments in major depression, which may be of considerable clinical relevance and might be addressed in treatment approaches. Future studies are desirable to investigate the nature of the association in more detail.

  12. 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.

  13. 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,…

  14. [Review of the new treatment guideline for major depressive disorder by the Japanese Society of Mood Disorders].

    PubMed

    Ogasawara, Kazuyoshi; Ozaki, Norio

    2012-10-01

    The Japanese Society of Mood Disorders (JSMD) published the "Treatment Guideline II: Major Depressive Disorder, 2012 Ver. 1" on July 26, 2012. This guideline (GL) is the first one published by an academic society in Japan. Presently in Japan, many people have depressive symptoms, and the socioeconomic loss (suicide, absence from work, etc.) induced by this condition cannot be overlooked. Although the Japanese society, including mass media and psychiatrists, has attempted to solve this public problem, a solution has not been found. JSMD regarded diagnosis and psychiatric management of depression, among other factors, as the key to solving this problem. For example, patients who meet the DSM-IV major depressive disorder (MDD) criteria still have numerous subtypes, and they often have other psychiatric comorbidities that a diagnosis of MDD alone cannot detect. Although the process for differential diagnosis and treatment planning is indispensable, its methodology has not been necessarily shared even among psychiatrists until today. In this GL, considering the research evidence and its limitations, JSMD suggests necessary steps for appropriate information intake, diagnosis, therapeutic alliance formation, psychoeducation, and treatment modality choice in every phase (acute and continuation/maintenance). This GL also considers pharmaco-, psycho-, and electroconvulsive therapy for major depressive subtypes (mild, moderate/severe, and psychotic). Simultaneously, psychiatrists are required to be alert to the risk from diffuse and multiple prescription of benzodiazepine receptor agonists (dependence, deterioration of sleep apnea, cognitive decline, paradoxical reaction, etc.), especially barbiturates. This GL will be revised on the basis of public comments, including criticism. In the future, treatment GLs for comorbid patients, return-to-work cases, primary care physicians, psychiatric residents, and patients with depressions other than MDD (subthreshold depression

  15. Remission in Major Depression: Results from a Geriatric Primary Care Population

    PubMed Central

    Azar, Armin R.; Chopra, Mohit P.; Cho, Lydia Y.; Coakley, Eugenie; Rudolph, James L.

    2010-01-01

    OBJECTIVES While a recent task force report recommended that remission from major depression be defined according to DSM criteria, most previous work has used depressive symptom rating scales. The current study sought to identify baseline factors associated with treatment outcome in major depression, diagnosed according to DSM-IV criteria. METHODS Data from the Primary Care Research in Substance Abuse and Mental Health for the Elderly (PRISM-E) study were utilized. This analysis focused on 792 geriatric primary care patients with major depression at baseline, who were randomized to services by a mental health professional in primary care or specialty settings. Major depression was diagnosed according to DSM-IV criteria based on a structured interview at baseline and six months. The primary outcome was the absence of any DSM-IV depressive disorder at six-month follow-up. Association with baseline demographic characteristics, comorbid anxiety disorder, “at risk” drinking, number of co-occurring medical conditions, and depressive symptom severity was examined using multiple logistic regression modeling. RESULTS Remission occurred in 228 (29%) patients with completed follow-up assessments, while 564 (71%) did not remit. Factors which increased the odds of non-remission included comorbid anxiety (OR=1.60, 95%CI 1.11–2.31), female sex (OR=1.49, 95%CI 1.04–2.15), general medical comorbidity (OR=1.15, 95%CI 1.07–1.24), and increased baseline depressive symptom severity (OR=1.04, 95%CI 1.03–1.06). CONCLUSIONS The findings underscore the importance of using DSM criteria to define remission from major depression, and suggest that concurrent measurement of depression severity, comorbid anxiety and medical comorbidity are important in identifying patients requiring targeted interventions to optimize remission from major depression. PMID:21157850

  16. Do different fairness contexts and facial emotions motivate 'irrational' social decision-making in major depression? An exploratory patient study.

    PubMed

    Radke, Sina; Schäfer, Ina C; Müller, Bernhard W; de Bruijn, Ellen R A

    2013-12-15

    Although 'irrational' decision-making has been linked to depression, the contribution of biases in information processing to these findings remains unknown. To investigate the impact of cognitive biases and aberrant processing of facial emotions on social decision-making, we manipulated both context-related and emotion-related information in a modified Ultimatum Game. Unfair offers were (1) paired with different unselected alternatives, establishing the context in which an offer was made, and (2) accompanied by emotional facial expressions of proposers. Responder behavior was assessed in patients with major depressive disorder and healthy controls. In both groups alike, rejection rates were highest following unambiguous signals of unfairness, i.e. an angry proposer face or when an unfair distribution had deliberately been chosen over an equal split. However, depressed patients showed overall higher rejection rates than healthy volunteers, without exhibiting differential processing biases. This suggests that depressed patients were, as healthy individuals, basing their decisions on informative, salient features and differentiating between (i) fair and unfair offers, (ii) alternatives to unfair offers and (iii) proposers' facial emotions. Although more fundamental processes, e.g. reduced reward sensitivity, might underlie increased rejection in depression, the current study provides insight into mechanisms that shape fairness considerations in both depressed and healthy individuals.

  17. 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

  18. Major depressive disorder and immunity to varicella-zoster virus in the elderly.

    PubMed

    Irwin, Michael R; Levin, Myron J; Carrillo, Carmen; Olmstead, Richard; Lucko, Anne; Lang, Nancy; Caulfield, Michael J; Weinberg, Adriana; Chan, Ivan S F; Clair, Jim; Smith, Jeff G; Marchese, R D; Williams, Heather M; Beck, Danielle J; McCook, Patricia T; Johnson, Gary; Oxman, Michael N

    2011-05-01

    Major depressive disorder has been associated with activation of inflammatory processes as well as with reductions in innate, adaptive and non-specific immune responses. The objective of this study was to evaluate the association between major depression and a disease-relevant immunologic response, namely varicella-zoster virus (VZV)-specific immunity, in elderly adults. A cross-sectional cohort study was conducted in 104 elderly community dwelling adults ≥ 60years of age who were enrolled in the depression substudy of the shingles prevention study, a double blind, placebo-controlled vaccine efficacy trial. Fifty-two subjects had a current major depressive disorder, and 52 age- and sex-matched controls had no history of depression or any mental illness. VZV-specific cell-mediated immunity (VZV-CMI) was measured by VZV responder cell frequency (VZV-RCF) and interferon-γ enzyme-linked immunospot (ELISPOT) assays, and antibody to VZV was measured by an enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA). VZV-CMI, measured by VZV-RCF, was significantly lower in the depressed group than in the controls (p<0.001), and VZV-RCF was inversely correlated with the severity of depressive symptoms in the depressed patients. In addition, an age-related reduction in VZV-RCF was observed in the depressed patients, but not in the controls. Furthermore, there was a trend for depressive symptom severity to be associated with lower ELISPOT counts. Finally, VZV-RCF was higher in depressed patients treated with antidepressant medications as compared to untreated depressed patients. Since lower levels of VZV-RCF appear to explain the increased risk and severity of herpes zoster observed in older adults, these findings suggest that, in addition to increasing age, depression may increase the risk and severity of herpes zoster.

  19. Rate and Predictors of Persistent Major Depressive Disorder in a Nationally Representative Sample.

    PubMed

    Walker, Elizabeth Reisinger; Druss, Benjamin G

    2015-08-01

    This study examined predictors of persistent major depressive disorder over 10 years, focusing on the effects of clinical variables, physical health, and social support. Data from the National Survey of Midlife Development in the United States in 1995-1996 and 2004-2006 were analyzed. Logistic regression was used to predict non-recovery from major depression among individuals who met clinical-based criteria for major depressive disorder at baseline. Fifteen percent of the total sample was classified as having major depression in 1995-1996; of these individuals, 37 % had major depression in 2004-2006. Baseline variables that were significantly associated with persistent major depression at follow-up were being female, having never married, having two or more chronic medical conditions, experiencing activity limitation, and less contact with family. Therefore, treatment strategies focused on physical health, social support, and mental health needs are necessary to comprehensively address the factors that contribute to persistent major depressive disorder.

  20. 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

  1. Genetic variants within the serotonin transporter associated with familial risk for major depression

    PubMed Central

    Talati, Ardesheer; Guffanti, Guia; Odgerel, Zagaa; Ionita-Laza, Iuliana; Malm, Heli; Sourander, Andre; Brown, Alan S.; Wickramaratne, Priya J.; Gingrich, Jay A.; Weissman, Myrna M.

    2015-01-01

    The role of the serotonin transporter promoter linked polymorphism (5HTTLPR) in depression, despite much research, remains unclear. Most studies compare persons with and without depression to each other. We show offspring at high (N=192) as compared to low (N=101) familial risk for major depressive disorder were almost four times as likely to have two copies of the short allele at 5HTTLPR, suggesting that incorporation of family history could be helpful in identifying genetic differences. PMID:25920807

  2. 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

  3. 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

  4. 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…

  5. Disentangling dysthymia from major depressive disorder in suicide attempters' suicidality, comorbidity and symptomatology.

    PubMed

    Holmstrand, Cecilia; Engström, Gunnar; Träskman-Bendz, Lil

    2008-01-01

    Dysthymia and major depressive disorder (MDD) are both risk diagnoses for suicidal behaviour. The aim of the present study was to identify clinical differences between these disorders, with a special reference to dysthymia. We studied suicidal behaviour, comorbidity and psychiatric symptoms of inpatient suicide attempters with dysthymia and MDD. We used DSM III-R diagnostics, the Suicide Assessment Scale (SUAS) and the Comprehensive Psychopathological Rating Scale (CPRS), part of which is the Montgomery and Asberg Depression Rating Scale (MADRS). Suicide mortality, number of repeated suicide attempts, method of suicide attempt and comorbidity of Axis I did not differ between the groups. Dysthymia patients, however, suffered more than MDD patients from DSM-III-R Axis II diagnoses (above all cluster B). There was no significant difference in Axis III comorbidity. Total SUAS, CPRS and MADRS scores did not differ significantly between the groups. When studying separate SUAS and CPRS items in a multivariate analysis, the CPRS items "aches and pains", "increased speech flow", increased "agitation" and "less tendency to worrying over trifles" as well as young age remained independently associated with dysthymia. Dysthymia patients, who later committed suicide, more often reported increased "aches and pains" than those who did not commit suicide. In this small sample of suicide attempters, we conclude that dysthymia suicide attempters, more often than MDD patients, have a comorbidity with personality disorders, which combined with a picture of aches and pains, could be factors explaining their suicidality.

  6. Differences in smoking expectancies in smokers with and without a history of major depression.

    PubMed

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

    2011-04-01

    Adults with depression evidence higher rates of smoking and lower quit rates than adults without depression. Little is known about the relationship between depression and smoking beliefs which are associated with both smoking and smoking cessation behavior. The primary aim of this study was to examine whether adult smokers with and without a history of major depressive disorder (MDD) differ in their endorsement of smoking expectancies. The secondary aim of the study was to examine whether there were interactions of depression and gender on the endorsement of expectancies. Adult cigarette smokers participating in a clinical trial of Selegiline hydrochloride for smoking cessation were classified as having a history of depression (MDD+, n=26) or no history of depression (MDD-, n=75). History of depression and smoking expectancies were assessed prior to randomization into the clinical trial. There was a main effect of depression on 7 out of 10 of the assessed beliefs. MDD+ smokers, compared to MDD- smokers, more strongly endorsed beliefs that smoking reduces negative affect, boredom, and cravings; smoking increases stimulation and social facilitation; smoking helps to manage cravings and weight; and that the taste is enjoyable. The main effect of gender and the interactive effect of depression and gender were not significant. Incorporating expectancies into cognitive-behavioral treatments for smoking cessation may be useful for smokers with a history of depression.

  7. 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.

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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

  13. 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.

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

    PubMed

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

    2014-03-01

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

  15. Magnetization Transfer Imaging of Suicidal Patients with Major Depressive Disorder

    PubMed Central

    Chen, Ziqi; Zhang, Huawei; Jia, Zhiyun; Zhong, Jingjie; Huang, Xiaoqi; Du, Mingying; Chen, Lizhou; Kuang, Weihong; Sweeney, John A.; Gong, Qiyong

    2015-01-01

    Magnetization transfer imaging (MTI) provides a quantitative measure of the macromolecular structural integrity of brain tissue, as represented by magnetization transfer ratio (MTR). In this study, we utilized MTI to identify biophysical alterations in MDD patients with a history of suicide attempts relative to MDD patients without such history. The participants were 36 medication-free MDD patients, with (N = 17) and without (N = 19) a history of a suicide attempt, and 28 healthy controls matched for age and gender. Whole brain voxel-based analysis was used to compare MTR across three groups and to analyze correlations with symptom severity and illness duration. We identified decreased MTR in left inferior parietal lobule and right superior parietal lobule in suicide attempters relative to both non-attempters and controls. Non-attempters also showed significantly reduced MTR in left inferior parietal lobule relative to controls, as well as an MTR reduction in left cerebellum. These abnormalities were not correlated with symptom severity or illness duration. Depressed patients with a history of suicide attempt showed bilateral abnormalities in parietal cortex compared to nonsuicidal depressed patients and healthy controls. Parietal lobe abnormalities might cause attentional dysfunction and impaired decision making to increase risk for suicidal behavior in MDD. PMID:25853872

  16. 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

  17. Fear Extinction as a Model for Synaptic Plasticity in Major Depressive Disorder

    PubMed Central

    Feige, Bernd; Blechert, Jens; Normann, Claus; Nissen, Christoph

    2014-01-01

    Background The neuroplasticity hypothesis of major depressive disorder proposes that a dysfunction of synaptic plasticity represents a basic pathomechanism of the disorder. Animal models of depression indicate enhanced plasticity in a ventral emotional network, comprising the amygdala. Here, we investigated fear extinction learning as a non-invasive probe for amygdala-dependent synaptic plasticity in patients with major depressive disorder and healthy controls. Methods Differential fear conditioning was measured in 37 inpatients with severe unipolar depression (International Classification of Diseases, 10th revision, criteria) and 40 healthy controls. The eye-blink startle response, a subcortical output signal that is modulated by local synaptic plasticity in the amygdala in fear acquisition and extinction learning, was recorded as the primary outcome parameter. Results After robust and similar fear acquisition in both groups, patients with major depressive disorder showed significantly enhanced fear extinction learning in comparison to healthy controls, as indicated by startle responses to conditioned stimuli. The strength of extinction learning was positively correlated with the total illness duration. Conclusions The finding of enhanced fear extinction learning in major depressive disorder is consistent with the concept that the disorder is characterized by enhanced synaptic plasticity in the amygdala and the ventral emotional network. Clinically, the observation emphasizes the potential of successful extinction learning, the basis of exposure therapy, in anxiety-related disorders despite the frequent comorbidity of major depressive disorder. PMID:25545818

  18. Help-seeking for emotional problems in major depression : findings of the 2006 Estonian health survey.

    PubMed

    Kleinberg, Anne; Aluoja, Anu; Vasar, Veiko

    2013-08-01

    To study help-seeking among the general population and people with major depression. 12-month help-seeking for emotional problems was assessed in a cross-sectional 2006 Estonian Health Survey. Non-institutionalized individuals aged 18-84 years (n = 6,105) were interviewed. A major depressive episode was assessed using the Mini-International Neuropsychiatric Interview. The factors associated with help-seeking, received help, and health service use were analyzed. The prevalence of 12-month help-seeking for emotional symptoms was 4.8%. The rate of 12-month help-seeking in the depressed sample was 34.1%. Depressed people used non-mental health services 1.5-3 times more than non-depressed persons even when adjusted for the chronic somatic disorder. Only one third of depressed persons sought help, which was most of all associated with severity of depression. Underdiagnosis and undertreatment of depression leads to an increased use of expensive but non-specific health services by depressed persons.

  19. 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

  20. Major Depression Duration Reduces Appetitive Word Use: An Elaborated Verbal Recall of Emotional Photographs

    PubMed Central

    Capecelatro, Maria R.; Sacchet, Matthew D.; Hitchcock, Peter F.; Miller, Samuel M.; Britton, Willoughby B.

    2013-01-01

    Introduction Major depressive disorder (MDD) is characterized by cognitive biases in attention, memory and language use. Language use biases often parallel depression symptoms, and contain over-representations of both negative emotive and death words as well as low levels of positive emotive words. This study further explores cognitive biases in depression by comparing the effect of current depression status to cumulative depression history on an elaborated verbal recall of emotional photographs. Methods Following a negative mood induction, fifty-two individuals (42 women) with partially-remitted depression viewed – then recalled and verbally described – slides from the International Affective Picture System (IAPS). Descriptions were transcribed and frequency of depression-related word use (positive emotion, negative emotion, sex, ingestion and death) was analyzed using the Linguistic Inquiry and Word Count program (LIWC). Results Contrary to expectations and previous findings, current depression status did not affect word use in any categories of interest. However, individuals with more than 5 years of previous depression used fewer words related to positive emotion (t(50) = 2.10, p = .04, (d = .57)), and sex (t(48) = 2.50, p = .013 (d = .81)), and there was also a trend for these individuals to use fewer ingestion words (t(50) = 1.95, p = .057 (d = .58)), suggesting a deficit in appetitive processing. Conclusions Our findings suggest that depression duration affects appetitive information processing and that appetitive word use may be a behavioral marker for duration related brain changes which may be used to inform treatment. PMID:23510497

  1. 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.

  2. Is blunted cardiovascular reactivity in depression mood-state dependent? A comparison of major depressive disorder remitted depression and healthy controls.

    PubMed

    Salomon, Kristen; Bylsma, Lauren M; White, Kristi E; Panaite, Vanessa; Rottenberg, Jonathan

    2013-10-01

    Prior work has repeatedly demonstrated that people who have current major depression exhibit blunted cardiovascular reactivity to acute stressors (e.g., Salomon et al., 2009). A key question regards the psychobiological basis for these deficits, including whether such deficits are depressed mood-state dependent or whether these effects are trait-like and are observed outside of depression episodes in vulnerable individuals. To examine this issue, we assessed cardiovascular reactivity to a speech stressor task and a forehead cold pressor in 50 individuals with current major depressive disorder (MDD), 25 with remitted major depression (RMD), and 45 healthy controls. Heart rate (HR), blood pressure and impedance cardiography were assessed and analyses controlled for BMI and sex. Significant group effects were found for SBP, HR, and PEP for the speech preparation period and HR, CO, and PEP during the speech. For each of these parameters, only the MDD group exhibited attenuated reactivity as well as impaired SBP recovery. Reactivity and recovery in the RMD group more closely resembled the healthy controls. Speeches given by the MDD group were rated as less persuasive than the RMD or healthy controls' speeches. No significant differences were found for the cold pressor. Blunted cardiovascular reactivity and impaired recovery in current major depression may be mood-state dependent phenomena and may be more reflective of motivational deficits than deficits in the physiological integrity of the cardiovascular system.

  3. 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

  4. 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

  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. Has analytical flexibility increased in imaging studies of bipolar disorder and major depression?

    PubMed

    Munafò, M R; Kempton, M J

    2015-02-01

    There has been extensive discussion of problems of reproducibility of research. Analytical flexibility may contribute to this, by increasing the likelihood that a reported finding represents a chance result. We explored whether analytical flexibility has increased over time, using human imaging studies of bipolar disorder and major depression. Our results indicate that the number of measures collected per study has increased over time for studies of bipolar disorder, but not for studies of major depression.

  8. 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

  9. The impact of cognitive challenges in major depression: the role of the primary care physician.

    PubMed

    Mattingly, Gregory; Anderson, Richard H; Mattingly, Stephen G; Anderson, Elizabeth Q

    2016-09-01

    Nearly 1 in 5 Americans will struggle with major depression in their lives; some will have recurring bouts. Recent psychiatric research has given new attention to the prevalence of cognitive deficits in major depression and the impact such deficits have on remission and overall life functioning. When depression is partially treated i.e., leaving residual symptoms, patients have higher rates of relapse and lower functional outcomes. Impaired cognitive functioning is a frequent residual symptom, persisting in about 45% of patients even when emotional symptoms have improved, and results in a disproportionate share of the functional impairment, particularly in the workplace. Patients with depression have disrupted circuitry in brain regions responsible for cognition and it is therefore important to screen depressed patients for cognitive as well as emotional symptoms. Cognitive dysfunction should be evaluated in every mood disordered patient with validated self-report scales such as the Patient Health Questionnaire-9 or the Beck Depression Inventory and objective measures of cognitive function are also very very useful. Two easily administered tests are the Trails B Test and the Digit Symbol Substitution Test. Each take less than two minutes and measure working memory, executive function, and processing speed and can track cognitive improvement in depressed patients. Treatment of cognitive dysfunction in major depression is complicated by the 'serotonin conundrum': SSRI's frequently do not treat to full remission, and can cause cognitive blunting-actually adding to cognitive problems. Based on recent data including results from a recently completed meta-analysis by McIntyre and colleagues, an evidence-based algorithm for treating cognitive symptoms in depression is presented. A hierarchy of antidepressants and augmentation strategies based on the best available evidence is discussed. In conclusion, cognitive symptoms in major depressive disorder have been recognized as

  10. Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder.

    PubMed

    Grosse, Laura; Carvalho, Livia A; Wijkhuijs, Annemarie J M; Bellingrath, Silja; Ruland, Tillmann; Ambrée, Oliver; Alferink, Judith; Ehring, Thomas; Drexhage, Hemmo A; Arolt, Volker

    2015-02-01

    Increased inflammatory activation might only be present in a subgroup of depressed individuals in which immune processes are especially relevant to disease development. We aimed to analyze demographic, depression, and trauma characteristics of major depressive disorder (MDD) patients with regard to inflammatory monocyte gene expression. Fifty-six naturalistically treated MDD patients (32 ± 12 years) and 57 healthy controls (HC; 31 ± 11 years) were analyzed by the Inventory of Depressive Symptomatology (IDS) and by the Childhood Trauma Questionnaire (CTQ). We determined the expression of 38 inflammatory and immune activation genes including the glucocorticoid receptor (GR)α and GRβ genes in purified CD14(+) monocytes using quantitative-polymerase chain reaction (RT-qPCR). Monocyte gene expression was age-dependent, particularly in MDD patients. Increased monocyte gene expression and decreased GRα/β ratio were only present in MDD patients aged ⩾ 28 years. Post hoc analyses of monocyte immune activation in patients <28 years showed two subgroups: a subgroup with a severe course of depression (recurrent type, onset <15 years) - additionally characterized by panic/arousal symptoms and childhood trauma - that had a monocyte gene expression similar to HC, and a second subgroup with a milder course of the disorder (73% first episode depression, onset ⩾15 years) - additionally characterized by the absence of panic symptoms - that exhibited a strongly reduced inflammatory monocyte activation compared to HC. In conclusion, monocyte immune activation was not uniformly raised in MDD patients but was increased only in patients of 28 years and older.

  11. Efficacy of tianeptine in major depressive disorders with or without melancholia.

    PubMed

    Ginestet, D

    1997-10-01

    The efficacy of tianeptine in the treatment of major depressive episodes was assessed in three double-blind placebo-controlled studies. In a first double-blind study comparing tianeptine (37.5 mg/day) with placebo, 126 patients with Major Depression or a Depressed Bipolar Disorder were treated for 42 days; 60% of these patients fulfilled DSM-III-R criteria for melancholia. Final MADRS scores showed the efficacy of tianeptine in comparison with placebo (P = 0.007). This result was confirmed by the time course of the Severity of Illness (CGI item 1) (P = 0.015). 58% of the patients responded to tianeptine versus 41% to placebo. In another study comparing tianeptine (37.5 mg/day), imipramine (150 mg/day), and placebo, 186 depressed patients were treated for 42 days. The patients had either Major Depression or Depressed Bipolar Disorder, without melancholia (DSM III-R). In the intention-to-treat analysis, final MADRS scores showed a better efficacy of tianeptine and imipramine than placebo (P = 0.012 and P = 0.034, respectively). There were 56% responders on tianeptine vs 48% on imipramine, and 32% on placebo. A third study involved 244 patients with Major Depression with or without melancholia (DSM-III-R). They were treated in a parallel group design with tianeptine (37.5 mg/day) or tianeptine (75 mg/day) or placebo for 42 days. The high rate of placebo-responders (> 65%) did not allow any conclusion about the efficacy of tianeptine. Altogether, tianeptine was shown to be an effective and safe medication for the treatment of major depressive episodes. However, a controlled study in endogenous depression would be useful to determine the position of tianeptine among the other antidepressants in this indication.

  12. 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

  13. Efficacy of vilazodone on anxiety symptoms in patients with major depressive disorder.

    PubMed

    Thase, Michael E; Chen, Dalei; Edwards, John; Ruth, Adam

    2014-11-01

    Anxiety symptoms are prevalent in patients with major depressive disorder. A post-hoc analysis of two phase III trials was conducted to evaluate the efficacy of vilazodone on depression-related anxiety. Using the 17-item Hamilton Depression Rating Scale (HAMD17) Anxiety/Somatization subscale, patients were classified as anxious or nonanxious. Improvements in depressive symptoms were based on least squares mean changes in HAMD17 and Montgomery-Asberg Depression Rating Scale total scores. Anxiety symptoms in the anxious subgroup were evaluated using Hamilton Anxiety Rating Scale (HAMA) total and subscale (Psychic Anxiety, Somatic Anxiety) scores, HAMD17 Anxiety/Somatization subscale and item (Psychic Anxiety, Somatic Anxiety) scores, and the Montgomery-Asberg Depression Rating Scale Inner Tension item score. Most of the pooled study population [82.0% (708/863)] was classified with anxious depression. After 8 weeks of treatment, least squares mean differences between vilazodone and placebo for changes in HAMA total and HAMD17 Anxiety/Somatization subscale scores were -1.82 (95% confidence interval -2.81 to -0.83; P<0.001) and -0.75 (95% confidence interval -1.17 to -0.32; P<0.001), respectively. Statistically significant improvements with vilazodone were also found on all other anxiety-related measures, except the HAMA Somatic Anxiety subscale. Vilazodone may be effective in treating patients with major depressive disorder who exhibit somatic and/or psychic symptoms of anxiety.

  14. 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

  15. 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.

  16. Depressive and Anxiety Disorders in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations

    PubMed Central

    Zhao, Yueyin; Cheng, Yuqi; Li, Shu; Lai, Aiyun; Xie, Zhongqi; Xu, Xinyu; Lu, Zhaoping

    2016-01-01

    Depressive and anxiety disorders are frequently observed in patients with Systemic Lupus Erythematosus (SLE). However, the underlying mechanisms are still unknown. We conducted this survey to understand the prevalence of depression and anxiety in SLE patients without major neuropsychiatric manifestations (non-NPSLE) and to explore the relationship between emotional disorders, symptoms, autoantibodies, disease activity, and treatments in SLE. 176 SLE patients were included, and SLE disease activity index (SLEDAI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) were recorded to evaluate their disease activity and emotional status. We found that depressive and anxiety disorders were common among SLE patients: 121 (68.8%) patients were in depression status while 14 (8.0%) patients could be diagnosed with depression. Accordingly, 101 (57.4%) were in anxiety status and 21 (11.9%) could be diagnosed with anxiety. Depression was associated with disease activity, and anxiety was associated with anti-P0 antibody, while both of them were associated with proteinuria. HAMA and HAMD scores were in strong positive correlation and they were independent risk factors of each other. We concluded that the high prevalence of depression and anxiety and the association between depression and SLE disease activity might reveal the covert damage of central nervous system in SLE. The role of anti-P0 antibody in SLE patients with emotional disorders warrants more researches. PMID:27747246

  17. PET quantification of serotonin transporter in suicide attempters with major depressive disorder

    PubMed Central

    Miller, Jeffrey M.; Hesselgrave, Natalie; Ogden, R. Todd; Sullivan, Gregory M.; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

    2013-01-01

    Background Several lines of evidence implicate abnormal serotonergic function in suicidal behavior and completed suicide, including low serotonin transporter binding in postmortem studies of completed suicide. We have also reported low in vivo serotonin transporter binding in major depressive disorder (MDD) during a major depressive episode using positron emission tomography with [11C]McN5652. We quantified regional brain serotonin transporter binding in vivo in depressed suicide attempters, depressed non-attempters, and healthy controls using positron emission tomography and a superior radiotracer, [11C]DASB. Methods 51 subjects with DSM-IV current MDD, 15 of whom were past suicide attempters, and 32 healthy controls underwent PET scanning with [11C]DASB to quantify in vivo regional brain serotonin transporter binding. Metabolite-corrected arterial input functions and plasma free-fraction were acquired to improve quantification. Results Depressed suicide attempters had lower serotonin transporter binding in midbrain compared with depressed non-attempters (p=0.031) and controls (p=0.0093). There was no difference in serotonin transporter binding comparing all depressed subjects to healthy controls considering six a priori regions of interest simultaneously (p=0.41). Conclusions Low midbrain serotonin transporter binding appears to be related to the pathophysiology of suicidal behavior rather than of major depressive disorder. This is consistent with postmortem work showing low midbrain serotonin transporter binding capacity in depressed suicides, and may partially explain discrepant in vivo findings quantifying serotonin transporter in depression. Future studies should investigate midbrain serotonin transporter binding as a predictor of suicidal behavior in MDD, and determine the cause of low binding. PMID:23453288

  18. 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

  19. 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…

  20. Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population.

    PubMed

    Wen, Zujia; Chen, Jianhua; Khan, Raja Amjad Waheed; Song, Zhijian; Wang, Meng; Li, Zhiqiang; Shen, Jiawei; Li, Wenjin; Shi, Yongyong

    2016-04-01

    Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye  = 0.015) and rs4512342 (Pallele  = 0.03, Pgenotye  = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye  = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population.

  1. 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

  2. Neural temporal dynamics of stress in comorbid major depressive disorder and social anxiety disorder

    PubMed Central

    2012-01-01

    Background Despite advances in neurobiological research on Major Depressive Disorder and Social Anxiety Disorder, little is known about the neural functioning of individuals with comorbid depression/social anxiety. We examined the timing of neural responses to social stress in individuals with major depression and/or social anxiety. We hypothesized that having social anxiety would be associated with earlier responses to stress, having major depression would be associated with sustained responses to stress, and that comorbid participants would exhibit both of these response patterns. Methods Participants were females diagnosed with pure depression (n = 12), pure social anxiety (n = 16), comorbid depression/social anxiety (n = 17), or as never having had any Axis-I disorder (control; n = 17). Blood oxygenation-level dependent activity (BOLD) was assessed with functional magnetic resonance imaging (fMRI). To induce social stress, participants prepared a speech that was ostensibly to be evaluated by a third party. Results Whereas being diagnosed with depression was associated with a resurgence of activation in the medial frontal cortex late in the stressor, having social anxiety was associated with a vigilance-avoidance activation pattern in the occipital cortex and insula. Comorbid participants exhibited activation patterns that generally overlapped with the non-comorbid groups, with the exception of an intermediate level of activation, between the level of activation of the pure depression and social anxiety groups, in the middle and posterior cingulate cortex. Conclusions These findings advance our understanding of the neural underpinnings of major depression and social anxiety, and of their comorbidity. Future research should elucidate more precisely the behavioral correlates of these patterns of brain activation. PMID:22738335

  3. Subchronic treatment with aldosterone induces depression-like behaviours and gene expression changes relevant to major depressive disorder.

    PubMed

    Hlavacova, Natasa; Wes, Paul D; Ondrejcakova, Maria; Flynn, Marianne E; Poundstone, Patricia K; Babic, Stanislav; Murck, Harald; Jezova, Daniela

    2012-03-01

    The potential role of aldosterone in the pathophysiology of depression is unclear. The aim of this study was to test the hypothesis that prolonged elevation of circulating aldosterone induces depression-like behaviour accompanied by disease-relevant changes in gene expression in the hippocampus. Subchronic (2-wk) treatment with aldosterone (2 μg/100 g body weight per day) or vehicle via subcutaneous osmotic minipumps was used to induce hyperaldosteronism in male rats. All rats (n = 20/treatment group) underwent a modified sucrose preference test. Half of the animals from each treatment group were exposed to the forced swim test (FST), which served both as a tool to assess depression-like behaviour and as a stress stimulus. Affymetrix microarray analysis was used to screen the entire rat genome for gene expression changes in the hippocampus. Aldosterone treatment induced an anhedonic state manifested by decreased sucrose preference. In the FST, depressogenic action of aldosterone was manifested by decreased latency to immobility and increased time spent immobile. Aldosterone treatment resulted in transcriptional changes of genes in the hippocampus involved in inflammation, glutamatergic activity, and synaptic and neuritic remodelling. Furthermore, aldosterone-regulated genes substantially overlapped with genes affected by stress in the FST. This study demonstrates the existence of a causal relationship between the hyperaldosteronism and depressive behaviour. In addition, aldosterone treatment induced changes in gene expression that may be relevant to the aetiology of major depressive disorder. Subchronic treatment with aldosterone represents a new animal model of depression, which may contribute to the development of novel targets for the treatment of depression.

  4. 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…

  5. 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

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

    PubMed

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

    2015-11-01

    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

  7. 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

  8. 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)…

  9. 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

  10. 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

  11. 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

  12. Mindfulness predicts relapse/recurrence in major depressive disorder after mindfulness-based cognitive therapy.

    PubMed

    Michalak, Johannes; Heidenreich, Thomas; Meibert, Petra; Schulte, Dietmar

    2008-08-01

    Empirical evidence for the effectiveness of mindfulness-based cognitive therapy (MBCT) is encouraging. However, data concerning the role of mindfulness in its relapse preventive effect are lacking. In our study, 25 formerly depressed patients received MBCT. Mindfulness was assessed before and immediately after MBCT using the Mindful Attention and Awareness Scale. Mindfulness significantly increased during MBCT, and posttreatment levels of mindfulness predicted the risk of relapse/recurrence to major depressive disorder in the 12-month follow-up period. Mindfulness predicted the risk of relapse/recurrence after controlling for numbers of previous episodes and residual depressive symptoms. The results provide preliminary evidence for the notion that mindfulness is an important factor in relapse prevention in major depression.

  13. 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

  14. 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

  15. 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

  16. Stress-evoked opioid release inhibits pain in major depressive disorder.

    PubMed

    Frew, Ashley K; Drummond, Peter D

    2008-10-15

    To determine whether stress-evoked release of endogenous opioids might account for hypoalgesia in major depressive disorder (MDD), the mu-opioid antagonist naltrexone (50mg) or placebo was administered double-blind to 24 participants with MDD and to 31 non-depressed controls. Eighty minutes later participants completed a painful foot cold pressor test and, after a 5-min interval, began a 25-min arithmetic task interspersed with painful electric shocks. Ten minutes later participants completed a second cold pressor test. Negative affect was greater in participants with MDD than in non-depressed controls throughout the experiment, and increased significantly in both groups during mental arithmetic. Before the math task, naltrexone unmasked direct linear relationships between severity of depression, negative affect while resting quietly, and cold-induced pain in participants with MDD. In contrast, facilitatory effects of naltrexone on cold- and shock-induced pain were greatest in controls with the lowest depression scores. Naltrexone strengthened the relationship between negative affect and shock-induced pain during the math task, particularly in the depressed group, and heightened anxiety in both groups toward the end of the task. Thus, mu-opioid activity apparently masked a positive association between negative affect and pain in the most distressed participants. These findings suggest that psychological distress inhibits pain via stress-evoked release of opioid peptides in severe cases of MDD. In addition, tonic endogenous opioid neurotransmission could inhibit depressive symptoms and pain in people with low depression scores.

  17. An Examination of Horace Wells' Life as a Manifestation of Major Depressive and Seasonal Affective Disorders.

    PubMed

    Martin, Ramon F; Desai, Sukumar P

    2016-01-01

    Horace Wells was a Hartford, Connecticut, dentist whose practice flourished because of his clinical skills. He had an imaginative mind that propelled him to the forefront in several aspects of dentistry. Unfortunately, he suffered a recurrent "illness" that began in the winter and resolved in the spring. These symptoms were compatible with both major depressive disorder and seasonal affective disorder as a qualifier. Wells' introduction of nitrous oxide as an anesthetic was also associated with self-inhalation. This led to periods of hypomania, followed by depression. With the progression to ether, then chloroform, there was an episode of mania in January 1848, followed by depression and suicide.

  18. "Nudges" to Prevent Behavioral Risk Factors Associated With Major Depressive Disorder.

    PubMed

    Woodend, Ashleigh; Schölmerich, Vera; Denktaş, Semiha

    2015-11-01

    Major depressive disorder-colloquially called "depression"-is a primary global cause of disability. Current preventive interventions, such as problem-solving therapy, are effective but also expensive. "Nudges" are easy and cheap interventions for altering behavior. We have explored how nudging can reduce three behavioral risk factors of depression: low levels of physical activity, inappropriate coping mechanisms, and inadequate maintenance of social ties. These nudges use cognitive biases associated with these behavioral risks, such as valuing the present more than the future, following the herd or the norm, making different choices in light of equivalent conditions, and deciding on the basis of salience or attachment to status quo.

  19. The role of the potassium channel gene KCNK2 in major depressive disorder.

    PubMed

    Congiu, Chiara; Minelli, Alessandra; Bonvicini, Cristian; Bortolomasi, Marco; Sartori, Riccardo; Maj, Carlo; Scassellati, Catia; Maina, Giuseppe; Trabucchi, Luigi; Segala, Matilde; Gennarelli, Massimo

    2015-02-28

    Six single nucleotide polymorphisms (SNPs) of the KCNK2 gene were investigated for their association with major depressive disorder (MDD) and treatment efficacy in 590 MDD patients and 441 controls. The A homozygotes of rs10779646 were significantly more frequent in patients than controls whereas G allele of rs7549184 was associated with the presence of psychotic symptoms and the severity of disease. Evaluating the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we confirmed our findings.

  20. 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…

  1. 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.

  2. Resting-state connectivity predictors of response to psychotherapy in major depressive disorder.

    PubMed

    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

    2015-06-01

    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

  3. Increased occipital delta dipole density in major depressive disorder determined by magnetoencephalography

    PubMed Central

    Fernández, Alberto; Rodriguez-Palancas, Alfonso; López-Ibor, MarÍa; Zuluaga, Pilar; Turrero, AgustÍn; Maestú, Fernando; Amo, Carlos; López-Ibor, Juan José; Ortiz, Tomás

    2005-01-01

    Objective To test the hypothesis that there is increased low-frequency activity located predominantly in the frontal lobe in patients with major depressive disorder using magnetoencephalography. Methods We carried out an unmatched or separate sampling case–control study of 31 medication-free patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for major depressive disorder and were outpatients of the Hospital Central de la Defensa, Madrid, and 22 healthy control subjects with no history of mental illness. A logistic regression analysis was employed to examine the predictive value of magnetoencephalography dipole density scores in the diagnosis of depression. We attempted to locate generators of focal magnetic slow waves by employing a single moving dipole model and by calculating dipole densities in prefrontal, frontal, parietal, temporal and occipital areas. The study lasted from February 2001 to January 2003. Results Only 2 dipole density scores, right occipital delta and left temporal delta, were significantly related to depression. According to the comparison of univariate and multivariate models and odds ratios, the right occipital delta dipole density is the factor with the greatest predictive power for depression, and the only one to show a significant correlation with severity of depression. Conclusions We did not find any frontal lobe functional alteration. Our study provides, to the best of our knowledge, the first evidence of abnormal focal magnetic low-frequency activity in the occipital lobe of untreated patients with depression. Increased occipital lobe delta dipole density seems to be a reliable risk factor for depression, which correlates with disease severity according to the Hamilton Rating Scale for Depression. PMID:15644993

  4. 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

  5. Posttraumatic Stress Disorder Increases Sensitivity to Long Term Losses among Patients with Major Depressive Disorder

    PubMed Central

    Vaughan, Christopher; Paulus, Martin P.; Dunlop, Boadie W.

    2013-01-01

    Background Decisions under risk and with outcomes that are delayed in time are ubiquitous in real life and can have a significant impact on the health and wealth of the decision-maker. Despite its potential relevance for real-world choices, the degree of aberrant risky and intertemporal decision-making in patients suffering from major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) has received little attention to date. Method We used a case-control design to compare decision-making in healthy control subjects (N=16) versus untreated depressed subjects in a current major depressive episode (N=20). In order to examine how major depressive disorder (MDD) may impact decision-making, subjects made decisions over (1) risky outcomes and (2) delayed outcomes in the domain of gains and losses using choice paradigms from neuroeconomics. In a pre-planned analysis, depressed subjects were subdivided into those with primary PTSD along with comorbid MDD (MDD+PTSD) versus those with primary MDD without PTSD (MDD-only). Choice behavior was modeled via a standard econometric model of intertemporal choice, a quasi-hyperbolic temporal discounting function, which was estimated for each subject group separately. Results Under conditions of potential gain, depressed subjects demonstrated greater discounting for gains across all time frames compared to controls. In the realm of losses, both subgroups of depressed subjects discounted more steeply than controls for short time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD subjects showed shallower discounting rates relative to MDD-only subjects, who continued to discount future losses steeply. Risk attitudes did not contribute to differences in intertemporal choice. Conclusions Depressed patients make choices that minimize current pain and maximize current reward, despite severe later consequences or lost opportunities. Anxiety associated with PTSD may serve as a partially protective factor in

  6. The symptom cluster-based approach to individualize patient-centered treatment for major depression.

    PubMed

    Lin, Steven Y; Stevens, Michael B

    2014-01-01

    Unipolar major depressive disorder is a common, disabling, and costly disease that is the leading cause of ill health, early death, and suicide in the United States. Primary care doctors, in particular family physicians, are the first responders in this silent epidemic. Although more than a dozen different antidepressants in 7 distinct classes are widely used to treat depression in primary care, there is no evidence that one drug is superior to another. Comparative effectiveness studies have produced mixed results, and no specialty organization has published recommendations on how to choose antidepressants in a rational, evidence-based manner. In this article we present the theory and evidence for an individualized, patient-centered treatment model for major depression designed around a targeted symptom cluster-based approach to antidepressant selection. When using this model for healthy adults with major depressive disorder, the choice of antidepressants should be guided by the presence of 1 of 4 common symptom clusters: anxiety, fatigue, insomnia, and pain. This model was built to foster future research, provide a logical framework for teaching residents how to select antidepressants, and equip primary care doctors with a structured treatment strategy to deliver optimal patient-centered care in the management of a debilitating disease: major depressive disorder.

  7. 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

  8. 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

  9. Major paternal depression and child consultation for developmental and behavioural problems

    PubMed Central

    Davé, Shreya; Sherr, Lorraine; Senior, Rob; Nazareth, Irwin

    2009-01-01

    Background It is well established that maternal depression is associated with enhanced child consultation for developmental and behaviour problems, but there is a dearth of research on paternal depression and child outcome. Aim To assess the association of major paternal depressed mood and child consultation for developmental and behaviour problems. Design of study Cross-sectional study. Setting General practices in London and Hertfordshire, UK. Method Fathers of children aged 4–6 years were recruited via 13 general practices. A sample of 248 biological father and mother dyads completed measures on depressive syndrome (Patient Health Questionnaire), child consultations with health professionals for developmental and behaviour problems, fathering, couple relationship quality, alcohol misuse, other psychiatric impairment, and sociodemographic factors. Results Eight out of 248 fathers (3%) had a major depressive syndrome. Sixty-five out of 247 (26%) fathers reported they were responsible for taking their child to see the doctor at least half the time compared with mothers. Children of fathers with a major depressive syndrome were almost nine times more likely to have consulted a health professional for speech and language problems (adjusted odds ratio [OR] = 8.67, 95% confidence interval [CI] = 1.99 to 37.67, P = 0.004) and seven times more likely to have consulted for externalising behaviour problems (adjusted OR = 6.98, 95% CI = 1.00 to 48.76, P = 0.05). Conclusion Children of fathers with major depression were more likely to consult for speech and language problems and externalising behaviour problems. A longitudinal study is recommended to identify causal mechanisms. PMID:19275834

  10. Reduced Specificity of Personal Goals and Explanations for Goal Attainment in Major Depression

    PubMed Central

    Dickson, Joanne M.; Moberly, Nicholas J.

    2013-01-01

    Objectives Overgeneralization has been investigated across many domains of cognitive functioning in major depression, including the imagination of future events. However, it is unknown whether this phenomenon extends to representations of personal goals, which are important in structuring long-term behaviour and providing meaning in life. Furthermore, it is not clear whether depressed individuals provide less specific explanations for and against goal attainment. Method Clinically depressed individuals and controls generated personally important approach and avoidance goals, and then generated explanations why they would and would not achieve these goals. Goals and causal explanations were subsequently coded as either specific or general. Results Compared to controls, depressed individuals did not generate significantly fewer goals or causal explanations for or against goal attainment. However, compared to controls, depressed individuals generated less specific goals, less specific explanations for approach (but not avoidance) goal attainment, and less specific explanations for goal nonattainment. Significance Our results suggest that motivational deficits in depression may stem partly from a reduction in the specificity of personal goal representations and related cognitions that support goal-directed behaviour. Importantly, the findings have the potential to inform the ongoing development of psychotherapeutic approaches in the treatment of depression. PMID:23691238

  11. 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.

  12. Hypothalamus-anchored resting brain network changes before and after sertraline treatment in major depression.

    PubMed

    Yang, Rui; Zhang, Hongbo; Wu, Xiaoping; Yang, Junle; Ma, Mingyue; Gao, Yanjun; Liu, Hongsheng; Li, Shengbin

    2014-01-01

    Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline) on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n = 12) both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.

  13. Cortical thickness predicts the first onset of major depression in adolescence.

    PubMed

    Foland-Ross, Lara C; Sacchet, Matthew D; Prasad, Gautam; Gilbert, Brooke; Thompson, Paul M; Gotlib, Ian H

    2015-11-01

    Given the increasing prevalence of Major Depressive Disorder and recent advances in preventative treatments for this disorder, an important challenge in pediatric neuroimaging is the early identification of individuals at risk for depression. We examined whether machine learning can be used to predict the onset of depression at the individual level. Thirty-three never-disordered adolescents (10-15 years old) underwent structural MRI. Participants were followed for 5 years to monitor the emergence of clinically significant depressive symptoms. We used support vector machines (SVMs) to test whether baseline cortical thickness could reliably distinguish adolescents who develop depression from adolescents who remained free of any Axis I disorder. Accuracies from subsampled cross-validated classification were used to assess classifier performance. Baseline cortical thickness correctly predicted the future onset of depression with an overall accuracy of 70% (69% sensitivity, 70% specificity; p=0.021). Examination of SVM feature weights indicated that the right medial orbitofrontal, right precentral, left anterior cingulate, and bilateral insular cortex contributed most strongly to this classification. These findings indicate that cortical gray matter structure can predict the subsequent onset of depression. An important direction for future research is to elucidate mechanisms by which these anomalies in gray matter structure increase risk for developing this disorder. PMID:26315399

  14. An everyday activity as a treatment for depression: The benefits of expressive writing for people diagnosed with major depressive disorder

    PubMed Central

    Krpan, Katherine M.; Kross, Ethan; Berman, Marc G.; Deldin, Patricia J.; Askren, Mary K.; Jonides, John

    2013-01-01

    Background The benefits of expressive writing have been well documented among several populations, but particularly among those who report feelings of dysphoria. It is not known, however, if those diagnosed with Major Depressive Disorder (MDD) would also benefit from expressive writing. Methods Forty people diagnosed with current MDD by the Structured Clinical Interview for DSM-IV participated in the study. On day 1 of testing, participants completed a series of questionnaires and cognitive tasks. Participants were then randomly assigned to either an expressive writing condition in which they wrote for 20 min over three consecutive days about their deepest thoughts and feelings surrounding an emotional event (n=20), or to a control condition (n=20) in which they wrote about non-emotional daily events each day. On day 5 of testing, participants completed another series of questionnaires and cognitive measures. These measures were repeated again 4 weeks later. Results People diagnosed with MDD in the expressive writing condition showed significant decreases in depression scores (Beck Depression Inventory and Patient Health Questionnaire-9 scores) immediately after the experimental manipulation (Day 5). These benefits persisted at the 4-week follow-up. Limitations Self-selected sample. Conclusions This is the first study to demonstrate the efficacy of expressive writing among people formally diagnosed with current MDD. These data suggest that expressive writing may be a useful supplement to existing interventions for depression. PMID:23790815

  15. Olfactory sulcus morphology in patients with current and past major depression.

    PubMed

    Takahashi, Tsutomu; Nishikawa, Yumiko; Yücel, Murat; Whittle, Sarah; Lorenzetti, Valentina; Walterfang, Mark; Sasabayashi, Daiki; Suzuki, Michio; Pantelis, Christos; Allen, Nicholas B

    2016-09-30

    Olfactory deficits have been reported in major depressive disorder (MDD). However, it remains largely unknown whether MDD is associated with abnormalities in olfactory sulcus morphology, a potential marker of olfactory system development. This magnetic resonance imaging study investigated the length and depth of the olfactory sulcus in 29 currently depressed patients, 27 remitted depressed patients, and 33 age- and gender-matched healthy control subjects. Both current and remitted MDD patients had significantly shallower olfactory sulci bilaterally as compared with controls. Only for male subjects, the right olfactory sulcus was significantly shorter in remitted MDD patients than in controls. The right sulcus depth was negatively correlated with number of depressive episodes in the entire MDD group and with residual depressive symptoms in the remitted MDD group. Medication status, presence of melancholia, and comorbidity with anxiety disorders did not affect the sulcus morphology. These findings suggest that abnormality of the olfactory sulcus morphology, especially its depth, may be a trait-related marker of vulnerability to major depression.

  16. Olfactory sulcus morphology in patients with current and past major depression.

    PubMed

    Takahashi, Tsutomu; Nishikawa, Yumiko; Yücel, Murat; Whittle, Sarah; Lorenzetti, Valentina; Walterfang, Mark; Sasabayashi, Daiki; Suzuki, Michio; Pantelis, Christos; Allen, Nicholas B

    2016-09-30

    Olfactory deficits have been reported in major depressive disorder (MDD). However, it remains largely unknown whether MDD is associated with abnormalities in olfactory sulcus morphology, a potential marker of olfactory system development. This magnetic resonance imaging study investigated the length and depth of the olfactory sulcus in 29 currently depressed patients, 27 remitted depressed patients, and 33 age- and gender-matched healthy control subjects. Both current and remitted MDD patients had significantly shallower olfactory sulci bilaterally as compared with controls. Only for male subjects, the right olfactory sulcus was significantly shorter in remitted MDD patients than in controls. The right sulcus depth was negatively correlated with number of depressive episodes in the entire MDD group and with residual depressive symptoms in the remitted MDD group. Medication status, presence of melancholia, and comorbidity with anxiety disorders did not affect the sulcus morphology. These findings suggest that abnormality of the olfactory sulcus morphology, especially its depth, may be a trait-related marker of vulnerability to major depression. PMID:27526191

  17. Delivering happiness: translating positive psychology intervention research for treating major and minor depressive disorders.

    PubMed

    Layous, Kristin; Chancellor, Joseph; Lyubomirsky, Sonja; Wang, Lihong; Doraiswamy, P Murali

    2011-08-01

    Despite the availability of many treatment options, depressive disorders remain a global public health problem. Even in affluent nations, 70% of reported cases either do not receive the recommended level of treatment or do not get treated at all, and this percentage does not reflect cases of depression that go unreported due to lack of access to health care, stigma, or other reasons. In developing countries, the World Health Organization estimates that <10% receive proper depression care due to poverty, stigma, and lack of governmental mental health resources and providers. Current treatments do not work for everyone, and even people who achieve remission face a high risk of recurrence and residual disability. The development of low-cost effective interventions that can serve either as initial therapy for mild symptoms or as adjunctive therapy for partial responders to medication is an immense unmet need. Positive activity interventions (PAIs) teach individuals ways to increase their positive thinking, positive affect, and positive behaviors. The majority of such interventions, which have obtained medium-size effect sizes, have been conducted with nondepressed individuals, but two randomized controlled studies in patients with mild clinical depression have reported promising initial findings. In this article, the authors review the relevant literature on the effectiveness of various types of PAIs, draw on social psychology, affective neuroscience and psychophamacology research to propose neural models for how PAIs might relieve depression, and discuss the steps needed to translate the potential promise of PAIs as clinical treatments for individuals with major and minor depressive disorders.

  18. 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.

  19. [Clinical Introduction of Repetitive Transcranial Magnetic Stimulation for Major Depression in Japan].

    PubMed

    Nakamura, Motoaki

    2015-01-01

    Therapeutic applications of repetitive transcranial magnetic stimulation (rTMS) have long been awaited for not only neurological but also psychiatric disorders as a low-invasive transcranial brain stimulation. In 2008, the Food and Drug Administration (FDA) of the United States finally approved repetitive transcranial magnetic stimulation (rTMS) for medication-resistant patients with major depression. More recently, at the beginning of 2013, a deep TMS device with the H-coil received FDA approval as the second TMS device for major depression. In Japan, it is estimated that more than 200,000 patients with medication-resistant major depression could be candidates for rTMS treatment. To promote the clinical introduction of rTMS for major depression, joint discussion has been ongoing including the Japanese Society of Psychiatry and Neurology (JSPN), the Japanese Ministry of Health, Labour, and Welfare (MHLW), and the Pharmaceutical and Medical Devices Agency (PMDA). On the other hand, some corporate efforts have begun to get MHLW/PMDA approval for a few types of rTMS device. In 2013, the JSPN established a new committee in order to discuss the introduction of neuromodulation methods such as rTMS in Japan. The committee has been discussing how rTMS should be introduced appropriately with expedition, considering the MHLW regulations for the expedited introduction or provisional use of advanced medical technology. Also, the MHLW has required related psychiatric societies to formulate clinical guidelines of rTMS for major depression in order to avoid any potential overuse or misuse. A number of controversies are ongoing, such as standards for the appropriate clinical application of rTMS, a suitable position of rTMS within the comprehensive treatment algorithm of major depression, and bioethical standards for brain stimulation (neuroethics). Moreover, there are some pragmatic issues. For instance, the Japanese Society of Clinical Neurophysiology (JSCN) has restricted

  20. [Clinical Introduction of Repetitive Transcranial Magnetic Stimulation for Major Depression in Japan].

    PubMed

    Nakamura, Motoaki

    2015-01-01

    Therapeutic applications of repetitive transcranial magnetic stimulation (rTMS) have long been awaited for not only neurological but also psychiatric disorders as a low-invasive transcranial brain stimulation. In 2008, the Food and Drug Administration (FDA) of the United States finally approved repetitive transcranial magnetic stimulation (rTMS) for medication-resistant patients with major depression. More recently, at the beginning of 2013, a deep TMS device with the H-coil received FDA approval as the second TMS device for major depression. In Japan, it is estimated that more than 200,000 patients with medication-resistant major depression could be candidates for rTMS treatment. To promote the clinical introduction of rTMS for major depression, joint discussion has been ongoing including the Japanese Society of Psychiatry and Neurology (JSPN), the Japanese Ministry of Health, Labour, and Welfare (MHLW), and the Pharmaceutical and Medical Devices Agency (PMDA). On the other hand, some corporate efforts have begun to get MHLW/PMDA approval for a few types of rTMS device. In 2013, the JSPN established a new committee in order to discuss the introduction of neuromodulation methods such as rTMS in Japan. The committee has been discussing how rTMS should be introduced appropriately with expedition, considering the MHLW regulations for the expedited introduction or provisional use of advanced medical technology. Also, the MHLW has required related psychiatric societies to formulate clinical guidelines of rTMS for major depression in order to avoid any potential overuse or misuse. A number of controversies are ongoing, such as standards for the appropriate clinical application of rTMS, a suitable position of rTMS within the comprehensive treatment algorithm of major depression, and bioethical standards for brain stimulation (neuroethics). Moreover, there are some pragmatic issues. For instance, the Japanese Society of Clinical Neurophysiology (JSCN) has restricted

  1. Correlates of Psychological Distress and Major Depressive Disorder Among African American Men

    PubMed Central

    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 demographic differences in depressive symptoms (measured by the Center for Epidemiological Studies Depression scale [CES-D]), SPD (measured by the K6), and 12-month and lifetime MDD among African American men. Findings illuminate the heterogeneity within the African American male population. Findings also demonstrate the need for additional research focusing on within-group differences and a comprehensive research and mental health promotion agenda that recognizes the importance of improving access to education and employment and promoting healthy coping behaviors, while acknowledging the larger social context in which African American men live. PMID:21666885

  2. Correlates of Psychological Distress and Major Depressive Disorder Among African American Men.

    PubMed

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

    2011-05-01

    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 demographic differences in depressive symptoms (measured by the Center for Epidemiological Studies Depression scale [CES-D]), SPD (measured by the K6), and 12-month and lifetime MDD among African American men. Findings illuminate the heterogeneity within the African American male population. Findings also demonstrate the need for additional research focusing on within-group differences and a comprehensive research and mental health promotion agenda that recognizes the importance of improving access to education and employment and promoting healthy coping behaviors, while acknowledging the larger social context in which African American men live.

  3. 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

  4. 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

  5. Comparison Between the Montgomery-Asberg Depression Rating Scale–Self and the Beck Depression Inventory II in Primary Care

    PubMed Central

    Nejati, Shabnam; Larsson, Maria E. H.; Petersson, Eva-Lisa; Westman, Jeanette; Ariai, Nashmil; Kivi, Marie; Eriksson, Maria; Eggertsen, Robert; Hange, Dominique; Baigi, Amir; Björkelund, Cecilia

    2015-01-01

    Objective: The Montgomery-Asberg Depression Rating Scale–Self (MADRS-S) and the Beck Depression Inventory II (BDI-II) are commonly used self-assessment instruments for screening and diagnosis of depression. The BDI-II has 21 items and the MADRS-S has 9 items. These instruments have been tested with psychiatric inpatients but not in outpatient primary care, where most patients with symptoms of depression initially seek treatment. The purpose of this study was to compare these 2 instruments in the primary care setting. Method: Data were collected from 2 primary care randomized controlled trials that were performed from 2010 to 2013 in Sweden: the Primary Care Self-Assessment MADRS-S Study and Primary Care Internet-Based Cognitive Behavioral Therapy Study. There were 146 patients (73 patients each from both trials) who had newly diagnosed mild or moderate depression (per DSM-IV recommendations) and who had assessment with both the MADRS-S and BDI-II at primary care centers. Comparability and reliability of the instruments were estimated by Pearson product moment correlation and Cronbach α. Results: A good correlation was observed between the 2 instruments: 0.66 and 0.62 in the 2 study cohorts. The reliability within the 2 study cohorts was good for both MADRS-S (Cronbach α: 0.76 for both cohorts) and BDI-II items (Cronbach α: 0.88 and 0.85). Conclusions: The 2 instruments showed good comparability and reliability for low, middle, and high total depression scores. The MADRS-S may be used as a rapid, easily administered, and inexpensive tool in primary care and has results comparable to the BDI-II in all domains. PMID:26644958

  6. Anterograde Amnesia during Electroconvulsive Therapy: A Prospective Pilot-Study in Patients with Major Depressive Disorder

    PubMed Central

    Boere, Elvira; Kamperman, Astrid M.; van 't Hoog, Arianne E.; van den Broek, Walter W.; Birkenhäger, Tom K.

    2016-01-01

    Electroconvulsive therapy (ECT) is considered an effective treatment for major depression with melancholic features. However, neurocognitive side-effects such as anterograde amnesia still regularly occur. The present study aims to evaluate the severity and course of anterograde amnesia in severely depressed patients undergoing ECT. In a prospective naturalistic study, anterograde memory function was assessed among inpatients who underwent ECT (n = 11). Subjects met DSM-IV criteria for major depressive disorder. Recruitment took place between March 2010-March 2011 and March 2012-March 2013. Controls treated with antidepressants (n = 9) were matched for age, gender and depression severity. Primary outcome measure was immediate recall; secondary outcome measures were delayed recall, recognition, and visual association. Differences were tested using repeated measures ANOVA and paired t-tests. Correlations with hypothesized covariates were calculated. In patients with major depressive disorder, ECT had a significant effect on delayed memory function (p<0.01 with large effect sizes). Findings on immediate recall were less consistent. Four weeks after treatment discontinuation, these memory functions had recovered. Age was identified as a very important covariate. The main limitations of our study are its naturalistic design, possibly compromising internal validity, and its small sample size. However, if these findings can be reproduced in a more comprehensive study group, then the possible induction of anterograde amnesia is not a justifiable reason for clinicians to disregard ECT as a treatment option. PMID:27768745

  7. Neural correlates of change in major depressive disorder anhedonia following open-label ketamine.

    PubMed

    Lally, Níall; Nugent, Allison C; Luckenbaugh, David A; Niciu, Mark J; Roiser, Jonathan P; Zarate, Carlos A

    2015-05-01

    Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive disorder in an open-label investigation. Additionally, participants received either oral riluzole or placebo daily beginning 4 hours post-infusion. A subgroup of patients underwent fluorodeoxyglucose positron emission tomography scans at baseline (1-3 days pre-infusion) and 2 hours post-ketamine infusion. Anhedonia rapidly decreased following a single ketamine infusion; this was sustained for up to three days, but was not altered by riluzole. Reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC). The tentative relationship between change in anhedonia and glucose metabolism remained significant in dACC and OFC, and at trend level in the hippocampus, a result not anticipated, when controlling for change in total depression score. Results, however, remain tenuous due to the lack of a placebo control for ketamine. In addition to alleviating overall depressive symptoms, ketamine could possess anti-anhedonic potential in major depressive disorder, which speculatively, may be mediated by alterations in metabolic activity in the hippocampus, dACC and OFC.

  8. Mirtazapine: a review of its use in major depression and other psychiatric disorders.

    PubMed

    Croom, Katherine F; Perry, Caroline M; Plosker, Greg L

    2009-01-01

    Mirtazapine (Remeron, Zispin) is a noradrenergic and specific serotonergic antidepressant (NaSSA) that is approved in many counties for use in the treatment of major depression. Monotherapy with mirtazapine 15-45 mg/day leads to rapid and sustained improvements in depressive symptoms in patients with major depression, including the elderly. It is as effective as other antidepressants and may have a more rapid onset of action than selective serotonin reuptake inhibitors (SSRIs). Furthermore, it may also have a higher sustained remission rate than amitriptyline. Preliminary data suggest that mirtazapine may also be effective in the treatment of anxiety disorders (including post-traumatic stress disorder, panic disorder and social anxiety disorder), obsessive-compulsive disorder, undifferentiated somatoform disorder and, as add-on therapy, in schizophrenia, although large, well designed trials are needed to confirm these findings. Mirtazapine is generally well tolerated in patients with depression. In conclusion, mirtazapine is an effective antidepressant for the treatment of major depression and also has the potential to be of use in other psychiatric indications. PMID:19453203

  9. 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

  10. Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder.

    PubMed

    Savitz, Jonathan; Drevets, Wayne C; Wurfel, Brent E; Ford, Bart N; Bellgowan, Patrick S F; Victor, Teresa A; Bodurka, Jerzy; Teague, T Kent; Dantzer, Robert

    2015-05-01

    Low-grade inflammation is characteristic of a subgroup of currently depressed patients with major depressive disorder (dMDD). It may lead to the activation of the kynurenine-metabolic pathway and the increased synthesis of potentially neurotoxic metabolites such as 3-hydroxykynurenine (3HK) and quinolinic acid (QA), relative to kynurenic acid (KynA). Nevertheless, few studies have examined whether abnormalities in this pathway are present in remitted patients with MDD (rMDD). Here we compared the serum concentrations of kynurenine metabolites, measured using high performance liquid chromatography with tandem mass spectrometry, across 49 unmedicated subjects meeting DSM-IV-TR criteria for MDD, 21 unmedicated subjects meeting DSM-IV-TR criteria for rMDD, and 58 healthy controls (HCs). There was no significant group difference in the concentrations of the individual kynurenine metabolites, however both the dMDD group and the rMDD group showed a reduction in KynA/QA, compared with the HCs. Further, there was an inverse correlation between KynA/QA and anhedonia in the dMDD group, while in the rMDD group, there was a negative correlation between lifetime number of depressive episodes and KynA/QA as well as a positive correlation between the number of months in remission and KynA/QA. Our results raise the possibility that a persistent abnormality exists within the kynurenine metabolic pathway in MDD that conceivably may worsen with additional depressive episodes. The question of whether persistent abnormalities in kynurenine metabolism predispose to depression and/or relapse in remitted individuals remains unresolved.

  11. 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

  12. 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

  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. 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

  15. 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.

  16. 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

  17. 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

  18. Reliability and Validity of the Beck Depression Inventory--II with Adolescent Psychiatric Inpatients

    ERIC Educational Resources Information Center

    Osman, Augustine; Kopper, Beverly A; Barrios, Frank; Gutierrez, Peter M.; Bagge, Courtney L.

    2004-01-01

    This investigation was conducted to validate the Beck Depression Inventory--II (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996) in samples of adolescent psychiatric inpatients. The sample in each substudy was primarily Caucasian. In Study 1, expert raters (N=7) and adolescent psychiatric inpatients (N=13) evaluated the BDI-II items to assess…

  19. Brain Serotonin 1A Receptor Binding as a Predictor of Treatment Outcome in Major Depressive Disorder

    PubMed Central

    Miller, Jeffrey M.; Hesselgrave, Natalie; Ogden, R. Todd; Zanderigo, Francesca; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

    2013-01-01

    Background We previously reported higher serotonin 1A receptor (5-HT1A) binding in subjects with major depressive disorder (MDD) during a major depressive episode using positron emission tomography imaging with [11C]WAY-100635. 5-HT1A receptor binding is also associated with treatment outcome after nonstandardized antidepressant treatment. We examined whether pretreatment 5-HT1A binding is associated with treatment outcome following standardized escitalopram treatment in MDD. We also compared 5-HT1A binding between all MDD subjects in this cohort and a sample of healthy control subjects. Methods Twenty-four MDD subjects in a current major depressive episode and 51 previously studied healthy control subjects underwent positron emission tomography scanning with [11C]WAY-100635, acquiring a metabolite-corrected arterial input function and free-fraction measurement to estimate 5-HT1A binding potential (BPF = Bmax/KD, where Bmax = available receptors and KD = dissociation constant). Major depressive disorder subjects then received 8 weeks of treatment with escitalopram; remission was defined as a posttreatment 24-item Hamilton Depression Rating Scale <10 and ≥50% reduction in Hamilton Depression Rating Scale. Results Remitters to escitalopram had 33% higher baseline 5-HT1A binding in the raphe nuclei than nonremitters (p = .047). Across 12 cortical and subcortical regions, 5-HT1A binding did not differ between remitters and nonremitters (p = .86). Serotonin 1A receptor binding was higher in MDD than control subjects across all regions (p = .0003). Remitters did not differ from nonremitters in several relevant clinical measures. Conclusions Elevated 5-HT1A binding in raphe nuclei is associated with subsequent remission with the selective serotonin reuptake inhibitor escitalopram; this is consistent with data from a separate cohort receiving naturalistic antidepressant treatment. We confirmed our previous findings of higher 5-HT1A binding in current MDD compared with

  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. Long term life dissatisfaction and subsequent major depressive disorder and poor mental health

    PubMed Central

    2011-01-01

    Background Poor mental health, especially due to depression, is one of the main public health problems. Early indicators of poor mental health in general population are needed. This study examined the relationship between long-term life dissatisfaction and subsequent mental health, including major depressive disorder. Method Health questionnaires were sent to a randomly selected population-based sample in 1998 and repeated in 1999 and 2001. In 2005, a clinically studied sub-sample (n = 330) was composed of subjects with (n = 161) or without (n = 169) repeatedly reported adverse mental symptoms at all three previous data collection times. Clinical symptom assessments were performed with several psychometric scales: life satisfaction (LS), depression (HDRS, BDI), hopelessness (HS), mental distress (GHQ), dissociative experiences (DES), and alexithymia (TAS). The long-term life dissatisfaction burden was calculated by summing these life satisfaction scores in 1998, 1999, 2001 and dividing the sum into tertiles. Psychiatric diagnoses were confirmed by SCID-I for DSM-IV in 2005. Logistic regression analyses were performed to assess the studied relationship. Results The previous life dissatisfaction burden associated with adverse socio-demographic, life style and clinical factors. In adjusted logistic regression analyses, it was independently and strongly associated with subsequent major depressive disorder in 2005, even when the concurrent LS score in 2005 was included in the model. Excluding those with reported major depressive disorder in 1999 did not alter this finding. Limitations MDD in 1999 was based on self-reports and not on structured interview and LS data in 2001-2005 was not available. Conclusions The life satisfaction burden is significantly related to major depressive disorder and poor mental health, both in cross-sectional and longitudinal settings. PMID:21861908

  2. 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

  3. Platelet 5-HT(1A) receptor correlates with major depressive disorder in drug-free patients.

    PubMed

    Zhang, Zhang-Jin; Wang, Di; Man, Sui Cheung; Ng, Roger; McAlonan, Grainne M; Wong, Hei Kiu; Wong, Wendy; Lee, Jade; Tan, Qing-Rong

    2014-08-01

    The platelet serotonergic system has potential biomarker utility for major depressive disorder (MDD). In the present study, platelet expression of 5-HT1A receptors and serotonin transporter (SERT) proteins, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were quantified in 53 patients with MDD and 22 unaffected controls. All were drug-free, non-smokers and had no other psychiatric and cardiovascular comorbidity. The severity of depression symptoms was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Self-rating Depression Scale (SDS). Patients with MDD had significantly higher expression of platelet 5-HT1A receptors but significantly lower contents of platelet 5-HT, platelet-poor plasma (PPP) 5-HT and PPP 5-HIAA compared to healthy controls, and this was correlated with the severity of depression. SERT expression did not differ between the two groups. Correlation analysis confirmed a strong, inverse relationship between the 5-HT1A receptor expression and the 5-HT and 5-HIAA levels. Thus overexpression of platelet 5-HT1A receptors and reduced 5-HT tone may function as a peripheral marker of depression.

  4. 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.

  5. Predictors of functional improvement in employed adults with major depressive disorder treated with desvenlafaxine.

    PubMed

    Lam, Raymond W; Endicott, Jean; Hsu, Ming-Ann; Fayyad, Rana; Guico-Pabia, Christine; Boucher, Matthieu

    2014-09-01

    We carried out a secondary analysis of a double-blind, placebo-controlled trial of desvenlafaxine for major depressive disorder (MDD) to explore the associations between depressive symptoms and subtypes, and functional outcomes, including work functioning. Employed outpatients with MDD were assigned randomly in a 2 : 1 ratio to receive desvenlafaxine 50 mg/day or placebo for 12 weeks. Analyses were carried out post-hoc with the intent-to-treat (ITT) sample (N=427) and a prospectively defined modified ITT sample (N=310), composed of patients with baseline 17-item Hamilton Rating Scale for Depression score of at least 20. Functional outcomes at week 12 included items and factors from the Montgomery-Åsberg Depression Rating Scale, Sheehan Disability Scale, and the Work Productivity and Activity Impairment questionnaire. In the modified ITT sample, but not in the ITT sample, desvenlafaxine-treated patients showed significantly greater improvement in several functional outcomes in the responder, nonanxious, and normal-energy patient subgroups. Improvement in the 17-item Hamilton Rating Scale for Depression total score at week 2 predicted change at week 12 in several functional outcomes. Functional improvement at 12 weeks was greater in subgroups of patients and was also significantly predicted by early improvement in depressive symptoms in employed patients with MDD treated with desvenlafaxine.

  6. Basolateral amygdala volume and cell numbers in major depressive disorder: a postmortem stereological study.

    PubMed

    Rubinow, Marisa J; Mahajan, Gouri; May, Warren; Overholser, James C; Jurjus, George J; Dieter, Lesa; Herbst, Nicole; Steffens, David C; Miguel-Hidalgo, Jose J; Rajkowska, Grazyna; Stockmeier, Craig A

    2016-01-01

    Functional imaging studies consistently report abnormal amygdala activity in major depressive disorder (MDD). Neuroanatomical correlates are less clear: imaging studies have produced mixed results on amygdala volume, and postmortem neuroanatomic studies have only examined cell densities in portions of the amygdala or its subregions in MDD. Here, we present a stereological analysis of the volume of, and the total number of, neurons, glia, and neurovascular (pericyte and endothelial) cells in the basolateral amygdala in MDD. Postmortem tissues from 13 subjects with MDD and 10 controls were examined. Sections (~15/subject) taken throughout the rostral-caudal extent of the basolateral amygdala (BLA) were stained for Nissl substance and utilized for stereological estimation of volume and cell numbers. Results indicate that depressed subjects had a larger lateral nucleus than controls and a greater number of total BLA neurovascular cells than controls. There were no differences in the number or density of neurons or glia between depressed and control subjects. These findings present a more detailed picture of BLA cellular anatomy in depression than has previously been available. Further studies are needed to determine whether the greater number of neurovascular cells in depressed subjects may be related to increased amygdala activity in depression.

  7. 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:…

  8. 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…

  9. Transcranial Brain Stimulation Techniques For Major Depression: Should We Extend TMS Lessons to tDCS?

    PubMed

    Dell'Osso, Bernardo; Altamura, A Carlo

    2014-01-01

    Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques that, by means of magnetic fields and low intensity electrical current, respectively, aim to interefere with and modulate cortical excitability, at the level of dorsolateral prefrontal cortex, in patients with major depression and poor response to standard antidepressants. While the clinical efficacy of TMS in major depression has been extensively investigated over the last 10 years, tDCS has attracted research interest only in the last years, with fewer randomized clinical trials (RCTs) in the field. Nevertheless, in spite of the different rationale and mechanism of action of the two techniques, tDCS recent acquisitions, in relation to the treatment of major depression, seem to parallel those previously obtained with TMS, in terms of treatment duration to achieve optimal benefit and patient's history of drug-resistance. After briefly introducing the two techniques, the article examines possible common pathways of clinical use for TMS and tDCS, emerging from recent RCTs and likely orienting future investigation with non invasive brain stimulation for the treatment of major depression.

  10. 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…

  11. 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…

  12. 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…

  13. 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)…

  14. Major Depression and Conduct Disorder in Youth: Associations with Parental Psychopathology and Parent-Child Conflict

    ERIC Educational Resources Information Center

    Marmorstein, Naomi R.; Iacono, William G.

    2004-01-01

    Background: This study examined conduct disorder (CD) and major depression (MDD) in adolescents in relationship to parent-child conflict and psychopathology in their parents. Method: Participants were drawn from a population-based sample of twins and their families. Affected participants had lifetime diagnoses of CD and/or MDD; controls had no…

  15. 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…

  16. 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…

  17. 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.

  18. 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…

  19. Behavioral Activation for Comorbid PTSD and Major Depression: A Case Study

    ERIC Educational Resources Information Center

    Mulick, Patrick S.; Naugle, Amy E.

    2004-01-01

    The present investigation details the assessment and use of Behavioral Activation (BA) therapy to treat a 37-year-old male police officer/military veteran suffering from posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). This case study is an attempt to expand empirical knowledge regarding BA, comorbid PTSD and MDD, and…

  20. 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).…

  1. 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…

  2. 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…

  3. 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,…

  4. 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

  5. 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…

  6. 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…

  7. 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…

  8. Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression.

    PubMed

    Haroon, E; Fleischer, C C; Felger, J C; Chen, X; Woolwine, B J; Patel, T; Hu, X P; Miller, A H

    2016-10-01

    Inflammation and altered glutamate metabolism are two pathways implicated in the pathophysiology of depression. Interestingly, these pathways may be linked given that administration of inflammatory cytokines such as interferon-α to otherwise non-depressed controls increased glutamate in the basal ganglia and dorsal anterior cingulate cortex (dACC) as measured by magnetic resonance spectroscopy (MRS). Whether increased inflammation is associated with increased glutamate among patients with major depression is unknown. Accordingly, we conducted a cross-sectional study of 50 medication-free, depressed outpatients using single-voxel MRS, to measure absolute glutamate concentrations in basal ganglia and dACC. Multivoxel chemical shift imaging (CSI) was used to explore creatine-normalized measures of other metabolites in basal ganglia. Plasma and cerebrospinal fluid (CSF) inflammatory markers were assessed along with anhedonia and psychomotor speed. Increased log plasma C-reactive protein (CRP) was significantly associated with increased log left basal ganglia glutamate controlling for age, sex, race, body mass index, smoking status and depression severity. In turn, log left basal ganglia glutamate was associated with anhedonia and psychomotor slowing measured by the finger-tapping test, simple reaction time task and the Digit Symbol Substitution Task. Plasma CRP was not associated with dACC glutamate. Plasma and CSF CRP were also associated with CSI measures of basal ganglia glutamate and the glial marker myoinositol. These data indicate that increased inflammation in major depression may lead to increased glutamate in the basal ganglia in association with glial dysfunction and suggest that therapeutic strategies targeting glutamate may be preferentially effective in depressed patients with increased inflammation as measured by CRP. PMID:26754953

  9. Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression

    PubMed Central

    Haroon, E; Fleischer, C C; Felger, J C; Chen, X; Woolwine, B J; Patel, T; Hu, X P; Miller, A H

    2016-01-01

    Inflammation and altered glutamate metabolism are two pathways implicated in the pathophysiology of depression. Interestingly, these pathways may be linked given that administration of inflammatory cytokines such as interferon-α to otherwise non-depressed controls increased glutamate in the basal ganglia and dorsal anterior cingulate cortex (dACC) as measured by magnetic resonance spectroscopy (MRS). Whether increased inflammation is associated with increased glutamate among patients with major depression is unknown. Accordingly, we conducted a cross-sectional study of 50 medication-free, depressed outpatients using single-voxel MRS, to measure absolute glutamate concentrations in basal ganglia and dACC. Multivoxel chemical shift imaging (CSI) was used to explore creatine-normalized measures of other metabolites in basal ganglia. Plasma and cerebrospinal fluid (CSF) inflammatory markers were assessed along with anhedonia and psychomotor speed. Increased log plasma C-reactive protein (CRP) was significantly associated with increased log left basal ganglia glutamate controlling for age, sex, race, body mass index, smoking status and depression severity. In turn, log left basal ganglia glutamate was associated with anhedonia and psychomotor slowing measured by the finger-tapping test, simple reaction time task and the Digit Symbol Substitution Task. Plasma CRP was not associated with dACC glutamate. Plasma and CSF CRP were also associated with CSI measures of basal ganglia glutamate and the glial marker myoinositol. These data indicate that increased inflammation in major depression may lead to increased glutamate in the basal ganglia in association with glial dysfunction and suggest that therapeutic strategies targeting glutamate may be preferentially effective in depressed patients with increased inflammation as measured by CRP. PMID:26754953

  10. Income inequality among American states and the incidence of major depression

    PubMed Central

    Pabayo, Roman; Kawachi, Ichiro; Gilman, Stephen E.

    2013-01-01

    Background Although cross-sectional and ecological studies have shown that higher area-level income inequality is related to increased risk for depression, few longitudinal studies have been conducted. This investigation examines the relationship between state-level income inequality and major depression among adults participating in a population-based, representative longitudinal study. Methods We used data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=34,653). Respondents completed structured diagnostic interviews at baseline (2001–2002) and follow-up (2004–2005). Weighted multi-level modeling was used to determine if US State-level income inequality (measured by the Gini coefficient) was a significant predictor of depression at baseline and at follow-up, while controlling for individual and state-level covariates. We also repeated the longitudinal analyses excluding those who had a history of depression or at baseline, in order to test whether income inequality was related to incident depression. Results State-level inequality was associated with increased incidence of depression among women but not men. In comparison to women residing in states belonging to the lowest quintile of income inequality, there was increased risks for depression among women in the second [Odds Ratio (OR)=1.18, 95% Confidence Interval (CI)=0.86,1.62], third (OR=1.22, 95% CI=0.91,1.62), fourth (OR=1.37, 95% CI=1.03,1.82), and fifth (OR=1.50, 95% CI=1.14,1.96) quintiles at follow-up (p<0.05 for the linear trend). Conclusion Living in a state with higher income inequality increases the risk for the development of depression among women. PMID:24064745

  11. 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

  12. Enriched pathways for major depressive disorder identified from a genome-wide association study.

    PubMed

    Kao, Chung-Feng; Jia, Peilin; Zhao, Zhongming; Kuo, Po-Hsiu

    2012-11-01

    Major depressive disorder (MDD) has caused a substantial burden of disease worldwide with moderate heritability. Despite efforts through conducting numerous association studies and now, genome-wide association (GWA) studies, the success of identifying susceptibility loci for MDD has been limited, which is partially attributed to the complex nature of depression pathogenesis. A pathway-based analytic strategy to investigate the joint effects of various genes within specific biological pathways has emerged as a powerful tool for complex traits. The present study aimed to identify enriched pathways for depression using a GWA dataset for MDD. For each gene, we estimated its gene-wise p value using combined and minimum p value, separately. Canonical pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta were used. We employed four pathway-based analytic approaches (gene set enrichment analysis, hypergeometric test, sum-square statistic, sum-statistic). We adjusted for multiple testing using Benjamini & Hochberg's method to report significant pathways. We found 17 significantly enriched pathways for depression, which presented low-to-intermediate crosstalk. The top four pathways were long-term depression (p⩽1×10-5), calcium signalling (p⩽6×10-5), arrhythmogenic right ventricular cardiomyopathy (p⩽1.6×10-4) and cell adhesion molecules (p⩽2.2×10-4). In conclusion, our comprehensive pathway analyses identified promising pathways for depression that are related to neurotransmitter and neuronal systems, immune system and inflammatory response, which may be involved in the pathophysiological mechanisms underlying depression. We demonstrated that pathway enrichment analysis is promising to facilitate our understanding of complex traits through a deeper interpretation of GWA data. Application of this comprehensive analytic strategy in upcoming GWA data for depression could validate the findings reported in this study.

  13. Influence of affective words on lexical decision task in major depression.

    PubMed Central

    Stip, E; Lecours, A R; Chertkow, H; Elie, R; O'Connor, K

    1994-01-01

    In cognitive science, lexical decision task is used to investigate visual word recognition and lexical access. The issue of whether or not individuals who are depressed differ in their access to affectively laden words and specifically to words that have negative affect was examined. Based on some aspects of the Resource Allocation Model (Ellis), it was postulated that patients suffering from depression take more time to recognize items from an affective-loaded list. In order to compare their behavior in a lexical decision task, patients suffering from depression and healthy controls were studied. We hoped to find an interaction between the mood state of subjects and the categories (affective or neutral) of words. Two groups of right-handed adults served as subjects in our experiment. The first group consisted of 11 patients suffering from depression (mean age: 40.2; sd: 6.8). All of this group met the DSM-III-R and the Research Diagnostic Criteria for major depressive disorder. Severity of their disease was rated using the 24-item Hamilton Depressive Rating Scale. All patients suffering from depression were without psychotropic medication. The control group was composed of 24 subjects (mean age: 32.7; sd: 7.9). A depressive word-list and a neutral word-list were built and a computer was used for the lexical-decision task. A longer reaction time to detect the non-word stimuli (F1,33 = 11.19, p < 0.01) was observed with the patients by comparison to the normal subjects. In the analysis of the word stimuli, a group by list interaction (F1,33 = 7.18, p < 0.01) was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8031744

  14. 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

  15. Effect of Sahaj Yoga on neuro-cognitive functions in patients suffering from major depression.

    PubMed

    Sharma, V K; Das, S; Mondal, S; Goswami, U; Gandhi, A

    2006-01-01

    Cognitive functions are impaired in Major Depression. Studies on the effects of Yoga on cognitive functions have shown improvement in memory, vigilance and anxiety levels. 30 patients suffering from Major depression (age 18 to 45 years) were randomly divided into two groups: Group 1: (10 males and 5 Females) Patients who practised Sahaj Yoga meditation and also received conventional anti-depressant medication. Group 2: (9 males and 6 Females) Patients who only received conventional antidepressant medication. Group 1 patients were administered Sahaj Yoga practice for 8 weeks. Neuro-cognitive test battery consisting of Letter cancellation test (LCT), Trail making test 'A' (TTA), Trail making test 'B' (TTB), Ruff figural fluency test (RFFT), Forward digit span (FDS) & Reverse digit span test (RDS) was used to assess following cognitive domains: Attention span, visuo-motor speed, short-term memory, working memory and executive functions. After 8 weeks, both Group 1 and Group 2 subjects showed significant improvement in LCT, TTA & TTB but improvement in LCT was more marked in Group 1 subjects. Also, there was significant improvement in RDS scores in only Group 1 subjects (P < 0.05). The results thereby, demonstrate that Sahaj Yoga practice in addition to the improvement in various other cognitive domains seen with conventional anti-depressants, can lead to additional improvement in executive functions like manipulation of information in the verbal working memory and added improvement in attention span and visuo-motor speed of the depressives.

  16. 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.

  17. Interpersonal psychotherapy (IPT) for major depression following perinatal loss: a pilot randomized controlled trial.

    PubMed

    Johnson, Jennifer E; Price, Ann Back; Kao, Jennifer Chienwen; Fernandes, Karen; Stout, Robert; Gobin, Robyn L; Zlotnick, Caron

    2016-10-01

    This randomized controlled pilot trial examined the feasibility, acceptability, and preliminary efficacy of an adapted interpersonal psychotherapy (IPT) for major depressive disorder (MDD) following perinatal loss (miscarriage, stillbirth, or early neonatal death). Fifty women who experienced a perinatal loss within the past 18 months, whose current depressive episode onset occurred during or after the loss, were randomized to the group IPT adapted for perinatal loss (the Group IPT for Major Depression Following Perinatal Loss manual developed for this study is available at no cost by contacting either of the first two authors) or to the group Coping with Depression (CWD), a cognitive behavioral treatment which did not focus on perinatal loss nor social support. Assessments occurred at baseline, treatment weeks 4 and 8, post-treatment, and 3 and 6 months after the end of treatment. IPT was feasible and acceptable in this population. Although some participants were initially hesitant to discuss their losses in a group (as occurred in IPT but not CWD), end of treatment satisfaction scores were significantly (p = 0.001) higher in IPT than in CWD. Confidence intervals around between-groups effect sizes favored IPT for reductions in depressive symptoms during treatment as well as for improvement in mode-specific targets (social support, grief symptoms) and recovery from a post-traumatic stress disorder over follow-up. This group IPT treatment adapted for MDD after perinatal loss is feasible, acceptable, and possibly efficacious. PMID:27003141

  18. Personality disorder comorbidity with major depression and response to treatment with sertraline or citalopram.

    PubMed

    Ekselius, L; von Knorring, L

    1998-09-01

    The purpose of this study was to investigate the frequency of DSM-III-R personality disorders in depressed patients treated in primary care, and to examine the effect of sertraline or citalopram on the diagnosis of personality disorders. A total of 308 patients with a major depressive disorder were assessed with the Swedish version of the Structured Clinical Interview for Personality Disorders (SCID) screen questionnaire, before and after 24 weeks double-blind treatment with sertraline (50-150 mg/day) or citalopram (20-60 mg/day). Following treatment, significant reductions in the frequency of paranoid, borderline, avoidant and dependent personality disorder diagnoses were seen in both treatment groups. When the personality disorders were analysed as continuous, dimensional personality traits significant reductions were seen for most personality categories. To elucidate if the observed reductions in personality disorder criteria could be explained by the improvement in depressive symptomatology, a series of multiple regressions were made. Reduction of depression scores was of some importance for the changes in most personality disorders. However, the multiple R never exceeded 0.24 (cluster C). Type of drug was of importance only as concerns obsessive-compulsive personality disorder. Overall, the results suggest that sertraline and citalopram may be beneficial in the treatment of certain personality disorder traits in patients with major depressive disorders.

  19. Increased frontal sleep slow wave activity in adolescents with major depression.

    PubMed

    Tesler, Noemi; Gerstenberg, Miriam; Franscini, Maurizia; Jenni, Oskar G; Walitza, Susanne; Huber, Reto

    2016-01-01

    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.

  20. Association Study of Genotype by Depressive Response during Acute Tryptophan Depletion in Subjects Recovered from Major Depression

    PubMed Central

    Moreno, Francisco A.; Erickson, Robert P.; Garriock, Holly A.; Gelernter, Joel; Mintz, Jim; Oas-Terpstra, Jennifer; Davies, Marilyn A.; Delgado, Pedro L.

    2015-01-01

    Purpose To study the brief and reversible mood response to acute tryptophan depletion (ATD) as a trait marker in subjects considered at risk for major depressive disorder (MDD). Procedures ATD was administered to 64 subjects (54 European-Americans and 10 from other races) with a personal and family history of MDD. They were in remission and had been medication-free for at least 3 months. Subjects were randomly assignment to an active or sham condition in a double-blind crossover design. They were genotyped for serotonin-related candidate genes, and mood response was quantified with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using Poisson regression with repeated measures and latent trajectory models. Results Compared to the sham controls, active ATD caused modest depressive changes showing significant main effects of test condition (χ2 = 5.14, d.f. = 1, p = 0.023) and time (χ2 = 12.22, d.f. = 3, p = 0.007), but no significant interaction of time and test condition. Latent trajectory analysis revealed two groups, identified as depletion responders and non-responders. Those with the HTR2A rs6313 CC genotype had significantly higher HDRS scores during ATD (χ2 = 11.72, d.f. = 1, p = 0.0006). Conclusions ATD may help identifying the biological subtypes of MDD. These data are consistent with imaging reports implicating 5-HT2A receptor function in ATD phenotypes. PMID:26528486

  1. Increased activities of both superoxide dismutase and catalase were indicators of acute depressive episodes in patients with major depressive disorder.

    PubMed

    Tsai, Meng-Chang; Huang, Tiao-Lai

    2016-01-30

    Oxidative stress may play an important role in the pathophysiology of major depressive disorder (MDD). The aim of this study was to investigate the serum levels of oxidative stress biomarkers and S100B in patients with MDD in an acute phase, and evaluate the changes in superoxide dismutase (SOD), protein carbonyl content (PCC), glutathione peroxidase (GPX), 8-hydroxy 2'-deoxyguanosine after treatment (8-OHdG), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and S100B. We consecutively enrolled 21 MDD inpatients in an acute phase and 40 healthy subjects. Serum oxidative stress markers were measured with assay kits. Serum SOD and CAT activities in MDD patients in an acute phase were significantly higher than those of healthy subjects, and serum PCC levels were significantly lower. The HAM-D scores had a significantly positive association with S100B levels. Eighteen depressed patients were followed up, and there was no significant difference among all of the markers after treatment. In conclusion, our results suggest that increased activities of both SOD and CAT might be indicators of acute depressive episodes in MDD patients.

  2. A review of lifestyle factors that contribute to important pathways associated with major depression: diet, sleep and exercise.

    PubMed

    Lopresti, Adrian L; Hood, Sean D; Drummond, Peter D

    2013-05-15

    Research on major depression has confirmed that it is caused by an array of biopsychosocial and lifestyle factors. Diet, exercise and sleep are three such influences that play a significant mediating role in the development, progression and treatment of this condition. This review summarises animal- and human-based studies on the relationship between these three lifestyle factors and major depressive disorder, and their influence on dysregulated pathways associated with depression: namely neurotransmitter processes, immuno-inflammatory pathways, hypothalamic-pituitary-adrenal (HPA) axis disturbances, oxidative stress and antioxidant defence systems, neuroprogression, and mitochondrial disturbances. Increased attention in future clinical studies on the influence of diet, sleep and exercise on major depressive disorder and investigations of their effect on physiological processes will help to expand our understanding and treatment of major depressive disorder. Mental health interventions, taking into account the bidirectional relationship between these lifestyle factors and major depression are also likely to enhance the efficacy of interventions associated with this disorder.

  3. 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…

  4. 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

  5. Residential Transience, Major Depressive Episodes, and the Risk of Suicidal Thoughts, Plans, and Attempts.

    PubMed

    Glasheen, Cristie; Forman-Hoffman, Valerie L

    2015-12-01

    The association between past-year residential transience (frequent moving) and suicidal ideation among a nationally representative sample of over 190,000 U.S. adults was evaluated. Suicidal thoughts, plans, and attempts were more prevalent among transient adults. Among adults without major depressive episodes (MDE), transience was associated with 70% to 90% greater odds of suicidal ideation compared to nontransient adults. Among adults with MDE, transience was associated with a 60% to 80% increased odds of suicidal ideation compared to nontransient adults. Residential transience may be an indicator for increased suicide risk even in the absence of depression. PMID:25823805

  6. Major depressive disorder and smoking relapse among adults in the United States: a 10-year, prospective investigation.

    PubMed

    Zvolensky, Michael J; Bakhshaie, Jafar; Sheffer, Christine; Perez, Adriana; Goodwin, Renee D

    2015-03-30

    This study investigated the relation between major depressive disorder (MDD) and smoking relapse in the U.S. over a 10-year period. Data were drawn from the Midlife Development in the United States (MIDUS) Survey Waves I & II. Logistic regression analyses were used to explore the associations between past-year MDD in 1994, past-year MDD in 2005 and persistent depression (1994 and 2005) and risk of smoking relapse in 2005 among former smokers, adjusting for demographics, anxiety disorders, and substance use problems and smoking characteristics. Among former smokers, MDD in 1994, compared to without MDD in 1994, was associated with significantly increased odds of smoking relapse by 2005. Current MDD in 2005 was associated with an even stronger risk of relapse in 2005 and persistent depression even more strongly predicted relapse by 2005. These associations remained significant and were not substantially attenuated by the covariates. In conclusion, MDD appears to confer long-term vulnerability to smoking relapse among adults in the general population. These results suggest interventions for smoking cessation should include screening and treatment for MDD if programs are to be optimally effective at achieving initial quit success as well as enduring abstinence.

  7. Recurrent major depression, ataxia, and cardiomyopathy: association with a novel POLG mutation?

    PubMed Central

    Verhoeven, Willem MA; Egger, Jos IM; Kremer, Berry PH; de Pont, Boudewijn JHB; Marcelis, Carlo LM

    2011-01-01

    At present, more than 100 disease mutations in mitochondrial DNA polymerase γ (POLG) have been indentified that are causally related to an array of neuropsychiatric diseases affecting multiple systems. Both autosomal recessive and autosomal dominant forms can be delineated, the latter being associated with Parkinsonism and depressive or psychotic syndromes. In this report, a middle-aged female patient with recurrent major depression with melancholic features, slowly progressive gait instability, and dilated cardiomyopathy is described. Detailed diagnostic evaluation was performed to elucidate the supposed relationship between ataxia, cardiomyopathy, and major depression with melancholia. After extensive genetic and metabolic investigation, a nucleotide substitution c.2207 A→G in the POLG gene resulting in amino acid change Asn 736Ser in exon 13 was demonstrated. This mutation was considered to be compatible with a mitochondrial disorder and implicated in the pathophysiology of the neuropsychiatric syndrome. It is concluded that this novel POLG mutation forms the most parsimonious etiological explanation for the here-described combination of ataxia, major depression, and cardiomyopathy. Therefore, in patients with a complex neuropsychiatric presentation, extensive diagnostic analysis is warranted, including the search for mitochondriopathies, in order to avoid unnecessary delay of adequate treatment. PMID:21654874

  8. A population-based longitudinal study of risk factors for suicide attempts in major depressive disorder.

    PubMed

    Bolton, James M; Pagura, Jina; Enns, Murray W; Grant, Bridget; Sareen, Jitender

    2010-10-01

    No longitudinal study has examined risk factors for future suicide attempts in major depressive disorder in a nationally representative sample. The objective of this study was to investigate baseline sociodemographic characteristics, comorbid mental disorders, specific depressive symptoms, and previous suicidal behavior as potential risk factors for suicide attempts at 3 years follow-up. Data came from the national epidemiologic survey on alcohol and related conditions (NESARC), a large nationally representative longitudinal survey of mental illness in adults [Wave 1 (2001-2002); Wave 2 (2004-2005) n=34,653]. Logistic regression examined associations between risk factors present at Wave 1 and suicide attempts at Wave 2 (n=169) among individuals with major depressive disorder at baseline assessment (n=6004). Risk factors for incident suicide attempts at Wave 2 (n=63) were identified among those with major depressive disorder at Wave 1 and no lifetime history of suicide attempts (n=5170). Results revealed specific comorbid anxiety, personality, and substance use disorders to be associated with incident suicide attempts at Wave 2. Comorbid borderline personality disorder was strongly associated with suicide attempts in all models. Several comorbid disorders were strongly associated with suicide attempts at Wave 2 even after adjusting for previous suicidal behavior, notably posttraumatic stress disorder (adjusted odds ratio (AOR)=2.20; 95% confidence interval (95% CI) 1.27-3.83) and dependent personality disorder (AOR=4.43; 95% CI 1.93-10.18). These findings suggest that mental illness comorbidity confers an increased risk of future suicide attempts in major depressive disorder that is not solely accounted for by past suicidal behavior.

  9. Sympathetic skin response following painful electrical stimulation is increased in major depression.

    PubMed

    Boettger, Michael Karl; Greiner, Wolf; Rachow, Tobias; Brühl, Christiane; Bär, Karl-Jürgen

    2010-04-01

    Patients with major depressive disorder have repeatedly been described to exhibit increased thresholds upon experimentally applied pain stimuli to the skin as compared to respective controls. Since the sensory-discriminative component of stimulus perception, e.g. for warmth, cold and vibration, appears to be unaltered in depression, higher central nervous centres have been assumed to cause this phenomenon. To date, hardly any attention has been paid to the efferent components of the noxious reflex loop. Here, we aimed to assess the autonomic reaction upon a painful stimulus and to examine whether this is likewise reduced in major depression. For this purpose, sympathetic skin response was obtained from 22 patients with major depression and 20 matched controls. To induce sympathetic skin responses, we applied either noxious electrical stimuli (12 and 18 mA) or innocuous acoustic stimuli (85 dB SPL). Pain intensity was rated using a numeric analogue scale. In contrast to our a priori hypothesis patients showed shorter latencies and higher amplitudes of skin potentials upon noxious stimulation, i.e. a stronger sympathetic response. Intriguingly, the noxious stimuli were still perceived less painful in the patient group. Pain perception weakly correlated with disease severity. From these data, we conclude that despite the diminished pain perception, the autonomic reflex loop following noxious stimulation is not affected in patients with major depressive disorder, and that the increase in sympathetic outflow is not directly related to the perceived pain as in controls, but might rather be attributed to the autonomic dysfunction known for the disease.

  10. Toward Dysfunctional Connectivity: A Review of Neuroimaging Findings in Pediatric Major Depressive Disorder

    PubMed Central

    Hulvershorn, Leslie; Cullen, Kathryn; Anand, Amit

    2011-01-01

    Child and adolescent psychiatric neuroimaging research typically lags behind similar advances in adult disorders. While the pediatric depression imaging literature is less developed, a recent surge in interest has created the need for a synthetic review of this work. Major findings from pediatric volumetric and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity studies converge to implicate a corticolimbic network of key areas that work together to mediate the task of emotion regulation. Imaging the brain of children and adolescents with unipolar depression began with volumetric studies of isolated brain regions that served to identify key prefrontal, cingulate and limbic nodes of depression-related circuitry elucidated from more recent advances in DTI and functional connectivity imaging. Systematic review of these studies preliminarily suggests developmental differences between findings in youth and adults, including prodromal neurobiological features, along with some continuity across development. PMID:21901425

  11. 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.

  12. The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications.

    PubMed

    Moylan, S; Maes, M; Wray, N R; Berk, M

    2013-05-01

    In some patients with major depressive disorder (MDD), individual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems, inflammatory, oxidative and nitrosative stress pathways, neurotrophins and regulation of neurogenesis, cortisol and the hypothalamic-pituitary-adrenal axis modulation, mitochondrial dysfunction and epigenetic and dietary influences. Evidence-based novel treatments informed by this knowledge are discussed.

  13. 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

  14. 'Interrupted by fits of weeping': Cicero's major depressive disorder and the death of Tullia.

    PubMed

    Evans, Kathleen M

    2007-03-01

    The letters of Marcus Tullius Cicero (106-43 Bc), the Roman statesman, lawyer, orator and author, were analysed as part of a larger study that systematically examined ancient Greek and Roman literature to recover descriptions of mental illness. A degree of necessary caution was exercised, but the wealth of material revealed in the letters about Cicero's physical and emotional state enable a diagnosis of Major Depressive Disorder to be made with some certainty according to the DSM-IV-TR. Cicero appears to have experienced increasingly severe bouts of suicidal depression that seriously impaired his relationships with his friends, family and political colleagues, and possibly shortened his life. His last depressive episode following the death of his daughter Tullia is addressed here in some detail.

  15. 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

  16. 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

  17. 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

  18. Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients.

    PubMed

    Li, Jianying; Xu, Cheng; Cao, Xiaohua; Gao, Qiang; Wang, Yan; Wang, Yanfang; Peng, Juyi; Zhang, Kerang

    2013-06-25

    A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for

  19. 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

  20. Autonomous neurobiological pathways to late-life major depressive disorder: clinical and pathophysiological implications.

    PubMed

    Kumar, Anand; Mintz, Jim; Bilker, Warren; Gottlieb, Gary

    2002-02-01

    The objective of our study was to elucidate distinct paths to depression in a model that incorporates age, measures of medical comorbidity, neuroanatomical compromise, and cognitive status in a sample of patients with late-life major depressive disorder (MDD) and nondepressed controls. Our study was cross-sectional in nature and utilized magnetic resonance imaging (MRI) estimates of brain and high-intensity lesion volumes together with clinical indices of cerebrovascular and nonvascular medical comorbidity. Neuroanatomic and clinical measures were incorporated into a structural covariance model in order to test pathways to MDD. Our data indicate that there are two paths to MDD; one path is represented by vascular and nonvascular medical comorbidity that contribute to high-intensity lesions that lead to depression. Smaller brain volumes represent a distinct path to the mood disorder. Age influences depression by increasing atrophy and overall medical comorbidity but has no direct impact on MDD. These findings demonstrate that there are distinct biological substrates to the neuroanatomical changes captured on MRI. These observations further suggest that neurobiological mechanisms acting in parallel may compromise brain structure/function, thereby predisposing individuals to clinical brain disorders such as depression. PMID:11790518

  1. 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

  2. Duloxetine: a review of its use in the management of major depressive disorder in older adults.

    PubMed

    Dhillon, Sohita

    2013-01-01

    Duloxetine (Cymbalta(®)) is a selective serotonin norepinephrine reuptake inhibitor indicated for the treatment of major depressive disorder (MDD). This article reviews the therapeutic efficacy and tolerability of duloxetine in older adults with MDD and summarizes its pharmacological properties. Treatment with duloxetine significantly improved several measures of cognition, depression, anxiety, pain and health-related quality-of-life (HR-QOL) in older adults with MDD in two 8-week, double-blind, placebo-controlled trials. However, no significant improvements in measures of depression were observed at week 12 (primary endpoint) of a 24-week, double-blind trial, although symptoms of depression did improve significantly at earlier timepoints. Benefit of treatment was also observed during continued therapy in the 24-week study (i.e. after the 12-week primary endpoint) and in an open-label, 52-week study, with improvements being observed in some measures of depression, pain and HR-QOL. Duloxetine was generally well tolerated in these studies, with nausea, dizziness and adverse events reflecting noradrenergic activity (e.g. dry mouth, constipation) being the most common treatment-emergent adverse events during treatment for up to 52 weeks. Duloxetine therapy had little effect on cardiovascular parameters and bodyweight. Although further well designed and long-term studies in this patient population are required to confirm the efficacy of duloxetine and to compare it with that of other antidepressants, current evidence suggests that treatment with duloxetine may be beneficial in older adults with MDD.

  3. Mood symptoms, cognition, and everyday functioning: in major depression, bipolar disorder, and schizophrenia.

    PubMed

    Harvey, Philip D

    2011-10-01

    People with depression, bipolar disorder, and schizophrenia manifest considerable cognitive deficits and impairments in everyday functional outcomes. The severity of current mood symptoms is associated with the severity of cognitive deficits in people with unipolar and bipolar disorder, but impairments are clearly still present in cases with minimal current mood symptoms. In people with schizophrenia, depression is less strongly associated with cognitive deficits on a cross-sectional basis, and some evidence suggests that depression and cognitive impairments are inversely related. Furthermore, in schizophrenia, mood symptoms seem to affect everyday functioning in a way that is unassociated with the severity of deficits in cognition and functional capacity. In contrast, in bipolar disorder, mood symptoms seem to affect real-world functioning through an adverse effect on the ability to perform critical functional skills. In both mood disorders and schizophrenia, depression appears to impact the motivation to perform potentially reinforcing acts, possibly through the induction of anhedonia. Clearly, depression has a major adverse impact on everyday functioning in all variants of severe mental illness, and improving its recognition (in the case of schizophrenia) and management has the potential to reduce the adverse impact of severe mental illness on everyday functioning. Reducing disability has the potential to have positive impacts in multiple objective and subjective aspects of functioning in severe mental illness.

  4. 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

  5. Identifying major depressive disorder using Hurst exponent of resting-state brain networks.

    PubMed

    Wei, Maobin; Qin, Jiaolong; Yan, Rui; Li, Haoran; Yao, Zhijian; Lu, Qing

    2013-12-30

    Resting-state functional magnetic resonance imaging (fMRI) studies of major depressive disorder (MDD) have revealed abnormalities of functional connectivity within or among the resting-state networks. They provide valuable insight into the pathological mechanisms of depression. However, few reports were involved in the "long-term memory" of fMRI signals. This study was to investigate the "long-term memory" of resting-state networks by calculating their Hurst exponents for identifying depressed patients from healthy controls. Resting-state networks were extracted from fMRI data of 20 MDD and 20 matched healthy control subjects. The Hurst exponent of each network was estimated by Range Scale analysis for further discriminant analysis. 95% of depressed patients and 85% of healthy controls were correctly classified by Support Vector Machine with an accuracy of 90%. The right fronto-parietal and default mode network constructed a deficit network (lower memory and more irregularity in MDD), while the left fronto-parietal, ventromedial prefrontal and salience network belonged to an excess network (longer memory in MDD), suggesting these dysfunctional networks may be related to a portion of the complex of emotional and cognitive disturbances. The abnormal "long-term memory" of resting-state networks associated with depression may provide a new possibility towards the exploration of the pathophysiological mechanisms of MDD.

  6. The effects of respiratory sinus arrhythmia on anger reactivity and persistence in major depression.

    PubMed

    Ellis, Alissa J; Shumake, Jason; Beevers, Christopher G

    2016-10-01

    The experience of anger during a depressive episode has recently been identified as a poor prognostic indicator of illness course. Given the clinical implications of anger in major depressive disorder (MDD), understanding the mechanisms involved in anger reactivity and persistence is critical for improved intervention. Biological processes involved in emotion regulation during stress, such as respiratory sinus arrhythmia (RSA), may play a role in maintaining negative moods. Clinically depressed (MDD; n = 49) and nondepressed (non-MDD; n = 50) individuals were challenged with a stressful computer task shown to increase anger, while RSA (high frequency range 0.15-0.4 Hz) was collected. RSA predicted future anger, but was unrelated to current anger. That is, across participants, low baseline RSA predicted anger reactivity during the task, and in depressed individuals, those with low RSA during the task had a greater likelihood of anger persistence during a recovery period. These results suggest that low RSA may be a psychophysiological process involved in anger regulation in depression. Low RSA may contribute to sustained illness course by diminishing the repair of angry moods. PMID:27401801

  7. 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.

  8. Support vector machine classification of major depressive disorder using diffusion-weighted neuroimaging and graph theory.

    PubMed

    Sacchet, Matthew D; Prasad, Gautam; Foland-Ross, Lara C; Thompson, Paul M; Gotlib, Ian H

    2015-01-01

    Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on "support vector machines" to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.

  9. Reward-Related Decision-Making in Pediatric Major Depressive Disorder: An fMRI Study

    PubMed Central

    Forbes, Erika E.; May, J. Christopher; Siegle, Greg J.; Ladouceur, Cecile D.; Ryan, Neal D.; Carter, Cameron S.; Birmaher, Boris; Axelson, David A.; Dahl, Ronald E.

    2007-01-01

    Background Although reward processing is considered an important part of affective functioning, few studies have investigated reward-related decisions or responses in young people with affective disorders. Depression is postulated to involve decreased activity in reward-related affective systems. Methods Using functional MRI, we examined behavioral and neural responses to reward in young people with depressive disorders using a reward decision-making task. The task involved choices about possible rewards involving varying magnitude and probability of reward. The study design allowed the separation of decision/anticipation and outcome phases of reward processing. Participants were 9–17 years old and had diagnoses of Major Depressive Disorder (MDD), anxiety disorders, or no history of psychiatric disorder. Results Participants with MDD exhibited less neural response than control participants in reward-related brain areas during both phases of the task. Group differences did not appear to be a function of anxiety. Depressive and anxiety symptoms were associated with activation in reward-related brain areas. Conclusions Results suggest that depression involves altered reward processing and underscore the need for further investigation of relations among development, affective disorders, and reward processing. PMID:17073982

  10. Essential elements in depression and anxiety. Part II.

    PubMed

    Młyniec, Katarzyna; Gaweł, Magdalena; Doboszewska, Urszula; Starowicz, Gabriela; Pytka, Karolina; Davies, Claire Linzi; Budziszewska, Bogusława

    2015-04-01

    In this paper we continue to discuss the involvement of essential elements in depression and anxiety, and the possible mechanisms that link elements to the neurobiology underlying depression/anxiety. The present paper is focused on copper, selenium, manganese, iodine and vanadium. Different aspects of relationship between elements and depression or anxiety are reviewed, e.g. the association of the amount of an element in a diet or the serum level of an element and depressive or anxiety-like symptoms. Moreover, the relation of selected elements to the pathophysiology of depression or anxiety is discussed in the context of enzymes which require these elements as co-factors and are involved in the underlying pathophysiology of these disorders.

  11. The Inventory Of Depressive Symptomatology (IDS-C(28)) is more sensitive to changes in depressive symptomatology than the Hamilton Depression Rating Scale (HAMD(17)) in patients with mild major, minor or subsyndromal depression.

    PubMed

    Helmreich, Isabella; Wagner, Stefanie; Mergl, Roland; Allgaier, Antje-Kathrin; Hautzinger, Martin; Henkel, Verena; Hegerl, Ulrich; Tadić, André

    2011-08-01

    Depression rating scales play a decisive role in the assessment of the severity of depression and the evaluation of the efficacy of antidepressant treatments. The Hamilton Depression Rating Scale (HAMD) is regarded as the 'gold standard'; nevertheless, studies suggest that the Inventory of Depressive Symptomatology (IDS) is more sensitive to detect symptom changes. The aim of the present study was to investigate whether the IDS is more sensitive in detecting changes in depression symptoms in patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C(28) and HAMD(17) data from 340 patients of a 10-week randomized, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural therapy in patients with MIND were analysed. We investigated sensitivity to change for both scales (1) from assessment-to-assessment, (2) in relation to depression severity level, and (3) in relation to DSM-IV depression criterion symptoms. The IDS-C(28) was more sensitive in detecting changes in depression symptomatology over the treatment course as well as for different severity levels, especially in patients with a low depression severity. It assesses the DSM-IV criteria more thoroughly, is better able to track the change of cognitive symptoms and to identify residual symptoms. Both scales are well able to assess depressive symptomatology. However, the IDS-C(28) surpasses the HAMD(17) in detecting small changes especially in the core symptoms of depression. This is important for an optimal treatment by capturing early improvements, enabling prompt reactions and detecting residual symptoms.

  12. 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

  13. 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

  14. A pooled analysis of two placebo-controlled trials of desvenlafaxine in major depressive disorder.

    PubMed

    Lieberman, Daniel Z; Montgomery, Stuart A; Tourian, Karen A; Brisard, Claudine; Rosas, Gregory; Padmanabhan, Krishna; Germain, Jean-Michel; Pitrosky, Bruno

    2008-07-01

    The efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) were evaluated in two similarly designed, phase 3, randomized, double-blind, placebo-controlled, venlafaxine-extended-release-referenced, flexible-dose studies of outpatients with a primary diagnosis of major depressive disorder. Owing to a high placebo response, the individual studies were underpowered. Therefore, a post-hoc pooled analysis was performed (desvenlafaxine and placebo data were pooled; venlafaxine extended release data were not, owing to different flexible-dose regimens in the two studies). The primary outcome measure was the change from baseline on the 17-item Hamilton Rating Scale for Depression; the Clinical Global Impressions-Improvement item score was a secondary outcome. Analysis of the pooled data (using a mixed-effect model for repeated measures) revealed that after 8 weeks of treatment, desvenlafaxine was significantly better than placebo on 17-item Hamilton Rating Scale for Depression [-14.21 vs. -11.87 for desvenlafaxine and placebo, respectively; magnitude of effect=-2.34 (P<0.001)] and Clinical Global Impressions-Improvement item scores [1.95 vs. 2.32 for desvenlafaxine and placebo, respectively; magnitude of effect=-0.37 (P<0.001)]. Adverse events were comparable to those found with other drugs sharing a similar mechanism of action. These data support the efficacy, safety, and tolerability of desvenlafaxine in the treatment of major depressive disorder.

  15. 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

  16. Treatment of major depression in later life: a life cycle perspective.

    PubMed

    Reynolds, C F

    1997-01-01

    The goal of this article is to provide a life-cycle perspective on the treatment of major depressive episodes in later life. Our studies have suggested that older patients appear to benefit as much, though perhaps more slowly, than mid-life patients from acute combined treatment (nortriptyline+interpersonal psychotherapy) of major depression. Given also the apparently higher relapse rate among the elderly, however, continuation treatment needs to be vigorous and closely monitored. The occurrence of severe life events prior to the index episode and the co-existence of an anxiety disorder both appear to prolong treatment response times, while chronic medical burden per se neither compromises response rates nor prolongs time to response. Self-rated perception of health improves with remission of depression in the elderly. As in mid-life patients, both antidepressant medication (nortriptyline) and interpersonal psychotherapy appear to possess chronic efficacy with respect to the prevention of recurrent episodes and prolongation of wellness. Finally, treatment of depression in the elderly results in improved quality of life, especially in domains of well being and coping. Particular challenges in the treatment of elderly patients are noncompliance and the prevention of suicide. The latter is closely linked to feelings of hopelessness, and these may be persistent in some patients. PMID:9237318

  17. 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.

  18. 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…

  19. 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

  20. EEG alpha power as an intermediate measure between brain-derived neurotrophic factor Val66Met and depression severity in patients with major depressive disorder.

    PubMed

    Zoon, Harriët F A; Veth, C P M; Arns, Martijn; Drinkenburg, W H I M; Talloen, Willem; Peeters, Pieter J; Kenemans, J L

    2013-06-01

    Major depressive disorder has a large impact on patients and society and is projected to be the second greatest global burden of disease by 2020. The brain-derived neurotrophic factor (BDNF) gene is considered to be one of the important factors in the etiology of major depressive disorder. In a recent study, alpha power was found to mediate between BDNF Met and subclinical depressed mood. The current study looked at a population of patients with major depressive disorder (N = 107) to examine the association between the BDNF Val66Met polymorphism, resting state EEG alpha power, and depression severity. For this purpose, repeated-measures analysis of variance, partial correlation, and multiple linear models were used. Results indicated a negative association between parietal-occipital alpha power in the eyes open resting state and depression severity. In addition, Met/Met patients showed lower global absolute alpha power in the eyes closed condition compared with Val-carriers. These findings are in accordance with the previously uncovered pathway between BDNF Val66Met, resting state EEG alpha power, and depression severity. Additional research is needed for the clarification of this tentative pathway and its implication in personalized treatment of major depressive disorder.

  1. 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

  2. The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder.

    PubMed

    Maurya, Pawan Kumar; Noto, Cristiano; Rizzo, Lucas B; Rios, Adiel C; Nunes, Sandra O V; Barbosa, Décio Sabbatini; Sethi, Sumit; Zeni, Maiara; Mansur, Rodrigo B; Maes, Michael; Brietzke, Elisa

    2016-02-01

    Major depressive disorder (MDD) affects millions of individuals and is highly comorbid with many age associated diseases such as diabetes mellitus, immune-inflammatory dysregulation and cardiovascular diseases. Oxidative/nitrosative stress plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative/neuropsychiatric disorders including MDD. In this review, we critically review the evidence for an involvement of oxidative/nitrosative stress in acceleration of aging process in MDD. There are evidence of the association between MDD and changes in molecular mechanisms involved in aging. There is a significant association between telomere length, enzymatic antioxidant activities (SOD, CAT, GPx), glutathione (GSH), lipid peroxidation (MDA), nuclear factor κB, inflammatory cytokines with MDD. Major depression also is characterized by significantly lower concentration of antioxidants (zinc, coenzyme Q10, PON1). Since, aging and MDD share a common biological base in their pathophysiology, the potential therapeutic use of antioxidants and anti-aging molecules in MDD could be promising.

  3. Estimating the genetic variance of major depressive disorder due to all single nucleotide polymorphisms.

    PubMed

    Lubke, Gitta H; Hottenga, Jouke Jan; Walters, Raymond; Laurin, Charles; de Geus, Eco J C; Willemsen, Gonneke; Smit, Jan H; Middeldorp, Christel M; Penninx, Brenda W J H; Vink, Jacqueline M; Boomsma, Dorret I

    2012-10-15

    Genome-wide association studies of psychiatric disorders have been criticized for their lack of explaining a considerable proportion of the heritability established in twin and family studies. Genome-wide association studies of major depressive disorder in particular have so far been unsuccessful in detecting genome-wide significant single nucleotide polymorphisms (SNPs). Using two recently proposed methods designed to estimate the heritability of a phenotype that is attributable to genome-wide SNPs, we show that SNPs on current platforms contain substantial information concerning the additive genetic variance of major depressive disorder. To assess the consistency of these two methods, we analyzed four other complex phenotypes from different domains. The pattern of results is consistent with estimates of heritability obtained in twin studies carried out in the same population.

  4. 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

  5. Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders.

    PubMed

    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.

  6. 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

  7. 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

  8. 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

  9. The double burden of age and major depressive disorder on the cognitive control network.

    PubMed

    Rao, Julia A; Kassel, Michelle T; Weldon, Anne L; Avery, Erich T; Briceno, Emily M; Mann, Megan; Cornett, Bridget; Kales, Helen C; Zubieta, Jon-Kar; Welsh, Robert C; Langenecker, Scott A; Weisenbach, Sara L

    2015-06-01

    Poor cognitive control (CC) is common among older individuals with major depressive disorder (OMDD). At the same time, studies of CC in OMDD with fMRI are relatively limited and often have small samples. The present study was conducted to further examine poor CC in OMDD with early onset depression, as well as to investigate the interactive effects of MDD and aging on cognitive control. Twenty OMDD, 17 older never-depressed comparisons (ONDC), 16 younger adults with MDD (YMDD), and 18 younger never-depressed comparisons (YNDC) participated. All participants completed the Go level of the Parametric Go/No-Go Test, which requires sustained attention and inhibitory control while undergoing functional MRI (fMRI). YNDC were faster in reaction times (RTs) to go targets relative to the other 3 groups, and the YMDD group was faster than the OMDD group. fMRI effects of both age and diagnosis were present, with greater activation in MDD, and in aging. Additionally, the interaction of age and MDD was also significant, such that OMDD exhibited greater recruitment of fronto-subcortical regions relative to older comparisons. These results are consistent with prior research reporting that OMDD recruit more fronto-striatal regions in order to perform at the same level as their never-depressed peers, here on a task of sustained attention and inhibitory control. There may be an interaction of cognitive aging and depression to create a double burden on the CC network in OMDD, including possible fronto-striatal compensation during CC that is unique to OMDD, as younger MDD individuals do not show this pattern.

  10. The double burden of age and major depressive disorder on the cognitive control network.

    PubMed

    Rao, Julia A; Kassel, Michelle T; Weldon, Anne L; Avery, Erich T; Briceno, Emily M; Mann, Megan; Cornett, Bridget; Kales, Helen C; Zubieta, Jon-Kar; Welsh, Robert C; Langenecker, Scott A; Weisenbach, Sara L

    2015-06-01

    Poor cognitive control (CC) is common among older individuals with major depressive disorder (OMDD). At the same time, studies of CC in OMDD with fMRI are relatively limited and often have small samples. The present study was conducted to further examine poor CC in OMDD with early onset depression, as well as to investigate the interactive effects of MDD and aging on cognitive control. Twenty OMDD, 17 older never-depressed comparisons (ONDC), 16 younger adults with MDD (YMDD), and 18 younger never-depressed comparisons (YNDC) participated. All participants completed the Go level of the Parametric Go/No-Go Test, which requires sustained attention and inhibitory control while undergoing functional MRI (fMRI). YNDC were faster in reaction times (RTs) to go targets relative to the other 3 groups, and the YMDD group was faster than the OMDD group. fMRI effects of both age and diagnosis were present, with greater activation in MDD, and in aging. Additionally, the interaction of age and MDD was also significant, such that OMDD exhibited greater recruitment of fronto-subcortical regions relative to older comparisons. These results are consistent with prior research reporting that OMDD recruit more fronto-striatal regions in order to perform at the same level as their never-depressed peers, here on a task of sustained attention and inhibitory control. There may be an interaction of cognitive aging and depression to create a double burden on the CC network in OMDD, including possible fronto-striatal compensation during CC that is unique to OMDD, as younger MDD individuals do not show this pattern. PMID:26030776

  11. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy.

    PubMed

    Redei, E E; Andrus, B M; Kwasny, M J; Seok, J; Cai, X; Ho, J; Mohr, D C

    2014-09-16

    An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (q< 0.05). Abundance of the DGKA, KIAA1539 and RAPH1 transcripts remained significantly different between subjects with MDD and ND controls even after post-CBT remission (defined as PHQ-9 <5). The ROC area under the curve for these transcripts demonstrated high discriminative ability between MDD and ND participants, regardless of their current clinical status. Before CBT, significant co-expression network of specific transcripts existed in MDD subjects who subsequently remitted in response to CBT, but not in those who remained depressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

  12. Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder.

    PubMed

    Cobb, J A; O'Neill, K; Milner, J; Mahajan, G J; Lawrence, T J; May, W L; Miguel-Hidalgo, J; Rajkowska, G; Stockmeier, C A

    2016-03-01

    Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness. Pathology in astrocytes may contribute significantly to this reduced volume and to the involvement of the hippocampus in MDD. Postmortem hippocampal tissues were collected from 17 subjects with MDD and 17 psychiatrically-normal control subjects. Sections from the body of the hippocampus were immunostained for glial fibrillary acidic protein (GFAP), a marker of intermediate filament protein expressed in astrocytes. The density of GFAP-immunoreactive astrocytes was measured in the hippocampus using 3-dimensional cell counting. Hippocampal subfields were also assessed for GFAP-immunoreactive area fraction. In CA1, there was a significant positive correlation between age and either density or area fraction in MDD. The density of astrocytes in the hilus, but not CA1 or CA2/3, was significantly decreased only in depressed subjects not taking an antidepressant drug, but not for depressed subjects taking an antidepressant drug. The area fraction of GFAP-immunoreactivity was significantly decreased in the dentate gyrus in women but not men with depression. In CA2/3, the area fraction of GFAP-immunoreactivity was inversely correlated with the duration of depression in suicide victims. Astrocyte contributions to neuronal function in the hilus may be compromised in depressed subjects not taking antidepressant medication. Due to the cross-sectional nature of the present study of postmortem brain tissue, it remains to be determined whether antidepressant drug treatment prevented a decrease in GFAP-immunoreactive astrocyte density or restored cell density to normal levels.

  13. Evolving refractory major depressive disorder diagnostic and treatment paradigms: toward closed-loop therapeutics.

    PubMed

    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.

  14. 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.

  15. 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

  16. Validating the Beck Depression Inventory-II for Hong Kong Community Adolescents

    ERIC Educational Resources Information Center

    Byrne, Barbara M.; Stewart, Sunita M.; Lee, Peter W. H.

    2004-01-01

    The primary purpose of this study was to test for the validity of a Chinese version of the Beck Depression Inventory-II (C-BDI-II) for use with Hong Kong community (i.e., nonclinical) adolescents. Based on a randomized triadic split of the data (N = 1460), we conducted exploratory factor analysis on Group1 (n = 486) and confirmatory factor…

  17. Quality of care for major depression and its determinants: a multilevel analysis

    PubMed Central

    2012-01-01

    Background Numerous studies highlight an important gap in the quality of care for depression in primary care. However, basic indicators were often used. Few of these studies examined factors associated with receiving adequate treatment, particularly with a simultaneous consideration of individual and organizational characteristics. The purpose of this study was to estimate the proportion of primary care patients with a major depressive episode (MDE) who receive adequate treatment and to examine the individual and organizational (i.e., clinic-level) characteristics associated with the receipt of at least one minimally adequate treatment for depression. Methods The sample used for this study included 915 adults consulting a general practitioner (GP), regardless of the motive of consultation, meeting DSM-IV criteria for MDE during the 12 months preceding the survey (T1), and nested within 65 primary care clinics. Data reported in this study were obtained from the “Dialogue” project. Adherence rates for 27 quality indicators selected to cover the most important components of depression treatment were estimated. Multilevel analyses were conducted. Results Adherence to guidelines was high (>75%) for one third of the quality indicators that were measured but was low (<60%) for nearly half of the measures. Just over half of the sample (52.2%) received at least one minimally adequate treatment for depression. At the individual level, determinants of receipt of minimally adequate care included age, having a family physician, a supplementary insurance coverage, a comorbid anxiety disorder and the severity of depression. At the clinic level, determinants included the availability of psychotherapy on-site, the use of treatment algorithms, and the mode of remuneration. Conclusions Our findings suggest that interventions are needed to increase the extent to which primary mental health care conforms to evidence-based recommendations. These interventions should target

  18. Neuromodulation of Attentional Control in Major Depression: A Pilot DeepTMS Study.

    PubMed

    Naim-Feil, Jodie; Bradshaw, John L; Sheppard, Dianne M; Rosenberg, Oded; Levkovitz, Yechiel; Dannon, Pinhas; 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

  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.

  20. Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder

    PubMed Central

    Kang, H.J.; Voleti, B.; Hajszan, T.; Rajkowska, G.; Stockmeier, C.; Licznerski, P.; Lepack, A.; Majik, M.S.; Jeong, L.S.; Banasr, M.; Son, H.; Duman, R.S.

    2012-01-01

    Previous imaging and postmortem studies have reported a reduction in brain volume and a decrease in the size and density of neurons in the dorsolateral prefrontal cortex (dlPFC, area 9) of subjects with major depressive disorder (MDD).1,2 These findings suggest that synapse number and function are decreased in dlPFC of depressed patients. However, there has been no direct evidence for synapse loss in MDD and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal decreased expression of synaptic function-related genes in dlPFC of MDD subjects and a corresponding reduction in the number of synapses. We also identify a transcriptional repressor that is increased in MDD, and that when expressed in PFC neurons is sufficient to decrease expression of synapse-related genes, cause loss of spines and dendrites, and produce depressive behavior in rodent models of depression. PMID:22885997

  1. Aberrant emotion networks in early major depressive disorder patients: an eigenvector centrality mapping study

    PubMed Central

    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–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

  2. 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

  3. Failure to segregate emotional processing from cognitive and sensorimotor processing in major depression.

    PubMed

    Epstein, Jane; Perez, David Lewis; Ervin, Kate; Pan, Hong; Kocsis, James Howard; Butler, Tracy; Stern, Emily; Silbersweig, David Alan

    2011-09-30

    Most functional neuroimaging studies of major depressive disorder (MDD) employ univariate methods of statistical analysis to localize abnormalities of neural activity. Less has been done to investigate functional relations between these regions, or with regions not usually implicated in depression. Examination of intraneuronal and interneural network relations is important for the advancement of emerging network models for MDD. Principal component analysis (PCA), a multivariate statistical method, was used to examine differences in functional connectivity between 10 unmedicated patients with MDD and 12 healthy subjects engaged in a positive word viewing task. In healthy subjects, principal component (PC) 1 (33% variance) revealed functional connectivity of task-specific sensory, linguistic, and motor regions, along with functional anticorrelations in the default mode network; PC2 (10% variance) displayed functional connectivity of areas involved in emotional processing. This segregation of functions did not occur in the depressed group, where regions involved in emotional functions appeared in PC1 (34% variance) co-varying with those involved in linguistic, motor, and default mode network processing. The lack of segregation of emotional processing from cognitive and sensorimotor functions may represent a systems level neural substrate for a core phenomenon of depression: the interconnection of affective disturbance with experience, cognition, and behavior.

  4. PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder.

    PubMed

    Schuhmacher, Anna; Mössner, Rainald; Höfels, Susanne; Pfeiffer, Ute; Guttenthaler, Vera; Wagner, Michael; Schwab, Sibylle G; Maier, Wolfgang; Zobel, Astrid

    2011-03-01

    Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity. We investigated the influence of the coding variant rs2522833 in the PCLO gene on treatment response in 205 in-patients with unipolar depression. Treatment response was measured (1) at the level of psychopathology using the Hamilton Depression Rating Scale (HAMD) and (2) with the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which is a refined tool for showing dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, a neurobiological finding in depression. While we did not find an association between variation in PCLO and HAMD scores, HPA dysregulation was less pronounced in carriers of the AA genotype than in carriers of one or two C alleles. HPA activity of individuals with the AA genotype only marginally changed during 4-wk antidepressant treatment, whereas C allele carriers showed a higher hormonal secretion at admission than carriers of the AA genotype but lower responsivity to the Dex/CRH challenge after 4 wk. Our results point to a moderating role of PCLO SNP rs2522833 on HPA regulation during antidepressant treatment, which may represent a neurobiological feature of stability of clinical response.

  5. 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.

  6. 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

  7. The significance of routine biochemical markers in patients with major depressive disorder

    PubMed Central

    Peng, You-Fan; Xiang, Yang; Wei, Ye-Sheng

    2016-01-01

    The aim of our study is to examine the levels of routine biochemical markers in patients with major depressive disorder (MDD), and combine multiple biochemical parameters to assess the discriminative power for patients with MDD. We used the Hamilton Depression (HAMD) score to evaluate the severity of depressive symptoms in 228 patients with MDD. The phase of depression severity was between moderate and severe in MDD patients. There were significant differences between MDD patients and healthy controls in alanine transaminase (ALT), urea nitrogen (UN), lactate dehydrogenase (LDH), uric acid (UA), total protein (TP), total bile acid (TBA), creatinine (Cr), total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil), high density lipoprotein-cholesterol (HDL-C), fasting blood-glucose (FBG) and fructosamine (SF). Multivariate analysis showed that UN, FBG, HDL-C, SF, TP, Cr and Tbil remained independently association with MDD. Further, a logit equation was established to identify patients with MDD. The composite markers exhibited an area under the curve of 0.810 with cut-off values of 0.410. Our results suggest the associations between UN, FBG, HDL-C, TP, Cr, Tbil, SF and MDD, use of these routine biochemical markers in combination may contribute to improve the complete management for patients with MDD. PMID:27683078

  8. The effect of severity and personality on the psychotic presentation of major depression.

    PubMed

    Tonna, Matteo; De Panfilis, Chiara; Provini, Cristiano; Marchesi, Carlo

    2011-11-30

    The aim of the present study was to evaluate whether symptom severity or personality traits are associated with psychotic symptoms in major depression (MD), since it is still debated whether psychotic depression represents the most severe form of depression or the effect of personality structure. The study included 163 patients affected by MD who were divided into four groups on the basis of the presence/absence of melancholic features and psychotic symptoms. All subjects completed the Structured Clinical Interview for DSM-IV Disorders (SCID-IV), the Structured Clinical Interview for DSM-IV Personality Disorders (SIDP-IV) and the Hamilton Rating Scale for Depression (Ham-D). Personality was assessed after MD remission (absence of DSM-IV criteria and Ham-D score lower than 7 for at least 2 months). Psychotic symptoms were positively associated with symptom severity (higher Ham-D total score) and with paranoid and schizotypal traits and negatively related to histrionic traits. Our data support the view that the effect of paranoid-schizotypal traits and symptom severity on the presence of psychotic symptoms in MD occurs separately and they are independent of each other.

  9. 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

  10. 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

  11. 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

  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.

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

    PubMed

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

    2016-10-01

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

  14. Effect of a psychoneurotherapy on brain electromagnetic tomography in individuals with major depressive disorder.

    PubMed

    Paquette, Vincent; Beauregard, Mario; Beaulieu-Prévost, Dominic

    2009-12-30

    Recent advances in power spectral analysis of electroencephalography (EEG) signals and brain-computer interface (BCI) technology may significantly contribute to the development of psychoneurotherapies. The goal of this study was to measure the effect of a psychoneurotherapy on brain source generators of abnormal EEG activity in individuals with major depressive disorder (MDD). Thirty participants with unipolar MDD were recruited in the community. The proposed psychoneurotherapy was developed based on the relationship between the localization of abnormal EEG activity and depressive symptomatology. Brain electromagnetic abnormalities in MDD were identified with low resolution brain electromagnetic tomography (LORETA) and a normative EEG database. Localization of brain changes after treatment was assessed through the standardized version of LORETA (sLORETA). Before treatment, excessive high-beta (18-30 Hz) activity was noted in several brain regions located in the fronto-temporal regions. After treatment, only participants who successfully normalized EEG activity in cortico-limbic/paralimbic regions could be considered in clinical remission. In these regions, significant correlations were found between the percentage of change of depressive symptoms and the percentage of reduction in high-beta activity. These results suggest that the normalization of high-beta activity in cortico-limbic/paralimbic regions can be associated with a significant reduction of depressive symptoms.

  15. Deconstructing major depression: a validation study of the DSM-IV symptomatic criteria

    PubMed Central

    Lux, V.; Kendler, K. S.

    2010-01-01

    Background The DSM-IV symptomatic criteria for major depression (MD) derive primarily from clinical experience with modest empirical support. Method The sample studied included 1015 (518 males, 497 females) Caucasian twins from a population-based registry who met criteria for MD in the year prior to the interview. Logistic regression analyses were conducted to compare the associations of: (1) single symptomatic criterion, (2) two groups of criteria reflecting cognitive and neurovegetative symptoms, with a wide range of potential validators including demographic factors, risk for future episodes, risk of MD in the co-twin, characteristics of the depressive episode, the pattern of co-morbidity and personality traits. Results The individual symptomatic criteria showed widely varying associations with the pattern of co-morbidity, personality traits, features of the depressive episode and demographic characteristics. When examined separately, these two criteria groups showed robust differences in their patterns of association, with the validators with the cognitive criteria generally producing stronger associations than the neurovegetative. Conclusions Among depressed individuals, individual DSM-IV symptomatic criteria differ substantially in their predictive relationship with a range of clinical validators. These results challenge the equivalence assumption for the symptomatic criteria for MD and suggest a more than expected degree of ‘ covert ’ heterogeneity among these criteria. Part of this heterogeneity is captured by the distinction between cognitive versus neurovegetative symptoms, with cognitive symptoms being more strongly associated with most clinically relevant characteristics. Detailed psychometric evaluation of DSM-IV criteria is overdue. PMID:20059797

  16. 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

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

    PubMed

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

    2016-10-01

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

  18. 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

  19. 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

  20. Prevalence and correlates of smoking status among veterans affairs primary care patients with probable major depressive disorder.

    PubMed

    Lombardero, Anayansi; Campbell, Duncan G; Harris, Kari J; Chaney, Edmund F; Lanto, Andrew B; Rubenstein, Lisa V

    2014-03-01

    In an attempt to guide planning and optimize outcomes for population-specific smoking cessation efforts, the present study examined smoking prevalence and the demographic, clinical and psychosocial characteristics associated with smoking among a sample of Veterans Affairs primary care patients with probable major depression. Survey data were collected between 2003 and 2004 from 761 patients with probable major depression who attended one of 10 geographically dispersed VA primary care clinics. Current smoking prevalence was 39.8%. Relative to nonsmokers with probable major depression, bivariate comparisons revealed that current smokers had higher depression severity, drank more heavily, and were more likely to have comorbid PTSD. Smokers with probable major depression were also more likely than nonsmokers with probable major depression to have missed a health care appointment and to have missed medication doses in the previous 5months. Smokers were more amenable than non-smokers to depression treatment and diagnosis, and they reported more frequent visits to a mental health specialist and less social support. Alcohol abuse and low levels of social support were significant concurrent predictors of smoking status in controlled multivariable logistic regression. In conclusion, smoking prevalence was high among primary care patients with probable major depression, and these smokers reported a range of psychiatric and psychosocial characteristics with potential to complicate systems-level smoking cessation interventions.

  1. The association of major depressive episodes with income inequality and the human development index.

    PubMed

    Cifuentes, Manuel; Sembajwe, Grace; Tak, SangWoo; Gore, Rebecca; Kriebel, David; Punnett, Laura

    2008-08-01

    The aim of this study was to estimate the association between country income distribution and human development with the 12-month occurrence of major depressive episodes across countries. A total of 251,158 people surveyed by the World Health Organization from 2002 to 2003 from 65 countries were included in the study. The survey contained items for identifying major depressive episodes (MDE) in the previous 12 months, attained education (used as an indicator of individual socioeconomic status) and other demographic information. Income inequality was measured with the Gini index, a national-level indicator; the United Nations human development index (HDI) measured overall country development. Country-level and multilevel linear regression models were utilized to study the associations. We found that moderately developed countries had the lowest adjusted prevalence of MDE followed by high and low developed countries. The Gini index was positively associated with major depressive episodes, but only among high HDI countries. After adjusting for age, gender, marital status, education and HDI, the multilevel prevalence ratio indicated a 4% increase in risk of MDE for a person living in a country associated with a 1% increment in income equality. This finding means, for example, that comparing two highly developed countries, one with low income inequality (Gini=0.25) with another with high income inequality (Gini=0.39), one would expect to see an increase in the prevalence of MDE from 4.0% to 6.2%. These findings raise important questions about the role of income inequality on social forces that can lead to depression.

  2. Dimensional and hierarchical models of depression using the Beck Depression Inventory-II in an Arab college student sample

    PubMed Central

    2010-01-01

    Background An understanding of depressive symptomatology from the perspective of confirmatory factor analysis (CFA) could facilitate valid and interpretable comparisons across cultures. The objectives of the study were: (i) using the responses of a sample of Arab college students to the Beck Depression Inventory (BDI-II) in CFA, to compare the "goodness of fit" indices of the original dimensional three-and two-factor first-order models, and their modifications, with the corresponding hierarchical models (i.e., higher - order and bifactor models); (ii) to assess the psychometric characteristics of the BDI-II, including convergent/discriminant validity with the Hopkins Symptom Checklist (HSCL-25). Method Participants (N = 624) were Kuwaiti national college students, who completed the questionnaires in class. CFA was done by AMOS, version 16. Eleven models were compared using eight "fit" indices. Results In CFA, all the models met most "fit" criteria. While the higher-order model did not provide improved fit over the dimensional first - order factor models, the bifactor model (BFM) had the best fit indices (CMNI/DF = 1.73; GFI = 0.96; RMSEA = 0.034). All regression weights of the dimensional models were significantly different from zero (P < 0.001). Standardized regression weights were mostly 0.27-0.60, and all covariance paths were significantly different from zero. The regression weights of the BFM showed that the variance related to the specific factors was mostly accounted for by the general depression factor, indicating that the general depression score is an adequate representation of severity. The BDI-II had adequate internal consistency and convergent/discriminant validity. The mean BDI score (15.5, SD = 8.5) was significantly higher than those of students from other countries (P < 0.001). Conclusion The broadly adequate fit of the various models indicates that they have some merit and implies that the relationship between the domains of depression probably

  3. The influence of comorbid personality disorder on the effects of behavioural activation vs. antidepressant medication for major depressive disorder: results from a randomized trial in Iran.

    PubMed

    Moradveisi, Latif; Huibers, Marcus J H; Renner, Fritz; Arasteh, Modabber; Arntz, Arnoud

    2013-08-01

    There is a disagreement about the impact of personality disorder (PD) on treatment outcome for patients with major depressive disorder (MDD). 100 out-patients with MDD were randomized to 16 sessions of behavioural activation (BA) (n = 50) or antidepressant medication (ADM) (n = 50) in Iran. Main outcome was depression severity, measured with the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HRSD), and assessed at 0, 4, 13 and 49 weeks. Participants with comorbid PDs had higher scores on BDI and HRSD at baseline and throughout the study than participants without comorbid PD. Patients with and without comorbid personality pathology responded equally to treatment on the short-and the long-term. Overall, BA was better in reducing symptoms in patients but this effect was not influenced by comorbid PD. Similar effects were found for a dimensional PD-measure. Only cluster-C PD-traits turned out to be associated with overall depression severity. Cluster-A PD-traits predicted poorer long-term treatment response to ADM and BA, but only on the BDI, not on the HRSD. No effects of cluster-B PD-traits were found. However, PD was associated with higher dropout. The general conclusion is that comorbid PD pathology, especially from cluster-C, is associated with higher depression severity, but not with less response to treatment. Comorbid PD did predict increased chance of dropout.

  4. 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

  5. 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

  6. Role of calcium, glutamate and NMDA in major depression and therapeutic application.

    PubMed

    Deutschenbaur, Lorenz; Beck, Johannes; Kiyhankhadiv, Anna; Mühlhauser, Markus; Borgwardt, Stefan; Walter, Marc; Hasler, Gregor; Sollberger, Daniel; Lang, Undine E

    2016-01-01

    Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-D-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties. Indeed, treatment with NMDA receptor antagonists has shown the ability to sprout new synaptic connections and reverse stress-induced neuronal changes. Based on glutamatergic signaling, a number of therapeutic drugs might gain interest in the future. Several compounds such as ketamine, memantine, amantadine, tianeptine, pioglitazone, riluzole, lamotrigine, AZD6765, magnesium, zinc, guanosine, adenosine aniracetam, traxoprodil (CP-101,606), MK-0657, GLYX-13, NRX-1047, Ro25-6981, LY392098, LY341495, D-cycloserine, D-serine, dextromethorphan, sarcosine, scopolamine, pomaglumetad methionil, LY2140023, LY404039, MGS0039, MPEP, 1-aminocyclopropanecarboxylic acid, all of which target this system, have already been brought up, some of them recently. Drugs targeting the glutamatergic system might open up a promising new territory for the development of drugs to meet the needs of patients with major depression. PMID:25747801

  7. 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

  8. 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

  9. The role of self-blame and worthlessness in the psychopathology of major depressive disorder

    PubMed Central

    Zahn, Roland; Lythe, Karen E.; Gethin, Jennifer A.; Green, Sophie; Deakin, John F. William; Young, Allan H.; Moll, Jorge

    2015-01-01

    Background Cognitive models predict that vulnerability to major depressive disorder (MDD) is due to a bias to blame oneself for failure in a global way resulting in excessive self-blaming emotions, decreased self-worth, hopelessness and depressed mood. Clinical studies comparing the consistency and coherence of these symptoms in order to probe the predictions of the model are lacking. Methods 132 patients with remitted MDD and no relevant lifetime co-morbid axis-I disorders were assessed using a phenomenological psychopathology-based interview (AMDP) including novel items to assess moral emotions (n=94 patients) and the structured clinical interview-I for DSM-IV-TR. Cluster analysis was employed to identify symptom coherence for the most severe episode. Results Feelings of inadequacy, depressed mood, and hopelessness emerged as the most closely co-occurring and consistent symptoms (≥90% of patients). Self-blaming emotions occurred in most patients (>80%) with self-disgust/contempt being more frequent than guilt, followed by shame. Anger or disgust towards others was experienced by only 26% of patients. 85% of patients reported feelings of inadequacy and self-blaming emotions as the most bothering symptoms compared with 10% being more distressed by negative emotions towards others. Limitations Symptom assessment was retrospective, but this is unlikely to have biased patients towards particular emotions relative to others. Conclusions As predicted, feelings of inadequacy and hopelessness were part of the core depressive syndrome, closely co-occurring with depressed mood. Self-blaming emotions were highly frequent and bothering but not restricted to guilt. This calls for a refined assessment of self-blaming emotions to improve the diagnosis and stratification of MDD. PMID:26277271

  10. Process irregularity of cortisol and adrenocorticotropin secretion in men with major depressive disorder.

    PubMed

    Posener, Joel A; Charles DeBattista; Veldhuis, Johannes D; Province, Michael A; Williams, Gordon H; Schatzberg, Alan F

    2004-10-01

    Although evidence suggests that major depressive disorder (MDD) is associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, research on basal HPA axis hormone levels in MDD patients has been inconclusive. Definitive characterization of basal cortisol and adrenocorticotropin (ACTH) secretion may be important for understanding the pathophysiology of this disorder. In recent years, a new approach to the analysis of basal hormone secretion has been developed involving the approximate entropy (ApEn) statistic, which represents the degree of disorderliness or serial irregularity in a time series of hormone levels. ApEn has been shown to reflect the degree of coordination in integrated network systems and has provided new insights into the pathophysiology of a number of endocrine conditions. In the study reported here, 15 medication-free men with MDD and 15 healthy control men were admitted to a General Clinical Research Center and had blood sampled for cortisol and ACTH determinations every hour over a 24-h period. The cortisol and ACTH time series were characterized with a cosinor analysis and with analysis of ApEn. Depressed patients and control subjects did not differ significantly on any parameter derived from the cosinor analysis or on several other standard indices of basal hormone secretion. However, the depressed men had significantly increased cortisol ApEn and significantly decreased ACTH ApEn compared with the healthy subjects. The ApEn findings suggest a loss of regulatory control over cortisol secretion, and possibly increased cortisol feedback on the pituitary in the depressed patients. Together, these results are most consistent with a primary abnormality of the adrenal gland and suggest that further investigation of adrenal gland physiology may be informative for the pathophysiology of depression.

  11. Association of periodontal health indicators and major depressive disorder in hospital outpatients

    PubMed Central

    Kumar, Amit; Kardkal, Asif; Debnath, Surangama; Lakshminarayan, Jyothi

    2015-01-01

    Background: Major depressive disorder (MDD) has been associated with changes in behavioral, neurophysiological, and neuroendocrinological factors and thought to be one of the leading causes of disability worldwide. There are various evidences that depression and periodontitis may also be related. Aim: The aim was to evaluate the association between MDD and periodontitis in a convenience sample of hospital outpatients. Materials and Methods: Sixty individuals (30 subjects with MDD and 30 subjects without MDD) of age 26–67 years were included in the study. Depression was assessed by means of structured clinical interview for diagnostic and statistical manual of mental disorders. The periodontal clinical examination included the number of missing teeth, plaque index, gingival index (GI), probing pocket depth, and clinical attachment level (CAL). Results: Mean number of missing teeth per patient was 1.14 (±1.2 standard deviation [SD]) in the control group and 2.58 (±1.64 SD) in case group (P < 0.001). The amount of plaque was significantly higher in cases compared with control (P = 0.001). The patients had an average GI of 1.82 (±0.65 SD) compared to 1.14 (±0.81 SD) for the controls (P < 0.001). Mean probing depth and CAL were 4.67 (±0.8 SD) mm and 4.96 (±0.2 SD) mm in the case group and 2.6 (±2.2 SD) mm and 2.7 (±0.43 SD) mm in the control group, respectively (P < 0.05). Conclusion: Our study confirms the significant association between depression and periodontitis and depression can be considered one of the important risk factors for periodontal diseases. PMID:26644715

  12. 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

  13. Discovering new genetic and psychosocial pathways in Major Depressive Disorder: the NewMood project.

    PubMed

    Freeborough, Annabel; Kimpton, Jessica

    2011-09-01

    The World Health Organisation predicts that Major Depressive Disorder (MDD) will be the second greatest contributor to the global burden of disease by 2020, however, the neurobiological mechanisms behind the disease and the risk factors for it are yet unknown. NewMood (New Molecules for Mood Disorders) was a research project funded by the EU, collaborating work from 10 European countries with the aim of finding new molecular mechanisms behind MDD to develop more effective treatment options. This review explains the aims and objectives of NewMood and how it intends to achieve them with regards to the current literature. It also outlines two of its most recent projects: genome wide association replication study for single nucleotide polymorphisms (SNPs) increasing susceptibility to MDD and stress related pathways in depression using the cortisol awakening response (CAR). Both of these studies had significant results and could further contribute to our current understanding of MDD.

  14. Computer-Assisted Cognitive Behavioral Therapy for Pregnant Women with Major Depressive Disorder

    PubMed Central

    Hantsoo, Liisa; Thase, Michael E.; Sammel, Mary; Epperson, C. Neill

    2014-01-01

    Abstract Background: Pregnant women with major depressive disorder (MDD) report that psychotherapy is a more acceptable treatment than pharmacotherapy. However, although results of several studies suggest that psychotherapy is an effective treatment for pregnant women, logistical barriers—including cost and traveling for weekly visits—can limit real-world utility. We hypothesized that computer-assisted cognitive behavior therapy (CCBT) would be both acceptable and would significantly decrease depressive symptoms in pregnant women with MDD. Methods: As a preliminary test of this hypothesis, we treated 10 pregnant women with MDD using a standardized CCBT protocol. Results: The pilot results were very promising, with 80% of participants showing treatment response and 60% showing remission after only eight sessions of CCBT. Conclusion: A larger, randomized controlled trial of CCBT in pregnant women with MDD is warranted. PMID:25268672

  15. Relationship of posttreatment decentering and cognitive reactivity to relapse in major depression.

    PubMed

    Fresco, David M; Segal, Zindel V; Buis, Tom; Kennedy, Sydney

    2007-06-01

    Z. V. Segal et al. (2006) demonstrated that depressed patients treated to remission through either antidepressant medication (ADM) or cognitive-behavioral therapy (CBT), but who evidenced mood-linked increases in dysfunctional thinking, showed elevated rates of relapse over 18 months. The current study sought to evaluate whether treatment response was associated with gains in decentering-the ability to observe one's thoughts and feelings as temporary, objective events in the mind-and whether these gains moderated the relationship between mood-linked cognitive reactivity and relapse of major depression. Findings revealed that CBT responders exhibited significantly greater gains in decentering compared with ADM responders. In addition, high post acute treatment levels of decentering and low cognitive reactivity were associated with the lowest rates of relapse in the 18-month follow-up period.

  16. 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

  17. Psycho-neuro-immunological treatment of hepatocellular carcinoma with major depression--a single case report.

    PubMed

    Jozuka, H; Jozuka, E; Suzuki, M; Takeuchi, S; Takatsu, Y

    2003-01-01

    A female patient, who was suffering major depression and advanced hepatocellular carcinoma (hepatoma), sought treatment in the Jozuka Mental Clinic. She was treated using a psycho-neuro-immunological approach. The treatments applied were psychotherapy, the antidepressant fluvoxamine, glycyrrhizinic acid and dehydroepiandrosterone (DHEA). Biochemical, endocrinological and immunological examinations were performed regularly. Improvement of liver function and reduction of alpha-fetoprotein were observed. The levels of DHEA, natural killer cell activity and cytokines (interleukines IL-2, IL-6, IL-12, interferon IFN-gamma) were normalised. Now, more than two and a half years after her admission, the patient is still well and symptom-free. While this may be a case of spontaneous regression, the results suggest that a psycho-neuro-immunological approach to treating the patient's depression and cancer was helpful for her recovery.

  18. Does Borderline Personality Disorder Manifest Itself Differently in Patients With Bipolar Disorder and Major Depressive Disorder?

    PubMed

    Zimmerman, Mark; Morgan, Theresa A; Young, Diane; Chelminski, Iwona; Dalrymple, Kristy; Walsh, Emily

    2015-12-01

    Perugi and colleagues (2013) recently reported that some features of borderline personality disorder (BPD) significantly predicted a diagnosis of bipolar disorder among depressed patients. They interpreted these findings as indicating that some BPD criteria are nonspecific and are indicators of bipolar disorder rather than BPD, whereas other criteria are more specific to BPD. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, the authors tested the hypothesis that BPD presents itself differently in psychiatric outpatients diagnosed with bipolar disorder or major depressive disorder. The authors found that the patients with bipolar disorder were significantly more likely to report impulsive behavior and transient dissociation. No criterion was significantly more common in the BPD patients with MDD. The authors therefore do not consider the BPD criteria to be nonspecific with regard to the distinction between BPD and bipolar disorder.

  19. 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.

  20. Neural Systems Approaches to Understanding Major Depressive Disorder: An Intrinsic Functional Organization Perspective

    PubMed Central

    Hamilton, J. Paul; Chen, Michael C.; Gotlib, Ian H.

    2012-01-01

    Recent research detailing the intrinsic functional organization of the brain provides a unique and useful framework to gain a better understanding of the neural bases of Major Depressive Disorder (MDD). In this review, we first present a brief history of neuroimaging research that has increased our understanding of the functional macro-architecture of the brain. From this macro-architectural perspective, we examine the extant body of functional neuroimaging research assessing MDD with a specific emphasis on the contributions of default-mode, executive, and salience networks in this debilitating disorder. Next, we describe recent investigations conducted in our laboratory in which we explicitly adopt a neural-systems perspective in examining the relations among these networks in MDD. Finally, we offer directions for future research that we believe will facilitate the development of more detailed and integrative models of neural dysfunction in depression. PMID:23477309

  1. Reduced emotional and cardiovascular reactivity to emotionally evocative stimuli in major depressive disorder.

    PubMed

    Jin, Alvin B; Steding, Lindsey H; Webb, Andrea K

    2015-07-01

    Major Depressive Disorder (MDD) is a highly debilitating mental health concern that affects a large number of adults in the United States. The emotional context insensitivity (ECI) hypothesis argues that individuals with MDD disengage from the environment to defend themselves from futile activity. In the current study, electrocardiogram and pupillometry were recorded from 50 participants (MDD n=25, never depressed control n=25) during the display of emotionally evocative images, sounds, and movie clips. Individuals with MDD reported reduced change in happiness to positively- and negatively-valenced images and sounds. Heart rate reactivity also was reduced in individuals with MDD when viewing images and watching movie clips. These results suggest that individuals with MDD may have some difficulty engaging with certain environmental stimuli. PMID:25931112

  2. 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

  3. Genetic susceptibility for bipolar disorder and response to antidepressants in major depressive disorder.

    PubMed

    Tansey, Katherine E; Guipponi, Michel; Domenici, Enrico; Lewis, Glyn; Malafosse, Alain; O'Donovan, Michael; Wendland, Jens R; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2014-01-01

    The high heterogeneity of response to antidepressant treatment in major depressive disorder (MDD) makes individual treatment outcomes currently unpredictable. It has been suggested that resistance to antidepressant treatment might be due to undiagnosed bipolar disorder or bipolar spectrum features. Here, we investigate the relationship between genetic susceptibility for bipolar disorder and response to treatment with antidepressants in MDD. Polygenic scores indexing risk for bipolar disorder were derived from the Psychiatric Genomics Consortium Bipolar Disorder whole genome association study. Linear regressions tested the effect of polygenic risk scores for bipolar disorder on proportional reduction in depression severity in two large samples of individuals with MDD, treated with antidepressants, NEWMEDS (n=1,791) and STAR*D (n=1,107). There was no significant association between polygenic scores for bipolar disorder and response to treatment with antidepressants. Our data indicate that molecular measure of genetic susceptibility to bipolar disorder does not aid in understanding non-response to antidepressants.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Novel therapeutic strategies in major depression: focus on RNAi and ketamine.

    PubMed

    Bortolozzi, Analia; Celada, Pau; Artigas, Francesc

    2014-01-01

    Major depression is a severe psychiatric syndrome with very high prevalence and - socioeconomic impact. Despite extensive research, its pathophysiology is poorly understood, yet several neurotransmitter systems and brain areas have been implicated. The pharmacological treatment of major depression is mainly based on drugs inhibiting serotonin (5-hydroxytryptamine, 5-HT) and/or noradrenaline (NA) reuptake. These drugs evoke a series of neuronal adaptive mechanisms that limit their full clinical action, making necessary for many patients the use of augmentation strategies. In spite of such strategies, many depressed patients show limited or no improvement, which worsens their quality of life and increases the risk of suicide. Several novel observations in recent years have shaken the antidepressant field, by showing that depressed patients with severe treatment resistance can rapidly experience clinical remission. Hence, deep brain stimulation (DBS) of ventral anterior cingulate cortex (Cg25) evokes rapid mood improvements in treatment-resistant patients. Likewise, single doses of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine evoke rapid and long-lasting (up to 10 days) antidepressant responses in treatment-resistant patients. On the other hand,