Depression

IMPORTANCE: Countering depressive disorders is a public health priority. Currently, antidepressants are the first-line treatment, although they show modest effects. In men, testosterone treatment is a controversial alternative or adjunct treatment option. OBJECTIVES: To examine the association of testosterone treatment with alleviation of depressive symptoms in men and to clarify moderating effects of testosterone status, depression status, age, treatment duration, and dosage...

BACKGROUND: The heterogeneous aetiology of major depressive disorder (MDD) might affect the presentation of depressive symptoms across the lifespan. We examined to what extent a range of mood, cognitive, and somatic/vegetative depressive symptoms were differentially present depending on patient's age. METHOD: Data came from 1404 participants with current MDD (aged 18-88 years) from two cohort studies: the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO)...

OBJECTIVE: To estimate the association between hippocampal and total brain volume and the course of depressive symptoms over eight years of follow-up in patients with a history of vascular disease. METHOD: Within the SMART-Medea study, 636 participants (62 ± 10 years) had a 1.5-tesla brain MRI obtaining hippocampal and total brain volumes. Depressive symptoms were assessed with the Patient Health Questionnaire-9 biannually during eight-year follow-up. Generalized estimating equation models with robust standard errors were used to assess the associations of hippocampal and total brain volumes with depressive symptoms during follow-up adjusting for age, sex, education, and intracranial volume...

IMPORTANCE: The increased risk of major depression in the offspring of depressed parents is well known. Whether the risk is transmitted beyond 2 generations is less well known. To our knowledge, no published study with direct interviews of family members and the generations in the age of risk for depression has evaluated beyond 2 generations. This information is important for detecting individuals at highest risk who may benefit from early intervention. OBJECTIVE: To examine the familial aggregation of psychiatric disorder and functioning in grandchildren by their biological parents' and grandparents' depression status...

Numerous studies have reported on the roles of genetic factors in the development of depression in adolescents and young adults. However, there are few systematic reviews that update our understanding of adolescent depression with the biological findings identifying the roles of gene expression and/or polymorphism(s). This review systematically summarized the findings that clearly identified the contribution of a gene to the risk of depression in adolescents between the ages of 10 and 19 years old and young adults between the ages of 20 and 25 years old...

OBJECTIVE: The authors conducted a systematic review and meta-analysis of ketamine and other N-methyl-d-aspartate (NMDA) receptor antagonists in the treatment of major depression. METHOD: Searches of MEDLINE, PsycINFO, and other databases were conducted for placebo-controlled, double-blind, randomized clinical trials of NMDA antagonists in the treatment of depression. Primary outcomes were rates of treatment response and transient remission of symptoms. Secondary outcomes included change in depression symptom severity and the frequency and severity of dissociative and psychotomimetic effects...

BACKGROUND: Anhedonia is a prominent symptom of major depressive disorder (MDD) and schizophrenia. At present, it is believed that hedonic processing rather consists of the anticipatory and consummatory phase. The aim of this research is to explore the different anhedonia components in MDD and schizophrenia in Chinese populations. METHODS: A Chinese version of the Temporal Experience of Pleasure Scale (TEPS) was used to evaluate 176 MDD patients, 346 schizophrenia patients, and 268 healthy controls...

OBJECTIVE: The authors compared measurement-based care with standard treatment in major depression. METHODS: Outpatients with moderate to severe major depression were consecutively randomized to 24 weeks of either measurement-based care (guideline- and rating scale-based decisions; N=61), or standard treatment (clinicians' choice decisions; N=59). Pharmacotherapy was restricted to paroxetine (20-60 mg/day) or mirtazapine (15-45 mg/day) in both groups. Depressive symptoms were measured with the Hamilton Depression Rating Scale (HAM-D) and the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR)...

IMPORTANCE: Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood. OBJECTIVES: To identify in youth diagnosed as having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions. DATA SOURCES: Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015...

IMPORTANCE: More than 50% of older adults with late-life major depressive disorder fail to respond to initial treatment with first-line pharmacological therapy. OBJECTIVES: To assess typical patterns of response to an open-label trial of extended-release venlafaxine hydrochloride (venlafaxine XR) for late-life depression and to evaluate which clinical factors are associated with the identified longitudinal response patterns. DESIGN, SETTING, AND PARTICIPANTS: Group-based trajectory modeling was applied to data from a 12-week open-label pharmacological trial conducted in specialty care as part of the Incomplete Response in Late Life: Getting to Remission Study...

Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified, despite analysis of more than 9,000 cases. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 2...

The pharmacogenetics of antidepressants has been not only a challenging but also frustrating research field since its birth in the 1990s. Indeed, great expectations followed the first evidence of familiar aggregation of antidepressant response. Despite the progress from candidate gene studies to genome-wide association studies (GWAS), results fell out the expectations and they were often inconsistent. Anyway, the cumulative evidence supports the involvement of some genes and molecular pathways in antidepressant efficacy...

Innate immune activation and inflammation have been posited to play a role in the pathophysiology of both depression and neoplastic growth. Cancer patients experience a threefold higher rate of depression than the general population within the first five years of diagnosis. Chronic depression is associated with increased cancer risk and shortened survival. Although the precise cellular and molecular mechanisms of this bidirectional relationship remain unclear, elevated concentrations of circulating plasma proinflammatory cytokines associated with depression may mediate the neuroendocrine, neural, and immune pathways that account for the relationship...

Ketamine is the prototype for a new generation of glutamate-based antidepressants that rapidly alleviate depression within hours of treatment. Over the past decade, there has been replicated evidence demonstrating the rapid and potent antidepressant effects of ketamine in treatment-resistant depression. Moreover, preclinical and biomarker studies have begun to elucidate the mechanism underlying the rapid antidepressant effects of ketamine, offering a new window into the biology of depression and identifying a plethora of potential treatment targets...

Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems...

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for pediatric major depressive disorder (MDD). We conducted a meta-analysis to examine the following: the time-course of response to SSRIs in pediatric depression; whether higher doses of SSRIs are associated with an improved response in pediatric depression; differences in efficacy between SSRI agents; and whether the time-course and magnitude of response to SSRIs is different in pediatric and adult patients with MDD...

Despite being considered primarily a mood disorder, major depressive disorder (MDD) is characterized by cognitive and decision making deficits. Recent research has employed computational models of reinforcement learning (RL) to address these deficits. The computational approach has the advantage in making explicit predictions about learning and behavior, specifying the process parameters of RL, differentiating between model-free and model-based RL, and the computational model-based functional magnetic resonance imaging and electroencephalography...

Postpartum depression (PPD) adversely affects the health and well being of many new mothers, their infants, and their families. A comprehensive understanding of biopsychosocial precursors to PPD is needed to solidify the current evidence base for best practices in translation. We conducted a systematic review of research published from 2000 through 2013 on biological and psychosocial factors associated with PPD and postpartum depressive symptoms. Two hundred fourteen publications based on 199 investigations of 151,651 women in the first postpartum year met inclusion criteria...

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The intuitive association between self-focused rumination in major depressive disorder (MDD) and the self-referential operations performed by the brain's default-mode network (DMN) has prompted interest in examining the role of the DMN in MDD. In this article, we present meta-analytic findings showing reliably increased functional connectivity between the DMN and subgenual prefrontal cortex (sgPFC)-connectivity that often predicts levels of depressive rumination. We also present meta-analytic findings that, while there is reliably increased regional cerebral blood flow in sgPFC in MDD, no such abnormality has been reliably observed in nodes of the DMN...