Functional Polymorphism in the Brain-Derived Neurotrophic Factor Gene Interacts With Stressful Life Events but Not Childhood Maltreatment in the Etiology of Depression

Brown, George W.; Craig, Tom; Harris, Dominique; Herbert, M B Joe; Hodgson, Karen; Tansey, Katherine E.; Uher, Rudolf

doi:10.1002/da.22221

Cited by 43 publications

(29 citation statements)

References 50 publications

(136 reference statements)

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“…The present study, however, is the first to document a stress sensitizing effect of the BDNF Met allele on negative affect in the context of daily stressful life events—an effect that was robust even when adjusting for other known determinants of stress reactivity, such as dysfunctional attitudes and internalizing and externalizing symptomatology. The findings thus support the construct validity of the BDNF gene–environment interaction hypothesis (Brown et al 2014). Considered more broadly, the findings add to an emerging line of research on the dynamic associations between cognitive vulnerability, molecular genetics, and emotional disorders (Gibb et al 2013), which is part of a general push toward a greater rapprochement of genetics, neuroscience, and psychology in the service of building more comprehensive, integrative explanatory models of mental and physical health (e.g., Caspi and Moffitt 2006; Kendler 2008; Slavich and Cole 2013).…”

Section: Discussionsupporting

confidence: 78%

“…Most relevant for psychopathology research is the fact that several longitudinal studies have now shown that Val66Met genotype predicts risk for major depression following exposure to severe stressful life events, with Met carriers exhibiting a greater likelihood of developing depression following major life stress compared to their Val/Val counterparts (e.g., Aguilera et al 2009; Brown et al 2014; Wichers et al 2008). Although some contradictory results have been reported (e.g., Bresin et al 2013) and some evidence suggests that BDNF gene–environment interactions may be more pronounced for childhood than for adulthood life stress (Perea et al 2012), a recent meta-analytic review of 22 studies found that having a Met allele at the Val66Met locus is a reliable marker of risk for stress-induced depression (Hosang et al 2014).…”

Section: Introductionmentioning

confidence: 99%

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Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

2014

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Despite decades of research examining diathesis-stress models of emotional disorders, it remains unclear whether dysfunctional attitudes interact with stressful experiences to shape affect on a daily basis and, if so, how clinical and genetic factors influence these associations. To address these issues, we conducted a multi-level daily diary study that examined how dysfunctional attitudes and stressful events relate to daily fluctuations in negative and positive affect in 104 young adults. Given evidence that clinical and genetic factors underlie stress sensitivity, we also examined how daily affect is influenced by internalizing and externalizing symptoms and brain-derived neurotrophic factor (BDNF) genotype, which have been shown to influence neural, endocrine, and affective responses to stress. In multivariate models, internalizing symptoms and BDNF Val66Met genotype independently predicted heightened negative affect on stressful days, but dysfunctional attitudes did not. Specifically, the BDNF Met allele and elevated baseline internalizing symptomatology predicted greater increases in negative affect in stressful circumstances. These data are the first to demonstrate that BDNF genotype and stress are jointly associated with daily fluctuations in negative affect, and they challenge the assumption that maladaptive beliefs play a strong independent role in determining affective responses to everyday stressors. The results may thus inform the development of new multi-level theories of psychopathology and guide future research on predictors of affective lability.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

2014

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“…To our knowledge, this is the first study to report this association in this setting although it is consistent with research indicating depression often develops in the context of multiple, cumulative stressful life events (Kendler et al . 1999; Brown et al . 2014; Swartz et al .…”

Section: Discussionmentioning

confidence: 99%

Trajectories of depressive symptoms after hip fracture

et al. 2016

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Background Hip fracture is often complicated by depressive symptoms in older adults. We sought to characterize trajectories of depressive symptoms arising after hip fracture and examine their relationship with functional outcomes and walking ability. We also investigated clinical and psychosocial predictors of these trajectories. Method We enrolled 482 inpatients, aged ≥60 years, who were admitted for hip fracture repair at eight St Louis, MO area hospitals between 2008 and 2012. Participants with current depression diagnosis and/or notable cognitive impairment were excluded. Depressive symptoms and functional recovery were assessed with the Montgomery–Asberg Depression Rating Scale and Functional Recovery Score, respectively, for 52 weeks after fracture. Health, cognitive, and psychosocial variables were gathered at baseline. We modeled depressive symptoms using group-based trajectory analysis and subsequently identified correlates of trajectory group membership. Results Three trajectories emerged according to the course of depressive symptoms, which we termed ‘resilient’, ‘distressed’, and ‘depressed’. The depressed trajectory (10% of participants) experienced a persistently high level of depressive symptoms and a slower time to recover mobility than the other trajectory groups. Stressful life events prior to the fracture, current smoking, higher anxiety, less social support, antidepressant use, past depression, and type of implant predicted membership of the depressed trajectory. Conclusions Depressive symptoms arising after hip fracture are associated with poorer functional status. Clinical and psychosocial variables predicted membership of the depression trajectory. Early identification and intervention of patients in a depressive trajectory may improve functional outcomes after hip fracture.

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“…Quality assessment of brain-derived neurotrophic factor (BDNF), life stress and depression studies [43,[65][66][67][68][69][70][71][73][74][75][76][77][78][79][80][81][82][83]85,88,89].…”

Section: Additional Filementioning

confidence: 99%

Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis

Hosang¹,

Shiles²,

McGuffin³

et al. 2014

Comprehensive Psychiatry

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Background: Major depression is a disabling psychiatric illness with complex origins. Life stress (childhood adversity and recent stressful events) is a robust risk factor for depression. The relationship between life stress and Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has received much attention. The aim of the present work was to review and conduct a meta-analysis on the results from published studies examining this interaction. Methods: A literature search was conducted using PsychINFO and PubMed databases until 22 November 2013. A total of 22 studies with a pooled total of 14,233 participants met the inclusion criteria, the results of which were combined and a meta-analysis performed using the Liptak-Stouffer z-score method. Results: The results suggest that the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression (P = 0.03). When the studies were stratified by type of environmental stressor, the evidence was stronger for an interaction with stressful life events (P = 0.01) and weaker for interaction of BDNF Val66Met with childhood adversity (P = 0.051). Conclusions:The interaction between BDNF and life stress in depression is stronger for stressful life events rather than childhood adversity. Methodological limitations of existing studies include poor measurement of life stress.

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Functional Polymorphism in the Brain-Derived Neurotrophic Factor Gene Interacts With Stressful Life Events but Not Childhood Maltreatment in the Etiology of Depression

Cited by 43 publications

References 50 publications

Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

Trajectories of depressive symptoms after hip fracture

Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis

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