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

ABSTRACT: 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.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.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).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.

SUBMITTER: Hosang GM

PROVIDER: S-EPMC3912923 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Hosang Georgina M GM Shiles Celia C Tansey Katherine E KE McGuffin Peter P Uher Rudolf R

BMC medicine 20140116

<h4>Background</h4>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.<h4>Methods</h4>A literat ...[more]

PMID: 24433458

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Project description:BackgroundBrain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder.MethodsBrain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined.ResultsSubjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity.ConclusionsThis study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Dataset Information

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

Publications

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

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