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

Abstract

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.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…However, available data do not support a significant effect of rs6265 on MDD susceptibility, as indicated by meta-analyses (Gratacos et al 2007;Gyekis et al 2013) that also provided negative findings for other BDNF SNPs (11757C/G, 270T/C, 712A/G and rs988748). Conversely, the rs6265 Met allele was demonstrated to moderate the relationship between life stress and depression (Hosang et al 2014;Gutierrez et al 2015).…”

The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model

“…Our findings, together with prior adolescent studies (Chen et al 2012;Cruz-Fuentes et al 2014;Gottfredson et al 2014), support the propostion that BDNF Val66Met 9 Environment might vary between adolescents and adults. Specifically, the Val version of BDNF appears to confer heightened susceptibility to environmental influences in the case of youth, whereas the Met version of BDNF operates in this manner with regard to depression and adversity in the case of adults (see meta-analysis in Hosang et al 2014).…”

“…A meta-analysis of G 9 E studies of mostly even if not exclusively adult participants revealed that it was Met-BDNF carriers who were most prone to depression in the face of life stress (Hosang et al 2014). Notably, though, a study of Chinese adolescents found that it was Val-BDNF carriers who proved most susceptible to depressive symptoms in the face of stressful life events (Chen et al 2012).…”

The Anti-Depressant Effect of Praeruptorin C on the Chronic Unpredictable Mild Stress Mouse Modely

“…Studies have demonstrated that the alteration in BDNF expression is closely associated with chronic stress-induced depression [33]. Infusion of BDNF into the brains produces antidepressant-like behavioral effects in rats [34].…”