Interaction between stress and the BDNFVal66Met polymorphism in depression: a systematic review and meta-analysis

Abstract

BackgroundMajor 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.MethodsA 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.ResultsThe 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).ConclusionsThe 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.

Predicting change in symptoms of depression during the transition to university: The roles of BDNF and working memory capacity

“…Similar to evidence on low working memory capacity, the met allele of the BDNF Val66Met polymorphism has been associated with impaired responses to stress and heightened vulnerability to depression (e.g., Alexander, Osinsky, Schmitz, Mueller, Kuepper, & Hennig, 2010; Classen, Wells, Knopik, McGeary, & Beevers, 2011; Colzato, Van der Does, Willem, Kouwenhoven, Elzinga, & Hommel, 2011; Gatt et al, 2009; Pandey & Dwivedi, 2009; Pei et al, 2012; Shalev et al, 2009; Vinberg, Trajkovska, Bennike, Knorr, Knudsen, & Kessing, 2009; see also a meta-analysis by Hosang, Shiles, Tansay, McGuffin, & Uher, 2014). The genetic variation in exon 11 of the BDNF gene results in an amino-acid substitution from valine to methionine at codon 66 (Val66Met) and influences BDNF protein production.…”

“…This pattern of findings suggests a differential susceptibility pattern (Roisman, Newman, Fraley, Haltigan, Groh, & Haydon, 2012), and it might explain inconsistencies in past research examining BDNF, stress, and depression. Some past studies found a relation between the BDNF met allele and increased stress reactivity or increased risk for depression in interaction with stress (see the recent meta-analysis by Hosang et al, 2014). Others, however, have found the opposite (e.g.…”

Spine synapse remodeling in the pathophysiology and treatment of depression

“…This is a functional SNP that reduces the processing of pro-BDNF to mature BDNF decreases BDNF transport to terminals, and thereby blocks activity dependent release of BDNF. The BDNF Met allele has been associated with reduced hippocampal volume and executive function in humans [28, 29] and increased risk for depression in patients exposed to early life stress or trauma [32, 45, 54]. BDNF Met knock-in mice display a reduction in the number and length of branch points of CA3 pyramidal neurons in the hippocampus (spine density was not examined) [57].…”

Genetic association of the transcription of neuroplasticity‐related genes and variation in stress‐coping style

“…Life stresses such as childhood adversity or a recent stressful event, are recognized as being risk factors for depression (Hosang et al. 2014). Notably, the Met allele of BDNF, Val66Met, has been shown to have significant associations with life stress and depression.…”