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

Hosang, Georgina M.; Shiles, Celia; Tansey, Katherine E.; McGuffin, Peter and Uher, Rudolf. 2014. Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis. BMC Medicine, 12(7), pp. 1-11. ISSN 1741-7015 [Article]

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Abstract or Description

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.

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stress; life events; childhood maltreatment; childhood adversity; child abuse; depression; brain-derived neurotrophic factor; BDNF; rs6265; gene-environment interaction

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16 January 2014Published

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Date Deposited:

23 Apr 2014 11:06

Last Modified:

29 Apr 2020 15:58

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Yes, this version has been peer-reviewed.


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