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Open Access Research article

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

Georgina M Hosang12*, Celia Shiles3, Katherine E Tansey24, Peter McGuffin2 and Rudolf Uher25

Author Affiliations

1 Psychology Department, Goldsmiths, University of London, New Cross, London SE14 6NW, UK

2 MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College, London, De Crespigny Park, London SE5 8AF, UK

3 King’s College London, Academic Centre, 2nd Floor Henriette Raphael House, Guy’s Campus, London SE1 1UL UL, UK

4 MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK

5 Department of Psychiatry, Dalhousie University, 5909 Veterans’ Memorial Lane, Halifax, Nova Scotia B3H 2E2, Canada

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BMC Medicine 2014, 12:7  doi:10.1186/1741-7015-12-7

Published: 16 January 2014



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.

Stress; Life events; Childhood maltreatment; Childhood adversity; Child abuse; Depression; Brain-derived neurotrophic factor; BDNF; rs6265; Gene-environment interaction