Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis
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
BMC Medicine 2014, 12:7 doi:10.1186/1741-7015-12-7Published: 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.