Stressful life events and the brain-derived neurotrophic factor gene in bipolar disorder

Background: Gene-environment interactions may contribute to the high heritability of bipolar affective disorder. The aim of the present study was to examine the interplay between the BDNF Val⁶⁶Met polymorphism and stressful life events (SLEs) in bipolar disorder. Method: A total of 1085 participants were recruited, including 487 bipolar I cases and 598 psychiatrically healthy controls. All participants completed the List of Threatening Life Events Questionnaire; bipolar subjects reported the events that occurred 6 months leading up to their worst manic episode and 6 months prior to their worst depressive episode, controls recorded events experienced 6 months before interview. The sample was genotyped for the BDNF Val⁶⁶Met polymorphism (rs6265). Results: Both Met carrier BDNF genotype and SLEs were significantly associated with the worst depressive episode of bipolar disorder. For the worst depressive episodes the effects of SLEs were also significantly moderated by BDNF genotype (gene × environment interaction). Limitations: The use of a self report questionnaire to measure stressful life events may increase recall inaccuracies, therefore caution should be taken when interpreting these results. Discussion: The findings of this study highlight the importance of the interplay between genes and the environment in bipolar disorder.