Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders.

It has been reported that the functional polymorphism in the serotonin transporter gene linked promoter region (5-HTTLPR) modifies the association between stressful life events (SLEs) and depression in child, adolescent, and adult populations. We sought to replicate this finding in elders and, additionally, to test modifying effects of the brain-derived neurotrophic factor (BDNF) val66met polymorphism. In 732 Korean community residents ages 65+, diagnosis of depression (Geriatric Mental State Schedule), information on SLEs, and genotypes for 5-HTTLPR and BDNF val66met were ascertained. Of those without depression at baseline, 521 (88%) were followed up 2.5 years later. Interactions between SLEs and the two genotypes were investigated for both prevalent depression at baseline and incident depression at follow-up. Significant interactions of SLEs with both 5-HTTLPR and BDNF genotypes were observed on risk of depression after adjustment for age, gender, education, and disability. A significant three-way interaction between 5-HTTLPR, BDNF, and SLEs was also found. The same findings were observed for predictors of incident depression in the prospective analysis. These findings suggest that environmental risk of depression is modified by at least two genes and that gene-environment interactions are found even into old age.