Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms

BDNF Val66Met by chronic stress interaction has been studied using childhood stress as a moderator, but has not been widely studied using chronic stress in adulthood.

Two independent samples were used: Duke-CG (238 Caucasians) and MESA (5524 Caucasians, African Americans and Hispanics). Chronic stress in Duke-CG was operationalized as having primary caregiving responsibility for a spouse or relative with diagnosed Alzheimer's disease or other major dementia; chronic stress in MESA was defined using chronic burden score constructed from self-reported problems of health (self and someone close), job, finance and relationships. CES-D scale was the measure of depression in both samples. The BDNF Val66Met by adulthood chronic stress interaction predicting CES-D was examined using linear regression, adjusted for covariates.

The main effect of BDNF Val66Met genotype on CES-D scores was non-significant (ps > 0.607) but the adulthood chronic stress indicator was significant (ps < 0.001) in both samples. The BDNF Val66Met genotype by adulthood chronic stress interaction was also significant (ps < 0.039) in both samples. The impact of chronic stress in adulthood on CES-D scores was significantly larger in Val/Val genotype individuals than Met carriers.

We found in two independent samples that depression levels increased significantly more as a function of adulthood chronic stress Val/Val genotype carriers than Met carriers. Individuals with the Val/Val genotype and chronic stress exposure could be targeted for interventions designed to reduce risk of depression if this finding is confirmed in future studies.