Longitudinal associations between BDNF promoter methylation and late-life depression.

Reduced brain-derived neurotrophic factor (BDNF) function has been suggested as a risk factor for late-life depression. BDNF secretion is influenced by epigenetic (DNA promoter methylation) and genetic (val66met polymorphism) profiles. We investigated the independent and interactive effects of BDNF methylation and val66met polymorphism on late-life depression. In total, 732 Korean community residents aged ≥ 65 years were evaluated, and 521 of them without depression at baseline were followed up 2 years later. Depression was determined using the Geriatric Mental State Schedule, and depression severity was evaluated with the Geriatric Depression Scale. Demographic and clinical covariates were obtained. The effects of BDNF methylation and polymorphism on the diagnosis of depression were investigated using a multivariate logistic regression model, and the relationships between BDNF methylation and depression severity were evaluated using partial correlation tests. Higher BDNF methylation was independently associated with the prevalence and incidence of depression and severe depressive symptoms. No significant methylation-genotype interactions were found. BDNF promoter methylation could be a proxy biomarker for depression late in life.