Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

Abstract

A large number of studies have examined associations between brain-derived neurotrophic factor (BDNF) gene polymorphisms and depressive symptoms. However, results still remain controversial. Recent studies suggested a significant age and gender effect on the heritability of depression. The potential neurobiological pathways that could possibly mediate this relationship have not been examined so far. Since BDNF is involved in the regulation of neurotransmitter production, a mediating role of neurotransmitters seems plausible. The present study aims to examine the association between three common BDNF single-nucleotid polymorphisms (SNPs; rs7103411, rs7124442, and rs6265) and depressive symptoms in a community-based elderly population taking into account the serum levels of four neurotransmitters, serotonin, dopamine, adrenalin, and noradrenalin, as potential mediating factors. We also examined whether age and gender had a modifying effect on this association. We collected and analyzed the genetic and laboratory data as well as Center for Epidemiologic Studies-Depression scores of 350 community-dwelling elderly individuals (aged 65+ years). We found that the BDNF rs6265 polymorphism was related to the severity of depressive symptoms, and that this association was independent of neurotransmitter levels. Stratified analyses showed that this association was restricted to older individuals (≥74 years) and men. The associations of SNPs rs7103411 or rs7124442 SNP with depressive symptoms were not statistically significant. This study importantly adds to the existing literature by affirming previous assumptions on an age and gender difference in the relation between BDNF genotype and depression. We moreover first-time report a missing mediating role of neurotransmitters in this association.