Brain-derived Neurotrophic Factor Genetic Variants are Associated with Major Depression Susceptibility and Serotonin Reuptake Inhibitor Antidepressant Treatment Response in Taiwanese

Abstract

The involvement of neurotrophic factors, notably brain-derived neurotrophic factor (BDNF) has been suggested in the pathogenesis of major depressive disorder (MDD) and in the response of antidepressant treatment both in preclinical and clinical studies. Thus, genetic variation in human BDNF gene may be associated with MDD susceptibility and be related to treatment response to antidepressants in patients with MDD. Two hundred and eighty-eight Taiwanese patients diagnosed with MDD and 397 participants with similar mean age and gender distribution were enrolled in the study, and three markers, including rs6265 (Val66Met) in the BDNF gene were examined for their association with MDD and 4-week response to selective serotonin reuptake inhibitors (SSRI) (n = 216) using single- and haplotype-based analyses. The results showed that the Met allele of rs6265 was in allelic association with MDD. Haplotype analysis of marker combination rs2049046-rs7103411-rs6265 further indicated the association between BDNF genetic polymorphisms and MDD (global permutation p = 0.0007). Regarding 4-week SSRI treatment response and controlling the effect of relevant covariates using logistic regression, the heterozygotes of rs7103411 and rs6265 had higher treatment responder percentage than their homozygous analogs. Furthermore, MDD patients carrying AGA-TAG diplotype tended to be the responders to 4-week SSRIs treatment compared with the non-AGA-TAG diplotype carriers (corrected p= 0.048). One strength of our study is the relatively large sample size. Our findings suggest that BDNF may be a susceptibility gene for MDD, and may also confer a heterosis effect for antidepressant treatment response. Keywords: Brain-derived neurotrophic factor association, depression, heterosis effect, polymorphism, selective serotonin reuptake inhibitor.