Genetic determinants of serum brain-derived neurotrophic factor (BDNF) after alcohol withdrawal

Peripheral brain-derived neurotrophic factor (BDNF) levels increase during alcohol abstinence in dependent subjects. Meanwhile, the genetic determinants of circulating BDNF this context are poorly understood. Studies of associations between circulating BDNF and single nucleotide polymorphisms (SNPs) of the corresponding gene are mainly restricted by the most studied BDNF SNP rs6265. A recent genome-wide association study demonstrated that the BDNF-related SNP rs75945125 is associated with serum BDNF. However, it is unknown whether this SNP is associated with changes in peripheral BDNF levels in the context of alcohol abstinence. We aimed to assess the association of the BDNF-related SNPs rs75945125 and rs6265 with changes in serum BDNF levels after alcohol withdrawal and the corresponding clinical manifestations. A total of 132 inpatients diagnosed with alcohol withdrawal syndrome were enrolled in the study. Serum BDNF levels were assessed on 2nd, 7th, and 21st days after alcohol withdrawal. Alcohol withdrawal syndrome severity, craving severity, affective symptoms, and cognitive impairment were assessed on 7th and 21st days. BDNF SNPs rs75945125 and rs6265 were genotyped using real-time PCR. BDNF concentrations in the carriers of the rs75945125 C allele on 21st day were higher as compared with TT genotype carriers. BDNF SNP rs75945125 C allele carriers had a longer duration of problem drinking, consumed a lesser volume of alcohol in the last 3 months, and had lower severity of withdrawal syndrome on 7th day compared with TT genotype carriers. BDNF levels were moderated by rs75945125 and rs6265, as well as by the interaction of rs75945125 × rs6265, whereas only the interaction of rs75945125 × rs6265 had an effect on depression scores during abstinence. Thus, the trajectory of serum BDNF changes during alcohol abstinence is determined by both rs75945125 and rs6265. Moreover, BDNF gene-related SNPs are associated with the clinical parameters of alcohol dependence and withdrawal. The longitudinal design without a control group and the relatively small sample size are the limitations of this study. Future studies on the revealed interactions are warranted.