Gender-specific effects of brain-derived neurotrophic factor Val66Met polymorphism and childhood maltreatment on anxiety

Background: Although the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is thought to play an important role in the pathophysiology of anxiety, studies on the association between the BDNF polymorphism and anxiety have reported inconsistent results. As possible confounders in determining anxiety, childhood maltreatment and gender as well as their interactions with BDNF polymorphism have been suggested. This study examined the effect of BDNF genotype, childhood maltreatment, and their interaction on anxiety levels by gender. Methods: A total of 206 unrelated Korean healthy young adults (108 were male and the mean age was 23.1 ± 3.2 years) were genotyped for the BDNFVal66Met polymorphism. Measures for anxiety and childhood maltreatment were completed. The main and interaction effects of BDNF polymorphism and childhood maltreatment on anxiety were analyzed by general linear models in all subjects and then in gender-stratified groups. Results: Gender-specific analyses revealed that the interaction effect was significant only in males (p = 0.014). Interestingly, male subjects with the Val/Met genotype tended to be resilient against the increased anxiety after childhood maltreatment. In females, the main effects of both BDNF genotype and childhood maltreatment were significant (p = 0.024 and p = 0.009, respectively) and post-hoc analysis revealed that the Val/Val genotype was associated with a higher anxiety than the Met/Met genotype (p = 0.004). Conclusions: Our results support the interaction effect between the BDNFVal66Met polymorphism and childhood maltreatment in determining anxiety and further emphasize the possible moderating role of gender in this gene-environment interaction.