An epistasis effect of functional variants on the BDNF and DRD2 genes modulates gray matter volume of the anterior cingulate cortex in healthy humans

Recent evidence suggests that mesolimbic dopaminergic pathways are regulated by the brain derived neurotrophic factor (BDNF). The present study shows that the prominent single nucleotide polymorphisms (SNPs) BDNF Val66Met and DRD2 Taq Ia/ANKK1 exert an epistasis effect on the anterior cingulate cortex (ACC) in 161 healthy Caucasian participants. Carriers with at least one 66Met allele (Val66Met and Met66Met) of the BDNF SNP and one A1 allele (A1/A1 and A1/A2) of the DRD2 SNP are associated with the lowest gray matter volume of the ACC in the current sample. As the smaller gray matter volume of the ACC has been associated with addiction before, this study yields evidence that especially carriers of both allele variants that have been associated with addiction and other psychopathological disorders before might have an increased risk to develop psychiatric symptoms under adverse environmental conditions.