Exploring the Impact of BDNF Val66Met Genotype on Serotonin Transporter and Serotonin-1A Receptor Binding

Background The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT 1A ) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT 1A binding potential (BP ND ) have demonstrated equivocal results. Methods We conducted an imaging genetics study investigating the effect of Val66Met genotype on 5-HTT or 5-HT 1A BP ND in 92 subjects. Forty-one subjects (25 healthy subjects and 16 depressive patients) underwent genotyping for Val66Met and PET imaging with the 5-HTT specific radioligand [ 11 C]DASB. Additionally, in 51 healthy subjects Val66Met genotypes and 5-HT 1A binding with the radioligand [ carbonyl - 11 C]WAY-100635 were ascertained. Voxel-wise and region of interest-based analyses of variance were used to examine the influence of Val66Met on 5-HTT and 5-HT 1A BP ND . Results No significant differences of 5-HTT nor 5-HT 1A BP ND between BDNF Val66Met genotype groups (val/val vs. met-carrier) were detected. There was no interaction between depression and Val66Met genotype status. Conclusion In line with previous data, our work confirms an absent effect of BDNF Val66Met on two major serotonergic structures. These results could suggest that altered protein expression associated with genetic variants, might be compensated in vivo by several levels of unknown feedback mechanisms. In conclusion, Val66Met genotype status is not associated with changes of in-vivo binding of 5-HTT and 5-HT 1A receptors in human subjects.