Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates.

摘要: Genetic variation in the serotonin transporter gene (SLC6A4) is associated with vulnerability to affective disorders and pharmacotherapy efficacy. We recently identified sequence polymorphisms common marmoset SLC6A4 repeat region (AC/C/G CT/T/C) individual differences anxiety-like trait, expression, response antidepressants. The mechanisms underlying effects of these are unknown, but a key mediator action 2A receptor (5HT2A). Thus, we correlated 5HT2A binding potential (BP) RNA expression 16 genotyped marmosets responsivity antagonism during human intruder test anxiety. Voxel-based analysis measurements showed reduction BP specifically right posterior insula individuals homozygous for anxiety-related variant AC/C/G. These same displayed an anxiogenic, dose-dependent after pharmacological antagonism, while CT/T/C no effect. A voxel-based correlation analysis, independent genotype, revealed that adjacent anterior proisocortex was negatively trait anxiety scores. Moreover, both regions good predictor size direction acute emotional threat antagonism. Our findings suggest genetic may contribute anxious phenotype via neurochemical changes brain areas implicated interoceptive processing, critical role regulation responses threat.