Impact of COMT Val158Met-polymorphism on appetitive conditioning and amygdala/prefrontal effective connectivity

Appetitive conditioning is an important mechanism for the development, maintenance, and treatment of psychiatric disorders like substance abuse. Therefore, it is important to identify genetic variations, which impact appetitive conditioning. It has been suggested that the Val(158) Met-polymorphism in the Catechol-O-Methyl-Transferase (COMT) is associated with the alteration of neural processes of appetitive conditioning due to the central role of the dopaminergic system in reward processing. However, no study has so far investigated the relationship between variations in the COMT Val(158) Met-polymorphism and appetitive conditioning. In this fMRI study, an appetitive conditioning paradigm was applied, in which one neutral stimulus (CS+) predicted appetitive stimuli (UCS) while a second neutral stimulus (CS-) was never paired with the UCS. As a main result, we observed a significant association between the COMT Val(158) Met-genotype and appetitive conditioning: skin conductance responses (SCRs) revealed a significant difference between CS+ and CS- in Val/Val-allele carriers but not in the other genotype groups. Val/Val-allele carriers showed increased hemodynamic responses in the amygdala compared with the Met/Met-allele group in the contrast CS+ > CS-. In addition, psychophysiological-interaction analysis revealed increased effective amygdala/ventromedial prefrontal cortex connectivity in Met/Met-allele carriers. The increased amygdala activity points to facilitated appetitive conditioning in Val/Val-allele carriers while the amygdala/prefrontal connectivity results could be regarded as a marker for altered emotion regulation during conditioning, which potentially impacts appetitive learning sensitivity. The SCRs finding indicates a stronger conditioned response in the Val/Val-allele group and dovetails with the neural differences between the groups. These findings contribute to the current research on COMT in emotional processing.