Network-Dependent Modulation of COMT and DRD2 Polymorphisms in Healthy Young Adults

Nonlinear modulation of the dopamine signaling on brain functions can be estimated by the interaction effects of dopamine-related genetic variations. We aimed to explore the interaction effects of COMT rs4680 and DRD2 rs1076560 on intra-network connectivity using independent component analysis. In 250 young healthy adults, we identified 11 meaningful resting-state networks (RSNs), including the salience, visual, auditory, default-mode, sensorimotor, attention and frontoparietal networks. A two-way analysis of covariance was used to investigate COMT×DRD2 interactions on intra-network connectivity in each network, controlling for age, gender and education. Significant COMT×DRD2 interaction was found in intra-network connectivity in the left medial prefrontal cortex of the anterior default-mode network, in the right dorsolateral frontal cortex of the right dorsal attention network, and in the left dorsal anterior cingulate cortex of the salience network. Post hoc tests revealed that these interactions were driven by the differential effects of DRD2 genotypes on intra-network connectivity in different COMT genotypic subgroups. Moreover, even in the same COMT subgroup, the modulation effects of DRD2 on intra-network connectivity were different across RSNs. These findings suggest a network-dependent modulation of the DA-related genetic variations on intra-network connectivity.