Comt By Drd3 Epistatic Interaction In Modulating Behaviors In Children With Adhd: A Pharmaco-Dynamic Behavioral Approach

Objective: Examining the joint effect of two functional variants in two dopamine-related genes (DRD3andCOMT) on ADHD-relevant behaviors under three experimental conditions (EC). Method: 362 children with ADHD were assessed by parents and teachers during a week of baseline evaluation, followed by 1 week of MPH and placebo, administered in a double-blind crossover design. Results: Statistically significant 3-way (DRD3-by-COMT-by-EC;p= .004) and 2-way interactions (COMTby EC;p= .002) were observed on Conners'-Teachers scores. Children with theCOMTMet/Met genotype had lower scores at baseline and on placebo compared to the other genotype groups. Furthermore, stratifying the children according to theirCOMTgenotypes helped to detect statistically significant and biologically meaningful effects ofDRD3genotype. Conclusions: These findings suggest thatCOMTandDRD3genetic variants may together play a role in ADHD symptomatology and response to treatment through gene-gene interaction.