Effects of COMT Suppression in a Randomized Trial on the Neural Correlates of Inhibitory Processing Among People With Alcohol Use Disorder

Abstract

Introduction- Youth antisocial behavior strongly associates with conduct problems (CP) and callous-unemotional (CU) traits. While CP has links to broad cognitive impairments, CU traits have specific links with cognitive control and affective theory of mind (ToM) difficulties. Evidence suggests cognitive control limitations impact affective processing in ToM amongst youth with elevated CU traits. Here we sought to improve on those initial findings by leveraging a randomized dual-task (within-trial) design to replicate and extend prior findings. Methods- In this double-blind, randomized controlled trial, 85 participants (47 % female) were stratified by sex and CU trait severity. The study employed a ToM task with cognitive, affective, and physical conditions, combined with an inhibitory processing task to tax cognitive control. Participants completed single and dual-task trials, counterbalanced to test within-subject effects. Primary hypotheses were tested with both CP and CU traits in the same model using repeated measure mixed effects to examine changes in accuracy and reaction time. Results- CU traits were uniquely associated with greater impairments in affective ToM under dual-task conditions, reflecting increased difficulty integrating affective information when cognitive demands were increased. CP associated with lower single ToM performance but no change during dual-task trials. Notably, participants resilient to dual-task effects reported fewer antisocial behaviors, even with elevated CU traits. Limitations- While appropriately powered for study aims, the sample was underpowered to detect any potential primary and secondary variant interactions on study outcomes. Conclusions- These findings support a CU trait specific cognitive-affective interaction as a mechanism critical for understanding youth antisocial behavior.