Reward Processing in Drug-Naive Youth with Various Levels of Risk for Substance Use Disorders: A Pilot Study

Background: It has been hypothesized that attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) share common neurobiological features. When abnormalities in the mesolimbic reward system are characteristic of children with ADHD, it is unclear whether youth at particularly elevated risk for SUD may exhibit any further disturbances. The objective of this pilot study is to examine possible neurobiological differences among youth with different levels of SUD risk before exposure to any abusable substances. Methods: We recruited 47 drug-naive children aged 8-13 divided into (1) Low Risk (LR)-ADHD only (n = 16); (2) High Risk (HR)-ADHD+familial SUD (n = 17); and (3) healthy controls (HC, n = 14) who underwent one functional magnetic resonance imaging scan while performing a hybrid task. We used the omnibus analysis of covariance model to assess for group differences in brain activation in regions linked to the brain reward and behavioral control systems. Results: Behavioral analysis showed significant Cue and Flanker main effects, but no significant main effect for Group. Whole-brain analysis showed significant differences in widely distributed networks related to both reward processing and behavioral control. Region of interest (ROI) activations showed that the HR group had the highest activation in the right putamen during both expected rewards and unexpected nonreward outcomes and in the anterior cingulate cortex (ACC) during unexpected nonreward outcomes, while LR and HC youth showed similarly low activation during these contrasts. Furthermore, the LR and HR groups showed lower activation than HC in the right ACC and the right caudate during flanker contrasts. Conclusions: These are the first preliminary results to demonstrate that the magnitude of activation during reward notification differs as a function of reward outcome in youth at high versus LR for SUD, such that youth at LR for SUD exhibit the highest activation for positive rewards, whereas those at HR for SUD exhibit the highest activation during negative rewards.