Stimulant vs. Non-stimulant Treatments and Reward Processing in Drug-naive Youth at SUD Risk

Longitudinal studies have shown that childhood Attention Deficit/Hyperactivity Disorder (ADHD) and child disruptive behavior disorders play an important role in the development of later Substance Use Disorders (SUD). Although available evidence suggests that abnormal reward processing is likely to mediate vulnerability for addiction, the functioning of the brain reward systems in at-risk individuals preceding the exposure to drugs remains largely unknown. Better understanding the baseline characteristics of reward processing in drug-naïve individuals at risk for later SUD is an important initial step in refining our knowledge of the neurobiological basis of addiction. Reward processing in at-risk individuals may be further influenced by exposure to first-line treatments (e.g. methylphenidate (MPH)) for ADHD that also happen to be controlled substances.

Findings from animal research have raised the possibility that stimulants such as methylphenidate (MPH) may have "sensitization" effects - which prime the brain reward system for enhanced responding to the rewarding effects of abusable substances, whereas non-stimulants such as atomoxetine (ATX) may diminish drug self-administration. However, no studies have examined the purported different effects of stimulants vs. non-stimulants on the brain reward system utilizing a targeted biomarker approach linked to an a priori model, which focuses on intermediate phenotypes. Such research could provide important knowledge regarding the biological basis of addiction vulnerability and aid in the development of preventive interventions.

This proposal will provide pilot data for the hypotheses that stimulant and non-stimulant medications have differential effects on activation in the brain reward system in High Risk (HR) youth, and that differences activation will be related to changes in measures of reward sensitivity on psychometric tests. The study team believes that this protocol is uniquely innovative in its approach to study drug-naïve children at the highest levels of risk for SUD, thus providing an opportunity to delineate differential effects of medication treatment in relation to SUD risk. This research is also significant since it will be the first neuroimaging study to assess the biological correlates of the effects of stimulants on reward sensitivity in HR children, and especially in relation to purported changes in reward processing.