Frontostriatal Resting State Functional Connectivity in Resilient and Non-Resilient Adolescents with a Family History of Alcohol Use Disorder.

Youth with parental substance use disorder (family-history positive [FH+]) are at an elevated risk for substance use problems, but not all FH+ youth experience this outcome. Frontostriatal brain networks involved in inhibitory control and reward responsivity underlie risk-taking behaviors, but the role of these networks in substance use heterogeneity among FH+ youth has not been examined. The present study examined resting state functional connectivity (RSFC) in frontostriatal networks in FH+ youth with and without risky substance use. Participants were 36 FH+ adolescents (mean age 14.96 years at the scan date; 36% female) from a longitudinal, community-based functional magnetic resonance imaging study enriched for parental alcohol use disorder. Groups were based on the absence (resilient) or presence (high-risk) of at least one occasion of any substance use by age 14 and also use of at least two different types of substances by the most recent substance use assessment (mean age 16.89 years). Bilateral masks of the dorsolateral prefrontal cortex (DLPFC) and the nucleus accumbens were used for seed-based RSFC due to the importance of these regions in executive control and salience networks, respectively. Compared with FH+/high-risk youth, FH+/resilient youth displayed greater connectivity between the left DLPFC seed and the left posterior cingulate cortex. No other brain regions showed significantly different RSFC between resilient and high-risk groups. FH+/resilient youth showed stronger synchrony between brain regions associated with cognitive control, particularly those associated with flexible adaptation of thoughts and behaviors. Although preliminary, the results of this study set the stage for a continued focus on risk-group heterogeneity to better identify neural markers of resilience against substance use problems in vulnerable populations.