Nucleus accumbens response to incentive stimuli anticipation in children of alcoholics: relationships with precursive behavioral risk and lifetime alcohol use.

Children of alcoholics (COAs) are at elevated risk to develop alcohol and other substance use disorders. The neurobiological underpinnings of this heightened vulnerability are presently not well understood. This study investigated whether, in humans, COAs have different functioning of the mesolimbic reward circuitry beyond previous substance use confounds and examined potential group differences in neural response in relation to alcohol use and behavioral risk. We studied 20 18- to 22-year-old COAs and 20 controls, developmentally well characterized for substance use and selected to match on sex, age, IQ, lifetime substance use and associated problems, and precursive (ages 12-14 years) externalizing behavioral risk. None met criteria for Diagnostic and Statistical Manual of Mental Disorders IV diagnosis. Neural responses to anticipation of reward and loss were assessed using functional magnetic resonance imaging during a monetary incentive delay task. Overall, COAs showed reduced ventral striatum activation during anticipation of monetary reward and loss compared with controls. However, additional analysis revealed that blunted nucleus accumbens (NAcc) response was only observed in COAs who have not demonstrated any problem drinking behavior. In addition, uniquely in COAs, NAcc activation was positively correlated with precursive externalizing risk, as well as current and lifetime alcohol consumption. These findings suggest a multilevel developmental process whereby lower precursive behavioral risk appears protective of later problem alcohol use in COAs, which is further associated with a blunted NAcc response to incentive anticipation, potentially reflecting a resilience mechanism. Moreover, the results suggest that a close association between motivational responses, alcohol consumption, and behavioral risk may underlie addiction vulnerability in COAs.