A family history (FH) of alcohol use disorder (AUD) is associated with increased personal risk for alcohol misuse and AUD. FH is also related to increased impulsivity as evidenced by performance on delay discounting tasks, representing a potential mechanistic link between FH and alcohol misuse. Delay discounting tasks assess individual differences in preferences for smaller, immediate versus larger, delayed rewards, the former being linked to substance misuse. Decision-making on such tasks is underpinned by multiple neural systems, including those supporting reward valuation, cognitive control, and future-oriented thinking. We hypothesized that FH would be associated with differences in one or more neural systems related to delay discounting, with these differences being related to increases in alcohol misuse in young adulthood. We tested 163 first-year college students (ages 18-19) with varying levels of familial risk for AUD on an fMRI delay discounting task. Alcohol misuse was self-reported at baseline and in three yearly follow-up surveys using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol misuse was modeled using a latent growth model, and we examined mediation between FH and alcohol misuse trajectory (AUDIT intercept and slope) through functional activation of brain regions implicated in reward valuation (nucleus accumbens), cognitive control (middle frontal gyrus), and future-oriented thinking (hippocampus). FH was associated with greater activation of the nucleus accumbens, which in turn predicted a steeper AUDIT slope. No other mediators were significant. Our results demonstrate that nucleus accumbens function may be a key mechanism by which FH increases risk for alcohol misuse and AUD.

The authors have declared no competing interest.

This work was supported by NIH grant K01AA026334.

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