The attention-deficit/hyperactivity disorder (ADHD) clinical phenotype has limitations for deciphering ADHD etiology and predicting prognosis. Although relative to the clinical phenotype, intermediate phenotypes may have better explanatory and prognostic power, the extent to which ADHD intermediate phenotypes are associated with ADHD risk and prognosis is unknown. The aim of this study was to evaluate evidence for event-related potential (ERP) measures of reward anticipation as ADHD risk and prognostic biomarkers. We examined, whether (1) in a sample of adolescents (N = 304; M = 15.78 years, SD = 1.08; 39.5% female), accounting for the effects of age, sex, ADHD severity and depression, ERPs are associated with ADHD polygenic risk scores (PRSs) (ADHD risk) and (2) in a sample of adolescents at-risk for ADHD (n = 99; M = 15.78 years, SD = 1.08; 39.5% female), accounting for the effects of age, sex, ADHD severity, depression, and baseline outcome values, ERPs are associated, prospectively, with alcohol misuse (ADHD prognosis). In adolescents, greater ADHD PRSs were associated with lower electrophysiological anticipatory attention to motivationally relevant feedback (b = -0.115, p = .046 95%CI [-0.228; -0.002]). The predictors accounted for 5% of the variance in the outcome. In adolescents at-risk for ADHD, at 18-month follow-up, lower electrophysiological anticipatory attention to motivationally relevant feedback was associated with greater alcohol consumption (b = -7.454, p = .007, 95%CI [-12.873; -2.034]). The predictors accounted for 31% of the variance in this outcome. These findings were replicated in sensitivity analyses with behavioral performance variables added as covariates. The current findings support the hypothesis that ERP amplitudes of reward anticipation may be ADHD risk and prognostic biomarkers and suggest that intermediate phenotypes may confer advantages over the ADHD clinical phenotype in delineating etiology and predicting prognosis.
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