Assessing orbitofrontal cortex volume as a predictor of subjective response to alcohol during early adolescence

Adolescence marks a critical window wherein individual differences in brain structure may influence the emergence of alcohol use behaviors. The orbitofrontal cortex (OFC), a region involved in reward processing and behavioral regulation, may play a key role in shaping early responses to alcohol. This study examined whether smaller OFC volume at ages 9-10 predicted likelihood of experiencing subjective effects of alcohol by ages 13-14. Participants (N = 206; 57 % female) were drawn from the Adolescent Brain Cognitive Development Study. Baseline medial and lateral OFC volumes were used. Subjective response to alcohol was measured during follow-up using a binary outcome (1 = any effect, 0 = no effects). Mixed-effects logistic regression models tested the association between OFC and alcohol response, adjusting for sex, parental education, race/ethnicity, intracranial volume, and site. Smaller left medial OFC at Baseline was significantly associated with greater odds of reporting subjective effects (OR = 1.70, p = .026). Youth who reported subjective effects also consumed more alcohol in the past year (p < .001), but did not differ in their alcohol expectancies. Among those reporting subjective effects, OFC volume was not significantly associated with the amount or frequency of alcohol use. These findings suggest that smaller OFC volume may not reflect pharmacological sensitivity per se, but instead relate to early drinking behavior sufficient to elicit noticeable effects. This may reflect underlying impulsivity-related traits or altered neurodevelopmental trajectories that predispose youth to early and potentially riskier patterns of alcohol use. Results underscore the potential value of identifying structural brain markers that contribute to individual vulnerability for alcohol use during adolescence.