The brain age gap as a predictor of alcohol initiation in adolescence

Growing evidence suggests regional and network-level brain imaging features in late childhood are predictive of alcohol use in adolescence. However, the directionality of these effects (i.e. whether they reflect accelerated or delayed neuromaturation) are mixed. We applied a Brain Age Gap Estimation (BrainAGE) model to examine whether overall deviations from typical brain aging trajectories are predictive of (1) alcohol initiation and (2) use behaviour (experimentation versus binge drinking) in adolescence.

Data from the Adolescent Brain Cognitive Development study release 6.0 were used. Baseline (ages 9-11) structural imaging features (cortical volume, area, and subcortical volume) were used to estimate BrainAGE. Alcohol use was determined using self-report data from the Substance Use Interview and Timeline Follow-Back across follow-ups (waves 1-6; ages 10-17). Logistic generalized mixed effects models examined whether BrainAGE predicted group status between (1) non-initiators (n = 3639) and initiators (n = 1176), and; (2) experimentation (at least one full drink, no binge episodes; n = 461) and binge drinking (at least one episode; n = 438).

When adjusting for age, sex, and pubertal status, a one-standard-deviation decrease in BrainAGE (equivalent to 1.64 years) at baseline was associated with a 9.5% increase in odds of alcohol initiation in adolescence. However, this effect did not survive adjustment for sociodemographic and prior alcohol exposure covariates. Further, BrainAGE did not discriminate between experimentation and binge drinking.

Findings suggest BrainAGE in late childhood may reflect potential risk for alcohol initiation, but not behaviours, in adolescence. However, this association likely reflects complex interactions between brain structure and broader contextual factors, rather than a direct effect of brain structure alone.