Examining associations between brain morphology in late childhood and early alcohol or tobacco use initiation in adolescence: Findings from a large prospective cohort

A prominent challenge in understanding neural consequences of substance use involves disentangling predispositional risk factors from resulting consequences of substance use. Existing literature has identified pre-existing brain variations as vulnerability markers for substance use throughout adolescence. As early initiation of use is an important predictor for later substance use problems, we examined whether pre-existing brain variations are associated with early initiation of use. In the Generation R Study, a prospective population-based cohort, brain morphology (gray matter volume, cortical thickness and surface area) was assessed at ages 10 and 14 using neuroimaging. In the second wave, participants reported on alcohol and tobacco use initiation. From a base study population (N = 3019), we examined the longitudinal (N = 2218) and cross-sectional (N = 1817) association between brain morphology of frontolimbic regions of interest known to be associated with substance use risk, and very early (age < 13) alcohol/tobacco use initiation. Additionally, longitudinal and cross-sectional associations were examined with a brain surface-based approach. Models were adjusted for age at neuroimaging, sex and relevant sociodemographic factors. No associations were found between brain morphology (ages 10 and 14) and early alcohol/tobacco use initiation (<13 years). Sex-specific analyses suggested a cross-sectional association between smaller brain volume and early initiated tobacco use in girls. Our findings are important for interpreting studies examining neural consequences of substance use in the general population. Future longitudinal studies are needed to specify whether these findings can be extended to initiation and continuation of alcohol/tobacco use in later stages of adolescence.