Brain morphology predictors of alcohol, tobacco, and cannabis use in adolescence: A systematic review

In the last decade, extensive research has emerged on the predictive value of brain morphology for substance use initiation and related problems during adolescence. This systematic review provides an overview of longitudinal studies on pre-existing brain variations and later initiation of alcohol, tobacco, and cannabis use (N = 18). Adolescent structural neuroimaging studies that started before substance use initiation suggest that a smaller anterior cingulate cortex (ACC) volume, thicker or smaller superior frontal gyrus, and larger nucleus accumbens (NAcc) volume are associated with future alcohol use. Also, both smaller and larger orbitofrontal cortex (OFC) volumes were associated with future cannabis and combined alcohol/cannabis use. Smaller amygdala volumes were related to future daily tobacco smoking. These findings could point to specific vulnerabilities for adolescent substance use, as these brain areas are involved in cognitive control (ACC), reward (NAcc), motivation (OFC), and emotional memory (amygdala). However, the reported findings were inconsistent in directionality and laterality, and the largest study on alcohol use predictors reported null findings. Therefore, large population-based longitudinal studies should investigate the robustness and mechanisms of these associations. We suggested future research directions regarding sample selection, timing of baseline and follow-up measurements, and a harmonization approach of study methods.