Orbitofrontal Cortex Volume and Effortful Control as Prospective Risk Factors for Substance Use Disorder in Adolescence.

BACKGROUND: Orbitofrontal cortex (OFC) dysfunction has been proposed to increase the risk for developing a substance use disorder (SUD) during adolescence. In this study, we suggest that a reduction in OFC volumes might underlie temperament-based risk factors for SUD, and examined whether smaller OFC volumes during early adolescence could predict later development of SUD.

METHODS AND MATERIALS: Adolescents (n = 107; 58 male, 49 female) underwent structural MRI and completed a self-report measure of temperamental effortful control at age 12. At 3 subsequent assessments (aged 15, 16, and 18) SUD was assessed via a semi-structured clinical interview. By the third assessment, 24 participants (22.4%) had received a lifetime diagnosis of SUD.

RESULTS: Smaller volumes of the left OFC, right OFC, and left medial subregions predicted lifetime history of SUD by age 18. Volumes of the left OFC and left lateral subregions were positively correlated with effortful control, and left OFC volumes mediated the relationship between effortful control and SUD.

CONCLUSIONS: Smaller volumes of the OFC and low effortful control during adolescence appear to be associated phenotypes that increase the risk of subsequent SUD. Further studies examining the temporal sequence of these risk factors are needed to fully understand this relationship.