Sex differences in emotion- and reward-related neural responses predicting increases in substance use in adolescence.

Adolescent substance use is a significant public health problem and there is a need for effective substance use preventions. To develop effective preventions, it is important to identify neurobiological risk factors that predict increases in substance use in adolescence and to understand potential sex differences in risk mechanisms. The present study used functional magnetic resonance imaging and hierarchical linear modeling to examine negative emotion- and reward-related neural responses in early adolescence predicting growth in substance use to middle adolescence in 81 youth, by sex. Adolescent neural responses to negative emotional stimuli and monetary reward receipt were assessed at age 12-14. Adolescents reported on substance use at age 12-14 and at 6 month, and 1, 2, and 3 year follow-ups. Adolescent neural responses did not predict initiation of substance use (yes/no), but, among users, neural responses predicted growth in substance use frequency. For girls, heightened right amygdala responses to negative emotional stimuli in early adolescence predicted growth in substance use frequency through middle adolescence. For boys, blunted left nucleus accumbens and bilateral ventromedial prefrontal cortex responses to monetary reward predicted growth in substance use frequency. Findings suggest different emotion and reward-related predictors of the development of substance use for adolescent girls versus boys.