Insular risk processing predicts alcohol use via externalizing pathway in male adolescents

Objective: Male adolescents exhibit greater impulsivity and externalizing symptomatology relative to female adolescents. Furthermore, externalizing symptomatology has been associated with greater alcohol use and differential anterior insula functioning. The current longitudinal study on adolescents examined whether activity in the anterior insula, when processing uncertain outcomes and representing risk, is directly associated with gender differences in later adolescent alcohol use frequency, as well as indirectly through externalizing symptomatology. Method: Using functional magnetic resonance imaging, we examined whether gender moderated these associations in a sample of 161 adolescents (53% male) with repeated annual measurements over 3 years. We monitored responding of a region implicated in risk processing during an economic lottery choice task involving uncertain outcomes. Self-reported externalizing symptomatology and alcohol use frequency were collected at all time points. Results: Results indicated that there was a significant indirect effect of anterior insula processing during the task at Time 1 on alcohol use at Time 3 through externalizing symptomatology at Time 2 for male, but not female, adolescents. Externalizing symptomatology predicted alcohol use for both male and female adolescents. Conclusions: The findings suggest gender differences in vulnerability to later alcohol use, specifically in terms of how a neurobiological susceptibility to risk insensitivity may disproportionately influence male adolescents’ externalizing symptomatology. Male adolescents who do not effectively integrate risk-related signals are likely to engage in externalizing behaviors, which in turn are related to later alcohol use. Findings also suggest differential roles of risk-related brain function that contribute to gendered pathways to adolescent health-risk behaviors. (J. Stud.