Alcohol use and abuse are significant concerns within adolescence and early adulthood. Although anxiety and depression frequently co-occur with alcohol use in adolescence and are postulated to be a pathway to alcohol problems (e.g., Chassin et al., 1993; Sher et al., 2005), prior work has predominantly focused on the so-called ‘externalizing’ pathway to alcohol use. One possibility is that the combination of both kinds of problems could be more pernicious than externalizing problems alone, but this has not been investigated. Furthermore, while the role of internalizing and/or externalizing problems on alcohol use could be exacerbated by the presence of neurobiological characteristics, the potential moderating role of factors such as the function of neural emotion-processing circuitry has been neglected. The current study examined the effects of both internalizing and externalizing disorders, symptom severity, and chronicity across development (between ages 8 to 17) on alcohol use and dependence at age 20. Also explored were the potential moderating effects of amygdala reactivity and functional connectivity measured during a face-processing paradigm at age 20. Study aims were tested within the context of a longitudinal study of 111 boys prospectively followed from early childhood to age 20. Although contrary to our hypotheses, results supported prior findings suggesting that internalizing symptomatology alone may be protective against problematic alcohol use/dependence. However, in combination with high externalizing problems or early onset of alcohol intoxication, high internalizing problems were related to alcohol use and dependence. Across the majority of study observations, it was the comorbid internalizing/externalizing group that demonstrated the highest scores on alcohol outcome measures. Moreover, these effects were exacerbated for some of the alcohol use outcomes by the strength of the functional connectivity between the amygdala and the anterior cingulate cortex (BA 32 and BA 24), a limbic area involved in emotion regulation. Conceivably, the combination of both types of problems combined with difficulty controlling negative emotion creates a pattern of dysregulation that makes youth vulnerable to the effects of alcohol and leads them to problems with controlling their use. Differences between this study and prior literature are explored and limitations of the present study are discussed
