A convergent network of evidence continues to indicate that one of the core risk pathways to SUD involves a vulnerability to disinhibitory processes. The vulnerability is expressed at the behavioral level by high undercontrol. It is exacerbated by social environmental factors likely to be highly aggregated in high-risk families, and it is regulated at the neural level by two systems, one involving effortful control, largely localized in prefrontal cortical circuitry, and the other involving incentive reactivity, localized in subcortical circuitry. These systems mature at different rates over the course of adolescence and early adulthood; they are also affected by environmental exposure to stress, family conflict, and possibly by precocious alcohol and other drug use. Work to date is suggestive of a considerable synergy across levels of system, and over time for the highest-risk subset of the population. However, the demonstration of such relationships is still in its infancy.
