Several processes might contribute to the transition from general to specific influences. For one, adolescents are more impulsive and risk-taking than adults (26). Personality traits such as disinhibition and sensation-seeking are not predispositions to use any particular substance, but rather to use whatever substances might be available (9, 27). Additionally, neurodevelopmental changes relevant to behavioral disinhibition continue throughout adolescence. For example, by adolescence, the nucleus accumbens—important in reward sensitivity—is well-developed, but poorly regulated by a still maturing prefrontal cortex (28–29), resulting in deficits of top-down control over the reward system that slowly improves into early adulthood. This developmental window is the same time period that we observed decreases in the comorbidity among different substance use disorders, suggesting that disinhibitory mechanisms with known neurological substrates may be in play. Further supporting this hypothesis, the earlier decline in comorbidity for females relative to males from age 17 to 20 (Figure 3) is consistent with the earlier pubertal (30), cortical (31), and personality (32) maturation in females compared to males.
