This study examined the prospective role of temperament and externalizing behavior as intermediate phenotypes in the association between genetic variants and substance use. Findings support the role of behavioral control, resiliency, and externalizing behavior as mediators by which specific polymorphisms of noradrenergic and GABAergic genes impact later substance use. Findings are consistent with the common vulnerability model, which posits that there is a common liability factor that underlies addiction across several classes of substances (Tsuang et al., 1998). Our results are also consistent with the notion that individual differences in temperament and externalizing behavior impart a non-specific vulnerability to abuse, not only to alcohol but also nicotine and marijuana.
