Second, clinical studies indicate that self-medication, a key mechanism posited to link affective disruption and substance use, is self-reported in treatment samples as a primary reason for addiction and is commonly targeted by treatment programs (McMahon, Kouzekanani, DeMarco & Kusel, 1992). Third, reformulations of the self-medication model identify vulnerable sub-groups for whom the effect of depression on SUDs is larger than previously found in the population at large. This suggests that the internalizing pathway may be particularly relevant in explaining SUDs for a subset of individuals (Cooper, Russell, Skinner, Frone, & Mudar, 1992; Kushner, Sher, Wood, & Wood, 1994; Kushner et al., 1994). Fourth, comorbidity rates of affective and anxiety disorders with SUDs are among the highest reported with any psychiatric disorder, particularly within treatment settings (Costello, Erkanli, Federman, & Angold, 1999; Merikangas et al., 1998; Skinstad & Swain, 2001). Fifth, evidence for Negative Affect Alcoholism as a subtype is growing, and thus understanding the pathways through which this endpoint is reached and whether this finding generalizes to other SUDs is needed (e.g., Mezzich et al., 1993; Nurnberger, Foroud, Flury, Meyer, & Wiegand, 2002).
