Previous work suggests that substance-induced and independent depressions might be etiologically distinct (Schuckit et al., 2007); in addition, although the comorbid phenotype might have a heritable component (Nurnberger et al., 2002), the genetics underlying this phenotype could be distinct from those underlying a comorbid phenotype of alcohol dependence and independent depression. In this case, the lack of distinction between independent and induced depression in the current study could be problematic. Unfortunately, our sample sizes are not large enough to conduct meaningful analyses on depressive symptoms that occur only within or only outside the context of alcohol/drug use. Furthermore, the mixed nature of the depressive episodes, and the fact that a number of cases met diagnostic criteria for abuse or dependence on other substances, reflects the nature of these disorders: they often appear in conjunction with other psychiatric problems, particularly in a clinical setting. To this end, we also recognize the possibility that the genes implicated in the current report are actually indexing risk to behavioral disinhibition rather than comorbid AD and depressive syndrome per se: the high prevalence of illicit substance use disorders among cases suggests that these individuals’ various substance and mood-related problems could have developed through high levels
