Specificity refers to the expectation that the endophenotype is more strongly associated with the disease of interest than to other psychiatric disorders. Given that subjective responses to alcohol are directly dependent upon alcohol consumption and its associated pharmacological effects, the argument can also be made that this phenotype is highly specific to the disorder of interest. However, the argument can be made that similar mechanisms of pharmacological response may be in play for substances other than alcohol, which in turn would argue for it being a broader phenotype for substance use disorders. Patterns of cross-tolerance between alcohol and benzodiazepines, for example, have been widely documented in the animal and human literature (e.g., Toki et al., 1996). Moreover, common neurotransmitter systems and pathways are involved in the reinforcing effects of multiple substances, as is the case for the dopaminergic and opioidergic systems, for example (Bond et al., 1998; Herz, 1997; Wise & Bozarth, 1987). In summary, responses to alcohol may be an alcohol-specific phenotype, although future research is needed to determine its specificity in relation to other substances of abuse and
