In sum, we argue that a theory-driven endophenotype pharmacogenetic approach can be used to enhance the pharmacological treatment of alcoholism4. Pharmacotherapies, in turn, may be useful in the context of multiple psychosocial treatment platforms and orientations, including abstinence-based and harm-reduction models. This model is interdisciplinary by nature, as it integrates aspects of behavioral genetics, pharmacology, clinical and experimental psychology. Focusing on theory-driven alcohol endophenotypes and genetic and neurobiological factors underlying these phenotypes may help us elucidate the mechanisms of action of pharmacotherapies, as well as moderators of response. Moreover, this approach has the potential to enhance the translation of basic science to treatment, as it more directly connects endophenotypes and genetic variants to pharmacotherapy outcomes for alcohol dependence. Ultimately, the endophenotype-pharmacogenetic model described herein offers a potentially useful framework for better understanding how endophenotypes and genetic factors concomitantly influence responses to pharmacotherapies for alcoholism. Similar approaches may be useful in optimizing psychosocial interventions by targeting more specific and narrowly defined components of the risk for alcoholism (i.e., prevention efforts) or the clinical syndrome itself (i.e., treatment efforts).
