Risk and resistance perspectives in translation-oriented etiology research

Risk for a disorder and the mechanisms that determine its elevation, risk factors, are the focus of medical research. Targeting risk factors should serve the goal of prevention and treatment intervention. Risk, however, is but one of the aspects of liability to a disorder, a latent trait that encompasses effects of all factors leading to or from the diagnostic threshold. The coequal but opposite aspect of liability is resistance to a disorder. The factors that increase resistance and thus enable prevention or recovery may differ from those that elevate risk. Accordingly, there are nontrivial differences between research perspectives that focus on risk and on resistance. This article shows how this distinction translates into goals and methods of research and practice, from the choice of potential mechanisms tested to the results sought in intervention. The resistance concept also differs from those of "resilience" and "protective factors," subsuming but not limited to them. The implications of the concept are discussed using substance use disorder as an example and substantiate the need for biomedical research and its translation to shift to the resistance perspective.