Embracing variability in the search for biological mechanisms of psychiatric illness

Abstract

Despite decades of research, we lack objective diagnostic or prognostic biomarkers of mental health problems. A key reason for this limited progress is a reliance on the traditional case-control paradigm, which assumes that each disorder has a single cause that can be uncovered by comparing average phenotypic values of cases and control samples. Here, we discuss the problematic assumptions on which this paradigm is based and highlight recent efforts that seek to characterize, rather than minimize, the inherent clinical and biological variability that characterizes psychiatric populations. We argue that embracing such variability will be necessary to understand pathophysiological mechanisms and to develop more targeted and effective treatments.