Clinical neuroscience seeks to understand the neurobiological mechanisms of mental illness and translate that knowledge into effective, biologically-informed interventions, including pharmacological approaches. The past two decades have witnessed the development of powerful new tools for quantifying variation in the human brain. Nonetheless, although substantial resources and efforts have been invested in identifying reliable neurobiological indicators of mental illness, or “biomarkers”, only modest progress has been made. A growing consensus attributes this lack of progress largely to the shortcomings of current categorical diagnostic systems, rather than intrinsic limitations of biological approaches [1].

Categorical diagnoses are suboptimal targets for research on the foundations of psychopathology, and subsequently on the development of biologically-informed interventions, due to their extensive comorbidity, within-disorder heterogeneity, and poor reliability [2]. Within-disorder heterogeneity is so extreme that, for many disorders, two patients may receive the same diagnosis despite sharing few or no overlapping symptoms. Further, no common mental disorder has ever been shown to be categorical rather than dimensional, and the cutoffs used to define diagnoses lack empirical justification, reduce statistical power, and reduce reliability and validity relative to the use of dimensional scores [2].

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