Neural circuitry and precision medicines for mental disorders: are they compatible?

Abstract

AbstractGiven the failure of psychiatry to develop clinically useful biomarkers for psychiatric disorders, and the concomitant failure to develop significant advances in diagnosis and treatment, the National Institute of Mental Health (NIMH) in 2010 launched the Research Domain Criteria (RDoC), a framework for research based on the assumption that mental disorders are disorders of identifiable brain neural circuits, with neural circuitry at the center of units of analysis ranging from genes, molecules, and cells to behavior, self-reports, and paradigms. These were to be integrated with five validated dimensional psychological constructs such as negative and positive valence systems. Four years later, the NIMH stated that the ultimate goal of RDoC is precision medicine for psychiatry, with the assumption that precision medications will normalize dysfunctional neural circuits. How this could be accomplished is not obvious, given that neural circuits are widely distributed, have unclear boundaries, and exhibit a significant degree of neuroplasticity, with multiple circuits present in any given disorder. Moreover, the early focus on neural circuitry has been criticized for its reductionism and neglect of the more recent RDoC emphasis on the integration and equivalence of biological and psychological phenomena. Yet this seems inconsistent with the priorities of the NIMH director, an advocate of the central role of neural circuitry and projects such as the Brain Initiative and the Human Connectome Project. Will such projects, at a cost of at least $10 billion, lead to precision medications for mental disorders, or further diminish funding for clinical care and research?