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NIMH project: Precision Medicine for Psychiatry


Senior Member

What would precision medicine look like for psychiatry? Could our approach to diagnosis be more precise as a guide to disease mechanisms or a predictor of treatment response? The current diagnostic systems, ICD and DSM, were developed to provide a common language based on observable signs and symptoms, explicitly agnostic about pathophysiology or treatment response. While we can improve psychiatric diagnostics by more precise clustering of symptoms, diagnosis based only on symptoms may never yield the kind of specificity that we have begun to expect in the rest of medicine. Behavioral symptoms are multidetermined, so diagnoses based only on presenting complaints are unavoidably heterogeneous in terms of pathophysiology. The symptom of anxiety, for instance, can represent an endocrine disorder, a psychotic process, a drug response, or one of the currently recognized anxiety disorders. Beyond heterogeneity, when diagnosis is limited to symptoms, treatments may be limited to symptom relief, precluding cures or preventive interventions.

Why don’t we use biomarkers to improve the precision of psychiatric diagnosis? So far, we don’t have rigorously tested, reproducible, clinically actionable biomarkers for any psychiatric disorder. Genetic findings are statistical associations of risk, not diagnostic of disease; neuroimaging findings report mean group changes, not individual differences; and metabolic findings are not specific. We can improve the resolution with each of these modalities, but we may never have a biomarker for any symptom-based diagnosis because these diagnostic categories were never designed for biological validity (3).

The National Institute of Mental Health (NIMH) launched the Research Domain Criteria project (RDoC; www.nimh.nih.gov/research-priorities/rdoc/index.shtml) to address the need for a new approach to classifying mental disorders, an approach that would begin with, but not be limited to, symptoms. The project was described in the Journal in 2010 (4), but there is continuing confusion about its intent. RDoC’s ultimate goal is precision medicine for psychiatry—a diagnostic system based on a deeper understanding of the biological and psychosocial basis of a group of disorders that is unambiguously among the most disabling disorders in medicine (5).

At this point, however, RDoC is not a diagnostic system, it’s merely a framework for organizing research ...