Research Domain Criteria: Strengths, Weaknesses, and Potential Alternatives for Future Psychiatric Research.

The Research Domain Criteria (RDoC) paradigm was launched 10 years ago as a superior approach for investigation of mental illness. RDoC conceptualizes normal human behavior, emotion, and cognition as dimensional, with mental illnesses as dimensional extremes. We suggest that RDoC may have value for understanding normal human psychology and some conditions plausibly construed as extremes of normal variation. By contrast, for the most serious of mental illnesses, including dementia, autism, schizophrenia, and bipolar disorder, we argue that RDoC is conceptually flawed. RDoC conflates variation along dimensional axes of normal function with quantitative measurements of disease phenotypes and with the occurrence of diseases in overlapping clusters or spectra. This moves away from the disease model of major mental illness. Further, RDoC imposes a top-down approach to research. We argue that progress in major mental illness research will be more rapid with a bottom-up approach, starting with the discovery of etiological factors, proceeding to investigation of pathogenic pathways, including use of cell and animal models, and leading to a refined nosology and novel, targeted treatments.