Furthermore, the RDoC posits that disturbances in the capacity for pleasure (eg, anhedonia) and negative valence systems (eg, chronic depression/rumination) are commonly encountered clinical phenotypes. Other examples of psychopathology captured in RDoC include disturbances in executive function, learning, and memory (ie, general cognitive processes); social cognition and theory of mind (ie, social cognitive processes); and fear and anxiety (ie, arousal processes). An additional advantage of RDoC is that the neuroscientific community has made progress [KT1] in characterizing many of the circuits, networks, and nodal structures that subserve the foregoing 5 RDoC domains.

An important deficiency of DSM-based illness categories, which is possibly improved upon by RDoC, is the suboptimal reliability and specificity of the diagnoses. The ability to develop transformative therapies is belied by the inability of clinicians to come to the unanimous agreement of what comprises essential features of a condition. For example, results from the DSM-5 field trials indicate that the kappa correlation coefficient (ie, interobserver agreement) in major depressive disorder (MDD) was a woeful 0.28.6


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The lack of any current baseline, pretreatment biomarker predictive of antidepressant efficacy begins with the absence of even modest agreement of what the phenotype of MDD looks like. As a derivative of this, it seems prudent to characterize consensually agreed-upon domains (with associated substrates) as the first step toward predictive biomarkers to realize the possibility of personalized, precision-based medicine.

The RDoC matrix is primarily intended for the research community and is not pragmatically applicable for clinical utility. Notwithstanding, it seems as though clinicians informally are approaching psychiatric patients with a “dimensional/domain” perspective (ie, lumpers vs splitters).7 The RDoC is not considered to be the alternative diagnostic manual to the DSM-5 and has at its essence an unrelated purpose. For example, the RDoC aims to transform by refining the disease model via data-supported domains of phenomenology. The DSM-5 aims to provide clinicians with a diagnostic lingua franca.

The DSM-5 has proven to be an excellent tool for its stated purpose; however, the DSM-5 categories are not able to transform drug discovery. It seems reasonable for advancement in the future to posit that future diagnostic and treatment approaches may be a conflation of the DSM-5 and RDoC approaches informed with domain-specific biomarkers/biosignatures. To achieve such a lofty goal, however, psychiatry does require a creative destruction of its status quo approaches to categorizing and conceptualizing mental disorders before transformative therapeutics can be offered.

Roger McIntyre, MD, is head of the Mood Disorders Psychopharmacology Unit at the University Health Network, in Toronto, Canada. He is also a member of the Psychiatry Advisor editorial board.

References

1. Vos T, Flaxman AD, Naghavi M, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; doi: 10.1016/S0140-6736(15)60692-4.

2. McIntyre RS. A vision for drug discovery and development: novel targets and multilateral partnerships. Adv Ther. 2014;31(3):245-246.

3. Insel TR. The NIMH Research Domain Criteria (RDoC) Project: precision medicine for psychiatry. Am J Psychiatry. 2014;171(4):395-397.

4. Insel T, Cuthbert B, Garvey M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010;167(7):748-751.

5. Insel TR. Translating scientific opportunity into public health impact: a strategic plan for research on mental illness. Arch Gen Psychiatry. 2009;66(2):128-133.

6. Freedman R, Lewis DA, Michels R, et al. The initial field trials of DSM-5: new blooms and old thorns. Am J Psychiatry. 2013;170(1):1-5.

7. McCoy TH, Castro VM, Rosenfield HR, Cagan A, Kohane IS, Perlis RH. A clinical perspective on the relevance of research domain criteria in electronic health records. Am J Psychiatry. 2015;172(4):316-320.