The NIMH RDoC Initiative: What Does it Mean for Psychiatric Nosology? Thomas McCoy, MD www.mghcme.org Disclosures Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest to disclose. www.mghcme.org April 29, 2013 In a few weeks, the APA will release its new edition of the DSM. ... Symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment. ... Patients with mental disorders deserve better. ... Going forward, we will be supporting research projects that look across current categories – or sub-divide current categories – to begin to develop a better system. https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2013/transforming-diagnosis.shtml www.mghcme.org April 29, 2013 In a few weeks, the APA will release its new Context edition of the DSM. ... Symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment. ... Patients with mental disorders deserve better. ... Going forward, we will be supporting research projects that look across current categories – or sub-divide current categories – to begin to develop a better system. https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2013/transforming-diagnosis.shtml www.mghcme.org April 29, 2013 In a few weeks, the APA will release its new edition of the DSM. ... Symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment. ... Patients with mental disorders deserve Why better. ... Going forward, we will be supporting research projects that look across current categories – or sub-divide current categories – to begin to develop a better system. https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2013/transforming-diagnosis.shtml www.mghcme.org April 29, 2013 In a few weeks, the APA will release its new edition of the DSM. ... Symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment. ... Patients with mental disorders deserve better. ... Going forward, we will be supporting research projects that look across current What categories – or sub-divide current categories – to begin to develop a better system. https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2013/transforming-diagnosis.shtml www.mghcme.org Categorical Nosology www.mghcme.org (Useful) Syndrome Soup Regier, D. A. et al (2013). DSM-5 field trials in the United States and Canada, Part II: test-retest reliaBility of selected categorical diagnoses. AJP, 170(1), 59-70. www.mghcme.org What is RDoC? • Structure for research – Multidimensional & continuous – Rooted in neurobiology (gene -> behavior) www.mghcme.org What is RDoC? • Structure for research – Multidimensional & continuous – Rooted in neurobiology (gene -> behavior) • Explicitly dynamic – E.g. Addition of motor domain www.mghcme.org What is RDoC? • Structure for research – Multidimensional & continuous – Rooted in neurobiology (gene -> behavior) • Explicitly dynamic – E.g. Addition of motor domain • Anticipates precision medicine www.mghcme.org What RDoC is Not • Comprehensive – Does not attempt to cover all conditions – (Required link between condition and biology) www.mghcme.org What RDoC is Not • Comprehensive – Does not attempt to cover all conditions – (Required link between condition and biology) • Clinical / policy – Not used for allocation / illness definition www.mghcme.org What RDoC is Not • Comprehensive – Does not attempt to cover all conditions – (Required link between condition and biology) • Clinical / policy – Not used for allocation / illness definition • Threshold setting – Hopes to move to threshold model but not inherent www.mghcme.org “ Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures” www.mghcme.org Research Domain Criteria ORIGIN STORY www.mghcme.org RDoC Origin 2008: NIMH Strategic Plan – Strategy 1.4 – Initiate a process for bringing together experts in clinical and basic sciences to jointly identify the fundamental behavioral components that may span multiple disorders (e.g., executive functioning, affect regulation, person perception) and that are more amenable to neuroscience approaches. – Determine the full range of variation, from normal to abnormal, among the fundamental components to improve understanding of what is typical versus pathological. – Develop reliable and valid measures of these fundamental components of mental disorders for use in basic studies and in more clinical settings. – Integrate the fundamental genetic, neurobiological, behavioral, environmental, and experiential components that comprise these mental disorders. www.mghcme.org RDoC Origin 2008: NIMH Strategic Plan – Strategy 1.4 – Initiate a process for bringing together experts in clinical and basic sciences to jointly identify the fundamental behavioral components that may span multiple disorders (e.g., executive functioning, affect regulation, person perception) and that are more amenable to neuroscience approaches. – Determine the full range of variation, from normal to abnormal, among the fundamental components to improve understanding of what is typical versus pathological. – Develop reliable and valid measures of these fundamental components of mental disorders for use in basic studies and in more clinical settings. – Integrate the fundamental genetic, neurobiological, behavioral, environmental, and experiential components that comprise these mental disorders. www.mghcme.org RDoC Origin 2008: NIMH Strategic Plan – Strategy 1.4 2010: Named RDoC Commentary Research Domain Criteria (RDoC): Toward a New Classification Framework for Research on Mental Disorders Current versions of the DSM and ICD have facilitated reliable clinical diagnosis and research. However, problems have increasingly been documented over the past several years, both in clinical and research arenas (e.g., 1, 2). Diagnostic categories based on clinical consensus fail to align with findings emerging from clinical neuroscience and genetics. The boundaries of these categories have not been predictive of treatment re- sponse. And, perhaps most important, these categories, based upon presenting signs and symptoms, may not capture fundamental underlying mechanisms of dysfunction. One consequence has been to slow the development of new treatments targeted to un- derlying pathophysiological mechanisms. History shows that predictable problems arise with early, descriptive diagnostic sys- tems designed without an accurate understanding of pathophysiology. Throughout medicine, disorders once considered unitary based on clinical presentationInsel haveT, CuthBert been B, Garvey M, et al. AJP. 2010;167:748-751. shown to be heterogeneous by laboratory tests—e.g., destruction of islet cells versus www.mghcme.org insulin resistance in distinct forms of diabetes mel- litus. From infectious diseases to subtypes of can- cer, we routinely use biomarkers to direct distinct “Our expectation . treatments. Conversely, history also shows that syn- is that identifying dromes appearing clinically distinct may result from syndromes based on the same etiology, as in the diverse clinical presenta- tions following syphilis or a range of streptococcus- pathophysiology will related disorders. eventually be able to While the potential advantages of a neuroscience- improve outcomes.” based approach to psychiatric classification are widely appreciated (3), no consensus exists about how to achieve this goal. The problem is not new. Four decades ago, Robins and Guze suggested five criteria for validating diagnosis (clinical description, laboratory tests, de- limitation, follow-up studies, and family data), where the goal was specifying prognosis (4). Reminiscent of the rationale for developing the Research Diagnostic Criteria in the 1970s that led to the innovative DSM-III for clinical use, the question now becomes one of when and how to build a long-term framework for research that can yield classifica- tion based on discoveries in genomics and neuroscience as well as clinical observation, with a goal of improving treatment outcomes. As the major federal research agency funding mental health research in the United States, the National Institute of Mental Health (NIMH) believes the time has arrived to begin moving in such a new direction. The NIMH is launching the Research Domain Criteria (RDoC) project to create a framework for research on pathophysiology, especially for genomics and neuroscience, which ultimately will inform future classification schemes. The RDoC project is intend- ed to be the next step in a long journey, one that continues the process begun in the 1970s of ensuring diagnosis that has both reliability and validity. While the focus of this journey over the past 30 years has been on refinements in clinically based classification, the time has come to lay the groundwork for the next step in this process: incorporat- ing data on pathophysiology in ways that eventually will help identify new targets for treatment development, detect subgroups for treatment selection, and provide a better match between