DSM-5 and RDoC: Shared Interests

Thomas R. Insel, M.D., Director, NIMH Jeffrey A. Lieberman, M.D., President-elect, APA NIMH and APA have a shared interest in ensuring that patients and health providers have the best available tools and information today to identify and treat mental health issues, while we continue to invest in improving and advancing mental disorder diagnostics for the future. Today, the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM), along with the International Classification of Diseases (ICD) represents the best information currently available for clinical diagnosis of mental disorders. Patients, families, and insurers can be confident that effective treatments are available and that the DSM is the key resource for delivering the best available care. The National Institute of Mental Health (NIMH) has not changed its position on DSM-5. As NIMH's Research Domain Criteria (RDoC) project website states, "The diagnostic categories represented in the DSM-IV and the International Classification of Diseases-10 (ICD-10, containing virtually identical disorder codes) remain the contemporary consensus standard for how mental disorders are diagnosed and treated." Yet, what may be realistically feasible today for practitioners is no longer sufficient for researchers. Looking forward, laying the groundwork for a future diagnostic system that more directly reflects modern brain science will require openness to rethinking traditional categories. It is increasingly evident that mental illness will be best understood as disorders of brain structure and function that implicate specific domains of cognition, emotion, and behavior. This is the focus of the NIMH’s Research Domain Criteria (RDoC) project. RDoC is an attempt to create a new kind of taxonomy for mental disorders by bringing the power of modern research approaches in genetics, neuroscience, and behavioral science to the problem of mental illness ceus for social workers The evolution of diagnosis does not mean that mental disorders are any less real and serious than other illnesses. Indeed, the science of diagnosis has been evolving throughout medicine. For example, subtypes of cancers once defined by where they occurred in the body are now classified on the basis of their underlying genetic and molecular causes. All medical disciplines advance through research progress in characterizing diseases and disorders. DSM-5 and RDoC represent complementary, not competing, frameworks for this goal. DSM-5, which will be released May 18, reflects the scientific progress seen since the manual's last edition was published in 1994. RDoC is a new, comprehensive effort to redefine the research agenda for mental illness. As research findings begin to emerge from the RDoC effort, these findings may be incorporated into future DSM revisions and clinical practice guidelines. But this is a long-term undertaking. It will take years to fulfill the promise that this research effort represents for transforming the diagnosis and treatment of mental disorders. By continuing to work together, our two organizations are committed to improving outcomes for people with some of the most disabling disorders in all of medicine.

New Data Reveal Extent of Genetic Overlap Between Major Mental Disorders

Schizophrenia, Bipolar Disorder Share the Most Common Genetic Variation Press Release • August 12, 2013 The largest genome-wide study of its kind has determined how much five major mental illnesses are traceable to the same common inherited genetic variations. Researchers funded in part by the National Institutes of Health found that the overlap was highest between schizophrenia and bipolar disorder; moderate for bipolar disorder and depression and for ADHD and depression; and low between schizophrenia and autism. Overall, common genetic variation accounted for 17-28 percent of risk for the illnesses. “Since our study only looked at common gene variants, the total genetic overlap between the disorders is likely higher,” explained Naomi Wray, Ph.D., University of Queensland, Brisbane, Australia, who co-led the multi-site study by the Cross Disorders Group of the Psychiatric Genomics Consortium (PGC), which is supported by the NIH’s National Institute of Mental Health (NIMH). “Shared variants with smaller effects, rare variants, mutations, duplications, deletions, and gene-environment interactions also contribute to these illnesses.” Dr. Wray, Kenneth Kendler, M.D., of Virginia Commonwealth University, Richmond, Jordan Smoller, M.D., of Massachusetts General Hospital, Boston, and other members of the PGC group report on their findings August 11, 2013, in the journal Nature Genetics. “Such evidence quantifying shared genetic risk factors among traditional psychiatric diagnoses will help us move toward classification that will be more faithful to nature,” said Bruce Cuthbert, Ph.D., director of the NIMH Division of Adult Translational Research and Treatment Development and coordinator of the Institute’s Research Domain Criteria (RDoC) project, which is developing a mental disorders classification system for research based more on underlying causes. Earlier this year, PGC researchers – more than 300 scientists at 80 research centers in 20 countries – reported the first evidence of overlap between all five disorders. People with the disorders were more likely to have suspect variation at the same four chromosomal sites. But the extent of the overlap remained unclear. In the new study, they used the same genome-wide information and the largest data sets currently available to estimate the risk for the illnesses attributable to any of hundreds of thousands of sites of common variability in the genetic code across chromosomes. They looked for similarities in such genetic variation among several thousand people with each illness and compared them to controls – calculating the extent to which pairs of disorders are linked to the same genetic variants. The overlap in heritability attributable to common genetic variation was about 15 percent between schizophrenia and bipolar disorder, about 10 percent between bipolar disorder and depression, about 9 percent between schizophrenia and depression, and about 3 percent between schizophrenia and autism. The newfound molecular genetic evidence linking schizophrenia and depression, if replicated, could have important implications for diagnostics and research, say the researchers. They expected to see more overlap between ADHD and autism, but the modest schizophrenia-autism connection is consistent with other emerging evidence. The study results also attach numbers to molecular evidence documenting the importance of heritability traceable to common genetic variation in causing these five major mental illnesses. Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained – not to mention non-inherited genetic factors. For example, common genetic variation accounted for 23 percent of schizophrenia, but evidence from twin and family studies estimate its total heritability at 81 percent. Similarly, the gaps are 25 percent vs. 75 percent for bipolar disorder, 28 percent vs. 75 percent for ADHD, 14 percent vs. 80 percent for autism, and 21 percent vs. 37 percent for depression. Among other types of genetic inheritance known to affect risk and not detected in this study are contributions from rare variants not associated with common sites of genetic variation. However, the researchers say that their results show clearly that more illness-linked common variants with small effects will be discovered with the greater statistical power that comes with larger sample sizes. “It is encouraging that the estimates of genetic contributions to mental disorders trace those from more traditional family and twin studies. The study points to a future of active gene discovery for mental disorders” said Thomas Lehner, Ph.D., chief of the NIMH Genomics Research Branch, which funds the project.

Common inherited genetic variation (single nucleotide polymorphisms, or SNPs) accounted for up to about 28 percent of the risk for some disorders, such as ADHD (dark green). Among pairs of disorders (light green), schizophrenia and bipolar disorder (SCZ-BPD) shared about 16 percent of the same common genetic variation (coheritabilities). Source: Cross-Disorder Group of the Psychiatric Genomics Consortium Professional Counselor Continuing Education Reference Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, August 11, 2013 Grants R01MH065562, R01MH43518, R01MH065554, R01MH65707, R01MH065571, R01MH65588, R01MH65578, R01MH65558 ### The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website. Press Contact(s) Jules Asher NIMH Press Office 301-443-4536 NIMHPress@nih.gov More Science News about: Attention Deficit Hyperactivity Disorder (ADHD) Autism Bipolar Disorder Depression Schizophrenia Contact the Press Office Phone: 301-443-4536 Email: NIMHpress@mail.nih.gov Press Resources Mental Health Information Statistics on Mental Disorders Summaries of Scientific Meetings Information about NIMH RePORTER: Research Portfolio Online Reporting Tool Expenditures and Results PubMed Central: An Archive of Life Sciences Journals Recommendations for Reporting on Suicide News from the Field News from the Field NIMH-Funded Science on EurekAlert Teen Eating Disorders Increase Suicide Risk The Love Hormone is 2-Faced Fear Factor: Missing Brain Enzyme Leads to Abnormal Levels of Fear in Mice, Reveals New Research More news from the field... Bookmark & Share Newsletters RSS Feeds Facebook