NIMH Director’s Blog
By Thomas Insel
April 29, 2013
In a few weeks, the American Psychiatric Association will release its new edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM-5]. This volume will tweak several current diagnostic categories, from autism spectrum disorders to mood disorders. While many of these changes have been contentious, the final product involves mostly modest alterations of the previous edition, based on new insights emerging from research since 1990 when DSM-IV was published. Sometimes this research recommended new categories [e.g., mood dysregulation disorder] or that previous categories could be dropped [e.g., Asperger’s syndrome].
The goal of this new manual, as with all previous editions, is to provide a common language for describing psychopathology. While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. Indeed, 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. NIMH has launched the Research Domain Criteria [RDoC] project to transform diagnosis by incorporating genetics, imaging, cognitive science, and other levels of information to lay the foundation for a new classification system. Through a series of workshops over the past 18 months, we have tried to define several major categories for a new nosology [see below]. This approach began with several assumptions:
- A diagnostic approach based on the biology as well as the symptoms must not be constrained by the current DSM categories,
- Mental disorders are biological disorders involving brain circuits that implicate specific domains of cognition, emotion, or behavior,
- Each level of analysis needs to be understood across a dimension of function,
- Mapping the cognitive, circuit, and genetic aspects of mental disorders will yield new and better targets for treatment.
It became immediately clear that we cannot design a system based on biomarkers or cognitive performance because we lack the data. In this sense, RDoC is a framework for collecting the data needed for a new nosology. But it is critical to realize that we cannot succeed if we use DSM categories as the “gold standard.” The diagnostic system has to be based on the emerging research data, not on the current symptom-based categories. Imagine deciding that EKGs were not useful because many patients with chest pain did not have EKG changes. That is what we have been doing for decades when we reject a biomarker because it does not detect a DSM category. We need to begin collecting the genetic, imaging, physiologic, and cognitive data to see how all the data – not just the symptoms – cluster and how these clusters relate to treatment response.
That is why NIMH will be re-orienting its research away from DSM categories. 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. What does this mean for applicants? Clinical trials might study all patients in a mood clinic rather than those meeting strict major depressive disorder criteria. Studies of biomarkers for “depression” might begin by looking across many disorders with anhedonia or emotional appraisal bias or psychomotor retardation to understand the circuitry underlying these symptoms. What does this mean for patients? We are committed to new and better treatments, but we feel this will only happen by developing a more precise diagnostic system. The best reason to develop RDoC is to seek better outcomes.RDoC, for now, is a research framework, not a clinical tool. This is a decade-long project that is just beginning. Many NIMH researchers, already stressed by budget cuts and tough competition for research funding, will not welcome this change. Some will see RDoC as an academic exercise divorced from clinical practice. But patients and families should welcome this change as a first step towards "precision medicine,” the movement that has transformed cancer diagnosis and treatment. RDoC is nothing less than a plan to transform clinical practice by bringing a new generation of research to inform how we diagnose and treat mental disorders. As two eminent psychiatric geneticists recently concluded, “At the end of the 19th century, it was logical to use a simple diagnostic approach that offered reasonable prognostic validity. At the beginning of the 21st century, we must set our sights higher.”
Research Domain Criteria [RDoC]: Toward a New Classification Framework for Research on Mental Disorders
by Thomas Insel, M.D.; Bruce Cuthbert, Ph.D.; Marjorie Garvey, M.B., B.CH.; Robert Heinssen, Ph.D.; Daniel S. Pine, M.D.; Kevin Quinn, Ph.D.; Charles Sanislow, Ph.D.; Philip Wang, M.D., DR.P.H.
American Journal of Psychiatry. 2010 167:748-751.
[full text on-line]
… NIMH plans to maintain liaison with the American Psychiatric Association and the World Health Organization regarding mutual interests in psychiatric classification. As an initial step, representatives of the APA, WHO, and NIMH met in July 2009 to map out common ground. These organizations have also articulated the importance of adding molecular and neurobiological parameters to future diagnostic systems, but at our current state of knowledge this step seems more appropriate for research than for immediate clinical use. NIMH views RDoC as the beginning of a transformative effort that needs to succeed over the next decade and beyond to implement neuroscience-based psychiatric classification. We recognize that the creation of such a new approach is a daunting task, which will likely require several mid-course corrections and may ultimately fail to deliver the transformation we seek in clinical care. However, NIMH hopes that the scientific and clinical communities will recognize the importance of joining in constructive dialogue on efforts aiming to accelerate the pace of new clinical discoveries and improve clinical outcomes.
New DSM-5 Ignores Biology of Mental Illness
By Ferris Jabr
April 17, 2013
[full text online]
This month the American Psychiatric Association [APA] will publish the fifth edition of its guidebook for clinicians, the Diagnostic and Statistical Manual of Mental Disorders, or DSM-5. Researchers around the world have eagerly anticipated the new manual, which, in typical fashion, took around 14 years to revise. The DSM describes the symptoms of more than 300 officially recognized mental illnesses — depression, bipolar disorder, schizophrenia and others — helping counselors, psychiatrists and general care practitioners diagnose their patients. Yet it has a fundamental flaw: it says nothing about the biological underpinnings of mental disorders. In the past, that shortcoming reflected the science. For most of the DSM‘s history, investigators have not had a detailed understanding of what causes mental illness.
That excuse is no longer valid. Neuroscientists now understand some of the ways that brain circuits for memory, emotion and attention malfunction in various mental disorders. Since 2009 clinical psychologist Bruce Cuthbert and his team at the National Institute of Mental Health have been constructing a classification system based on recent research, which is revealing how the structure and activity of a mentally ill brain differs from that of a healthy one. The new framework will not replace the DSM, which is too important to discard, Cuthbert says. Rather he and his colleagues hope that future versions of the guide will incorporate information about the biology of mental illness to better distinguish one disorder from another.Cuthbert, whose project may receive additional funding from the Obama administration’s planned Brain Activity Map initiative, is encouraging researchers to study basic cognitive and biological processes implicated in many types of mental illness. Some scientists might explore how and why the neural circuits that detect threats and store fearful memories sometimes behave in unusual ways after traumatic events — the kinds of changes that are partially responsible for post-traumatic stress disorder. Others may investigate the neurobiology of hallucinations, disruptions in circadian rhythms, or precisely how drug addiction rewires the brain. The ultimate goal is to provide new biological targets for medication. “We understand so much more about the brain than we used to,” Cuthbert says. “We are really in the middle of a big shift.”
"That is why NIMH will be re-orienting its research away from DSM categories. 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. What does this mean for applicants? Clinical trials might study all patients in a mood clinic rather than those meeting strict major depressive disorder criteria. Studies of biomarkers for “depression” might begin by looking across many disorders with anhedonia or emotional appraisal bias or psychomotor retardation to understand the circuitry underlying these symptoms."