1 Boring Old Man

Research Domain Criteria – RDoC
NIMH – Director’s Blog
by Thomas Insel
March 06, 2012

While basing diagnosis exclusively on signs and symptoms was typical of mid-twentieth century medicine, by the beginning of the twenty-first century, most disciplines had built many other sources of information, such as biomarkers, into their diagnostic toolkits. Imagine diagnosing heart attack only by characterizing chest pain or using the symptoms of fever to distinguish bacterial from viral pneumonia. A recent report from the National Academy of Sciences, Towards Precision Medicine [see my previous blog on improving diagnosis through precision medicine], described how improving diagnostic specificity for cancer has transformed outcomes by identifying the precise biology of each patient’s tumor and linking this diagnosis to targeted treatments.

In contrast to these changes in the rest of medicine, for the past century mental disorders have been considered "behavioral," implying that an exclusive focus on symptoms could yield a precise diagnosis. Problems with this narrow approach to diagnosis began to emerge as research demonstrated the inescapable heterogeneity underlying diagnostic labels such as depression or schizophrenia. Even attempts to subdivide these categories by considering additional symptoms, such as anxious depression, failed to give reliably better prediction of treatment response.

Recent research in genetics and brain imaging suggest that biological measures may help us to understand the heterogeneity within the symptoms of mental illness. Just as with chest pain and fever, by adding more tools to our diagnostic toolkit, current labels such as "depression" or "schizophrenia" might give way to more precise categories. These advances have the potential to revolutionize the way we classify and, importantly, treat mental disorders.

Last week, NIMH hosted the latest in a series of workshops to launch the Research Domain Criteria [RDoC] project. RDoC is an experimental approach to the classification of mental disorders that incorporates multiple dimensions: behavior, thought patterns, neurobiological measures, and genetics. The immediate aim of the project is not to develop a diagnostic system for clinicians or patients. While I expect RDoC will ultimately transform practice, the near-term goal is to provide a framework for research. For instance, the meeting this week focused on social processes, reviewing what we know and what we need to understand about the deficits in social cognition and social behavior in what we now call autism, schizophrenia, depression, and anxiety disorders in both adults and children. The underlying assumption is that approaching mental disorders along this dimension may yield a more precise, more individualized diagnosis that crosses our current labels. But this is not simply about finding links between the social deficits of people with autism and people with social anxiety. RDoC uses genetics, imaging, and cognitive science for understanding deficits in social behavior…

This is not as simple as it sounds. Genes identified as conveying risk for mental illness don’t track neatly with any of the currently recognized disorders. Nearly all of the genes associated with risk for schizophrenia also contribute to risk for bipolar disorder and autism. One could use this information to dismiss genetics as "non-specific." But certainly it is more parsimonious to conclude that nature does not define the disorders designated by our current diagnostic labels, all of which were devised by committees of clinicians who were voting on the symptoms. While the impact of individual genes on risk is likely to be small and not specific to any existing current diagnostic category, could genetics be showing us a different way to map the diagnostic landscape?…

IV. NEUROSES [300]

300 Neuroses
^{Anxiety is the chief characteristic of the neuroses. It may be felt and expressed directly, or it may be controlled unconsciously and automatically by conversion, displacement and various other psychological mechanisms. Generally, these mechanisms produce symptoms experienced as subjective distress from which the patient desires relief. The neuroses, as contrasted to the psychoses, manifest neither gross distortion or misinterpretation of external reality, nor gross personality disorganization. A possible exception to this is hysterical neurosis, which some believe may occasionally be accompanied by hallucinations and other symptoms encountered in psychoses. Traditionally, neurotic patients, however severely handicapped by their symptoms, are not classified as psychotic because they are aware that their mental functioning is disturbed.}

300.4 Depressive neurosis
^{This disorder is manifested by an excessive reaction of depression due to an internal conflict or to an identifiable event such as the loss of a love object or cherished possession. It is to be distinguished from Involutional melancholia and Manic-depressive illness. Reactive depressions or Depressive reactions are to be classified here.}

I actually miss it. I think it was closer to the truth than what we have now. But the point here is that Tom Insel’s comment is a scathing indictment of the DSM-5 effort, whether intended or not ["devised by committees of clinicians who were voting on the symptoms"]. When it’s all said and done, the DSM-III was a mistake. The mistake wasn’t the idea. It was in failing to see what the third party carriers, the pharmaceutical industry, and those among us with challenged morality would do with it. And the category – Major Depressive Disorder – is at the eye of the storm…