As a clinical psychology student during the 1970s, my training included the delivery of imaginary exposure therapies for fear (in the era before DSM-III when “phobic neurosis” was the only relevant diagnosis and functional behavioral assessments were the norm for behavioral therapies). For most patients, these treatments worked as promised, delivering positive outcomes after a systematic course of treatment.
However, on occasion the same therapeutic procedures failed. I particularly remember one young man whose fear reports seemed similar to those of other patients and who progressed through the “fear hierarchy” at a regular pace. In spite of this apparent progress, he reported that his anxiety levels in actual situations did not change and that the treatment was not working; he left therapy soon after. As for most clinicians who have experienced this unsuccessful outcome, it was difficult to say why. We simply had to accept that sometimes treatment does not work for unknown reasons—an unsatisfactory situation for too many clinicians and patients no matter what the disorder.
This situation is, of course, not confined to psychosocial treatments. Several pharmaceutical industry scientists recently noted:
On average, a marketed psychiatric drug is efficacious in approximately half of the patients who take it. One reason for this low response rate is the artificial grouping of heterogeneous syndromes with different pathophysiological mechanisms into one disorder.1
Heterogeneity poses great difficulty in specifying target engagement and relating target engagement to outcomes, which contributes to the inconsistent results in clinical trials so often noted for psychiatric drugs. These factors have played a major role in the small number of new compounds approved for market in recent years and the withdrawal of pharmaceutical companies from development programs for mental disorders in spite of the great need for innovative treatments.
Overall, the burden of mental disorders has shown virtually no change over recent decades, and significant problems such as suicide have, if anything, shown an upward trend (although, admittedly, the modest effectiveness of treatments is one aspect of a complex phenomenon that includes sociocultural, economic, and varied environmental factors).2
The mission statement of the National Institute of Mental Health (NIMH) is “to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.”3 Given this perspective, the lack of progress—particularly compared with marked decreases in morbidity and mortality seen in other areas of medicine—highlighted the need for new approaches to research concerning the etiology and mechanisms of mental disorders.
As the Institute invited input for the 2008 revision of its Strategic Plan, then-Director Thomas Insel shared informally with staff that an unexpectedly common complaint from members of the research community concerned the diagnostic system. The use of DSM (or the nearly identical ICD) categories had become a de facto standard, since the issue of DSM-III in 1980, for peer review committees evaluating research grant applications focused on the psychopathology or pathophysiology of mental disorders. Furthermore, because of the reification of the diagnostic concepts, the disorders were seen as unitary disease entities that were essentially the same for each patient (analogous to an infectious illness) but differed qualitatively across diagnoses, thus proscribing any explorations of heterogeneity within disorders or common mechanisms across disorders.
At the core: psychiatric research
Diagnostic manuals for mental disorders have generally served adequately for clinical practice, given contemporary diagnostic practices and treatments. However, it became increasingly clear that the situation was different for research. Results of studies using neuroimaging, behavioral science, and genetics were inconsistent; while differences between group averages for a clinical group and healthy controls could often be demonstrated, similar patterns were frequently observed for multiple disorders. Crucially, data that could inform the treatment of individuals were rare––a situation attributable to problems of heterogeneity, extensive comorbidity, and over-specification of categories.
It was apparent that the hegemony of the diagnostic system played a significant role in stifling the innovation needed to incorporate cutting-edge science from multiple areas into clinical research. Among other problems, there was a need to apply the methods used in other areas of medicine where traditional symptom-based diagnoses of disorders were gradually supplanted by an understanding of the mechanistic etiology of disorders considered in terms of deviations from normal functioning of various processes in the organism.
Dr. Cuthbert is Director of the Research Domain Criteria Unit, National Institute of Mental Health, Bethesda, MD.
The author reports no financial conflicts of interest.
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