DSM-5’s “Speculative” 2002 Diagnostic System Based On Expected Gene Findings

In 2002 the developers of DSM-5 published A Research Agenda for DSM-V, at a time when gene discoveries appeared imminent to the leaders of psychiatry.¹  This publication, edited by DSM-5 architects David Kupfer, Michael First, and Darrell Regier, consisted of six “white papers” related to the development of the DSM-5.²  One of these white papers, by Dennis Charney and his colleagues, was entitled “Neuroscience Research Agenda to Guide Development of a Pathophysiologically Based Classification System.”³  The authors expected that in the near future, psychiatric diagnoses would be based on neurobiological and genetic discoveries.  According to Charney and colleagues, “The field is getting closer” to gene discoveries, “and new advances in genetics (including the availability of the human genome sequence) portend rapid progress.”  Like many in psychiatry, including especially its subfield of psychiatric genetics, the Human Genome Project’s sequencing of the human genome was expected to lead to the rapid identification of the genes they believed underlie psychiatric disorders.  According to a leading group of psychiatric genetic researchers, writing in 1999, “From the perspective of psychiatric genetics, the Human Genome Project is an immense factory producing and refining the tools we will need to discover the genes that cause mental illness.”⁴

Charney and colleagues put forward a new “speculative outline,” which envisioned a future DSM-5 practice of classifying disorders on the basis of a revised Axis I that would be “set aside for recording the patient’s genotype, identifying symptom- or disease-related genes, resiliency genes, and genes related to therapeutic responses and side effects to specific psychotropic drugs” (emphasis in original).  The authors speculated that the future DSM-5, with a projected publication date of 2010, would be based on a revised five-axis system based on expected gene discoveries. Charney and colleagues’ 2002 “speculative outline” reads as follows:

“Outline for a Possible Future Multiaxial System”

• “Axis I:  Genotype.  Identification of disease- /symptom-related genes. Identification of   resiliency/protective genes.  Identification of genes related to therapeutic responses to and side effects of specific psychotropic drugs.”

• “Axis II: Neurobiological phenotype. Identification of intermediate phenotypes (neuroimaging, cognitive function, emotional regulation) related to genotype.  Relates to targeted pharmacotherapy.”

• “Axis III: Behavioral phenotype.  Range and frequency of expressed behaviors associated with genotype, neurobiological phenotype, and environment.  Relates to targeted therapies.”

• “Axis IV: Environmental modifiers or precipitants.  Environmental factors that alter the behavioral and neurobiological phenotype.”

• “Axis V: Therapeutic targets and response.”

This outline of a future DSM-5 diagnostic scheme leaned heavily on genetics, neurobiology, and psychopharmacological interventions.  People’s complex life experiences, relationships, and traumas, in addition to their social and political environments, were now reduced to “modifiers or precipitants” of the actions of the expected identification of genes that underlie their psychiatric disorders.

A dozen or so years ago, at least some of the DSM-5 architects believed that genes would at long last be identified and would be integrated into the next version of the DSM.  As we know, this did not happen.  The DSM-5 was finally published in 2013 and the multiaxial diagnostic system, used in DSM III through DSM-IV-TR (1980-2013), was completely eliminated.  A major reason appears to be psychiatry’s unexpected failure to uncover genes for its disorders, a failure that critics have argued for decades is the result not of illusive genes or “missing heritability,” but rather of its misplaced faith in the results of previous family, twin, and adoption studies.  Although Kupfer and the “DSM-5 Task Force” launched the DSM-5 in the spring of 2013 by admitting that “we’re still waiting” for the discovery of “biological and genetic markers” for psychiatric disorders, it is very unlikely that, in those heady early days of the “post-genomic era,” he and his colleagues could have imagined their inability over a decade later, in an official APA statement, to name even one genetic variant that caused a psychiatric disorder.⁵

*********************

References:

¹ Kupfer et al. (2002). A Research Agenda for DSM-V. Washington, DC: American Psychiatric Association.

² The APA had originally planned to continue its practice of using Roman numerals for the DSM, and in the early stages of research the Fifth Edition was called “DSM-V.” It was later decided to use Arabic numbers, leading to the current DSM-5.

³ Charney et al. (2002). Neuroscience research agenda to guide development of a pathophysiologically based classification system. In Kupfer et al. (Eds.),  A Research Agenda for DSM-V (pp. 31-83). Washington, DC: American Psychiatric Association.

⁴ Faraone, Tsuang, & Tsuang (1999). Genetics of Mental Disorders. New York: The Guilford Press.

⁵ American Psychiatric Association (2013, May 3rd). Chair of DSM-5 task force discusses future of mental health research; Statement by David Kupfer, M.D. American Psychiatric Association [Press release]