Psychiatry has begun the laborious effort of preparing the DSM-V, the new iteration of its diagnostic manual. In so doing, it once again wrestles with the task set by Carl Linnaeus, to “cleave nature at its joints.” However, these “joints,” the boundaries between psychiatric disorders, such as that between bipolar disorder and schizophrenia, are far from clear. Prior versions of DSM followed the path outlined by Emil Kraeplin in separating these disorders into distinct categories. Yet, we now know that symptoms of bipolar disorder may be seen in patients with schizophrenia and the reverse is true, as well.

Further, our certainty about the boundary of these disorders is undermined by growing evidence that both schizophrenia and bipolar disorder emerge, in part, from the cumulative impact of a large number of risk genes, each of which conveys a relatively small component of the vulnerability to these disorders. And since many versions of these genes appear to contribute vulnerability to both disorders, the study of common gene variations has raised the possibility that there may be diagnostic, prognostic, and therapeutic meaning embedded in the high degree of variability in the clinical presentations of patients with each disorder.

In addition, many symptoms of schizophrenia and bipolar disorder are traits that are present in the healthy population but are more exaggerated in patient populations. To borrow from Einstein, who struggled to reconcile the wave and particle features of light, our psychiatric diagnoses behave like waves (i.e., spectra of clinical presentations) and particles (traditional categorical diagnoses).

Although new genetic approaches may revise our current thinking, such as studies of microdeletions, microinsertions, and microtranslocations of the genome, the wave/particle approach to psychiatric diagnosis places a premium on understanding the “real” clustering of patients into subtypes as opposed to groups created to correspond to the current DSM-IV.

Latent class analysis is one statistical approach for estimating the clustering of subjects into groups. In their study of 270 Irish families, published in the July 15th issue of Biological Psychiatry, Fanous and colleagues conducted this type of analysis, with subjects clustered into the following groups: bipolar, schizoaffective, mania, schizomania, deficit syndrome, and core schizophrenia. When they divided the affected individuals in the study using this approach, they found four regions of the chromosome that were linked to the risk for these syndromes that were not implicated when subjects were categorized according to DSM-IV diagnoses. Dr. Fanous notes that this finding “suggests that schizophrenia as we currently define it may in fact represent more than one genetic subtype, or disease process.” According to John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System: “Their findings advance the hypothesis that the variability in the clinical presentation of patients diagnosed using DSM-IV categories is meaningful, providing information that may be useful as DSM-V is prepared. However, we do not yet know whether the categories generated by this latent class analysis will generalize to other populations.” This paper highlights an important aspect of the complexity of establishing valid psychiatric diagnoses using a framework adopted from traditional categorical models.

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Notes to Editors:

The article is “Novel Linkage to Chromosome 20p Using Latent Classes of Psychotic Illness in 270 Irish High-Density Families” by Ayman H. Fanous, Michael C. Neale, Bradley T. Webb, Richard E. Straub, Francis A. O’Neill, Dermot Walsh, Brien P. Riley and Kenneth S. Kendler. Dr. Fanous is affiliated with the Washington VA Medical Center and Georgetown University Medical Center in Washington, D.C. Dr. Fanous, along with Drs. Neale, Webb, Riley, and Kendler, is also affiliated with the Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia. Drs. Neale and Kendler are also with the Department of Human Genetics, also at Virginia Commonwealth University. Dr. Straub is with the Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. Dr. O’Neill is from Queen’s University, Belfast, United Kingdom. Dr. Walsh is with the Health Research Board, Dublin, Ireland. The article appears in Biological Psychiatry, Volume 64, Issue 2 (July 15, 2008), published by Elsevier.

Full text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at (215) 239-3674 or .(JavaScript must be enabled to view this email address) to obtain a copy or to schedule an interview.

About Biological Psychiatry
This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

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