Psychiatric Annals

Guest Editorial 

This Issue: Schizophrenia and Bipolar Disorder: No Dichotomy, A Continuum, or One Disease?

C. Ray Lake, MD, PhD

Abstract

The Kraepelinian dichotomy, which emphasizes the validity of schizophrenia as different from psychotic mood disorders, has been such an accepted tradition that any change has been resisted. Despite numerous authors suggesting that many, if not most, patients diagnosed with either schizoaffective disorder or schizophrenia actually suffer from a psychotic mood disorder, movement toward a new formulation has been slow.1–6 One major factor that has inhibited change is the lack of any specific pathophysiology, although recent findings in molecular genetics hold promise. One explanation for the misconception of a dichotomy between schizophrenia and bipolar disorder is the difference between psychotic and non-psychotic mood-disordered patients. Psychotic mood disorders, either mania or depression, are phenotypically indistinguishable from the traditional conceptualization of schizophrenia. Given the long-held idea that “even a trace of schizophrenia (psychosis) is schizophrenia,” it is not surprising that such patients have been misdiagnosed as having schizophrenia.

Abstract

The Kraepelinian dichotomy, which emphasizes the validity of schizophrenia as different from psychotic mood disorders, has been such an accepted tradition that any change has been resisted. Despite numerous authors suggesting that many, if not most, patients diagnosed with either schizoaffective disorder or schizophrenia actually suffer from a psychotic mood disorder, movement toward a new formulation has been slow.1–6 One major factor that has inhibited change is the lack of any specific pathophysiology, although recent findings in molecular genetics hold promise. One explanation for the misconception of a dichotomy between schizophrenia and bipolar disorder is the difference between psychotic and non-psychotic mood-disordered patients. Psychotic mood disorders, either mania or depression, are phenotypically indistinguishable from the traditional conceptualization of schizophrenia. Given the long-held idea that “even a trace of schizophrenia (psychosis) is schizophrenia,” it is not surprising that such patients have been misdiagnosed as having schizophrenia.

The Kraepelinian dichotomy, which emphasizes the validity of schizophrenia as different from psychotic mood disorders, has been such an accepted tradition that any change has been resisted. Despite numerous authors suggesting that many, if not most, patients diagnosed with either schizoaffective disorder or schizophrenia actually suffer from a psychotic mood disorder, movement toward a new formulation has been slow.1–6 One major factor that has inhibited change is the lack of any specific pathophysiology, although recent findings in molecular genetics hold promise. One explanation for the misconception of a dichotomy between schizophrenia and bipolar disorder is the difference between psychotic and non-psychotic mood-disordered patients. Psychotic mood disorders, either mania or depression, are phenotypically indistinguishable from the traditional conceptualization of schizophrenia. Given the long-held idea that “even a trace of schizophrenia (psychosis) is schizophrenia,” it is not surprising that such patients have been misdiagnosed as having schizophrenia.

Prof. Hans-Juergen Möller answers the question raised in the title of his article. He suggests caution against too hastily dropping the Kraepelinian dichotomy. He cites brain magnetic resonance imaging (MRI) abnormalities, chronicity of course, mood-incongruent delusions, neurocognitive defects, and the deficit syndrome as differentiating schizophrenia from bipolar disorder. He addresses the possibility that differences between classic (non-psychotic) bipolar and psychotic bipolar disorder (presumably misdiagnosed as schizophrenia) might explain results that suggest a dichotomy between schizophrenia and bipolar disorder. He conservatively suggests that a workable compromise would be a dichotomy/continuum classification system.

Profs. Lorenzo Mazzarini and Eduard Vieta modify the traditional criteria of Robinson and Guze by which we validate a psychiatric disorder as bona fide. They believe that their formulation may help in “reframing the boundaries and overlaps between schizophrenia and bipolar disorder.” They go straight to the core of the problem by emphasizing the flaw in the “traditional misconception that psychosis is pathognomonic of schizophrenia.” They also accurately recognize the potential for a malignant course in some patients with bipolar disorder, seemingly eliminating course as a dependable differentiating factor. They review and evaluate the endophenotypic overlap and similarities as well as differences across a wide range of disciplines. They compare the “temporal stability” of each diagnosis. They conclude by stating that, “We believe that a modular approach might better explain current clinical variance in the domain of the psychoses.”

Drs. Nathan Hurwitz and Dan Aires review studies of evoked response potential (ERP) endophenotypes that compared patients diagnosed with schizophrenia and psychotic bipolar disorder. They discuss “trait” and “state” endophenotypes. They focus on P50 Gating and P300 Amplitude. Drs. Hurwitz and Aires reason that if schizophrenia and psychotic bipolar disorder are the same disease, these trait endophenotypes should overlap. State endophenotypes are expected to overlap only when patients are in the same state. Thus, the authors anticipate that “state-dependent” endophenotypes should be similar in schizophrenia and “late or severe psychotic bipolar disorder, but different in early psychotic bipolar disorder [and non-psychotic bipolar disorder].” They conclude that results from trait and state studies suggest overlap. They address intermediate-level psychotic bipolar patients who showed “intermediate defects — somewhere between schizophrenia and control groups.” They emphasize that most ERP studies have been conducted in patients diagnosed with schizophrenia, but that subsequent studies often found similar results in psychotic bipolar patients for P300 Amplitude reduction and P50 Gating. They conclude that the data they reviewed, “… argue for a single disease with a broad spectrum of severity.”

Drs. Prossin, McInnis, Amand, Heitzeg, and Zubieta review the existing neuroimaging literature in which comparisons have been made between patients diagnosed with schizophrenia versus mood disorders “in an effort to illustrate the neurobiological evidence that either supports or refutes this dichotomy.” They reviewed six types of neuroimaging: 20 studies that met their criteria and these studies encompassed postmortem anatomy, MRI, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Some of the studies reveal differences between the patient groups, while others, even in the same domains, showed similarities and overlap. The authors note that functional and structural “domains affected in bipolar disorders have been identified as being more widespread and more closely related to schizophrenia than originally expected. However, the degree of severity of these is disparate, with schizophrenia resulting in a typically more severe neuropsychological deterioration than that of bipolar disorder.” They conclude that “the existence of overlap with schizophrenia appears more consistent in psychotic forms of bipolar disorder as compared with non-psychotic bipolar disorder.” In summary, they state that, “the available neuroimaging findings … support the presence of an overlap and a distinction between the circuitry that appears to be involved in the pathophysiology of schizophrenia and bipolar disorder.” The above findings neither refute nor approve the Kraepelinian dichotomy but certainly provide evidence for an overlap between neurobiological factors underlying both disorders. The authors suggest that we “transition away from descriptive clinical classifications and toward a diagnostic system that is aligned with the complex neurobiological underpinnings of these disorders and more akin to clusters of biological disparities and similarities.”

Drs. Fred Goodwin and Nassir Ghaemi review “the conundrum of schizoaffective disorder.” They outline five potential models for considering schizoaffective disorder. They review the phenomenology, genetics, course, and treatment response and conclude that such patients generally fall into one of three groups. Most useful is the description of a patient, initially diagnosed with schizoaffective disorder because of “periods of florid psychosis,” but who was correctly diagnosed as bipolar-1, severe with psychotic features, and who responded to lithium and valproate (Depakote). Readers of this contribution are referred to the article by Drs. Aires and Hurwitz that addresses the place of schizoaffective disorder in future nomenclature and comes to a different conclusion.

References

  1. Abrams R, Taylor MA, Gaztanaga P. Manic-depressive illness and paranoid schizophrenia. Arch Gen Psychiatry. 1974;31(5):640–642.
  2. Kendell RE, Gourlay J. The clinical distinction between the affective psychoses and schizophrenia. Br J Psychiatry. 1970;117(538):261–266.
  3. Pope HG, Lipinski JF. Diagnosis in schizophrenia and manic-depressive illness, a reassessment of the specificity of “schizophrenic” symptoms in the light of current research. Arch Gen Psychiatry. 1978;35(7):811–828.
  4. Ollerenshaw DP. The classification of the functional psychoses. Br J Psychiatry. 1973;122(570):571–530. doi:10.1192/bjp.122.5.517 [CrossRef]
  5. Lake CR. Disorders of thought are severe mood disorders: the selective attention defect in mania challenges the Kraepelinian dichotomy — a review. Schizophren Bull. 2008;34(1):109–117. doi:10.1093/schbul/sbm035 [CrossRef]
  6. Lake CR. Hypothesis: grandiosity and guilt cause paranoia; paranoid schizophrenia is a psychotic mood disorder; a review. Schizophren Bull. 2008;34(6):1151–1162. doi:10.1093/schbul/sbm132 [CrossRef]

C. Ray Lake, MD, PhD, is Professor Emeritus of Psychiatry, University of Kansas School of Medicine, Kansas City.

Dr. Lake graduated from Tulane University in 1965. He received an MS in Insect Physiology, also from Tulane, in 1966. He graduated from Duke University, School of Medicine and Duke Graduate School (Department of Physiology and Pharmacology), in 1971 and 1972. He studied at Oxford University and at St. Bartholomew’s Hospital, London. His residency in psychiatry was completed at Duke and at the National Institute of Mental Health (NIMH). He remained at the NIMH, Laboratory of Clinical Sciences, as a research associate and staff psychiatrist until 1979 when he took a professorship of psychiatry and pharmacology at the new Uniformed Services University of the Health Sciences (USUHS) School of Medicine. He secured two Research Project Grants (RO1s) and continued his research on the regulation of the sympathetic nervous system in health and in patients with neuropsychiatric and/or cardiovascular disorders.

In 1993, he accepted the chairmanship of psychiatry at the University of Kansas School of Medicine for 3 years, after which he continued on the full-time faculty until his recent partial retirement. As Professor Emeritus, he continues to publish and teach students and residents about mood disorders, and follow his long-term patients. He has more than 250 publications and has achieved fellowship status in the American Psychiatric Association (APA) and the American College of Neuropsychopharmacology (ACNP). He is under contract for a book regarding the misdiagnosis of schizophrenia.

His wife has a PhD in psychology and was a member of the clinical psychology faculty at the University of Kansas for 10 years. She is currently in her third year of study at Georgetown Law Center in Washington, DC. They have three wonderful children. Dr. Lake is competitive in tennis.

10.3928/00485713-20100303-02

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