Research reportThe comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders?
Introduction
The relationship between Bipolar I (B-I) and Bipolar II (B-II) disorders has been the subject of considerable theorizing and empirical research for the past decades. Some evidence indicates that these are likely to be separate disorders. For example, Endicott et al. (1985) have reported in a well-characterized cohort of mood disorder patients, followed in the NIMH Collaborative Depression Study (CDS), that Bipolar I and Bipolar II as well as recurrent unipolar disorders are not the same, but rather three separate disorders. Also using data from the CDS, Coryell et al., 1984, Coryell et al., 1989, Coryell et al., 1995 concluded that BP-I and BP-II are separate disorders, based on family history (1984), 5-year course (1989) and diagnostic stability (1995). More recently Vieta et al. (1997) reported that BP-II patients experienced significantly more prior affective episodes and switched polarity more often than BP-I patients, whereas BP-I patients had more frequent hospitalizations and an increased lifelong prevalence of psychotic symptoms. Their data indicated that while BP-II is less severe than BP-I, BP-II has as a more chronic course, supporting the idea that the two disorders are different. Ayuso-Gutierrez and Ramos-Brieva (1982) had earlier arrived at the same conclusion. The results of these investigations were preliminary, as both had small cell sizes of bipolar II.
On the other hand, it has been proposed that all forms of bipolar disorder—and perhaps all primary affective disorders—are best conceptualized as a spectrum of related illnesses (Gershon et al., 1982, Akiskal, 1983, Akiskal, 1996, Tsuang et al., 1985, Cassano et al., 1989), clinically overlapping, but not necessarily genetically uniform, illnesses. The concept of bipolar spectrum has been heuristically and clinically useful, but it still awaits full empirical validation. The present analyses were designed to provide detailed comparison of the clinical characteristics, patterns of comorbidity, and longitudinal episode course of BP-I and BP-II. The goal was to develop data to clarify further the relationship between Bipolar I and Bipolar II as well as to provide an indirect evaluation of the bipolar spectrum hypothesis—a direct test will require molecular genetic investigations. Our à-priori hypothesis was: if the two disorders exist in a spectrum, they should be much more similar than different in all aspects of their phenotypic clinical presentation and longitudinal course. The NIMH CDS provides a unique opportunity to conduct detailed comparisons of substantial cohorts of Bipolar I and Bipolar II patients who have been followed prospectively, naturalistically, longitudinally and systematically for up to 20 years (Katz and Klerman, 1979, Katz et al., 1979).
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Subjects
The analysis samples consisted of 135 BP-I and 71 BP-II patients entering the CDS from 1978 through 1981, at one of five academic centers (New York State Psychiatric Institute/Columbia University in New York, Washington University School of Medicine in St. Louis, Massachusetts General Hospital/Harvard Medical School in Boston, University of Iowa College of Medicine in Iowa City, and Rush Presbyterian St. Luke Medical center in Chicago), for treatment of an index affective episode (Katz and
Demographic characteristics and clinical history
Bipolar I and II patients did not differ in terms of age, sex, marital status, or level of education (see Table 1). Bipolar II patients tended to have more lifetime affective episodes before intake (mean=36.6; S.D.=51.2; median=8) than Bipolar I patients (mean=24.2; S.D.=45.5; median=6), although the difference was not statistically significant (P=0.077) (see Table 2). The first lifetime affective episode of about 60% of both groups was a depressive episode. Significantly more of the BP-I
Commentary
This is the first detailed comparison of the characteristics of the clinical phenotype and the episode course of Bipolar I and Bipolar II patients in which all types of affective episodes were evaluated—including minor/intermittent depressive episodes and hypomanic episodes, not just syndromal level episodes of major depression and mania. In addition, to ensure that comparison of the episode course was based upon relatively uniform periods of prospective follow-up, we contrasted the first
Conclusions
The number of significant differences between BP-I and BP-II presents an argument to support the conceptualization of these two disorders as being different illnesses. At the same time, there are sufficient number of qualitative similarities between BP-I and BP-II to suggest they exist in a clinical spectrum. By definition, BP-I is more severe in terms of symptoms and episodes in the manic spectrum. However, the current data, showing BP-II to be even more chronic than BP-I in terms of major and
Acknowledgements
This manuscript has been reviewed by the Publications Committee of the Collaborative Depression Study, and has its endorsement. Funds for the conduct of the present analyses were provided in part by the Roehr Fund of the University of California, San Diego, CA, USA.
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Conducted with the participation of the following investigators: M.B. Keller, M.D. (Chairperson, Providence, RI, USA); W. Coryell, M.D. (Co-Chairperson, Iowa City, IA, USA); T.I. Mueller, M.D., D.A. Solomon, M.D., (Providence); J. Fawcett, M.D., W.A. Scheftner, M.D., (Chicago, IL, USA); W. Coryell, M.D., J. Haley (Iowa City); J. Endicott, Ph.D., A.C. Leon, Ph.D., J. Loth, M.S.W. (New York, NY, USA); J. Rice, Ph.D., T. Reich, M.D., (St. Louis, USA). Other contributors include: H.S. Akiskal, M.D., N.C. Andreasen, M.D., Ph.D., P.J. Clayton, M.D., J. Croughan, M.D., R.M.A. Hirschfeld, M.D., L. Judd, M.D., M.M. Katz, Ph.D., P.W. Lavori, Ph.D., J.D. Maser, Ph.D., M.T. Shea, Ph.D., R.L. Spitzer, M.D., M.A. Young, Ph.D. Deceased: G.L. Klerman, M.D., E. Robins, M.D., R.W. Shapiro, M.D. and G. Winokur, M.D.