A new bipolar spectrum concept: a brief review

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Copyright ª Blackwell Munksgaard 2002 Bipolar Disorders 2002: 4(Suppl. 1): 11–14


Review Article

A new bipolar spectrum concept: a brief review Angst J, Gamma A. A new bipolar spectrum concept: a brief review. Bipolar Disord 2002: 4(Suppl. 1): 11–14. ª Blackwell Munksgaard, 2002 Research on the broad bipolar spectrum is dependent on the definition of hypomania. We recently proposed a new, softer syndromal definition with clinical validity. This broadens the diagnosis of bipolar II (BP-II) disorder at the expense of major depressive disorder (MDD). There is evidence for a third group of suspected BP-II manifesting major depression plus hypomanic symptoms. The two bipolar-II groups together are as prevalent as MDD. A new concept of minor bipolar disorder embracing dysthymia, minor and recurrent brief depression with hypomanic syndromes and symptoms is discussed. Some methodological pitfalls of research on drug-induced hypomania as an element of the bipolar spectrum are also summarized.

Jules Angst* and Alex Gamma Zurich University Psychiatric Hospital, Zurich, Switzerland

Key words: bipolar-II disorder – definition – hypomania – minor bipolar disorder

Diagnostic concepts of bipolar disorders

The definition of hypomanic syndromes

As shown in the recent summary of the history of the concept of bipolar disorders (1, 2), the terms used first for bipolarity were folie circulaire (3, 4) and folie a` double forme (5). The terms ÔunipolarÕ and ÔbipolarÕ were coined by Karl Kleist (6) and his pupils Neele (7) and Leonhard (8), and included explicitly cycloid psychoses. Both pure melancholia and pure mania were considered by them to be ÔhomonomicÕ, unipolar or monopolar disorders. Pure mania without melancholia was not an element of bipolar disorder as it is in modern diagnostic manuals; it was integrated into bipolar disorders as a consequence of the monographs of Angst 1966 (9), Perris 1966 (10) and Winokur et al. 1969 (11), which initiated modern bipolar research. A further important distinction, between bipolar I and bipolar II disorders, was made by Dunner et al. in 1976 (12); later a wide bipolar spectrum was posited, comprising six groups (13) and eight groups (14). In addition, the concepts of brief hypomania and recurrent brief hypomania (15) and, recently, of minor bipolar disorders (1) were described. Most contemporary studies on bipolar disorders are still unfortunately devoted to BP-I disorders, with a relative neglect of BP-II and other subgroups of the suggested bipolar spectrum.

The definition of mania is relatively well established, but that of hypomania has undergone many changes and is still in a state of flux. The main problem is the diagnostic criteria for hypomania, which is based on clinical concepts that have not been validated by epidemiological studies, making the definition of bipolar-II disorders and that of other subthreshold bipolar syndromes a subject of debate. Our most recent analysis challenges fundamentally the definition of hypomania (1), suggesting that two important diagnostic criteria are probably not valid: (1) the decisive hierarchical position given to mood items (not considering overactivity) and (2) the minimum duration of 4 days. In a recent paper in 2001, Akiskal et al. (16), proposed overactivity rather than mood changes as the only obligatory symptom (criterion A) for a diagnosis of hypomania. Our analysis, more conservatively, adds overactivity to euphoria and irritability for the definition of criterion A of DSM-IV. Many clinical studies have used a minimum 2 days’ rather than 4 days’ duration (DSM-IV) for the diagnosis of hypomania (17–22). Our concept of hypomania goes further, including explicitly 1-day or shorter episodes as observed in adolescents, in whom very brief rapid cycling episodes are a typical feature of bipolar illness (23). Our analyses of validity led to the following syndromal definition of hypomania: a syndrome

* Presenting author


Angst and Gamma

(no minimum duration) characterized by the presence of a) overactivity, euphoria or irritability plus and b) three of seven DSM-IV criterial symptoms leading to subjective or social consequences (1). A soft, suspected or hidden case of hypomania is defined by the presence of a diagnosis of depression plus hypomanic symptoms. Bipolar-II disorders: definition and prevalence

BP-II disorders are defined as major depressive episodes with hypomania. Any failure to diagnose hypomania produces false positive diagnoses of major depressive disorder (MDD). The application of a wider definition of hypomania does not produce higher prevalence rates of mood disorders, but merely reduces the rates of MDD. Modern epidemiological studies have reported low lifetime prevalence rates of BP-II disorders but high rates of MDD. The Epidemiological Catchment Area (ECA) study reported 0.5% BP-II and 4.9% MDD (24). The Munich study by Wittchen et al. (25) investigating adolescents and young adults found 0.4% of BP-II and 11.8% of MDD, and the Hungarian study by Szadoczky et al. (26) found 2.0% of BP-II and 15.1% of MDD. In contrast to these findings, the Zurich cohort study, applying syndromal definitions of hypomania, identified 5.3% of BP-II and 17.1% of MDD. A further 4.7% with major depressives episodes (MDE) plus hypomanic symptoms probably constituted a suspected (hidden) group of BP-II disorders. In total, 11.0% of cases represented certain and suspected cases of BP-II disorders vs. 11.4% with pure MDD. This would suggest that half of all cases with major depressive episodes may be bipolars. These findings are comparable to the 40% undiagnosed cases of BP reported by Ghaemi et al. 1999 (27) and compatible with a French follow-up study of 537 psychiatric MDE patients (28), which identified 39.8% of MDE as BP-II cases. They are also in agreement with Benazzi (20) and Benazzi and Akiskal (29), who found 45% BP-II vs. 55% MDD (n ¼ 525) when the stem question related to mood, and 60% BP-II vs. 40% MDD (n ¼ 168) when the stem question was based on overactivity. In community and clinical studies BP-II cases, if assessed properly, are more prevalent than BP-I cases. The same seems to be true for some genetic studies: Simpson et al. (30) found BP-II disorders in 22% of 219 first-degree relatives of 48 BP-I probands and in 40% of 47 relatives of eight BP-II probands. The authors concluded that ÔBP-II disorder was the most prevalent affected phenotype in both bipolar I and bipolar II familiesÕ.


Further work is required to test the clinical validity of the proposed new syndromal and the symptom-based definitions of BP-II compared to MDD, with special consideration of familial occurrence of hypomania ⁄ mania, age of onset, recurrence, comorbidity and personality. Drug-induced switches from depression to hypomania

This proposed new definition of hypomania would have a major impact on treatment strategies, the selection of patients for clinical trials and the interpretation of the alleged drug-induced hypomania. Drug-induced switches are an element of the bipolar spectrum concepts of both Klerman (13) and Akiskal (14). Drug-induced switches occur mainly or even solely in subjects with a genetic bipolar disposition and are clearly observed more frequently in bipolar than unipolar depressives (31). What we need is new drug trials on major depression, identifying suspected BP-II subgroups (today diagnosed as MDD), which measure not only antidepressant effects but also systematically assess hypomanic symptoms before and during treatment. Our hypothesis that the alleged druginduced switches are natural phenomena of remission from bipolar depression could then be tested seriously (32–36). Such trials would, in our view, find that switches occur mainly in suspected BP-II cases and only exceptionally in pure MDD cases. Given that a switch into a mixed state or into hypomania requires first of all a marked improvement of a depressive episode, and that switches do not occur in non-responders to treatment (if observed only over the 4–8 weeks of a conventional drug trial), the switch rate is correlated with treatment efficacy. Because drug treatments increase the number of responders (37), switches should occur more often in drug-treated than placebotreated groups. Methodologically, the number of switches should be computed as a function of the number of responders and not of the total number of treated subjects, which of course includes the non-responders. Total numbers as denominator should only be used in the case of a follow-up to the remission of all the subjects in a trial. This methodological process has never been applied. Minor bipolar disorders (MinBP): definition and prevalence

The current diagnostic classification of depression is problematic. Dysthymic disorders are considered

A new bipolar spectrum concept The group of minor bipolar disorders (MinBP) definitely constituted a milder form of mood disorder, intermediate between BP-II disorders and controls in most validators. However, the MinBP group had a threefold higher positive family history rate for mania ⁄ hypomania than MDD and controls.

to be an important diagnostic category, but there is no validated operational definition of minor depression. In our view, dysthymia is a chronic form of minor depression. In the Zurich cohort study minor depression is defined by the presence of three to four of nine criterial symptoms for depression with a minimum 2 weeks’ duration. A further category, recurrent brief depression, was defined according to DSM-IV (38) and ICD-10 (39) criteria, but with the more difficult criterion of work impairment. Parallel with these categories of depression, we can conceptualize minor bipolar disorder (MinBP) by the presence of minor or recurrent brief depression plus hypomania. Cyclothymic disorder in this context is considered to be a chronic form of minor bipolar disorder; every case meeting the criteria for dysthymia plus hypomania would qualify for cyclothymia. As with BP-II, we can define suspected (hidden) cases of MinBP by the presence of any diagnosis of depression plus hypomanic symptoms. The Zurich study found a lifetime prevalence rate of 3.2% of MinBP and 6.2% of suspected (hidden) MinBP. In addition we observed 3.3% of ÔpureÕ hypomania. Taken together, these subthreshold bipolar ⁄ hypomanic disorders show a prevalence rate of 12% compared with 13% for subthreshold depressive disorders. The ratio is about 1:1. Further studies are needed to analyse the predictive power of MinBP for BP-II disorders. So far we have only the prospective data of the Oregon Adolescent Depression Project by Lewinsohn et al. 1995, which at the first interview (mean age 18) identified ÔcoreÕ manic symptoms predicting MDD, bipolar, anxiety disorders and suicidal behaviour (23) at age 19.

This work was supported by Grant 3200-050881.97 ⁄ 1 of the Swiss National Science Foundation.

Validity of the bipolar spectrum


For validation purposes, the Zurich study compared BP-II cases with MDD and controls. Both subtypes of mood disorder had high family history rates for depression, high rates of suicide attempts and treatment for depression. Both BP-II subgroups (defined by hypomanic syndromes or by symptoms only) had equally high family histories rates for mania ⁄ hypomania, whereas MDD subjects did not differ from controls. Compared with MDD subjects, those with BP-II disorders had significantly higher rates of conduct problems in childhood ⁄ adolescence and higher rates of substance abuse ⁄ dependence, especially of alcohol; they also showed a trend to an earlier age of onset (1).


Research in bipolar disorders is dominated currently by studies on mania, to the disadvantage of bipolar II disorders and subthreshold minor bipolar disorders. Research on the bipolar spectrum is dependent on the definition of hypomania, which is unsatisfactory, and requires revision on the basis of sound data obtained from more methodologically orientated epidemiological and clinical research. Research should not be limited to the operationalized diagnoses of the diagnostic manuals, otherwise it is circular and self-fulfilling. Improved instruments for assessing diverse syndromes lying under the diagnostic thresholds are required urgently. There is growing evidence for the existence of a broad bipolar spectrum; its identification will help reverse the overdiagnosis of major and minor depressive disorders. It will open new perspectives for research into bipolar syndromes in the fields of genetic epidemiology, developmental psychopathology and treatment, including comorbidity with anxiety disorders and substance abuse ⁄ dependence. Acknowledgements

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