A new bipolar spectrum concept: a brief review
Descrição do Produto
Copyright ª Blackwell Munksgaard 2002 Bipolar Disorders 2002: 4(Suppl. 1): 11–14
Lihat lebih banyak...
BIPOLAR DISORDERS ISSN 1399-2406
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
1. Angst J, Gamma A, Benazzi F, Ajdacic-Gross V, Eich D, Ro¨ssler HW. Toward a re-deﬁnition of subthreshold bipolarity: epidemiology and proposed criteria for bipolarII, minor bipolar disorders and hypomania. J Aﬀect Disord 2002: (in press). 2. Angst J, Hantouche E. Epidemiologı´ a del trastorno bipolar menor y de la hipomanı´ a: un territorio nuevo. In: Vieta E ed. Hipomanı´ a. Madrid: Bibliothecas Aula Me´dica, 2002: 13–31. 3. Falret JP. Marche de la folie. Gazette Hopitaux 1851; 24: 18–19. 4. Falret JP. De la folie circulaire ou forme de maladie mentale caracte´rise´e par l’alternative re´gulie`re de la manie et de la me´lancholie. Bull Acad Med 1854; 19: 382. 5. Baillarger J. De la folie a` double forme. Ann Med Psychol 1854; 6: 369–384. 6. Kleist K. Die Gliederung der neuropsychischen Erkrankungen. Monatsschr Psychiatr Neurol 1953; 125: 526–554.
Angst and Gamma 7. Neele E. Die phasischen Psychosen nach ihrem Erscheinungs- und Erbbild. Leipzig: Johann Ambrosius Barth Verlag, 1949. 8. Leonhard K. Aufteilung der Endogenen Psychosen. Berlin: Akademie Verlag, 1957. 9. Angst J. Zur Aetiologie und Nosologie endogener depressiver Psychosen. Eine genetische, soziologische und klinische Studie. Berlin: Springer, 1966. 10. Perris C. A study of bipolar (manic-depressive) and unipolar recurrent depressive psychoses. Acta Psychiatr Scand 1966; 42 (Suppl. 194): 1–189. 11. Winokur G, Clayton PJ, Reich T. Manic depressive illness. St Louis, MO: Mosby, 1969. 12. Dunner DL, Fleiss JL, Fieve RR. The course of development of mania in patients with recurrent depression. Am J Psychiatry 1976; 133: 905–908. 13. Klerman GL. The spectrum of mania. Compr Psychiatry 1981; 22: 11–20. 14. Akiskal HS. Classiﬁcation, diagnosis and boundaries of bipolar disorder: a review. In: Maj M, Akiskal HS, LopezIbor JJ, Sartorius N eds. Bipolar Disorder. Chichester: Wiley, 2002: 1–52. 15. Angst J. Recurrent brief psychiatric syndromes of depression, hypomania, neurasthenia, and anxiety from an epidemiological point of view. Neurol Psychiatry Brain Res 1992; 1: 5–12. 16. Akiskal HS, Hantouche EG, Bourgeois ML et al. Toward a reﬁned phenomenology of mania: combining clinicianassessment and self-report in the French EPIMAN study. J Affect Disord 2001; 67: 89–96. 17. Cassano GB, Akiskal HS, Savino M, Musetti L, Perugi G. Proposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament. J Affect Disord 1992; 26: 127–140. 18. Manning JS, Haykal RF, Connor PD, Akiskal HS. On the nature of depressive and anxious states in a familiy practice setting: the high prevalence of bipolar II and related disorders in a cohort followed longitudinally. Compr Psychiatry 1997; 38: 102–108. 19. Akiskal H, Bourgeois ML, Angst J, Post R, Mo¨ller H-J, Hirschfeld R. Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000; 59 (Suppl. 1): 5–30. 20. Benazzi F. Bipolar II depression in late life. prevalence and clinical features in 525 depressed outpatients. J Affect Disord 2001; 66: 13–18. 21. Benazzi F. Is 4 days the minimum duration of hypomania in bipolar II disorder? Eur Arch Psychiatry Clin Neurosci 2001; 251: 32–34. 22. Benazzi F. Sensitivity and speciﬁcity of clinical markers for the diagnosis of bipolar II disorder. Compr Psychiatry 2001; 42: 461–465. 23. Lewinsohn PM, Seeley JR, Klein DN. Bipolar disorder in a community sample of adolescents: epidemiology and suicidal behavior. In: Geller B, Del Bello M eds. Child and
Early Adolescent Bipolar Disorder. New York: Guilford Press, 2002: in press. Weissman MM, Bruce LM, Leaf PJ et al. Aﬀective disorders. In: Robins LN, Regier DA eds. Psychiatric Disorders in America. The Epidemiologic Catchment Area Study. New York: The Free Press, 1990: 53–80. Wittchen H-U, Nelson CB, Lachner G. Prevalence of mental disorders and psychosocial impairments in adolescents and young adults. Psychol Med 1998; 28: 109–126. Szadoczky E, Papp Z, Vitrai J, Rihmer Z, Fu¨redi J. The prevalence of major depressive and bipolar disorders in Hungary. Results from a National Epidemiologic Survey. J Affect Disord 1998; 50: 153–162. Ghaemi SN, Sachs GS, Chiou AM, Pandurangi AK, Goodwin FK. Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? J Affect Disord 1999; 52: 135–144. Allilaire J-F, Hantouche E-G, Sechter D et al. Fre´quence et aspects cliniques du trouble bipolaire II dans une e´tude multicentrique franc¸aise: EPIDEP. Ence´phale 2001; XXVII: 149–158. Benazzi F, Akiskal HS. Reﬁning the evaluation of bipolar II. Beyond the strict SCID-CV guidelines for hypomania. J Affect Disord 2002; in press. Simpson SG, Folstein SE, Meyers DA et al. The most common bipolar phenotype? Am J Psychiatry 1993; 150: 901–903. Angst J. Zur Prognose antidepressiver Behandlungen – Verlaufsuntersuchungen Genetische Studie [The prognosis of antidepressive treatments – longitudinal and genetic studies]. Anglo-German Med Rev 1965; 2: 733–751. Angst J. Switch from depression to mania – a record study over decades between 1920 and 1982. Psychopathology 1985; 18: 140–154. Angst J. Switch from depression to mania, or from mania to depression. J Psychopharmacol 1987; 1: 13–19. Angst J. Switch from depression to mania, or from mania to depression. Role of psychotropic drugs. Psychopharmacol Bull 1987; 23: 66–67. Angst J. Recurrent brief depression. A new concept of mild depression. Abstracts of the XVIth CINP Congress, Munich, 1988. Psychopharmacology 1988; 96 (Suppl.): 123 [Abstract FR 04.05]. Angst J, Sellaro R. Historical perspectives and natural history of bipolar disorder. Biol Psychiatry 2000; 48: 445–457. Stassen HH, Angst J, Delini-Stula A. Delayed onset of action of antidepressant drugs? Survey of recent results. Eur Psychiatry 1997; 12: 166–176. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Washington, DC: American Psychiatric Association, 1994. World Health Organization. The ICD-10 Classiﬁcation of Mental and Behavioural Disorders. Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization, 1992.