- Email: [email protected]
Validating ‘hard’ and ‘soft’ phenotypes within the bipolar spectrum: continuity or discontinuity?
Journal of Affective Disorders 73 (2003) 1–5 www.elsevier.com / locate / jad
Introduction to the Special Issue
Validating ‘hard’ and ‘soft’ phenotypes within the bipolar spectrum: continuity or discontinuity? Hagop S. Akiskal* University of California at San Diego and VA Psychiatry Service (116 A), 3350 La Jolla Village Drive, San Diego, CA 92161, USA
Abstract The unitary Kraepelian concept of manic-depressive illness which incorporated attenuated forms, personal dispositions to mood instability, as well as much of the terrain of remitting depressions, may be considered by many to be too broad. On the other hand, the presently preferred unipolar–bipolar dichotomy in official nosology fails to account for the very common occurrence of clinical and subclinical conditions in the interface of major depressive disorders and bipolarity. The emerging concept of the bipolar spectrum represents a provocative working hypothesis to account for these conditions. 2002 Elsevier Science B.V. All rights reserved.
This special issue brings together the largest collection of original research on the ‘hard’ (psychotic and non-psychotic bipolar I) and, in particular, ‘soft’ (bipolar II and beyond) phenotypes within the clinical spectrum of bipolar disorders. The present monograph provides extensive data on aspects of the bipolar spectrum (hypomania, cyclothymia, switching on antidepressants, and depressive mixed states) about which the literature has hitherto been rather sparse. Different research teams from both the US and Europe concur on the existence of a broad constellation of clinical manifestations within the bipolar spectrum. In the spirit of the Robins–Guze criteria (1970), validation is examined along demographic, phenomenologic, comorbid, course, temperamental, familial and, whenever applicable, biological characteristics. Whether common underlying *Tel.: 1 1-858-552-8585, ext. 2226; fax: 1 1-858-534-8598. E-mail address: [email protected] (H.S. Akiskal).
genetic traits account for the bipolar spectrum is a provocative possibility on which definitive data are presently unavailable; whether a genetic cleavage exists between bipolar I and bipolar II is also presently unsettled. However, the confluence of data from different research teams across the Atlantic— utilizing diverse methodology, but generally within the foregoing validating principles—indicates that the clinical reality of a highly prevalent bipolar spectrum can no longer be in doubt. Re-analyses of largely epidemiological databases reported in this monograph testify that the figure of 1% is too conservative and pertains primarily to bipolar I; and that at least 5% of the general population has disabling bipolar disorder and / or traits, and manifesting clinically largely within the ‘soft’ bipolar realm. The substantive findings reported in this monograph have profound implications for practice, research and theory for the larger field of affective disorders.
0165-0327 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. PII: S0165-0327( 02 )00390-7
2
H.S. Akiskal / Journal of Affective Disorders 73 (2003) 1–5
Kraepelin (1899) had envisaged a broad concept of manic-depressive illness which not only encompassed attenuated forms and what today we might consider temperamental instability, but also much of the domain of major depressive disorders. The unipolar–bipolar distinction (Angst, 1966; Perris, 1966; Winokur et al., 1969) which attempted to dethrone this unitary concept, separated a large chunk of depressive disorders from bipolar disorder proper. Indeed, current official nosology as reflected in ICD-10 (WHO, 1992) and DSM-IV (APA, 1994) largely conforms to this dichotomous conceptualization. Nonetheless, in the research community there has been considerable dissatisfaction with this dichotomy (Akiskal, 1983; Goodwin and Jamison, 1990; Gershon, 2000; Maj et al., 2002). It is of historic interest, as reflected in an epidemiological contribution in the present issue, that Jules Angst now embraces a concept of bipolar spectrum which is the broadest. Actually, Marneros and Angst (2000) had invited an international cadre of clinical investigators, most of whom endorsed the broader perspective. It is of considerable clinical and theoretical interest that within the broad spectrum of bipolarity, the most common manifestations are depressive in nature, whether one examines patients across the spectrum (Akiskal et al., 2000), within bipolar pedigrees (Gershon et al., 1982; Simpson et al., 1993), in the offspring of manic-depressive probands (Akiskal et al., 1985), or during the prospective course of bipolar I (Judd et al., 2002). This issue represents a systematic attempt to examine the concept of bipolar spectrum that I have proposed during the past two decades, resulting, in successive iterations, in both modification and greater enlargement of the bipolar realm (Akiskal, 1983, 1996, 2002; Akiskal and Mallya, 1987; Akiskal and Akiskal, 1988; Akiskal and Pinto, 1999). This issue brings together the largest number of research reports under one cover devoted to the validation of this broad conceptualization of bipolarity. Preliminary versions of most of these papers were presented at an international conference on ‘The Coming of Age of the Bipolar Spectrum’ which took place in La Jolla, under the auspices of the International Mood Center, University of California at San Diego, in November 2000. These papers have been thoroughly peer-reviewed, and extensively rewritten,
and updated. Several other papers were invited to complete aspects of the spectrum that were not specifically covered in the conference and, likewise, subjected to the same rigorous peer-review process. With the exception of three review articles, and a translation of a classical historical text by Ewald Hecker (on what might be the first clinical description of today’s concept of bipolar II), all papers in this issue report primary data never published before. These data derive from research teams using diverse methodologies, but generally within the external validating principles as formulated by Robins and Guze (1970). As biological markers have been elusive, Table 1 lists validating principles suitable for ascertaining putative clinical bipolar subtypes. The ensemble of data in this monograph should challenge those in the literature (Soares and Gershon, 2000; Baldessarini, 2000) who are skeptical of the existence of a rich research basis for the ‘attenuated’—and highly prevalent—extensions of bipolarity into, among others, the conventional territories of major depressive disorders, anxiety states, cluster B personality disorders, and the subthreshold realm in the community. It is relevant to point out in this context that the concept of at least some, if not extensive, continuity between depressive, related periodic psychopathology, and bipolar disorders has been endorsed (without necessarily invoking a specific bipolar spectrum construct) by many contemporary authorities in the field of affective disorders (Dunner et al., 1976; Mendels, 1976; Bertelsen et al., 1977; Taylor and Abrams, 1980; Klerman, 1981; Gershon et al., 1982; Tsuang et al., 1985; Endicott,
Table 1 Clinical validating principles for a putative bipolar spectrum condition Phenomenology Comorbidity Family History Course Age at onset Temperament Switching Cyclicity Mixity Seasonality
H.S. Akiskal / Journal of Affective Disorders 73 (2003) 1–5
1989; Cassano et al., 1992; McElroy et al., 1996; Manning et al., 1997; Benazzi, 1997; and Ghaemi et al., 2000). The Bipolar Spectrum incorporates overlapping subtypes of bipolar disorder (Akiskal, 1999, 2002). Much of the literature is devoted to bipolar I disorder where a manic or mixed manic state has been documented. The literature is relatively sparse on bipolar II, where depression dominates the clinical course, interspersed with hypomanic episodes which per se do not produce marked dysfunction. Although the Research Diagnostic Criteria (Spitzer et al., 1978) defined the lower operational threshold of hypomania to be 2 days, in DSM-IV (in which bipolar II appeared for the first time in official nosology) this threshold is set at 4 days. Several of the papers published in this special issue are devoted to the validation of the 2-day threshold. Actually, this issue contains 10 papers which address various aspects of hypomania. Many bipolar II patients with brief hypomanias are cyclothymic in temperament, giving rise to boundary questions with atypical depression and cluster B personality disorders. This subject receives extensive coverage in the present issue. Also covered are clinically depressed patients who manifest hypomanic symptoms and / or behaviors during their depression This rather large group of patients with depressive mixed states is essentially ignored within the DSM-IV and ICD-10 diagnostic schemas. As for the diagnostic status of hypomania occurring during antidepressant treatment, it is left in a diagnostic limbo in both DSM-IV and ICD-10. This monograph presents convincing data from a large French national study, as a rationale for their inclusion in the bipolar spectrum as a provisional type III disorder. Related to bipolar II and III are the rapid cycling patients whose course has been examined in a long term follow-up study in Rome and reported in this issue. It is presently unclear whether the foregoing bipolar subtypes represent a clinical or a genetic continuum. Some have argued for the genetic uniqueness of euphoric, remitting and lithium responsive bipolar I (Alda et al., 1994; Duffy and Grof, 2001). It is also possible that bipolar II represents a genetically (MacKinnon et al., 1998) and / or clinically (Perugi and Akiskal, 2002; Rihmer and Pestality,
3
1999) unique subtype. Consideration should also be given to the fact that pleomorphic expressions can occur even within each of the bipolar subtypes. For instance, mania manifests in ‘pure’, depressive, hostile and psychotic presentations, a subject which is covered in the opening paper in the present issue. It is presently unclear whether central ‘activation’ or ‘impulsivity’ underlies these clinical presentations. At least three papers address this question. Another paper, deriving from the NIMH collaborative study database, provides a comparative prospective analysis of bipolar I and II subtypes. A review paper provides an in depth examination of the possible genetic basis of the concept of the bipolar spectrum or alternatives thereof. It is obvious to those working in the field of bipolar disorder that the figure of 1% quoted in the classical epidemiological literature (Regier et al., 1988; Weissman et al., 1996) represents a gross underestimate (summarized in Akiskal, 2002). Although previous research (summarized in Akiskal et al., 2000) has suggested rates of up to 5% for the broadly conceived bipolar spectrum, for the first time definitive data are presented for the entire US population and the canton of Zurich, Switzerland, which place the rates of bipolarity in the community to be even higher than 5%. This is a reflection of several factors. First, nearly 50% of so-called major depressive disorders can be reclassified as bipolar II on the basis of a systematic search for hypomania (Hantouche et al., 1998). Second, the terrain of subclinical bipolarity in the community is now being assessed with more ‘sensitive’ methodology for detecting bipolarity (Hirschfeld et al., 2000). If indeed bipolar illness is the extreme expression of oligogenic inheritance (Gershon, 2000), considerable overlap must exist at the milder end of the spectrum with normality. The diagram (Fig. 1) illustrates this concept in which severity and prevalence are inversely related. Of all the temperaments, cyclothymia is the one most relevant to bipolarity, and in a non-ill Italian population was found to have a prevalence until age 25 of 6.3% (Placidi et al., 1998). Although treatment was not the primary focus of this special issue, such clinically troubling aspects of bipolarity as rapid cycling and exacerbation of mania are in part addressed. Finally, the entire concept of mood stabilization is re-examined, and the special
4
H.S. Akiskal / Journal of Affective Disorders 73 (2003) 1–5
Fig. 1. Community prevalence of bipolar (BP) phenotypes as a function of severity.
psychotherapeutic needs of patients within the bipolar spectrum are considered. While a great deal more research needs to be done in the bipolar spectrum, I submit that this collection of original research papers lays the research based groundwork for future developments. I feel greatly honored that I have had the privilege to collaborate intimately with most of the research teams featured in this special issue. It gives me great satisfaction to see the publication of this collaborative effort, representing both established and upcoming talent from different parts of the world.
Acknowledgements The International Conference from which this special issue in part derives, was supported by an unrestricted educational grant from Eli Lilly & Co.
References Akiskal, H.S., 1983. The bipolar spectrum: new concepts in classification and diagnosis. In: Grinspoon, L. (Ed.). Psychiatry Update: The American Psychiatric Association Annual Review, Vol. 2. American Psychiatric Press, Washington, DC, pp. 271– 292. Akiskal, H.S., Downs, J., Jordan, P., Watson, S., Daugherty, D., Pruitt, D.B., 1985. Affective disorders in referred children and younger siblings of manic depressives: mode of onset and prospective course. Arch. Gen. Psychiatry 42, 996–1003.
Akiskal, H.S., Mallya, G., 1987. Criteria for the ‘soft’ bipolar spectrum: treatment implications. Psychopharmacol. Bull. 23, 68–73. Akiskal, H.S., Akiskal, K., 1988. Reassessing the prevalence of bipolar disorders: clinical significance and artistic creativity. Psychiatr. Psychobiol. 3, 29s–36s. Akiskal, H.S., 1996. The prevalent clinical spectrum of bipolar disorders: Beyond DSM-IV. J. Clin. Psychopharmacol. 16 (suppl 1), 4s–14s. Akiskal, H.S., Pinto, O., 1999. The evolving bipolar spectrum. Prototypes I, II, III and IV. Psychiatr. Clin. North Am. 22, 517–534. Akiskal, H.S. (Ed.), 1999. Bipolarity: Beyond Classic Mania. WB Saunders, Philadelphia. ¨ Akiskal, H.S., Bourgeois, M.L., Angst, J., Post, R., Moller, H.J., Hirschfeld, R., 2000. Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J. Affect. Disord. 59, S5–S30. Akiskal, H.S., 2002. Classification, diagnosis and boundaries of bipolar disorders. In: Maj, M., Akiskal, H.S., Lopez-Ibor, J.J., Sartorius, N. (Eds.), Bipolar Disorder. John Wiley and Sons, London, pp. 1–52. Alda, M., Grof, P., Grof, E., Zvolsky, P., Walsh, M., 1994. Mode of inheritance in families of patients with lithium-responsive affective disorders. Acta Psychiatr. Scand. 90, 304–310. American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th ed. APA Press, Washington DC. Angst J., 1966 / 1973 (trans.). The etiology and nosology of endogenous depressive psychoses. Foreign Psychiatry 2, 1– 108. Baldessarini, R.J., 2000. A plea for integrity of the bipolar disorder concept. Bipolar Disord. 2, 3–7. Benazzi, F., 1997. Prevalence of bipolar II disorder in outpatient depression: A 203-case study in private practice. J. Affect. Disord. 43, 163–166. Bertelsen, A., Harvald, B., Hauge, M., 1977. A Danish twin study of manic-depressive disorders. Br. J. Psychiatry 130, 330–351. Cassano, G.B., Akiskal, H.S., Savino, M., Musetti, L., Perugi, G., Soriani, A., 1992. Proposed subtypes of bipolar II disorder: With hypomanic episodes and / or with hyperthymic temperament. J. Affect. Disord. 26, 127. Duffy, A., Grof, P., 2001. Psychiatric diagnoses in the context of genetic studies of bipolar disorder. Bipolar Disord. 3, 270–275. Dunner, D.L., Gershon, E.S., Goodwin, F.K., 1976. Heritable factors in the severity of affective illness. Biol. Psychiatry 11, 31–42. Endicott, N.A., 1989. Psychophysiological correlates of ‘bipolarity’. J. Affect. Disord. 17, 47–56. Gershon, E.S., 2000. Bipolar illness and schizophrenia as oligogenic diseases: Implications for the future. Biol. Psychiatry 47, 240–244. Gershon, E.S., Hamovit, J., Guroff, J.J., Dibble, E., Leckman, J.F., Sceery, W., Targum, S.D., Nurnberger, Jr. J.I., Goldin, L.R., Bunney, Jr. W.E., 1982. A family study of schizoaffective, bipolar I, bipolar II, unipolar and control probands. Arch. Gen. Psychiatry 39, 1157–1167.
H.S. Akiskal / Journal of Affective Disorders 73 (2003) 1–5 Ghaemi, S.N., Boiman, E.E., Goodwin, F.K., 2000. Diagnosing bipolar disorder and the effect of antidepressants: A naturalistic study. J. Clin. Psychiatry 61, 804–808. Goodwin, F.K., Jamison, K.R., 1990. Manic-Depressive Illness. Oxford University Press, New York. Hantouche, E.G., Akiskal, H.S., Lancrenon, S., Allilaire, J.F., ˆ Sechter, D., Azorin, J.M., Bourgeois, M., Fraud, J.P., Chatenetˆ Duchene, L., 1998. Systematic clinical methodology for validating bipolar-II disorder: Data in mid-stream from a French national multisite study (EPIDEP). J. Affect. Disord. 50, 163– 173. Hirschfeld, R.M., Williams, J.B., Spitzer, R.L., Calabrese, J.R., Flynn, L., Keck, Jr. P.E., Lewis, L., McElroy, S.L., Post, R.M., Rapport, D.J., Russell, J.M., Sachs, G.S., Zajecka, J., 2000. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am. J. Psychiatry 157, 1873–1875. Judd, L.L., Akiskal, H.S., Schettler, P.J., Endicott, J., Maser, J., Solomon, D.A., Leon, A.C., Rice, J.A., Keller, M.B., 2002. The long-term natural history of the symptomatic structure of bipolar-I disorder. Arch. Gen. Psychiatry 59, 530–537. Klerman, G.L., 1981. The spectrum of mania. Compr. Psychiatry 22, 11–20. Kraepelin E., 1899 / 1921 (trans.). Manic-depressive Insanity and Paranoia. E and S Livingstone, Edinburgh. MacKinnon, D., Xu, J., McMahon, F.J., Simpson, S.G., Stine, C., McInnis, M.G., DePaulo, J.R., 1998. Bipolar disorder and panic disorder in families: an analysis of chromosome 18 data. Am. J. Psychiatry 55, 829–831. Maj, M., Akiskal, H.S., Lopez-Ibor, J.J., Sartorius, N. (Eds.), 2002. Bipolar Disorder. World Psychiatric Association Series Evidence and Experience in Psychiatry. John Wiley and Sons, London. Manning, J.S., Haykal, R.F., Connor, P.D., Akiskal, H.S., 1997. On the nature of depressive and anxious states in a family practice setting: The high prevalence of bipolar II and related disorders in a cohort followed longitudinally. Compr. Psychiatry 38, 102–108. Marneros, A., Angst, J. (Eds.), 2000. Bipolar Disorders: 100 Years After Manic Depressive Insanity. Kluwer, UK. McElroy, S.L., Pope, Jr. H.G., Keck, Jr. P.E., Hudson, J.I., Phillips, K.A., Strakowski, S.M., 1996. Are impulse-control disorders related to bipolar disorder? Compr. Psychiatry 37, 229–240.
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Mendels, J., 1976. Lithium in the treatment of depression. Am. J. Psychiatry 133, 373–378. Perris, C. (Ed.), 1966. A Study of Bipolar (manic-depressive) and Unipolar Recurrent Depressive Psychoses, Vol. 194. Acta Psychiatr. Scand, pp. 9–14. Perugi G., Akiskal H.S., 2002. The soft bipolar spectrum redefined: Focus on the anxious-senstivite, impulse-dyscontrol and binge-eating connection in bipolar II and related conditions. Psychiatr. Clin. N. Am. 25, 713–737. Placidi, G.F., Signoretta, S., Liguori, A., Gervasi, R., Maremmani, I., Akiskal, H.S., 1998. The semi-structured affective temperament interview (TEMPS-I): reliability and psychometric properties in 1010 14–26 year students. J. Affect. Disord. 47, 1–10. Regier, D.A., Boyd, J.H., Burke, Jr. J.D., Rae, D.S., Myers, J.K., Kramer, M., Robins, L.N., George, L.K., Karno, M., Locke, B.Z., 1988. One-month prevalence of mental disorders in the United States. Based on five Epidemiologic Catchment Area sites. Arch. Gen. Psychiatry 45, 977–986. Rihmer, Z., Pestality, P., 1999. Bipolar II disorder and suicidal behavior. Psychiatr. Clin. North Am. 22, 667–673. Robins, E., Guze, S.B., 1970. Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. Am. J. Psychiatry 126, 983–986. Simpson, S.G., Folstein, S.E., Meyers, D.A., McMahon, F.J., Brusco, D.M., DePaulo, Jr. J.R., 1993. Bipolar II: The most common bipolar phenotype? Am. J. Psychiatry 150, 901–903. Soares, J.C., Gershon, S., 2000. The diagnostic boundaries of bipolar disorder. Bipolar Disord. 2, 1–2. Spitzer, R.L., Endicott, J., Robins, E., 1978. Research diagnostic criteria: rationale and reliability. Arch. Gen. Psychiatry 35, 773–782. Taylor, M.A., Abrams, R., 1980. Reassessing the bipolar–unipolar dichotomy. J. Affect. Disord. 2, 195–217. Tsuang, M.T., Faraone, S.V., Fleming, J.A., 1985. Familial transmission of major affective disorders. Is there evidence supporting the distinction between unipolar and bipolar disorders? Br. J. Psychiatry 146, 268–271. Weissman, M.M., Bland, R.C., Canino, G.J., Faravelli, C. et al., 1996. Cross-national epidemiology of major depression and bipolar disorder. J. Am. Med. Assoc. 276, 293–299. Winokur, G., Clayton, P.J., Reich, T., 1969. Manic-Depressive Illness. CV Mosby, St. Louis. World Health Organization, 1992. The ICD-10 Classification of Mental and Behavioral Disorders. WHO, Geneva.
Introduction to the Special Issue
Validating ‘hard’ and ‘soft’ phenotypes within the bipolar spectrum: continuity or discontinuity? Hagop S. Akiskal* University of California at San Diego and VA Psychiatry Service (116 A), 3350 La Jolla Village Drive, San Diego, CA 92161, USA
Abstract The unitary Kraepelian concept of manic-depressive illness which incorporated attenuated forms, personal dispositions to mood instability, as well as much of the terrain of remitting depressions, may be considered by many to be too broad. On the other hand, the presently preferred unipolar–bipolar dichotomy in official nosology fails to account for the very common occurrence of clinical and subclinical conditions in the interface of major depressive disorders and bipolarity. The emerging concept of the bipolar spectrum represents a provocative working hypothesis to account for these conditions. 2002 Elsevier Science B.V. All rights reserved.
This special issue brings together the largest collection of original research on the ‘hard’ (psychotic and non-psychotic bipolar I) and, in particular, ‘soft’ (bipolar II and beyond) phenotypes within the clinical spectrum of bipolar disorders. The present monograph provides extensive data on aspects of the bipolar spectrum (hypomania, cyclothymia, switching on antidepressants, and depressive mixed states) about which the literature has hitherto been rather sparse. Different research teams from both the US and Europe concur on the existence of a broad constellation of clinical manifestations within the bipolar spectrum. In the spirit of the Robins–Guze criteria (1970), validation is examined along demographic, phenomenologic, comorbid, course, temperamental, familial and, whenever applicable, biological characteristics. Whether common underlying *Tel.: 1 1-858-552-8585, ext. 2226; fax: 1 1-858-534-8598. E-mail address: [email protected] (H.S. Akiskal).
genetic traits account for the bipolar spectrum is a provocative possibility on which definitive data are presently unavailable; whether a genetic cleavage exists between bipolar I and bipolar II is also presently unsettled. However, the confluence of data from different research teams across the Atlantic— utilizing diverse methodology, but generally within the foregoing validating principles—indicates that the clinical reality of a highly prevalent bipolar spectrum can no longer be in doubt. Re-analyses of largely epidemiological databases reported in this monograph testify that the figure of 1% is too conservative and pertains primarily to bipolar I; and that at least 5% of the general population has disabling bipolar disorder and / or traits, and manifesting clinically largely within the ‘soft’ bipolar realm. The substantive findings reported in this monograph have profound implications for practice, research and theory for the larger field of affective disorders.
0165-0327 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. PII: S0165-0327( 02 )00390-7
2
H.S. Akiskal / Journal of Affective Disorders 73 (2003) 1–5
Kraepelin (1899) had envisaged a broad concept of manic-depressive illness which not only encompassed attenuated forms and what today we might consider temperamental instability, but also much of the domain of major depressive disorders. The unipolar–bipolar distinction (Angst, 1966; Perris, 1966; Winokur et al., 1969) which attempted to dethrone this unitary concept, separated a large chunk of depressive disorders from bipolar disorder proper. Indeed, current official nosology as reflected in ICD-10 (WHO, 1992) and DSM-IV (APA, 1994) largely conforms to this dichotomous conceptualization. Nonetheless, in the research community there has been considerable dissatisfaction with this dichotomy (Akiskal, 1983; Goodwin and Jamison, 1990; Gershon, 2000; Maj et al., 2002). It is of historic interest, as reflected in an epidemiological contribution in the present issue, that Jules Angst now embraces a concept of bipolar spectrum which is the broadest. Actually, Marneros and Angst (2000) had invited an international cadre of clinical investigators, most of whom endorsed the broader perspective. It is of considerable clinical and theoretical interest that within the broad spectrum of bipolarity, the most common manifestations are depressive in nature, whether one examines patients across the spectrum (Akiskal et al., 2000), within bipolar pedigrees (Gershon et al., 1982; Simpson et al., 1993), in the offspring of manic-depressive probands (Akiskal et al., 1985), or during the prospective course of bipolar I (Judd et al., 2002). This issue represents a systematic attempt to examine the concept of bipolar spectrum that I have proposed during the past two decades, resulting, in successive iterations, in both modification and greater enlargement of the bipolar realm (Akiskal, 1983, 1996, 2002; Akiskal and Mallya, 1987; Akiskal and Akiskal, 1988; Akiskal and Pinto, 1999). This issue brings together the largest number of research reports under one cover devoted to the validation of this broad conceptualization of bipolarity. Preliminary versions of most of these papers were presented at an international conference on ‘The Coming of Age of the Bipolar Spectrum’ which took place in La Jolla, under the auspices of the International Mood Center, University of California at San Diego, in November 2000. These papers have been thoroughly peer-reviewed, and extensively rewritten,
and updated. Several other papers were invited to complete aspects of the spectrum that were not specifically covered in the conference and, likewise, subjected to the same rigorous peer-review process. With the exception of three review articles, and a translation of a classical historical text by Ewald Hecker (on what might be the first clinical description of today’s concept of bipolar II), all papers in this issue report primary data never published before. These data derive from research teams using diverse methodologies, but generally within the external validating principles as formulated by Robins and Guze (1970). As biological markers have been elusive, Table 1 lists validating principles suitable for ascertaining putative clinical bipolar subtypes. The ensemble of data in this monograph should challenge those in the literature (Soares and Gershon, 2000; Baldessarini, 2000) who are skeptical of the existence of a rich research basis for the ‘attenuated’—and highly prevalent—extensions of bipolarity into, among others, the conventional territories of major depressive disorders, anxiety states, cluster B personality disorders, and the subthreshold realm in the community. It is relevant to point out in this context that the concept of at least some, if not extensive, continuity between depressive, related periodic psychopathology, and bipolar disorders has been endorsed (without necessarily invoking a specific bipolar spectrum construct) by many contemporary authorities in the field of affective disorders (Dunner et al., 1976; Mendels, 1976; Bertelsen et al., 1977; Taylor and Abrams, 1980; Klerman, 1981; Gershon et al., 1982; Tsuang et al., 1985; Endicott,
Table 1 Clinical validating principles for a putative bipolar spectrum condition Phenomenology Comorbidity Family History Course Age at onset Temperament Switching Cyclicity Mixity Seasonality
H.S. Akiskal / Journal of Affective Disorders 73 (2003) 1–5
1989; Cassano et al., 1992; McElroy et al., 1996; Manning et al., 1997; Benazzi, 1997; and Ghaemi et al., 2000). The Bipolar Spectrum incorporates overlapping subtypes of bipolar disorder (Akiskal, 1999, 2002). Much of the literature is devoted to bipolar I disorder where a manic or mixed manic state has been documented. The literature is relatively sparse on bipolar II, where depression dominates the clinical course, interspersed with hypomanic episodes which per se do not produce marked dysfunction. Although the Research Diagnostic Criteria (Spitzer et al., 1978) defined the lower operational threshold of hypomania to be 2 days, in DSM-IV (in which bipolar II appeared for the first time in official nosology) this threshold is set at 4 days. Several of the papers published in this special issue are devoted to the validation of the 2-day threshold. Actually, this issue contains 10 papers which address various aspects of hypomania. Many bipolar II patients with brief hypomanias are cyclothymic in temperament, giving rise to boundary questions with atypical depression and cluster B personality disorders. This subject receives extensive coverage in the present issue. Also covered are clinically depressed patients who manifest hypomanic symptoms and / or behaviors during their depression This rather large group of patients with depressive mixed states is essentially ignored within the DSM-IV and ICD-10 diagnostic schemas. As for the diagnostic status of hypomania occurring during antidepressant treatment, it is left in a diagnostic limbo in both DSM-IV and ICD-10. This monograph presents convincing data from a large French national study, as a rationale for their inclusion in the bipolar spectrum as a provisional type III disorder. Related to bipolar II and III are the rapid cycling patients whose course has been examined in a long term follow-up study in Rome and reported in this issue. It is presently unclear whether the foregoing bipolar subtypes represent a clinical or a genetic continuum. Some have argued for the genetic uniqueness of euphoric, remitting and lithium responsive bipolar I (Alda et al., 1994; Duffy and Grof, 2001). It is also possible that bipolar II represents a genetically (MacKinnon et al., 1998) and / or clinically (Perugi and Akiskal, 2002; Rihmer and Pestality,
3
1999) unique subtype. Consideration should also be given to the fact that pleomorphic expressions can occur even within each of the bipolar subtypes. For instance, mania manifests in ‘pure’, depressive, hostile and psychotic presentations, a subject which is covered in the opening paper in the present issue. It is presently unclear whether central ‘activation’ or ‘impulsivity’ underlies these clinical presentations. At least three papers address this question. Another paper, deriving from the NIMH collaborative study database, provides a comparative prospective analysis of bipolar I and II subtypes. A review paper provides an in depth examination of the possible genetic basis of the concept of the bipolar spectrum or alternatives thereof. It is obvious to those working in the field of bipolar disorder that the figure of 1% quoted in the classical epidemiological literature (Regier et al., 1988; Weissman et al., 1996) represents a gross underestimate (summarized in Akiskal, 2002). Although previous research (summarized in Akiskal et al., 2000) has suggested rates of up to 5% for the broadly conceived bipolar spectrum, for the first time definitive data are presented for the entire US population and the canton of Zurich, Switzerland, which place the rates of bipolarity in the community to be even higher than 5%. This is a reflection of several factors. First, nearly 50% of so-called major depressive disorders can be reclassified as bipolar II on the basis of a systematic search for hypomania (Hantouche et al., 1998). Second, the terrain of subclinical bipolarity in the community is now being assessed with more ‘sensitive’ methodology for detecting bipolarity (Hirschfeld et al., 2000). If indeed bipolar illness is the extreme expression of oligogenic inheritance (Gershon, 2000), considerable overlap must exist at the milder end of the spectrum with normality. The diagram (Fig. 1) illustrates this concept in which severity and prevalence are inversely related. Of all the temperaments, cyclothymia is the one most relevant to bipolarity, and in a non-ill Italian population was found to have a prevalence until age 25 of 6.3% (Placidi et al., 1998). Although treatment was not the primary focus of this special issue, such clinically troubling aspects of bipolarity as rapid cycling and exacerbation of mania are in part addressed. Finally, the entire concept of mood stabilization is re-examined, and the special
4
H.S. Akiskal / Journal of Affective Disorders 73 (2003) 1–5
Fig. 1. Community prevalence of bipolar (BP) phenotypes as a function of severity.
psychotherapeutic needs of patients within the bipolar spectrum are considered. While a great deal more research needs to be done in the bipolar spectrum, I submit that this collection of original research papers lays the research based groundwork for future developments. I feel greatly honored that I have had the privilege to collaborate intimately with most of the research teams featured in this special issue. It gives me great satisfaction to see the publication of this collaborative effort, representing both established and upcoming talent from different parts of the world.
Acknowledgements The International Conference from which this special issue in part derives, was supported by an unrestricted educational grant from Eli Lilly & Co.
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