bipolarity from ancient to modern times: conception, birth and rebirth

Journal of Affective Disorders 67 (2001) 3–19www.elsevier.com/ locate / jad

Millennial article

Bipolarity from ancient to modern times:conception, birth and rebirth

a b ,*Jules Angst , Andreas Marnerosa

¨Department of Psychiatry, University of Zurich, Zurich, SwitzerlandbDepartment of Psychiatry and Psychotherapy, Martin-Luther University Halle-Wittenberg, 06097 Halle, Germany

Received 20 October 1999; accepted 6 January 2000

Abstract

We review the history of bipolar disorders from the classical Greek period to DSM-IV. Perhaps the first person whodescribed mania and melancholia as two different phenomenological states of one and the same disease was the Greekphysician of the 1st century AD, Aretaeus of Cappadocia. The modern concept of bipolar disorders was born in France, withthe publications of Falret (1851) and Baillarger (1854). Emil Kraepelin, however, in 1899, unified all types of affectivedisorders in ‘manic-depressive insanity’; in spite of some opposition, Kraepelin’s unitary concept was adopted worldwide. Inthe 1960s, however, the rebirth of bipolar disorders took place through the publications of Jules Angst, Carlo Perris, andGeorge Winokur, who independently showed that there exist clinical, familial and course characteristics validating thedistinction between unipolar and bipolar disorders; in addition, they verified several of the corresponding opinions of theWernicke-Kleist-Leonhard school. The concept of unipolar and bipolar disorders has further advanced in the last threedecades: landmark developments include the renaissance of Kraepelin’s mixed states and of Kahlbaum’s and Hecker’scyclothymia and related affective temperaments, the concept of soft bipolar spectrum (Akiskal), and the distinction ofschizoaffective disorders into unipolar and bipolar forms. 2001 Published by Elsevier Science B.V.

Keywords: Bipolar; Schizoaffective; Cyclothymia; Hypomania; Mixed states; Bipolar spectrum; History

1. The classical period cholia are two of the earliest described humandiseases. Morbid states of depression and exaltation

The origin of the concept of bipolar disorders has were known to the physicians and philosophers ofits roots in the work and views of the Greek the pre-Hippocratic era. Heroes in the poems ofphysicians of the classical period. Mania and melan- Homer were used by ancient Greek physicians and

philosophers (e.g. Aristoteles (1962, 1991) andAretaeus of Cappadocia (1847)) as examples of

*Corresponding author. Tel.: 1 49-345-557-3651; fax: 1 49-mania or melancholia. Hippocrates (460–337 BC),345-557-3607.however, was the first who systematically describedE-mail address: [email protected] (A.

Marneros). mania and melancholia. Hippocrates based his work

0165-0327/01/$ – see front matter 2001 Published by Elsevier Science B.V.PI I : S0165-0327( 01 )00429-3

4 J. Angst, A. Marneros / Journal of Affective Disorders 67 (2001) 3 –19

on the materialistic views of Pythagoras and his those mentioned above through the brain when it1scholars Alcmaeon and Empedocles of Crotona. is ill . . . ’’ .

Alcmaeon may have been the first Greek philosopherand scientist who experimented with the brains of Although the etymology of the term ‘melancholia’animals (Anaxagoras may have done so around the is clear, the origin of ‘mania’ is less so, because ofsame time, 500–400 BC). Alcmaeon tried to find its roots in the mythological area. ‘Melancholia’

´auditory and visual channels to the brain. He thought (‘melas’ means black, and ‘chole’ means bile) wasthat the origin of diseases was the disturbed inter- based on the humoral theories of Alcmaeon ofaction of body fluids with the brain. Alcmaeon’s Crotona and the pre-Hippocratic Greek physicianswork ‘On Nature’ was probably the most fundamen- who explained psychopathological states of severetal text used by pre-Hippocratic writers (Alexander sadness and other mental disorders with an inter-and Selesnick, 1966). action of body liquids, especially bile, and the brain.

Hippocrates supplemented such theories with ex- Later Hippocrates, as well as Aristotle, distinguishedcellent bedside observations as well as longitudinal between the disease ‘melancholia’ (nosos melan-

´follow-up. Psychiatry was one of Hippocrates’ main cholike) and the corresponding personality type´interests and he formulated the first classification of (typos melancholicos). The etymology of ‘mania’ is

mental disorders, namely melancholia, mania and difficult in that the word has a lot of meanings. Itparanoia (Hippokrates, 1897). Hippocratic physi- was used in mythology and poems (e.g. like those ofcians also described organic and toxic deliria, post- Homer) to describe different states. The Romanpartum psychoses and phobias, and coined the term physician Caelius Aurelianus, a member of the‘hysteria’. Furthermore, they made the first attempts Methodist School and a student of Soranus ofto describe personality in terms of their humoral Ephesus, gave in his book ‘On Acute Diseases’theories dividing the different types of personality (Chapter V) at least seven possible etymologies. Heinto choleric, phlegmatic, sanguine and melancholic wrote:(Erich Mendel reactivated Hippocrates’ term ‘hypo-mania’ in 1881). Hippocrates and his school, though ‘‘The school of Empedocles holds that onestrictly biologists, pointed out the relevance for form of madness consists in a purification of thedisease (including mental disease) of biography and soul, and the other in an impairment of the reasonof the social and topographical environment as well resulting from a bodily disease or indisposition. Itas the significance of a strong relationship between is this latter form that we shall now consider. Thephysician and patient (Marneros, 1999). Hippocrates Greeks call it mania because it produces greatassumed the brain as the organ of mental functions, mental anguish (Greek ania); or else becausemental disturbances and mental disorders. In his there is excessive relaxing of the soul or mind, thefamous work ‘On the Sacred Disease’ (i.e. epilepsy) Greek word for ‘relaxed’ or ‘loose’ being manos;he wrote: or because the disease defiles the patient, the

Greek word ‘to defile’ being lymaenein; or be-‘‘The people ought to know that the brain is the cause it makes the patient desirous of being alone

sole origin of pleasures and joys, laughter and and in solitude, the Greek word ‘to be bereft’ andjests, sadness and worry as well as dysphoria and ‘to seek solitude’ being monusthae; or becausecrying. Through the brain we can think, see, hear the disease holds the body tenaciously and is notand differentiate between feeling ashamed, good, easily shaken off, the Greek word for ‘persist-bad, happy . . . Through the brain we become ence’ being monia; or because it makes theinsane, enraged, we develop anxiety and fears, patient hard and enduring (Greek hypo-which can come in the night or during the day, we meneticos).’’ (Caelius Aurelianus, translated bysuffer from sleeplessness, we make mistakes and Drabkin, 1950).have unfounded worries, we lose the ability to

1recognize reality, we become apathetic and we Translation of original Greek and German quotations by Andreascannot participate in social life . . . We suffer all Marneros.

J. Angst, A. Marneros / Journal of Affective Disorders 67 (2001) 3 –19 5

In the classical era four meanings of ‘mania’ were melancholic personality, with genius and creativity.described: Aristotle asked in his book ‘Problemata physica’:

1. A reaction to an event with the meaning of rage, ‘‘ ‘Why are extraordinary men in philosophy,anger or excitation (like Homer in his Iliad who politics or the arts melancholics?’ Hippocratesdescribed ‘Aias maenomenos’, meaning ‘Ajax in himself discussed after examining the famousa rage’) ‘atomical’ philosopher Democritus and after ex-

2. A biologically defined disease (Hippocrates, citing discussions with him, the connection be-Aretaeus of Cappadocia and others) tween melancholia and genius. He addressed to

3. A divine state (Socrates, Plato) the citizens of Abdira the happy message that4. A kind of temperament, especially in its mild their fellow citizen Democritus suffered not from

form (Hippocrates) melancholia but he is simply a genius’’ (Temkin,1985).

Caelius Aurelianus wrote in his book on chronicdiseases: Some authors have claimed that the concept of

mania and melancholia as described by Hippocrates,‘‘In the Phaedrus, Plato declares that there are Aretaeus and other ancient Greek physicians is

two kinds of mania, one involving a mental strain different from the modern concepts (Ackerknecht,that arises from a bodily cause of origin, the other 1959), but this is not correct. Rather, the classicaldivine or inspired, with Apollo as the source of concepts of melancholia and mania were broaderthe inspiration. This latter kind, he says, is now than modern concepts (they included melancholia orcalled ‘divination’, but in early times was called mania, mixed states, schizoaffective disorders, some‘madness’; that is, the Greeks now call it types of schizophrenia and some types of acute‘prophetic inspiration’ (mantice), though in re- organic psychoses and ‘atypical’ psychoses; Mar-mote antiquity it was called ‘mania’. Plato goes neros, 1999).on to say that another kind of divine mania is sent Many classical Greek and Roman physicians, suchby Father Bacchus, that still another, called ‘erotic as Asclepiades (who established Greek medicine ininspiration’, is sent by the god of love and that a Rome), Aurelius Cornelius Celsus (who translatedfourth kind comes from the Muses and is called the most important Greek medical authors into‘protreptic inspiration’ because it seems to inspire Latin), Soranus of Ephesus and his scholar Caeliusmen to song. The Stoics also say that madness is Aurelianus (who wrote down the views of hisof two kinds, but they hold that one kind consists teacher, extensively on phrenitis, mania and melan-in lack of wisdom, so that they consider every cholia), and later Galenus of Pergamos, focussedimprudent person mad; the other kind, they say, their interest on mental disorders, especially melan-involves a loss of reason and a concomitant cholia and mania (Fischer-Homberger, 1968; Alex-bodily affection.’’ (Caelius Aurelianus, translated ander and Selesnick, 1966). However, principally itby Drabkin, 1950). was Aretaeus of Cappadocia who most explicitly

described the intimate link between them.The views of Empedocles regarding the meanings

of the term ‘mania’ have been cited above. But whenSocrates, in Plato’s Phaidros (Phaedrus) said: ‘‘The 2. Aretaeus of Cappadociahighest of all good things are given to us by themania’’ (Platon, 1991), he certainly meant the ‘di- Aretaeus of Cappadocia lived in Alexandria in thevine mania’, and also creativity in some states which 1st century AD (his dates of birth and death are nottoday will be called ‘hypomania’ or ‘hyperthymia’ or known: some authors say he lived from | 30 to 90‘hyperthymic temperament’ (as Jamison (1994) AD, others from 50 to 130 AD). Aretaeus is the mostshows in her book ‘Touched with Fire’). But the prominent representative of the ‘Eclectics’. TheGreeks also associated melancholia, especially Eclectics were strongly influenced by Hippocrates


and they were so called because they were not bound changed into happiness; the patients then de-by any systems of therapy. Eclecticism meant choos- veloped a mania’’.ing the best from many sources, a meaning it still hastoday, especially in psychotherapy. Aretaeus was The position of Aretaeus, as described in his twovery careful in his description of diseases (Aretaeus books, can be summarized as following (Marneros,of Cappadocia, 1847) and he favored observations of 1999):details. He was free of dogma and superstition. In hisbooks ‘On the Aetiology and Symptomatology of 1. Melancholia and mania have the same aetiology,Chronic Diseases’ and ‘The Treatment of Chronic namely disturbances of the function of the brainDiseases’ he described mental disorders very careful- and some other organs.ly. Chapter V in the former book addresses melan- 2. Mania is a worsening of melancholia.cholia, and Chapter VI mania. Mental disorders are, 3. Mania is the phenomenological counterpart ofaccording to Aretaeus (in agreement with Hippoc- melancholia.rates), biological in cause, but he differentiated 4. His concepts of melancholia and mania werebetween a biologically caused melancholia and a broader than the modern concepts: depression,psychologically caused ‘reactive depression’. He psychotic depression, schizoaffective disorders,wrote in Chapter V: mixed states, schizophrenia with affective symp-

tomatology and some organic psychoses wereinvolved.‘‘It has been reported about a man who had

5. He differentiated between melancholia, which is abeen assumed to suffer from an incurable melan-biologically caused disease, and reactive depres-cholia, and the physicians were not able to helpsion, a psychologically caused state.him. But the love of a young girl was able to cure

him. In my opinion he was always in love withIn brief, although Aretaeus’ views on affectiveher but because he thought that she did not have

states were broader than what today we call bipolarany interest in him he became dysphoric and sad,disorder, his connection of mania and melancholiaso that he suffered from melancholia. But he didcan be justifiably considered the first conception ofnot express his feelings to the girl. When he didbipolarity.so, and the girl responded, his sadness, dysphoria

and anger disappeared and he became happy. Inthis sense love was the physician’’.

3. From Aretaeus to Jean-Pierre Falret

Aretaeus was the first to explicitly link mania and The change from mania to melancholia and vicemelancholia (Marneros, 1999). Of his contem- versa was also noted by later authors, after the longporaries, Caelius Aurelianus, though against the view mediaeval night. Wilhelm Griesinger, one of thethat mania and melancholia belong together, none- most important founders of German scientific psychi-theless cited Apollonius, who believed the two atry, also described (1845) the change from melan-affective states were related. Aretaeus conceived cholia to mania, which, in his opinion, is ‘usual’. Hemania and melancholia as two different images of believed that the disease is ‘a circle of both typesone single disease. In Chapter V of ‘On the Aetiology with regular changes’. Griesinger further describedand Symptomatology of Chronic Diseases’ he says: ‘seasonal affective disorders’: melancholia usually

has its beginning in autumn and winter, mania in‘‘ . . . I think that melancholia is the beginning spring. He finally described rapid cycling types of

and a part of mania . . . The development of a affective disorders. Karl Kahlbaum, in introducingmania is really a worsening of the disease (melan- Falret’s term ‘folie circulaire’ into German-speakingcholia) rather than a change into another disease psychiatry (1863), wrote that the observations and. . . In most of them (melancholics) the sadness opinions of Griesinger (1845) were decisive for thebecame better after various lengths of time and development of the concept of the French school.


´Haustgen (1995) mentioned in his history of weeks later he presented it in the Academie de la´ ´bipolar disorders that in the 17th and 18th century Medecine under the title ‘Memoire sur la folie

´Willis (1676), Morgagni (1761) and Lorry (1765) circulaire, form de maladie mentale characterisee par´ ` ´described the recurrent longitudinal association of la reproduction successive et reguliere de l’etat

´ ´mania and melancholia. As Stone (1979) observes, maniaque, de l’etat melancholique, et d’un intervalle´the development of scientific inquiry in the 18th lucide plus ou moin prolonge’. He defined the

century brought significant progress in the under- sequential change from mania to melancholia andstanding of mental disorders: in England, Richard vice versa and the interval in between as an in-Mead (1673–1754) suspected that mania and melan- dependent disease of its own, namely the ‘foliecholia were different aspects of the same process circulaire’ (Angst, 1997a; Langer, 1994; Marneros,(like Aretaeus of Cappadocia). Vincenzo Chiarugi 1999; Pichot, 1995).(1759–1820), in Tuscany, developed a taxonomy Three years after Falret’s first publication Jules

`based on melancholia, mania and amentia (imbecili- Baillarger presented in 1854 his concept of ‘folie aty) and wrote: ‘‘Mania signifies raving madness. The double forme’, both in protocols of a meeting of the

´ ´maniac is like a tiger or a lion, and in this respect Academie de la Medecine and in his paper ‘De la`mania may be considered as a state opposite to true folie a double forme’ (arguing aggressively against

melancholia’’ (Areteaus had expressed himself simi- Falret). Indeed, the conclusions drawn by the twolarly | 2000 years earlier). In the 19th century very different, hostile ‘fathers’ of the concept ofFrench psychiatry rose to preeminence as a conse- bipolar disorders vary considerably: Baillarger as-quence of its careful descriptive psychopathology sumed a type of disease in which mania and melan-(Pichot, 1995). Pinel (1801) and Esquirol (1838) still cholia change into one another but the interval is ofadhered to the traditional concept that manic and no importance. In contrast, Falret involved themelancholic episodes were separate syndromes of interval between the manic and the melancholicmental illness. episode in his concept; even episodes of mania and

melancholia separated by a long interval belongtogether, forming the ‘folie circulaire’.

4. The ‘birth’ of the modern concept of bipolar The real progress from the views of Aretaeus ofdisorder Cappadocia, of Richard Mead, Vincenzo Chiarugi or

Esquirol was Jean-Pierre Falret’s concept of ‘folie`Nevertheless, neither the ancient physicians nor circulaire’; Jules Baillarger’s concept of ‘folie a

the psychiatrists of the 19th century mentioned above double form’ was very similar to the views of hisdrew the conclusion that bipolar disease is an entity teacher Esquirol (Angst, 1997a; Pichot, 1995). The

`of its own. This conclusion was drawn for the first concepts of ‘folie circulaire’ and ‘folie a doubletime in France in the middle of the 19th century at forme’ found widespread distribution in France, and

ˆthe hospital La Salpetriere in Paris by a pupil of very soon also in other European nations, especiallyEsquirol, Jean-Pierre Falret. In 1851 Falret published in the German-speaking countries. In 1863 Karla 14-sentence-long statement in the Gazette des Kahlbaum introduced both terms into German psy-

ˆHopitaux (‘De la folie circulaire ou forme de chiatry in his important book: ‘The Grouping and´maladie mentale characterisee par l’alternative Classification of Mental Disorders’. Kahlbaum sup-

´ ´reguliere de la manie et de la melancholie’). In this ported Falret and opposed Baillarger. In the samestatement Falret described for the first time a sepa- book Kahlbaum pointed out that the observations andrate entity of mental disorder which he named ‘folie opinions of Griesinger (1845), as mentioned above,circulaire’, characterized by a continuous cycle of were of fundamental importance for Falret’s concept.

¨depression, mania and free intervals of varying With his paper ‘Uber cyclisches Irresein’ (‘Onlength. Jean-Pierre Falret completed his concept in Circular Insanity’; Karlbaum, 1882) and inthe following 3 years, and published it in 1854 ‘Katatonia’ (Karlbaum, 1884) Kahlbaum contributed

´(Falret, 1854) in the ‘Lecons cliniques de medecine to its final establishment.` `mentale faites a l’hospice de la Salpetriere’. Some The concept of ‘folie circulaire’ found not only


enthusiastic supporters, but also critical opponents described Falret’s concept of ‘folie circulaire’ as ‘asuch as Ludwig Meyer (1874), who labelled it very well established type of mental disorder’. The‘meaningless’. But 10 years later Kahlbaum (1884) first roots of the unification and development of the

¨presumed that the concept of ‘circulares Irresein’ concept of ‘manic-depressive insanity’ originated at(‘circular insanity’) had finally found general accept- the beginning of the 1890s. In the edition of 1893 theance; this acceptance was demonstrated in other concept is already clear and in 1899 complete. Hecountries by publications in ‘Brain’ (Foville, 1882), wrote in ‘The Clinical Position of Melancholia’:and in the American Journal of Insanity (Hurd, 1884;Angst, 1997a; Langer, 1994; Marneros, 1999; Pichot, ‘‘Unfortunately our textbooks not help us at all1995). in distinguishing between circular depression and

mania in cases where the course itself is notinformative. The description of melancholic states

5. Emil Kraepelin: unification and regression is absolutely identical with that of circular depres-sion and we can hardly doubt that the most

The work of Emil Kraepelin is so fundamental that beautiful and exciting descriptions of melancholiato label him the ‘father of modern psychiatry’ is are mostly derived from observations of circularabsolutely justified. The dichotomy of ‘endogenous’ cases.’’ (Kraepelin, 1899a, p. 328).psychoses into ‘dementia praecox’ and ‘manic-depre-ssive insanity’ (Kraepelin, 1893, 1896) was of And some pages later:critical importance for the development of psychi-atry, in spite of some weaknesses (of which ‘‘Apart from our experience that in a wholeKraepelin himself was aware). In particular his series of manic episodes a depressive one cancontribution to the understanding, diagnosis and occur unexpectedly, and those cases are immense-prognosis of manic-depressive illness was enormous. ly rare in which apart from manic irritability notHowever, the elimination of the distinction between the slightest feature of depression is visible, it isdepressive and circular forms, and the inclusion of absolutely impossible to distinguish these manicall types of affective disorders in the unitary concept episode fits of circular insanity from periodicof manic-depressive illness, proved later to be a step mania. But if periodic mania is identical withback (Angst, 1997a; Marneros, 1999). But it was not circular insanity we cannot deny the possibilityKraepelin himself who was dogmatic, but his epi- that also periodic melancholia, or at least some ofgones (Angst, 1999). Kraepelin himself had serious the cases designated so, must in fact be under-doubts. He expressed his unanswered questions and stood as a kind of circular insanity in which allhe was always seeking solutions, as he demonstrated the episodes take on a depressive hue, just as inin his last important work in 1920, ‘Die periodic mania they all have a manic tinge.’’Erscheinungsformen des Irreseins’ (‘The Phe- (Kraepelin, 1899a, p. 333).nomenological Forms of Insanity’). The unification

¨of ‘circulares Irresein’ (‘circular insanity’) with Contrary to current opinion, Kraepelin himselfdepressive types into ‘manisch-depressives Irresein’ was not rigid concerning his taxonomies or concepts.(‘manic-depressive insanity’) was carried out in two The opposite is true; he was open to persuasion byfundamental publications in 1899: the first of them data-orientated research, even by his own fellows,was ‘Die klinische Stellung der Melancholie’ (‘The and he often revised his concepts. Doubts andClinical Position of Melancholia’), published in the remaining questions regarding his taxonomies and

¨‘Monatsschrift fur Psychiatrie und Neurologie’ concepts were not a taboo, but were discussed in his(Kraepelin, 1899a), and the second was the sixth publications, such as his last very important publi-edition of his handbook (Kraepelin, 1899b). This cation of 1920 cited above. His epigones, however,unification was a new conclusion of Kraepelin, lacking his flexibility, ignored the important contri-which contradicts former opinions. In earlier editions butions of Wernicke, Kleist, Leonhard and others.of his handbook (Kraepelin, 1883, 1887), Kraepelin The consequence was nosologic stagnation for al-


most 70 years with regard to new developments in morphous phasic disorders’ (‘vielgestaltige phasischethe field of bipolar disorders (Angst, 1999; Marneros, Psychosen’). To the last-mentioned category belong1999). manic-depressive illness and the cycloid psychoses

(Leonhard, 1957, 1995). Neither Kleist nor Leonhardconsidered monopolar mania to be a component of

6. The opposition to Kraepelin bipolar disorders in present-day terms. On the con-trary, they described monopolar mania separately

In opposition to Kraepelin’s view in Scandinavia from manic-depressive disorders (Leonhard, 1957).‘depressio mentis periodica’ remained a separate This does not detract from the great significance ofaffective disorder in the work of Lange (1896), their role in stimulating research and paving the wayChristiansen (1919) and Pedersen et al. (1948). for further development (Angst, 1997a; Marneros,Benon (1926) proposed separating periodic depres- 1999).sion from manic-depressive disorder but met with The classification of Wernicke, Kleist andlittle approval. Leonhard was nevertheless very complicated, with

Kraepelin’s unification of all affective disorders its multiple subgroups and distinctions, and did notwithin the concept of manic-depressive illness also find broad acceptance. Unfortunately, one of thecaused strong opposition in Germany, especially most important aspects of their system, namely theunder the leadership of Carl Wernicke and later also unipolar /bipolar distinction, remained largely unre-his colleague in Halle, Karl Kleist. Wernicke dif- cognized by international psychiatry.ferentiated very subtly the different kinds of affectivesyndromes. For example, he distinguished five differ-ent types of melancholia: affective melancholia, 7. The ‘rebirth’ of bipolar disorderdepressive melancholia, melancholia agitata, melan-cholia attonita and melancholia hypochondriaca The rebirth of bipolar disorders occurred in 1966(Wernicke, 1900, 1906). He challenged Kraepelin’s with two important publications. The first was theopinion that melancholia is only a part of the manic- monograph of Jules Angst in Switzerland: ‘Zur

¨depressive illness. In Wernicke’s opinion manic-de- Atiologie und Nosologie Endogener Depressiverpressive illness should only be understood as de- Psychosen’ (‘On the Aetiology and Nosology ofscribed by Falret (folie circulaire) or by Baillarger Endogenous Depressive Psychoses’). The second

`(folie a double forme). Single episodes of mania or was published some months later in a supplement ofmelancholia respectively, recurrent depression or Acta Psychiatrica Scandinavica by Carlo Perrisrecurrent mania without changing into one another (partly in cooperation with d’Elia) with the title: ‘Aare something different from manic-depressive in- Study of Bipolar (Manic-Depressive) and Unipolarsanity (Wernicke, 1900). The opinion of Wernicke Recurrent Depressive Psychoses’ (Perris, 1966).was the basis for the work of his fellows, such as Both publications supported, independently of oneKleist, Neele and Leonhard (Angst, 1997a, 1999; another, the nosological differentiation between un-Marneros, 1999; Pillmann et al., 2000). ipolar and bipolar disorders. Thus, 67 years after

Karl Kleist (a colleague of Wernicke in Halle and Kraepelin’s creation of ‘manic-depressive insanity’later head of the university hospitals in Rostock and and some 150 years after Falret’s and Baillarger’sFrankfurt) opposed Kraepelin’s concept of manic- statements, the concept of bipolar disorders ex-depressive insanity. Kleist differentiated between perienced a ‘rebirth’ (Pichot, 1995). Due to the workunipolar (‘einpolig’) and bipolar (‘zweipolig’) affec- of Angst and Perris, as well as that of Winokur et al.tive disorders (Kleist, 1911, 1926, 1928, 1953). The (1969), who published similar findings in a mono-concepts of Wernicke and Kleist were completed by graph 3 years later in the USA (Winokur andKarl Leonhard (a collegue of Kleist and later head of Clayton, 1967), not only Falret’s and Baillarger’s

´the Charite in Berlin), who classified the ‘phasic concepts have been replicated, completed and de-psychoses’ into ‘pure phasic psychoses’ (such as veloped, but also essential aspects of the work of‘pure melancholia’, ‘pure mania’, etc.) and ‘poly- Wernicke (1900, 1906), Kleist (1928), Leonhard


(1934, 1937, 1957), Neele (1949) and others. There- grouped cyclothymia together with dysthymia andfore, the year 1966 can be seen as the ‘year of rebirth hyperthymia as ‘partial mental disorder’ (‘partielle

¨of bipolar disorders’ (Marneros et al., 1991; Mar- Seelenstorungen’) with ‘non-degenerative outcome’.neros, 1999; Pichot, 1995). By ‘cyclothymia’ Kahlbaum meant the mildest type

The study of Jules Angst was based on inves- of bipolar disorder, a definition which was acceptedtigations on 326 patients, treated between 1959 and also by Hecker (1898) and by Kraepelin (1899b),1963 at the University Hospital of Zurich (Burgh- together with other authors at the beginning of theolzli). The four most important conclusions of this 20th century. Jelliffe (1911) imported the opinions ofstudy were: Hecker, Kahlbaum, Falret and Kraepelin to the

American psychiatric literature with his work1. Genetic and environmental factors have a syner- ‘Cyclothymia — The Mild Forms of Manic-Depres-

gic impact on the aetiology of endogenous de- sive Psychoses and the Manic-Depressive Constitu-pression. tion’. Ernst Kretschmer and Kurt Schneider con-

2. Gender plays an important role in the aetiology of tributed to a dichotomy of the term ‘cyclothymia’.endogenous depression. There is a relationship Kretschmer, in his fundamental work ‘Body Consti-

¨between female gender and endogenous depres- tution and Character’ (‘Korperbau und Charakter’)sion, but bipolar disorders are equally represented (1921–1950), described the ‘cyclothymic averagein males and females. man’ and the cycloid temperaments. Cyclothymia is,

3. Manic-depressive illness is nosologically not in his opinion, ‘‘a broad constitutional overtermhomogeneous. Unipolar depression differs sig- involving health and disease in the same way’’. Innificantly from bipolar disorders in many charac- contrast, Schneider (1950–1992) accepted this termteristics such as genetics, gender, course and only for diseases, and he used it synonymously withpremorbid personality. manic-depressive illness. His influence is still extant

4. Late-onset depression (Kraepelin’s ‘Involution- in Germany, so that two meanings of cyclothymiasmelancholie’) seems to belong to unipolar de- persist: manic-depressive illness (increasingly rare)pression and has only a weak relationship to and cyclothymia according to ICD-10 and DSM-IVbipolar disorders. (increasingly common). The boundaries of

cyclothymia as a disorder of the bipolar spectrum orThe study of Perris was carried out between 1963 as a disorder of temperament or personality are not

and 1966 in Sidsjon Mental Hospital, Sundsfall, fully established (Akiskal et al., 1977, 1979, 1995;Sweden on 280 patients. Perris’ findings were very Akiskal, 1994, 1996). Thus it is not absolutely clearsimilar to those of Angst (Angst and Perris, 1968). whether a labile-cyclothymic temperament can beThey showed also that ‘unipolar mania’ is genetic- clinically distinguished from bipolar II (Akiskal etally very strongly related to bipolar disorders, so that al., 1995; Marneros, 1999).clinical and genetic factors support the assumptionthat the separation of the group of unipolar mania isan artefact. 9. Hypomania

Hypomania was described, conceptualized and8. Cyclothymia named by Erich Mendel in 1881 in his book ‘Die

Manie’ (oriented on Hippocrates, the first to use theCyclothymia also belongs to the group of bipolar term ‘hypomaenomenoi’, i.e. ‘hypomanics’) to char-

disorders. ‘Cyclothymia’ is an old and controversial acterize a type of hyperthymic personality.term (Brieger and Marneros, 1997a,b,c; Marneros, Mendel wrote: ‘‘I recommend (taking under con-1999), first published by Hecker (1877), but coined sideration the word used by Hippocrates ‘u(p-by his teacher and brother-in-law Kahlbaum. He omaino/menoi)’ the types of mania, having a lowerdescribed with the term (‘Cyklothymie’) periodic intensity of its phenomenological picture, to namechanges of depression and ‘exaltation’. Kahlbaum them hypomania’’ (Mendel, 1881, p. 109).


C.G. Jung, in an early publication (Jung, 1904), ‘cases-in-between’ were a problem for him, a nuis-recorded in detail a number of cases of manic mood ance, but on the other hand an interesting conundrumchanges (‘manische Verstimmung’) in patients char- to be solved. As is well known, Kraepelin dichotom-acterized by a stable submanic complex of symp- ized the so-called endogenous psychoses into twotoms, which had mostly developed in youth and groups, namely ‘dementia praecox’ (with a poorlasted many years without remission. Jung found that outcome) and the ‘manic-depressive insanity’ (with aexacerbations could occur in the course of the favourable outcome). But he already knew that notdisorder and saw social restlessness and social all cases of endogenous mental disorders can readilyproblems, alcoholism, delinquency, and what he be classified into the two categories. Some cases oftermed ‘moral insanity’, characterizing these patients mixed states, delirious mania and other mentalas submanic symptoms. The symptoms described by disorders described by Kraepelin (1893, 1920) couldJung would correspond to today’s hyperthymia or be allocated to either category or to neither of them.very mild mania. Hypomania won more relevance in In a critical appraisal of his own taxonomy,the last few decades due to the descriptions of Kraepelin wrote in his important paper of 1920, ‘Diebipolar II disorders (Dunner et al., 1976), recurrent Erscheinungsformen des Irreseins’ (‘The Phe-brief hypomania (Angst, 1997b) and its relationship nomenological Forms of Insanity’), that mentalwith hyperthymic temperament (Akiskal, 1992; Ak- disorders can have elements of both groups of mentaliskal and Akiskal, 1992). disorders, namely ‘dementia praecox’ and ‘manic-

depressive insanity’ and they also can have a differ-ent course and a different prognosis than ‘dementia

10. Expanding the group of bipolar disorders praecox’. He knew that the boundaries between thetwo groups of mental disorders are elastic and that

After experiences in pharmacotherapy and prophy- there are bridges connecting them. His doubtslaxis of unipolar and bipolar disorders, intensive became stronger in the wake of an investigation byresearch on this topic began. One of the many his pupil and collegue Zendig. Zendig reported in hisimportant consequences was the ‘expansion’ of the paper ‘Contributions to Differential Diagnosis ofgroup of bipolar and unipolar disorders, as well as Manic-Depressive Insanity and Dementia Praecox’the knowledge that they are not homogeneous (Mar- (Zendig, 1909) that | 30% of Kraepelin’s sampleneros, 1999b). The most important expansions con- diagnosed with ‘dementia praecox’ (usingcern the following points: Kraepelin’s guidelines) had a course and outcome

not corresponding to that of ‘dementia praecox’;1. The distinction of schizoaffective disorders into Zendig attributed the good outcome to an incorrect

unipolar and bipolar as well as mixed types diagnosis. Later Kraepelin saw in such cases a2. The renaissance of Kraepelin’s mixed states weakness of his dichotomy concept. He wrote: ‘‘The3. The renaissance of Kahlbaum’s and Hecker’s cases which are not classifiable (namely to manic-

concept of cyclothymia and other bipolar spec- depressive insanity or dementia praecox) are un-trum disorders fortunately very frequent’’ (Kraepelin, 1920, p. 26).

Two pages later he made a decisive and for him10.1. Schizoaffective disorders certainly not an easy statement: ‘‘We have to live

with the fact that the criteria applied by us are notKarl Kahlbaum can be considered the first sufficient to differentiate reliably in all cases between

psychiatrist in modern times to describe schizoaffec- schizophrenia and manic-depressive insanity. Andtive disorders as a separate group in ‘vesania typica there are also many overlaps in this area’’ (i.e.circularis’ (Kahlbaum, 1863). For this definition between schizophrenia and affective disorders;Kahlbaum applied cross-sectional and longitudinal Kraepelin, 1920, p. 28).aspects. Emil Kraepelin was also acquainted with As early as 1966, Jules Angst investigated thecases between ‘dementia praecox’ and ‘manic-depre- schizoaffective disorders, under the term ‘Mis-ssive insanity’ (Kraepelin, 1893, 1896, 1920). These chpsychosen’ (‘mixed psychoses’), as a part of the


affective disorders (Angst, 1966). This was an rooted in the work of the Greek physicians ofoutlier’s position, not only against the ‘Zeitgeist’, but classical times, especially Hippocrates (460–337also contrary to the opinion of his teacher Manfred BC) and Aretaeus of Cappadocia (1st century AD).Bleuler, who assumed them to be a part of schizo- In 1852, Pohl, in Prague, described in a largephrenia. Later investigations by Angst et al. (1979, monograph on melancholia mixed states occurring1989, 1990), by Clayton et al. (1968), by other during the transition from melancholia to maniamembers of the Winokur group (Fowler et al., 1972), (Pohl, 1852, pp. 121, 127), ‘poriomanic’ melancholiaby Cadoret et al. (1974) and the comparative studies (p. 186) and marked anxiety states as transitionalof Marneros et al. (1986a,b,c, 1988a,b,c, 1989a,b,c, phenomena of depression (pp. 111–121). He also1991) supported more and more the opinion that the described rapid cycling between melancholia andrelationship between schizoaffective and affective brief mania (p. 111), later described as a moredisorders is stronger than that between schizoaffec- regular alternation of cyclicity by Focke (1862), astive and schizophrenic disorders. lasting 3–4 weeks by Jules Falret (1879), pp. 58, 66)

Studies in the last three decades (Angst, 1989; or just a few (6) days by Kelp (1862).¨Marneros, 1999; Marneros et al., 1989a,b,c, Kraepelin used the term ‘Mischzustande’ (‘mixed

1990a,b,c, 1991) have yielded evidence as follows: states’) resp. ‘Mischformen’ (‘mixed forms’) for thefirst time in the fifth edition of his textbook

1. Schizoaffective disorders should be separated into (Kraepelin, 1896, p. 634) and conceptualized themunipolar and bipolar disorders, like affective definitively in the sixth edition (Kraepelin, 1899b).disorders. Kraepelin, as well as his pupil Wilhelm Weygandt,

2. Bipolar schizoaffective disorders have a stronger described in 1899 six types of mixed statesrelationship to bipolar affective disorders than (Weygandt, 1899):either group has to unipolar schizoaffective dis-orders. 1. Depressive or anxious mania (‘depressive oder

angstliche Manie’)Marneros and co-workers proposed that bipolar 2. Excited or agitated depression (‘agitierte Depres-

schizoaffective disorders belong together with bipo- sion’)lar affective disorders, and unipolar schizoaffective 3. Mania with thought poverty (‘ideenarme Manie’)together with unipolar affective disorders, in two 4. Manic stupor (‘manischer Stupor’)voluminous groups (Marneros et al., 1990a,b,c, ¨5. Depression with flight of ideas (‘ideenfluchtige1991; Marneros, 1999). Depression’)

6. Inhibited mania (‘gehemmte Manie’)10.2. Mixed states

Kraepelin further distinguished two groups ofIn recent years there has been renewed interest in

mixed states:mixed states or mixed bipolar disorders, especially inthe USA (Himmelhoch et al., 1976; Post et al., 1989;

1. ‘Transition forms’ — a stage-in-between, whenAkiskal, 1992a,b, 1996; McElroy et al., 1992; Bauerdepression changes into mania or vice versaet al., 1994b), but also in Italy (the Pisa group,

2. ‘Autonomic forms’ — a disorder of its ownPerugi et al., 1997), in France (the EPIMAN study,Akiskal et al., 1998), and in Germany (Marneros etal., 1991, 1996a,b, Marneros, 1999). Although the An interesting enrichment — really the first newcreator of the concept is doubtless Emil Kraepelin, conceptual aspect since 1899 — was contributed bywith the assistance of his co-worker Wilhelm Akiskal, based on Kraepelin’s ‘mixed concept’ (Ak-Weygandt (Weygandt, 1899; Marneros, 1999, 2001), iskal, 1992a,b, 1996; Akiskal and Mallya, 1987).such disorders were observed and described much Kraepelin suggested a mixing of manic or depressiveearlier. The first descriptions of mental disorders symptoms with cyclothymic, hyperthymic or depres-which could be characterised as ‘mixed states’ are sive temperament. The mixing of symptoms and


temperament created in Akiskal’s view, three differ- recently, brief hypomania, lying under the thresholdent types of mixed states: of DSM-IV hypomania, with a duration of as little as

1–3 days, has been described, and there is also some• Depressive temperament 1 manic psychosis evidence for a valid subcategory of recurrent brief• Cyclothymic temperament 1 depression hypomania (Angst, 1990, 1997a,b,c; Angst et al.,• Hyperthymic temperament 1 depression 1990; Angst and Merikangas, 1997).

Over the past 20 years Akiskal has providedIt is noteworthy that in the scheme of Akiskal evidence, based on good clinical observation and

(1992b), mixed states (at least the first and last types) sound knowledge of the classical literature, for thearise when an episode arises from a temperament of desirability of enlarging the continuum to encompassopposite polarity. Partial support for the foregoing several diagnostic subgroups, including what heschema has derived from collaborative research terms the ‘soft’ bipolar spectrum (Akiskal, 1983a,conducted in Italy and France (Dell’Osso et al., 1996; Akiskal and Mallya, 1987; Akiskal and Pinto,1991, 1993; Perugi et al., 1997; Akiskal et al., 1998). 1999). A new concept includes ‘pseudo-unipolarThere is also increasing support for the idea that disorders’, defined as recurrent depressions withoutsubthreshold admixtures of depression with mania — spontaneous hypomania but often with bipolar familyor hypomanic intrusions into major depression — history; alternatively considered bipolar III, thisrepresent sufficient grounds for the diagnosis of category refers to recurrent depression switching tomixed states (Akiskal and Mallya, 1987; Bauer et al., hypomania under antidepressant treatment. Bipolar1994b; McElroy et al., 1995; Perugi et al., 1997; IV describes major depressions superimposed onAkiskal et al., 1998). hyperthymic temperament. Akiskal and Pinto (1999),

In the last two decades has also been described a to emphasize the concept of a continuum within this‘mixed type of schizoaffective disorders’, which is a broad spectrum, have actually made provision for

1]combination of mixed bipolar affective disorders and intermediary forms, such as bipolar I (protracted2

1]schizophrenic symptoms (Marneros et al., 1986a,b,c, hypomania), bipolar II (cyclothymic2

1]1988a,b,c, 1991, 1996a,b). The mixed type of temperament 1 major depression), and bipolar III 2

schizoaffective disorder is analogous to the mixed (major depression 1 stimulant abuse).type of affective disorders (Marneros, 1999). There are several problems with the concept of a

bipolar spectrum. One is that hypomanic symptomsin ‘drug-induced hypomania’ have not been the

11. Bipolar spectrum object of systematic assessment in clinical trials ofantidepressants and there is no proof coming from

The concept of a continuum of manic conditions placebo-controlled studies. However, prospectivedeveloped by Kretschmer (1921–1950) and Eugen follow-up studies indicate that depressions withBleuler (1922) has undergone various modern at- hypomania first manifested on antidepressants, oftentempts at elaboration into subtypes (Angst, 1997a; progresses to bipolar disorder (Akiskal et al., 1979,Marneros, 1999). Klerman (1981) distinguished six 1983a,b; Strober and Carlson, 1982). The moresubtypes of bipolar disorders: mania, hypomania, serious problem with the concept of a bipolarhypomania or mania precipitated by drugs, spectrum is that family studies do not fully support itcyclothymic personality, depression with a family (Coryell, 1999). Thus, as proposed by Akiskalhistory of bipolar disorder, and mania without de- (1996), the spectrum concept refers to a clinicalpression. Dunner et al. (1976) distinguished depres- rather than a genetic spectrum.sions with hypomania (bipolar II) from those with Although somewhat controversial, there is emerg-mania (bipolar I). Angst (1978) based his approach ing consensus that a rapid-cycling course, oftenon a continuum distinguishing between hypomania associated with excessive antidepressant use, belongs(m), cyclothymia (md), mania (M), mania with mild to the realm of broadly conceived bipolar disordersdepression (Md), mania and major depression (MD), (Koukopoulos et al., 1980; Wehr and Goodwin,and major depression and hypomania (Dm). More 1987; Coryell et al., 1992; Bauer et al., 1994a).


There is good evidence supporting Kraepelin’s disorders (Akiskal et al., 1985) needed further clarifi-assumption that subjects with ‘manic-type’ (hyper- cation. The modern concept of a bipolar spectrumthymic) temperaments belong to the bipolar spectrum would embrace all these conditions and include the(Akiskal, 1992a; von Zerssen et al., 1996). In hyperthymic and cyclothymic temperaments (Akisk-addition, certain subtypes of personality disorders al, 1983a, 1996). Marneros (1999) further suggested(‘histrionic-sociopathic’ or ‘borderline-narcissistic’) a continuum between normal fluctuations of anmay also belong to cyclothymic temperaments (Ak- ‘adjustable homeostasis’ of affectivity all the way upiskal et al., 1977; Akiskal, 1981, 1994; Akiskal et al., to highly psychotic disorders (Fig. 1).1985). The borderline concept propounded by Ker- A proposal for a psychotic continuum was obvi-nberg (1967, 1975) has given further impetus to ously supported by operational data (see also contri-research into bipolar disorder in the work of Stone butions in Marneros et al., 1995).(1979, 1980) who, through careful family study,showed borderline disorder to be closer to manic-depressive disorder than to the schizophrenic spec- 12. Future worktrum. The affiliation to manic-depressive disorderwould also explain the high suicidality in borderline Research into the subgroups of bipolar disorders isstates. But there are difficulties in identifying this undoubtedly still in its infancy. Most studies have sosubtype of borderline personality as indicated by far been restricted to mania and have reported, forGunderson and Phillips (1991): boundaries between instance, low lifetime prevalence of bipolar disorderborderline disorders and recurrent and labile mood (0.2–1.6%; Picinelli and Gomez Homen, 1997). The

Fig. 1. Bipolar and unipolar continuum (Marneros, 1999).


inclusion of hypomania, brief hypomania and Such a broad spectrum concept of bipolarity —cyclothymic disorders raises the rates to 3–7% contemporaneously reborn in the clinical work of(Angst, 1995a,b, 1998) and underlines the signifi- Akiskal (1983a) and the epidemiologic research ofcance of the ‘soft bipolar spectrum’ (Akiskal and Angst (1998) — has received endorsement in theMallya, 1987). Further studies are needed in order to classic modern monograph of Goodwin and Jamisondistinguish clearly between hyperthymic and (1990).cyclothymic temperaments on the one hand andrecurrent brief hypomania or recurrent briefcyclothymia on the other. The same is true for the

Referencessubgroups M, Md, MD, DM, md, m (Angst, 1978), aclassification that moves beyond the dichotomy

Ackerknecht, E.H., 1959. A Short History of Psychiatry. Hafner,between bipolar I and bipolar II disorders. In 1976New York, S. Wolff, Trans.Dunner and co-workers distinguished bipolar II from

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bipolarity from ancient to modern times: conception, birth and rebirth

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