Copyright ª Blackwell Munksgaard 2002

Bipolar Disorders 2002: 4(Suppl. 1): 11–14 BIPOLAR DISORDERS

ISSN 1399-2406

Review Article

A new bipolar spectrum concept: a brief review

Angst J, Gamma A. A new bipolar spectrum concept: a brief review. Jules Angst* and Alex Gamma
Bipolar Disord 2002: 4(Suppl. 1): 11–14. ª Blackwell Munksgaard, 2002 Zurich University Psychiatric Hospital, Zurich,
Switzerland
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 Key words: bipolar-II disorder – definition –
element of the bipolar spectrum are also summarized. 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 à 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 sub-
groups of the suggested bipolar spectrum.
* Presenting author
The definition of mania is relatively well estab-
lished, 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 fundamen-
tally 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 con-
servatively, adds overactivity to euphoria and irrit-
ability 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

11
Angst and Gamma
(no minimum duration) characterized by the pres-
ence 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 sus-
pected (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 dis-
order was the most prevalent affected phenotype in
both bipolar I and bipolar II familiesÕ.
12
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 occur-
rence of hypomania ⁄ mania, age of onset, recur-
rence, 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 hypo-
mania. 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 drug-
induced 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 improve-
ment 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 placebo-
treated 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

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 subthresh-
old bipolar ⁄ hypomanic disorders show a preva-
lence 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 Lewin-
sohn 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.
Validity of the bipolar spectrum
For validation purposes, the Zurich study com-
pared 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).
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.
Conclusions
Research in bipolar disorders is dominated cur-
rently 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 unsatisfac-
tory, and requires revision on the basis of sound
data obtained from more methodologically ori-
entated epidemiological and clinical research. Re-
search 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 psycho-
pathology and treatment, including comorbidity
with anxiety disorders and substance abuse ⁄
dependence.
Acknowledgements
This work was supported by Grant 3200-050881.97 ⁄ 1 of the
Swiss National Science Foundation.
References
1. Angst J, Gamma A, Benazzi F, Ajdacic-Gross V, Eich D,
Rössler HW. Toward a re-definition of subthreshold
bipolarity: epidemiology and proposed criteria for bipolar-
II, minor bipolar disorders and hypomania. J Affect
Disord 2002: (in press).
2. Angst J, Hantouche E. Epidemiologı́a del trastorno
bipolar menor y de la hipomanı́a: un territorio nuevo. In:
Vieta E ed. Hipomanı́a. Madrid: Bibliothecas Aula
Médica, 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 caractérisée par l’alternative régulière de la manie
et de la mélancholie. Bull Acad Med 1854; 19: 382.
5. Baillarger J. De la folie à double forme. Ann Med Psychol
1854; 6: 369–384.
6. Kleist K. Die Gliederung der neuropsychischen Erkrank-
ungen. Monatsschr Psychiatr Neurol 1953; 125: 526–554.
13
Angst and Gamma
7. Neele E. Die phasischen Psychosen nach ihrem Er-
scheinungs- 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 de-
pressiver Psychosen. Eine genetische, soziologische und
klinische Studie. Berlin: Springer, 1966.
10. Perris C. A study of bipolar (manic-depressive) and uni-
polar 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 develop-
ment 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, Lopez-
Ibor JJ, Sartorius N eds. Bipolar Disorder. Chichester:
Wiley, 2002: 1–52.
15. Angst J. Recurrent brief psychiatric syndromes of depres-
sion, hypomania, neurasthenia, and anxiety from an epi-
demiological 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 clinician-
assessment 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 hyperthy-
mic 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, Möller H-J,
Hirschfeld R. Re-evaluating the prevalence of and diag-
nostic 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
14
Early Adolescent Bipolar Disorder. New York: Guilford
Press, 2002: in press.
24. Weissman MM, Bruce LM, Leaf PJ et al. Affective dis-
orders. In: Robins LN, Regier DA eds. Psychiatric Dis-
orders in America. The Epidemiologic Catchment Area
Study. New York: The Free Press, 1990: 53–80.
25. Wittchen H-U, Nelson CB, Lachner G. Prevalence of
mental disorders and psychosocial impairments in adoles-
cents and young adults. Psychol Med 1998; 28: 109–126.
26. Szadoczky E, Papp Z, Vitrai J, Rihmer Z, Füredi J. The
prevalence of major depressive and bipolar disorders in
Hungary. Results from a National Epidemiologic Survey.
J Affect Disord 1998; 50: 153–162.
27. 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.
28. Allilaire J-F, Hantouche E-G, Sechter D et al. Fréquence
et aspects cliniques du trouble bipolaire II dans une
étude multicentrique française: EPIDEP. Encéphale 2001;
XXVII: 149–158.
29. Benazzi F, Akiskal HS. Refining the evaluation of bipolar
II. Beyond the strict SCID-CV guidelines for hypomania.
J Affect Disord 2002; in press.
30. Simpson SG, Folstein SE, Meyers DA et al. The most
common bipolar phenotype? Am J Psychiatry 1993; 150:
901–903.
31. 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.
32. Angst J. Switch from depression to mania – a record study
over decades between 1920 and 1982. Psychopathology
1985; 18: 140–154.
33. Angst J. Switch from depression to mania, or from mania
to depression. J Psychopharmacol 1987; 1: 13–19.
34. Angst J. Switch from depression to mania, or from mania
to depression. Role of psychotropic drugs. Psychophar-
macol Bull 1987; 23: 66–67.
35. 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].
36. Angst J, Sellaro R. Historical perspectives and natural his-
tory of bipolar disorder. Biol Psychiatry 2000; 48: 445–457.
37. Stassen HH, Angst J, Delini-Stula A. Delayed onset of
action of antidepressant drugs? Survey of recent results.
Eur Psychiatry 1997; 12: 166–176.
38. American Psychiatric Association. Diagnostic and Statis-
tical Manual of Mental Disorders (DSM-IV). Washington,
DC: American Psychiatric Association, 1994.
39. World Health Organization. The ICD-10 Classification of
Mental and Behavioural Disorders. Clinical Descriptions
and Diagnostic Guidelines. Geneva: World Health Orga-
nization, 1992.