. 16
( 68 .)


bipolar disorder in two adults with profound mental retardation. J. Intellect. Disabil. Res.,
(36), 269“81.
Maj, M. (2001). Diagnosis and treatment of rapidly cycling bipolar disorder. Eur. Arch.
Psychiatry Clin. Neurosci., 251 (suppl. 2), II62“5.
Maj, M., Magliano, L., Pirozzi, R., Marasco, C., and Guarneri, M. (1994). Validity of rapid
cycling as a course specifier for bipolar disorder. Am. J. Psychiatry, 151, 1015“19.
Marneros, A. and Angst, J. (2000). Bipolar Disorders. 100 Years After Manic-Depressive Insanity.
Dordrecht: Kluwer.
McCandless, F., Jones, I., Harper, K., and Craddock, N. (1998). Intrafamilial association of
pericentric inversion of chromosome 9, inv(9)(p11-q21), and rapid cycling bipolar disorder.
Psychiatr. Genet., 8, 259“62.
McKeon, P., Manley, P., and Swanwick, G. (1992). Manic depressive illness I: Clinical char-
acteristics of bipolar sybtypes. Irish J. Psychol. Med., 9, 6“9.
Moller, H. J. and Grunze, H. (2000). Have some guidelines for the treatment of acute bipolar
depression gone too far in the restriction of antidepressants? Eur. Arch. Psychiatry Clin.
Neurosci., 250, 57“68.
Nierenberg, A. A., Gray, S. M., and Grandin, L. D. (2001). Mood disorders and suicide. J. Clin.
Psychiatry, 62 (suppl. 25), 27“30.
Nurnberg, J. I. Jr., Guroff, J. J., Hamovit, V., Berrettini, W., and Gershon, E. (1988). A family
study of rapid cycling bipolar illness. J. Affect. Disord., 115, 87“91.
86 O. Elhaj and J. R. Calabrese

Oomen, H. A., Schipperijn, A. J., and Drexhage, H. A. (1996). The prevalence of affective
disorder and in particular rapid cycling bipolar disorder in patients with abnormal thyroid
function tests. Clini. Endocrinol., 45, 215“23.
Perugi, G., Micheli, C., Akiskal, H. S., et al. (2000). Polarity of the first episode, clinical
characteristics, and course of manic depressive illness: a systematic retrospective investigation
of 320 bipolar I patients. Compr. Psychiatry, 41, 13“18.
Post, R. M., Kramlinger, K. G., Joffe, R. T., et al. (1997). Rapid cycling bipolar affective disorder:
lack of relation to hypothyroidism. Psychiatry Res., 72, 1“7.
Post, R. M., Frye, M. A., Denicoff, K. D., et al. (2000). Emerging trends in the treatment of rapid
cycling bipolar disorder: a selected review. Bipolar Disord., 2, 305“15.
Regier, D. A., Farmer, M. F., Rae, D. S., et al. (1990). Comorbidity of mental disorders with
alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) study.
J. A. M. A., 264, 2511“18.
Sachs, G. S., Koslow, C. L., and Ghaemi, S. N. (2000a).The treatment of bipolar depression.
Bipolar Disord., 2, 256“60.
Sachs, G. S., Printz, D. J., Kahn, D. A., Carpenter, D., and Docherty, J. P. (2000b). The expert
consensus guideline series: medication treatment of bipolar disorder 2000. Postgrad. Med.,
Special no., 1“104.
Sachs, G. S., Yan, L. J., Swann, A. C., and Allen, M. H. (2001). Integration of suicide prevention
into outpatient management of bipolar disorder. J. Clin. Psychiatry, 62 (suppl. 25), 3“11.
Schraufnagel, C. D., Brumback, R. A, Harper, C. R. and Weinberg, W. A. (2001). Affective illness
in children and adolescents: patterns of presentation in relation to pubertal maturation and
family history. J. Child Neurol., 16, 553“61.
Schreiner, R., Mirisch, S., Vesely, Z., and Wiegand, M. H. (2001). Sleep and sleep“wake cycle in
an 81-year-old patient with de novo ultra-rapid cycling bipolar disorder. Eur. Arch. Psychiatry
Clin. Neurosci., 251, 29“31.
Shen, Q. (1992). [A comparative study of rapid and non“rapid cycling types in bipolar affective
disorder.] Chung Hua Shen Ching Shen Ko Tsa Chih, 25, 199“202, 252.
Sonne, S. C., Brady, K. T., and Morton, W. A. (1994). Substance abuse and bipolar affective
disorder. J. Nerv. Ment. Dis., 182, 349“52.
Suppes, T., Leverich, G. S., Keck, P. E., et al. (2001). The Stanley foundation bipolar treatment
outcome network, 2: demographics and illness characteristics of the first 261 patients. J. Affect.
Disord., 67, 45“59.
Swann, A. C. (2001). Prediction of treatment response in acute mania: controlled clinical trials
with divalproex. Encephale., 27, 277“9.
Swann, A. C., Bowden, C. L., Calabrese, J. R., Dilsaver, S. C., and Morris, D. D. (2000). Mania:
differential effects of previous depressive and manic episodes on response to treatment. Acta
Psychiatr. Scand., 101, 444“51.
Tondo, L., Baldessarini, R. J., and Floris, G. (2001). Long-term clinical effectiveness of lithium
maintenance treatment in types I and II bipolar disorders. Br. J. Psychiatry, 41(suppl.),
Veit, S. E., Faedda, G. L., Lachman, H. M., and Papolos, D. F. (1998). Rapid-cycling bipolar
disorder: does homozygosity for the COMT low activity allele represent a risk factor for the
87 Rapid-cycling bipolar disorder

development of rapid cycling? New research abstract 454. American Psychiatric Association
1998 Annual Meeting Scientific Program, 191.
Viguera, A. C., Baldessarini, R. J., and Tondo, L. (2001). Response to lithium maintenance
treatment in bipolar disorders: comparison of women and men. Bipolar Disord., 3, 245“52.
Voderholzer, U., Weske, G., Ecker, S., et al. (2002). Neurobiological findings before and during
successful lithium therapy of a patient with 48-hour rapid-cycling bipolar disorder.
Neuropsychobiology, 45 (suppl. 1), 13“19.
Walden, J., Schaerer, L., Schloesser, S., and Grunze, H. (2000). An open longitudinal study of
patients with bipolar rapid cycling treated with lithium or lamotrigine for mood stabilization.
Bipolar Disord, 2, 336“9.
Wehr, T. A., Sack, D. A., Rosenthal, N. E., and Cowdry, R. W. (1988). Rapid cycling affective
disorder: contributing factors and treatment responses in 51 patients. Am. J. Psychiatry,
145, 179“84.
Weske, G., Berger, M., Riemann, D., and Voderholzer, U. (2001). Neurobiological findings in a
patient with 48-hour rapid cycling bipolar affective disorder. Nervenarzt, 72, 549“54.

Bipolar I and bipolar II: a dichotomy?
Eduard Vieta, Maria Reinares and Marc L. Bourgeois
University of Barcelona, Barcelona, Spain

The distinction between unipolar and bipolar forms, rooted in the work of Pierre
Falret (1851) and Jules Baillarger (1854), was later established by Karl Kleist (1928,
1953) and his school (Neele, 1949; Leonhard, 1957), and subsequently validated by
Angst (1966), Perris (1966), and Winokur et al. (1969), who showed that clinical,
familial, and course features supported the nosological differentiation between
unipolar and bipolar disorders (Angst and Marneros, 2001; Marneros, 2001).
However, there are many areas of overlap between those extremes, pointing up
the question of possible clinical subtypes in the interface of depressive and manic
extremes of affective illness (Akiskal, 2002a).
Bipolar disorder occurs in multiple forms and degrees of severity. The recogni-
tion of the existence of so-called milder forms of manic-depressive illness has been
a major endeavor in the last decade. The distinctions hinge on the classification of
elated states and this poses some difficulty because it depends on the arbitrary
gradation of severity and duration. Bipolar disorder with mania and strict unipolar
depression without manic or hypomanic episodes would represent the extremes of
a spectrum (Akiskal, 1983); recurrent depressions with hypomania would occupy
a middle territory (Akiskal, 2002b). Goodwin and Jamison (1990) point out that
the exploration of spectrum models of manic-depressive illness would enhance
research on genetic markers and modes of genetic transmission, provide an
approach for identifying individuals at risk for the development of bipolar illness,
and permit the evaluation of treatments for milder forms, including the question
of whether early intervention could lessen the chance of progression to bipolar
illness. In fact, a great number of individuals with the so-called soft or sub-
syndromal states belong to the bipolar spectrum by virtue of their positive family
histories, their pharmacological response, and their tendency to progress to full
clinical disorder. Regarding nosological classification, Diagnostic and Statistical
Manual of Mental Disorders, 3rd edn (DSM-III: American Psychiatric Association,

Cambridge University Press, 2005.
89 Bipolar I and bipolar II: a dichotomy?

1987) (DSM-III) was a symptom-based diagnostic system that resulted in a
narrowing of the diagnosis of schizophrenia and a broadening of the diagnosis
of affective disorders, particularly bipolar affective disorders (Dunner, 1998). In
DSM-III, the bipolar mood disorders included bipolar disorder, cyclothymic
disorder, and atypical bipolar disorder. The mood-disorder definitions were
slightly modified in DSM-IIIR (American Psychiatric Association, 1987), includ-
ing bipolar disorder, cyclothymia, and bipolar disorder not otherwise specified,
which included bipolar II, and the criterion of duration for manic episode was
deleted. Two aspects not included in DSM-III or DSM-IIIR were rapid cycling and
bipolar II as a separate disorder, which were incorporated by DSM-IV. In contrast,
The ICD-10 Classification of Mental and Behavioural Disorders (ICD-10: World
Health Organization, 1993) does not recognize bipolar II disorder as a specific
nosologic category.
Bipolar II disorder, sometimes wrongly called ˜˜soft bipolar disorder,™™ is actually
a severe pathology, as it resembles a milder form of classic manic-depressive
illness in regards to symptom intensity, but implies a higher episode frequency,
comorbidity, suicidal behavior, and rapid cycling (Vieta et al., 1997a, 1999). In
DSM-IV, hypomanic episodes occurring in response to treatment with antide-
pressant pharmacotherapy would not count toward the diagnosis of bipolar II but
would instead be termed substance-induced hypomania. Many clinicians consider
antidepressant-induced mania or hypomania to be an indication of the capacity to
develop mania or hypomania spontaneously and therefore a sign of a type of
bipolar mood disorder. Besides, DSM-IV requires a duration of 4 days or more as
minimal criteria for hypomania, while other authors have proposed a brief
hypomania reducing the duration of symptoms to 1“3 days (Wicki and Angst,
1991; Angst, 1995, 1998).
Failing to identify minor elated states leads to misdiagnosis of bipolar-spectrum
patients as unipolar. A recent study found that 37% of bipolar patients had been
misdiagnosed with unipolar depression at first presentation (Ghaemi et al., 2000).
A prior study showed that only 9% of bipolar II patients were accurately diagnosed
(Vieta et al., 1994). In fact, it may be that current diagnostic criteria lack the
sensitivity to detect the full range of conditions within the bipolar spectrum.
Moreover, episodes of hypomania rarely lead to treatment, so the accurate diag-
nosis depends on how rigorously the clinician queries about hypomania, the
recollections of patients, and the interview with the relatives. A wrong diagnosis
would condition the treatment and would affect the course and prognosis of
bipolar patients.
A still unresolved issue is whether bipolar II disorder represents an autonomous
type of bipolar disorder or a transitory condition between unipolar and bipolar I
disorder. In this chapter, we will try to offer a review of some of the studies that
90 E. Vieta et al.

have focused on the distinctions and similarities between bipolar I and bipolar II
disorders, and to draw some conclusions about the validity of such a dichotomy.

Is there a true dichotomy between bipolar I and bipolar II disorder?
Epidemiologic studies
There are similarities across countries in patterns of bipolar disorder (Weissman
et al., 1996). In regard to gender, bipolar I disorder occurs with equal frequency in
both men and women but bipolar II disorder may be more common in women
(American Psychiatric Association, 1994).
The prevalence rate of bipolar disorder depends on how it is defined; many
prevalence studies have required the presence of mania for a bipolar diagnosis to
be recorded. The lifetime prevalence rates of bipolar disorder have been settled in
1.2% by Regier et al. (1988) and 1.6% by Kessler et al. (1994). Weissman and Myers
(1978) found that bipolar I and bipolar II disorders each had a lifetime prevalence
of 0.6%, which combine to 1.2% for all bipolar patients. Schatzberg (1998)
suggested that bipolar disorders appear in approximately 1.3% of the population,
with a prevalence rate of 0.8% for bipolar I and 0.5% for bipolar II. From a
dimensional point of view (bipolar spectrum), this lifetime prevalence would
increase to at least 5% (Lewinsohn et al., 1995; Angst, 1998; Szadocky et al.,
1998). The prevalence rate of the group of brief hypomania, characterized by
short episodes of 1“3 days™ duration, was 2.2% (Angst, 1995).
Benazzi (1997) studied the prevalence of bipolar II disorder in a sample of major
depressive outpatients in a private setting. Hypomania was diagnosed according to
DSM-IV criteria, but antidepressant-induced hypomania was not excluded. The
author found that 45% of patients attending a private clinic had bipolar II
disorder. This rate is even higher than the 10“40% previously reported in clinical
samples (Akiskal and Mallya, 1987; Bourgeois, 1996; Cassano et al., 1992).

Age at onset
The first onset of bipolar disorder usually occurs by the second or third decade of
life, although prepubertal and pubertal illness onset is no longer uncommon.
McMahon et al. (1994) found that patients with affective disorder in both parental
lines experienced an earlier onset. It seems that an earlier onset of illness might be
associated with greater case complexity, episode severity, and comorbidity (Sachs
and Thase, 2000).
The age of initiation of the disease seems to be higher in bipolar II patients
(Gershon et al., 1982; Vieta et al., 1997a; Tondo et al., 1998); nevertheless, other
studies did not find differences in age-at-onset distributions between bipolar I and
bipolar II patients (Benazzi, 1999; Coryell et al., 1985; Egeland et al., 1987;
91 Bipolar I and bipolar II: a dichotomy?

Table 4.1 Differential quantitative features between bipolar I and bipolar II disorder: mean Æ
standard deviation

Variable Bipolar I Bipolar II t P

Age 35.6 11.9 39.7 12.3 “1.25 NS
Previous episodes 6.3 4.2 12.6 7.5 “3.67 0.001
Manic episodes 3.7 3.4 0 0 NA
Hypomanic episodes 3.2 3.7 7.0 5.4 “2.96 0.006
Depressive episodes 2.6 2.2 5.6 4.1 “3.28 0.003
Hospitalizations 3.0 3.3 1.0 1.2 3.43 0.001
Age at onset 21.9 8.0 31.2 9.7 “4.01 <0.001

NS, not significant; NA, not applicable.
Reproduced with permission from Vieta et al. (1997a).

McMahon et al., 1994). Benazzi (1999) has suggested that the discrepant results
across the studies might be related to different criteria at onset, samples, settings,
diagnostic criteria, diagnostic interview, interviewers, methods of analysis, and
cohort effect.

Clinical course and outcome
Dunner et al. (1976) distinguished bipolar II from bipolar I disorder on the basis of
hospitalization for depression and excited periods that did not require hospital-
ization. According to the American Psychiatric Association (1994), the essential
feature of bipolar I disease is a clinical course consisting of the occurrence of one or
more manic or mixed episodes, and the essential feature of bipolar II disorders is a
clinical course characterized by the occurrence of one or more major depressive
episodes with at least one hypomanic episode.
Vieta et al. (1997a), after studying differential features between bipolar I and
bipolar II disorders, found that bipolar II patients had had a greater number of
previous episodes, but had been hospitalized and had presented psychotic symp-
toms less frequently (Table 4.1 and 4.2). The authors concluded that bipolar II
disorder was less severe than bipolar I with regard to symptom intensity, but was
more severe with respect to episode frequency. Similar results with respect to the
higher number of recurrences in bipolar II patients have been found by other
authors (Ayuso-Gutierrez and Ramos-Brieva, 1982; Coryell et al., 1987; Pallanti
et al., 1999), although other studies did not confirm these findings (Koukopoulos
et al., 1980; Cassano et al., 1989). With regard to severity, Benazzi (1999) observed
that recurrences, psychosis, and chronicity were higher in bipolar I patients. When
92 E. Vieta et al.

Table 4.2 Differential qualitative features between bipolar I and bipolar II disorder

Bipolar I Bipolar II

Variable No. % No. % P


. 16
( 68 .)