. 7
( 68 .)


HABILOS, in which the investigators tried to allocate disorders with manic
symptomatology into pure mood disorders or schizoaffective disorders, according
to DSM-IV, ICD-10, and to an empirical definition by the Marneros group
(as defined above). Applying the ICD-10 definition, the findings illustrated in
Figure 1.13 were produced. As shown, only 8.3% of the 277 patients could be
allocated longitudinally as schizoaffective bipolar and 36.1% as affective bipolar,
while the majority of patients (55.6%) could not be allocated longitudinally because
of the occurrence of different types of episodes (schizophrenic, schizoaffective,
affective) at different times.
However, if we use the empirical definition with its cross-sectional and sequen-
tial aspect, all patients can be allocated: 36.1%, as in the ICD-10 categorization,
could be allocated as bipolar mood disorder, and 63.9% could be allocated as
schizoaffective disorder (Fig. 1.14).
Recent research has confirmed earlier assumptions that schizoaffective disor-
ders occupy a position between affective and schizophrenic disorders as regards
relevant sociodemographic and premorbid features, as well as patterns of course,
outcome, treatment response, and prophylaxis (Maj, 1985; Maj and Perris, 1985;
33 Beyond major depression and euphoric mania

Bipolar patients
(n = 277)

Bipolar affective
(n = 100)

Bipolar schizoaffective
(n = 177) 63.9%

Fig. 1.14 Empirical longitudinal classification of bipolar patients in the Halle Bipolarity Longitudinal
Study (HABILOS). Schizoaffective ¼ occurence of schizoaffective episodes or sequentially
schizophrenic and affective episodes.

Angst, 1986, 1989; Marneros et al., 1988a“c, 1989a“c, 1991a, b; Deister et al., 1990;
see also various contributions in Marneros 1989; and in Marneros and Tsuang,
1986, 1990; as well as Marneros et al., 1995).
It seems certain that schizoaffective disorders are not simply a type of schizo-
phrenic disorder, although in some cases with schizo-dominance, the relationship
to schizophrenia is clear. With respect to the relationship between schizoaffective
and mood disorders, the similarities are more compelling than the differences
(Marneros and Tsuang, 1986, 1990; Marneros et al., 1995; Marneros, 1999).

Atypical depressions
The DSM-IV defines non-melancholic and non-catatonic major depressive epi-
sodes or dysthymic disorders as forms of ˜˜atypical depression™™ (full title: ˜˜criteria
for atypical features specifier™™) when they fulfill the criteria shown in Table 1.6.
A look in the historical literature shows that the term ˜˜atypical depression™™ has
many meanings (Angst et al., 2002; Parker et al., 2002). In 1959, West and Dally in
London identified a group of patients with good response to monoamine oxidase
inhibitors as having atypical depression ˜˜resembling anxiety hysteria with second-
ary depression,™™ who had previous phobias and ˜˜hysterical conversions™™ and were
less likely to have clinical features of ˜˜classical endogenous depression.™™ The
34 A. Marneros and F. K. Goodwin

Table 1.6 Criteria for atypical features specifiers (Diagnostic and Statistical Manual of Mental
Disorders: DSM-IV)

A. Mood reactivity (i.e., mood brightens in response to actual or potential positive events)
B. Two (or more) of the following features:
1. significant weight gain or increase in appetite
2. hypersomnia
3. leaden paralysis (i.e., heavy, leaden feeling in arms or legs)
4. long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of
mood disturbances) that results in significant social or occupational impairment
C. Criteria are not met for ˜˜with melancholic features™™ or ˜˜with catatonic features™™ during the
same period

definition of West and Dally differs from the later definition applied by the
Columbia group (Quitkin et al., 1978, 1993; Davidson et al., 1982; Parker et al.,
2002). Angst et al. (2002) pointed out that a major impediment to the validity of
atypical depression is the lack of consistency in the definitions employed by studies
that have investigated the clinical significance of this depressive subtype.
According to Parker et al. (2002), the current definition and modelling of the
DSM-IV atypical features specifier for a major depressive episode and major
depressive disorder appears problematic. As suggested by earlier descriptions of
atypical depression, certain manifestations of anxiety may have primacy, and
some clinical features associated with the DSM-IV model may be adaptive
homeostatic responses, rather than pathological symptoms. The authors support
the opinion of Davidson et al. (1982) that the relationship between anxiety and
atypical depression requires further investigation. Substantial clinical research
has also yielded indirect support for an association between atypical depression
and the bipolar subtype of affective disorders, particularly subthreshold bipolar
disorders and bipolar disorder II (Perugi et al., 1998; Angst et al., 2002; see
Chapter 6). But, nevertheless, the results of recent research are controversial.
While Angst et al. (2002) conclude that their findings from the Zurich study
support the validity of the atypical depression subtype, considering it to be an
important classifier, Parker et al. (2002) recommended a redefinition of atypical
depression. Benazzi suggests in this book (see Chapter 6) a significant relation-
ship between atypical depression and bipolar II disorder, which is consistent
with the findings of Perugi et al. (1998) and Benazzi (1999a, b).
For a long time, agitated depression has been considered by some authors to be a
type of mixed state (Koukopoulos and Koukopoulos, 1999; Akiskal and Pinto,
2000; Marneros, 2001). Kraepelin (1899, 1913) and Weygandt (1899) described
35 Beyond major depression and euphoric mania

states of agitated depression as belonging to the mixed states. However, according
to Kraepelin™s concept of manic-depressive insanity, a distinction between bipolar
or unipolar was not important. According to his concept, all affective disorders
belong together, and the mixed states were for Kraepelin the strongest argument
for such a unification (Kraepelin, 1899). But the rebirth of the unipolar“bipolar
distinction in the mid-1960s again raised the question of the nature of agitated
depression. For Koukopoulos et al., the answer is clear: agitated depression is a
bipolar disorder belonging to the mixed states (Koukopoulos and Koukopoulos,
1999; see Chapter 7). They concluded:

Agitated depression should be considered a mixed affective state given its phenomenology and
response to treatments. Antidepressants worsen the condition of these patients and, in many
cases, induce agitation or psychosis in cases with otherwise simple depression. The authors
propose new diagnostic criteria for agitated depression and introduce the term minor agitated
depression for the cases with psychic agitation without motor agitation or psychotic symptoms.
Three forms of agitated depression(mixed depression) are described:
(1) psychotic agitated depression
(2) agitated depression with psychomotor agitation and
(3) minor agitated depression.
All these forms may be induced or aggravated by antidepressants and improve with mood-
stabilizing and antipsychotic treatments, as well as ECT.

Akiskal coined the term ˜˜hyperthymic depression™™ (Akiskal and Pinto, 2000),
which is similar to Koukopoulos˜s ˜˜excited depression™™ (Koukopoulos et al., 1992).
According to Akiskal and Pinto (2000), hyperthymic depression is a subtype of
bipolar disorder (bipolar IV). For this category, they proposed using patients
with clinical depression that occurs later in life and that is superimposed on a
lifelong hyperthymic temperament. They are typically males in their 50s whose life-
long drive, ambition, high energy, confidence, and extroverted interpersonal skills
helped them to advance in life, to achieve success in a variety of business domains and/
or political life.
The major external validation of the bipolar status of depressions in association
with hyperthymic temperament is familial bipolarity comparable to that of bipolar
II patients (Cassano et al., 1992).
The criteria of bipolar depressive mixed states according to Akiskal and Pinto
are given in Table 1.7:
Recurrent brief depression, as described by Jules Angst (1988), recurrent brief
hypomania (Angst, 1992), and recurrent brief anxiety (Angst and Wicki, 1992), share
an ultrarapid-cycling pattern of mood symptoms according to the findings of Angst
et al. (see Chapter 5). The authors point out that the example of recurrent
brief depression demonstrates that severe measures of mood disorders should not
36 A. Marneros and F. K. Goodwin

Table 1.7 Clinical picture of (bipolar) depressive mixed state

Meets minimum criteria for major depressive disorder plus three or more of the following:
Unrelenting dysphoria, irritability, and instability

Dramatic expressions of suffering

Psychomotoric agitation against a background of retardation

Intense sexual excitement

Extreme fatigue with racing thoughts

Free-floating anxiety, as well as panic attacks

Suicidal obsessions and impulses

Modified from Akiskal and Mallya (1987).

be restricted to the number of symptoms, the duration of episodes, and the con-
sequences, but should also include recurrence (i.e., course). The concept of recurrent
brief depression and of combined mood disorders and their integration into psy-
chiatric practice is, according to the authors, clinically relevant because it enables
psychiatrists to identify a highly prevalent, severely impaired, and often suicidal
subgroup of patients and also opens the way for new therapeutic research (see
Chapter 5).

Polymorphic psychotic disorders as a possible atypical bipolar disorder
In ICD-10, the World Health Organization defined the category ˜˜acute and
transient psychotic disorders™™ (F23). This category involves a broad group of
disorders corresponding to national original concepts (Marneros and Pillmann,
2004). But the core group of this category “ the polymorphic psychotic disorders “
has a high concordance with the so-called cycloid psychoses (Pillmann et al. 2002;
Marneros and Pillmann, 2004). The creator of the concept of cycloid disorders,
Karl Kleist, was convinced that they present a kind of bipolar disorder (Kleist, 1929;
Pillmann et al., 2000; Marneros and Pillmann, 2004). In fact, there are some
similarities between polymorphic psychotic disorders (also cycloid disorders) and
the ˜˜typical™™ bipolar disorders, but there are also differences, as elaborated elsewhere
in this book (see Chapter 9).
Family, premorbid, course “ especially kind of episode “ and outcome data
support the assumption that the acute polymorphic psychoses are related to the
affective spectrum. It seems that the acute polymorphic psychotic disorders could
belong to a psychotic continuum between schizophrenia and affective disorder, in
a way similar to the schizoaffective disorders, but at a different position and with a
different relationship (Marneros and Pillmann, 2004).
37 Beyond major depression and euphoric mania

Lessons from the past and options for the future
Obviously, bipolar disorders belong to a great family, including members with
very strong family similarities, but also individual characteristics, separating them
from other members and characterizing them in an unchangeable way. But the
basic characteristics remain common for all members. This is not a new concept,
but one that is 2000 years old, originated by the father of bipolar disorders “
Aretaeus of Cappadocia. We agree with what Aretaeus wrote 2000 years ago:
˜˜tro/poi ei)desi/ men mu/rioi, ge/nei de/ mou=no ei(j ™™: ˜˜There are many different phenom-
/ =
enological types of the illness, but they all belong to one and the same family.™™
But, nevertheless, we still need definitions and concepts with compelling
validity. As Sachs and Graves point out in this book (see Chapter 17),
The psychiatric literature includes relatively few adequately powered and controlled double-blind
clinical trials reporting results for bipolar disorders. The majority of these randomized clinical
trials report results for treatment of acute mania in hospitalized bipolar I (BP-I) patients. The
majority of bipolar patients are, however, not BP-I, and manic states are relatively infrequent. Why
are there so few published controlled treatment studies dealing with common clinical problems
like rapid cycling, mixed episodes, and atypical bipolar disorder? (see Chapter 17).

The authors give the answer:
˜˜The first consideration is the conceptual dissimilarity of the terms rapid cycling, mixed
episodes, and atypical bipolar disorder. These terms correspond to three distinct organizational
levels used in the DSM-IV mood disorder nosology and represent the concepts of course
specifier, acute episode, and subtype of bipolar (American Psychiatric Association, 1994).
Study designs for each require attention to sample selection, outcome measures and an analysis
plan matched to the appropriate level in the organizational hierarchy of the DSM-IV mood
disorder classification (see Chapter 17).

The purpose of this book is to establish the evidence that can enhance the validity
of our definitions and nosological allocations, which in turn might be expected to
enhance our clinical care and lead to more focused research questions.


Akiskal, H. S. (1981). Subaffective disorders: dysthymic, cyclothymic and bipolar II disorders in
the ˜˜border-line™™ realm. Clin. North Am., 4, 25“46.
Akiskal, H. S. (1992). The mixed states of bipolar I, II, III. Clin. Neuropsychopharm., 15 (suppl.
1a), 632“3.
Akiskal, H. S. (1997). Overview of chronic depressions and their clinical management. In
Dysthymia and the Spectrum of Chronic Depressions, ed. H. S. Akiskal and G. B. Cassano,
pp. 1“34. New York: Guilford Press.
38 A. Marneros and F. K. Goodwin

Akiskal, H. S. and Mallya, G. (1987). Criteria for the ˜˜soft-bipolar spectrum™™: treatment
implications. Psychopharm. Bull., 23, 68“73.
Akiskal, H. S. and Puzantian, V. R. (1979). Psychotic forms of depression and mania. Psychiatr.
Clin. North Am., 2, 419“39.


. 7
( 68 .)