Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 1043 1050

www.elsevier.com/locate/pnpbp

A continuity between bipolar II depression and major

depressive disorder?
Franco Benazzi
Hecker Psychiatry Research Center, Forli, Italy
University of California at San Diego (USA) Collaborating Center, United States
Department of Psychiatry, University of Szeged, Szeged, Hungary
Department of Psychiatry, National Health Service, Forli, Italy
Available online 8 May 2006

Abstract

Background: A recent series of studies has questioned the current categorical split of mood disorders into bipolar and depressive disorders. Mixed
states, especially mixed depression (i.e., depression plus co-occurring, noneuphoric, hypomanic symptoms) might support a continuity between
bipolar II (BP-II) depression and major depressive disorder (MDD). The aim of the study was to assess the distribution of intradepressive
hypomanic symptoms rating between BP-II and MDD depressions. A bi-modal distribution would support a categorical distinction, and no bi-
modality would support continuity.
Methods: Consecutive 389 BP-II and 261 MDD major depressive episode (MDE) outpatients were interviewed (off psychoactive drugs) with the
Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide (HIG, to assess intradepressive hypomanic symptoms), and the Family
History Screen, by a mood specialist psychiatrist in a private practice. Mixed depression was defined as MDE plus 3 or more intradepressive,
noneuphoric hypomanic symptoms, a definition validated by Akiskal and Benazzi. The distribution of intradepressive hypomanic symptoms
rating was studied by Kernel density estimate and by histogram.
Results: BP-II depression, versus MDD depression, had significantly lower age at onset, was significantly more likely to be atypical and mixed,
had more depression recurrences, and a higher bipolar family history loading. BP-II depression, versus MDD depression, had significantly more
irritability, racing/crowded thoughts, distractibility, psychomotor agitation, talkativeness, increased goal-directed activity, and excessive risky
activities. HIG scores were significantly higher in BP-II. The distribution of intradepressive hypomanic symptoms rating showed no bi-modality in
the entire depression sample.
Conclusions: Interpretation of study findings relies on the method used to define a categorical disorder. By using classic diagnostic validators
(such as family history and age at onset), BP-II and MDD depressions would seem to be distinct disorders. Instead, by using the bi-modality
approach, a continuity would seem to be supported. Which of these methods for classification is the best has yet to be shown.
2006 Elsevier Inc. All rights reserved.

Keywords: Bipolar disorder; Bipolar II disorder; Continuity; Major depressive disorder; Spectrum

1. Introduction

The current diagnostic systems split mood disorders categori-

Abbreviations: BP-I, bipolar I disorder; BP-II, bipolar II disorder; DSM-IV-
TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
Text-Revised; GAF, Global Assessment of Functioning scale; HIG, Hypomania
Interview Guide; ICD-10, International Classification of Diseases, Tenth
Edition; MDD, major depressive disorder; MDE, major depressive episode;
nc, not calculable; OR, Odds Ratio; SCID-CV, Structured Clinical Interview for
DSM-IV Axis I DisordersClinician Version; YMRS, Young Mania Rating
Scale; 95% CI, 95% Confidence Interval.
Via Pozzetto 17, 48015 Castiglione di Cervia RA, Italy. Tel.: +39 335 6191
852; fax: +39 054 330 069.
E-mail address: FrancoBenazzi@FBenazzi.it.
0278-5846/$ - see front matter 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.pnpbp.2006.03.037
cally into bipolar and depressive disorders (DSM-IV-TR, Diag-
nostic and Statistical Manual of Mental Disorders, Fourth Edition,
Text-Revised, American Psychiatric Association, 2000; ICD-10,
International Classification of Diseases, Tenth Edition, World
Health Organization, 1992). Recent studies have instead supported
a continuity/spectrum of mood disorders, including overlapping
and dimensional disorders ranging from bipolar I (BP-I) and bipolar
II (BP-II) disorders to major depressive disorder (MDD) (Angst
et al., 2003; Akiskal, 2003; Cassano et al., 2004; Dunner, 2003).
1044 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050
According to Kraepelin (1921), the mood disorders he united in his
manic-depressive insanity had a common root with gradual
transitions between the individual forms, were without sharp
boundaries, and delimitation of individual clinical forms of the
malady was wholly artificial and arbitrary.
Some features supporting a continuity/spectrum of mood
disorders may be the following: 1) mixed states (especially mixed
depression), because of the combination of opposite polarity
symptoms in the same episode, 2) MDD found to be the most
common mood disorder in relatives of bipolar probands (Duffy
et al., 2000), 3) MDD found to have low diagnostic stability
(Angst et al., 2005a; Goldberg et al., 2001), 4) many lifetime
manic/hypomanic symptoms found in MDD (Cassano et al.,
2004), showing no bi-modal distribution (Cassano et al., 2002)
and 5) correlation found between lifetime manic/hypomanic
symptoms and current depressive symptoms in MDD (Cassano
et al., 2004).
Instead, some features supporting a categorical distinction
between bipolar and depressive disorders may be the following:
differences on 1) family history (Coryell, 1999; Duffy et al., 2000),
2) age at onset (McMahon et al., 1994), 3) gender (Winokur et al.,
1993a,b; Winokur et al., 1995), 3) clinical picture of BP-I depres-
sion versus MDD depression (Mitchell and Malhi, 2004) and 4)
course of illness (Winokur et al., 1993a,b, 1995).
According to Kendell and Jablensky (2003), finding a bi-modal
distribution of distinguishing, cross-sectional symptoms between
two related syndromes would support a categorical distinction. BP-
II is the closest of the bipolar disorders to MDD, and it could be the
one to be compared to MDD. The cross-sectional symptoms to
study should be symptoms distinguishing the two depressive
syndromes. BP-II depression, versus MDD depression, was found
to have more concurrent DSM-IV-TR hypomanic symptoms (i.e.,
to be more likely to be a mixed depression). According to Kraepelin
(1921), mixed states were one of the main building blocks of his
unitary view of mood disorders. Finding a bi-modal distribution of
the intradepressive hypomanic symptoms rating between BP-II and
MDD depressions could support a categorical distinction, while
finding no bi-modality could support a continuity.
1.1. Mixed depression
Mixed depression is the combination of depression and manic/
hypomanic symptoms, not including elevated mood by definition.
It is not present in DSM-IV-TR. Apart from the classic descriptions
by Kraepelin (1921), in modern times mixed depression has been
repeatedly described in BP-I, BP-II, and MDD (Abrams and Taylor,
1980; Andreasen and Grove, 1982; Akiskal, 1996; Akiskal and
Benazzi, 2003; Benazzi, 2005a,b; Biondi et al., 2005; Himmelhoch
et al., 1976a,b; Koukopoulos and Koukopoulos, 1999; Perugi et al.,
2001; Maj et al., 2003; Mantere et al., 2004; Sato et al., 2003;
Raskin et al., 1969).
The most frequent DSM-IV-TR manic/hypomanic symptoms of
mixed depression were irritability, mental overactivity (flight of
ideas, racing thoughts, crowded thoughts), and motor overactivity
(psychomotor agitation, more talkativeness) (Akiskal, 1996;
Akiskal and Benazzi, 2003; Benazzi, 2005a,b; Biondi et al.,
2005; Koukopoulos and Koukopoulos, 1999; Perugi et al., 2001;
Maj et al., 2003; Maj et al., in press; Mantere et al., 2004; Sato et al.,
2003, 2005). The depressive mixed states (mixed depression)
described by Kraepelin (1921) included the same symptoms found
in modern studies. The manic foundation of mild depressive
mixed states (corresponding to those seen in the study setting) was
indicated by slight flight of ideas, restlessness, talkativeness, and
irritability (p 112). Kraepelin described a grading of the severity of
the thought disorders of hypomania, including crowded thoughts,
described as non-stop thoughts filling the mind.
Frequency of mixed depression, defined as a major depressive
episode (MDE) plus at least 2 or 3 intradepressive manic/hypo-
manic symptoms, was up to 70% in BP-I and BP-II, and up to 30%
in MDD.
1.2. Study aim
The study's aim was to find if there was a continuity (i.e., no bi-
modality) between BP-II depression and MDD depression. In order
to do this testing, the distribution of hypomanic symptoms rating
between BP-II and MDD depressions was assessed.
2. Methods
2.1. Study setting
The setting of the study is an outpatient psychiatry private
practice in Emilia-Romagna region, northern Italy. This setting is
more representative of the mood disorders usually seen in
psychiatric clinical practice in this area (apart from the psychotic
ones) because 1) it is the first or second (after general practitioners)
line of treatment of mood disorders, 2) the most severe and socially
disadvantaged individuals are usually seen in tertiary-care centers
(i.e., national health services and academic centers), 3) mood
disorder patients do not like to be treated in the national health
services for fear of stigma, and 4) most individuals can afford a
private psychiatrist (fee-for-service) in this area, reducing a possible
income bias.
2.2. Interviewer
The interviewer of the study was a senior clinical (21 years in
practice) and research mood disorder specialist psychiatrist.
2.3. Patient population
Consecutive 389 BP-II and 261 MDD outpatients, presenting
voluntarily (i.e., self-referred, apart from a small number referred by
general practitioners) for major depressive episode (MDE)
treatment, were included in the last 6 years. Substance-related
disorders and borderline personality disorder were excluded
because these disorders may confound the diagnosis of BP-II and
mixed states due to their high background mood instability
(Akiskal and Pinto, 1999). Anyway, these disorders are rare in the
study setting (Benazzi, 2000). Clinically significant general
medical illnesses and cognitive disorders were also excluded. Pa-
tients had to present off psychoactive drugs for at least 2 weeks
(apart from a few individuals on small doses of benzodiazepines),
 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050
in order to exclude patients with drug-induced or drug-suppressed
intradepressive hypomanic symptoms. Informed consent was
obtained by all patients, as the interview's questions are part of
the usual clinical assessment of each new patient in the study
setting. The Italian law does not require further steps for a study like
the present one.
2.4. Assessment instruments
All diagnostic procedure and instruments described represent
the systematic clinical routine of the author. During the first visit
(when presenting for the first time), the following instruments were
used in a cross-sectional assessment:
1) the Structured Clinical Interview for DSM-IV Axis I Dis-
ordersClinician Version (First et al., 1997) (SCID-CV,
reported inter-rater reliability k= 0.701.0), as modified by
Benazzi and Akiskal (described below) to improve the probing
for BP-II (Akiskal and Benazzi, 2005; Benazzi and Akiskal,
2003); the question on racing thoughts was supplemented by
Kraepelin's (1921) description of crowded thoughts: the
patients complain that they have so many thoughts in their
head, they have no settled thoughts (p 14), a patient complains
that he must meditate so much, that fresh thoughts are always
coming to him, that he has too much in his head, that he finds no
rest (p 75), patients cannot hold fast their thoughts at all,
constantly things come crowding into their head (pp 107108);
in DSM-IV-TR, only racing thoughts are reported, defined by
speedy thinking, and by rapid jumping of thinking in the more
severe states;
2) the Global Assessment of Functioning scale (GAF, in the SCID-
CV) for assessing MDE severity;
3) the Hypomania Interview Guide (HIG) (Williams et al., 1994) to
better assess intradepression hypomanic symptoms;
4) the Family History Screen (Weissman et al., 2000) (reported
inter-rater reliability k= 0.85) for assessing Bipolar (type I and
type II) family history in probands' first-degree relatives.
The interviewer's inter-rater reliability k for the diagnosis of BP-
II had been previously tested versus a psychiatrist trained in bipolar
disorders, and found to be 0.73 (Benazzi, 2003a). This k statistics is
similar to that found using similar interview methods by trained
clinicians in genetic investigations (Simpson et al., 2002).
Often, family members or close friends supplemented clinical
information during the interview, increasing the validity of the
diagnosis of BP-II and of the family history (American Psychiatric
Association, 2000).
2.5. The Hypomania Interview Guide (HIG)
The Hypomania Interview Guide (HIG) (Williams et al., 1994)
was the basic instrument used in the present study. The HIG
assesses all DSM-IV-TR hypomanic symptoms better than the
YMRS (Young Mania Rating Scale) (Young et al., 1978), which
has several items biased toward inpatient mania. It was validated in
BP-I, BP-II and MDD (Goel et al., 1999). The HIG showed high
internal consistency. Normal controls had lower scores than MDD,
1045
which had lower scores than BP-I and BP-II. The total score
correctly classified as MDD or BP 91% of the patients. Its reported
inter-rater reliability is k= 0.88, total score range is 0 to 60, item
score range is 0 to 4 (Williams et al., 1994).
2.6. Interview methods
Systematic data gathering are part of the clinical routine in the
study setting. Systematic interviews about history of hypomanic
and manic episodes were always conducted soon after the diagnosis
of MDE and before the assessment of study variables, in order to
avoid a possible bias related to knowledge of bipolar signs (Ghaemi
et al., 2002). It is well known that patients do not report spon-
taneously about past hypomanic episodes, because hypomanic
episodes are often pleasant periods of improved functioning and/or
periods without marked impairment. Indeed, patients even view
hypomania as a state of real self-normality which they hope will
last as much as possible. The key informants often present during
the interview were therefore very helpful in supporting a diagnosis
of past hypomania, as they could remember the change in func-
tioning associated with hypomania. The SCID-CV is partly semi-
structured and based on clinical evaluation (not on simple yes/no
answers to structured questions). Wording of the sentences can be
changed to improve and to check the understanding of the inter-
viewee. This is an important advantage versus fully structured
interviews, because this interview method has been shown to
reduce the false negative mood disorders, especially BP-II (Aalto-
Setala et al., 2002; Benazzi, 2003b; Brugha et al., 2001; Dunner and
Tay, 1993; Simpson et al., 2002). The skip out instruction of the
stem question on history of mood changes (elevated/irritable mood)
was not followed, because a negative answer would force to shift
the interview to nonbipolar disorders. A period of elevated or
irritable mood can be seen as normality by patients (everybody has
ups and downs), while asking about a period of much elevated or
irritable mood can be easily seen as a sign of a severe mental
disorder and soon denied. This is one of the reasons why some
researchers have been focusing the interview more on history of
overactivity (increased goal-directed activity) (Akiskal and Be-
nazzi, 2005; Angst et al., 2003; Benazzi, 2003b). It was so possible
to assess all past hypomanic symptoms by not following the skip
out instruction of the SCID-CV stem question. This approach
followed previous reports showing the diagnostic utility of a
probing for history of hypomania more focused on overactivity
than on mood changes (Akiskal and Benazzi, 2005; Angst et al.,
2003; Benazzi, 2003b; Dunner and Tay, 1993; Simpson et al.,
2002). Overactivity (the most striking feature of hypomania,
according to Kraepelin, 1921) is an observable behavior easier to
remember than mood changes. Mood changes were always
required for the diagnosis of BP-II (American Psychiatric Asso-
ciation, 2000), and were more easily remembered after remember-
ing overactivity. In order to carefully assess history of overactivity,
it was always requested that patients described the periods of
overactivity (by giving examples), to know if the patient had
correctly understood the meaning of the questions on overactivity
(e.g., increase in efficiency, accomplishments, creativity, planning
of, and participation in, multiple activities, often creative and
productive, increased sociability, increased sexual activity, with or
1046 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050

Table 1 compared to hypomania (required for BP-II diagnosis). Instead, in

Sample features the present study a lot of effort was made to diagnose hypomania in
Variables: mean (SD), % BP-II MDD OR (95% CI) the relatives (Akiskal and Benazzi, 2005).
n = 389 n = 261 Mixed depression (depressive mixed state) was defined as MDE
Age, years 41.3 (12.9) 46.8 (14.8) 0.7 (0.60.8) (depression) plus 3 or more co-occurring, intradepressive DSM-IV-
Age at onset first MDE 22.8 (10.6) 31.8 (13.8) 0.5 (0.40.6) TR hypomanic symptoms (elevated mood and increased self-
Females 67.0 61.6 1.2 (0.91.7)
esteem were always absent by definition), a definition validated by
N=5 MDEs 78.9 58.2 2.6 (1.83.7)
MDE symptoms N2 years 37.5 34.8 1.1 (0.81.5) clinical, family history, and psychometric validators by Akiskal and
Axis I comorbidity 54.2 47.5 1.3 (0.91.7) Benazzi (2003), and by Benazzi (2005b). Other authors require 2 or
Psychotic features 7.7 8.4 0.9 (0.51.6) more intradepressive hypomanic symptoms (Bauer et al., 2005;
Melancholic features 12.0 13.0 0.9 (0.51.4) Sato et al., 2003), but the definition of mixed depression used in the
Atypical depression 52.6 28.7 2.7 (1.93.8)
present study is the most validated. The noneuphoric hypomanic
Mixed depression 64.5 32.1 3.8 (2.75.3)
GAF 50.2 (9.2) 50.9 (9.6) 0.9 (0.81.0) symptoms had to appear during the MDE (i.e., a hypomanic
Bipolar (type I + type II) 44.7 15.3 4.4 (2.87.0) symptom-free interval of at least one month before the MDE was
family history required), to last at least one week, and to be present at the time of
Bipolar-II disorder (BP-II) versus major depressive disorder (MDD), by the interview (to increase validity).
univariate logistic regression. Atypical depression was defined, according to DSM-IV-TR
MDE = major depressive episode; Mixed Depression = MDE plus N = 3 criteria, as an MDE presenting the atypical features specifier.
intradepressive hypomanic symptoms; GAF = Global Assessment of Function-
ing scale; OR = Odds Ratio; 95% CI = 95% Confidence Interval; p b 0.05;
p b 0.01. 2.8. Testing the study's aim

To find if BP-II depression and MDD depression were distinct

without mild impairment of functioning, a clear change in func- categories, or were instead overlapping disorders along a
tioning compared to the usual self). If the patient did not remember continuum, Kendell and Jablensky's (2003) method was
periods of overactivity and mood changes, it was asked how were followed, by looking for a bi-modality in the distribution of the
his/her mood and behavior in spring and summer compared to HIG rating of the intradepressive hypomanic symptoms between
winter, how were his/her mood and behavior soon after/before a the depressive syndromes (MDE) of BP-II and MDD. Intrade-
depression, and soon after skipping a night sleep (these are further pressive hypomanic symptoms were chosen because these
probes likely to show periods of overactivity, if present). symptoms were reported to be much more common in BP-II
versus MDD depressive syndromes (Akiskal and Benazzi, 2003;
2.7. Hypomania duration Benazzi, 2005a; Bauer et al., 2005; Henry et al., 2005; Maj et al.,
in press; Mantere et al., 2004; Sato et al., 2003), and because
A minimum duration of hypomania of 2 days was required mixed states would support, according to Kraepelin (1921), a lack
(instead, DSM-IV-TR requires a minimum duration of 4 days), on of boundaries between mood disorders. If BP-II depression were a
the basis of data supporting this cutoff, i.e., no differences on category distinct from MDD depression, the distribution of the
diagnostic validators between BP-II with history of hypomania HIG rating should have shown a bi-modality between the two
lasting less than 4 days, and DSM-IV-TR BP-II (Angst et al.,
2003; Benazzi, 2001; Benazzi and Akiskal, in press; Judd et al.,
2003), while DSM-IV-TR cutoff is not data-based (Dunner, Table 2
2003). Among the present study BP-II, around 30% met this 2- Intradepressive hypomanic symptoms in bipolar-II depression (BP-II) versus
day cutoff for hypomania. Therefore, the frequency of DSM-IV- major depressive disorder (MDD) depression, by univariate logistic regression
TR BP-II in the present sample was around 40%, a frequency very Variables: %, mean (SD) BP-II MDD OR (95% CI)
close to that found in other outpatient sample studies (Dunner and n = 389 n = 261
Tay, 1993; Hantouche et al., 1998; Manning et al., 1999; Elevated mood 0.0 0.0 nc
Rybakowski et al., 2005; Smith et al., 2005). Irritable mood 61.6 34.8 3.0 (2.14.1)
Recurrences were defined as recurrences of MDE, as Inflated self-esteem, grandiosity 0.0 0.0 nc
Decreased need for sleep 1.5 0.0 nc
hypomanic episodes are more difficult to count, partly because
More talkative than usual 24.6 9.5 3.0 (1.94.9)
hypomanic episodes are often not seen as abnormal periods by Racing/crowded thoughts 75.3 54.7 2.6 (1.93.7)
patients, partly because hypomania duration may be brief (Angst Distractibility 78.9 65.1 1.9 (1.32.7)
et al., 2003; Benazzi and Akiskal, in press). Recurrences were Increase in goal-directed activity 7.7 0.7 10.8 (2.545.6)
categorically divided by a cutoff of 5 episodes, because 5 or more Psychomotor agitation 35.9 17.6 2.6 (1.73.8)
Excessive risky activities 19.5 6.5 3.4 (2.06.0)
episodes was shown to identify highly recurrent mood disorders
N hypomanic symptoms 3.0 (1.4) 1.8 (1.2) 1.9 (1.62.2)
(Kessing et al., 2004). Hypomania Interview Guide 8.5 (3.7) 5.3 (3.2) 1.2 (1.21.3)
Bipolar disorders family history included history of BP-I and (HIG) score
BP-II in proband's first-degree relatives. Usually, only BP-I family HIG median 8 6 z = 8.6
history is studied, because mania (which is often psychotic, and HIG = Hypomania Interview Guide; OR = Odds Ratio; 95% CI= 95%
often requires hospital care) is simpler to diagnose by history Confidence Interval; p b 0.05; p b 0.01; nc = not calculable.
 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050 1047

.1
.08
.06
Density
.04
.02
0

0 5 10 15 20 25
HIG

Kernel density estimate

Normal density

Fig. 1. Kernel density estimate (a normal curve is superimposed) of the Hypomania Interview Guide (HIG) scores of intradepressive hypomanic symptoms in the
combined bipolar-II disorder plus major depressive disorder depression sample.

depressive syndromes, while no bi-modality would have sup- nonparametric histogram smoothers which can reveal skewness
ported a continuity. and multi-modality. Disadvantages of the histogram method are
that it is parametric, and that the fixed bin width results in
2.9. Data analysis disproportional representation of density at the center and in the
tails of the distribution. The Kernel density estimate overcomes
The distribution of the HIG rating was studied by univariate the limitations of the histogram method and can better evaluate
Kernel density estimation, and by histogram. Normality of the multi-modality. For an overview of the Kernel density estimate,
Kernel density estimation curve was also checked. While histo- see Salgado-Ugarte et al. (1994).
grams provide accurate pictures of categorical variables, smooth Logistic regression was used to study associations. Medians
density functions (Kernel estimators) are better to represent were compared by the MannWhitney test. STATA Statistical
noncategorical variables. Kernel estimators can be regarded as Software, Release 8.2, was used (Stata Corporation, College
.1
.08
.06
Density
.04 .02
0

0 5 10 15 20 25
HIG

Fig. 2. Histogram of the Hypomania Interview Guide (HIG) scores of intradepressive hypomanic symptoms between bipolar-II depression and major depressive
disorder depression.
1048 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050
Station, TX, USA, 2003). P values were two-tailed, and alpha
level was set at 0.01, to correct for multiple comparisons (Alt-
man et al., 2000).
3. Results
Comparisons between BP-II and MDD are presented in
Table 1. BP-II depression, versus MDD depression, had
significantly lower age and age at onset, was significantly
more likely to be atypical and mixed, had more depression
recurrences, and had a higher bipolar family history loading.
Table 2 shows the comparison of the intradepressive
hypomanic symptoms between BP-II and MDD depressions.
BP-II had significantly more irritability, racing/crowded
thoughts, distractibility, psychomotor agitation, talkativeness,
increased goal-directed activity, and excessive involvement in
pleasurable activities. The mean and median HIG scores were
significantly higher in BP-II. The modal item scores were 2 to 3
for the most common symptoms (irritability, racing/crowded
thoughts, distractibility, psychomotor agitation, and talkative-
ness) in BP-II and MDD.
Fig. 1 shows the Kernel density estimate distribution of the
intradepressive hypomanic symptoms rating in the entire BP-II and
MDD depression sample. No bi-modality was present.
Fig. 2 shows the histogram of the distribution of the intra-
depressive hypomanic symptoms in the entire BP-II and MDD
depression sample. No bi-modality was present.
4. Discussion
4.1. Differences between BP-II and MDD on diagnostic
validators
Comparisons between BP-II and MDD depressions showed
significant differences on several diagnostic validators, such as
bipolar family history, age at onset, course (recurrences), and clinical
picture. These findings are in line with previous reports (Angst et al.,
2002; Bauer et al., 2005; Hantouche et al., 1998; McMahon et al.,
1994; Mitchell and Malhi, 2004; Perugi et al., 2003; Sato et al.,
2003). These differences on diagnostic validators could support a
categorical distinction between BP-II depression and MDD
depression, following a classic approach (Kendler, 1990).
4.2. Lack of bi-modality between BP-II and MDD depressions
According to Kendell and Jablensky (2003), using diagnos-
tic validators is biased toward a categorical classification of
mental disorders. According to the same authors, the current
best approach to the categorical versus dimensional classifica-
tion would be to study if there is a bi-modality in the distribution
of some cross-sectional, distinguishing clinical features be-
tween two related syndromes. BP-II is the closest of the bipolar
disorders to MDD. A clinical feature shown to distinguish the
depressive syndromes of BP-II and MDD is a higher frequency
of intradepression hypomanic symptoms in BP-II (Benazzi,
2005b; Mantere et al., 2004; Sato et al., 2003; Serretti and
Olgiati, 2005).
The distribution of the scores of the intradepression
hypomanic symptoms was expected to be bi-modal, because
of the differences in the frequency of these symptoms between
BP-II and MDD depressions. Instead, in the present study it was
shown that intradepression hypomanic symptoms rating had no
bi-modality, supporting a continuity between BP-II and MDD
depressions. The lack of bi-modality in the distribution of the
intradepression hypomanic symptoms rating between BP-II and
MDD found in the present study is mirrored by a similar, non-
bi-modal, distribution of lifetime manic/hypomanic symptoms
in BP-I and MDD, and of the intramania depressive symptoms
(Bauer et al., 2005; Cassano et al., 2002). These studies com-
plement and support each other.
4.3. Interpretation
Interpretation of study findings relies on the method used to
define a categorical disorder. By using classic diagnostic
validators, BP-II and MDD depressions would seem to be
distinct disorders. By using the bi-modality method, a
continuity between BP-II and MDD depressions would seem
to be supported. Which of these methods for classification is the
best has yet to be shown. At present, the study's findings seem
to support a continuity between BP-II and MDD if Kendell and
Jablensky's bi-modality method is followed. Further studies
are clearly required, in order to replicate the present study
findings in different settings, and to find the best method to use
for the definition of categorical mental disorders.
4.4. Limitations
A single interviewer may limit the validity of the findings.
However, the reliability of BP-II diagnosis was found to be high
when trained clinicians used semi-structured interviews as in the
present study (Simpson et al., 2002). Clinicians using semi-
structured interviews made more correct diagnoses of mood
disorders, especially BP-II, compared to structured interviewing
(Aalto-Setala et al., 2002; Brugha et al., 2001; Dunner and Tay,
1993). The interview was conducted by a clinician studying and
treating mood disorders for a long time, systematically using
validated structured and semi-structured instruments for each
new patient, often supplemented by key informants. Assess-
ment of all consecutive patients in a systematic manner by
validated instruments should have avoided any unintentional
systematic bias. The interviewer inter-rater reliability for the
diagnosis of BP-II had been shown to be acceptable (Benazzi,
2003a). The validity of the interview method is supported by the
close similarities found between a BP-II sample of the present
setting and a BP-II sample of an independent group (Angst et
al., 2005b). An interviewer's bias is also unlikely as the present
study aim had not been planned when the variables were
collected for different study goals.
4.5. Conclusions
By using classic diagnostic validators, BP-II and MDD
depressions would seem to be distinct disorders. By using the
 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050
bi-modality method, a continuity between BP-II and MDD
would seem to be supported by the study's findings. Which of
these methods for classification is the best has yet to be
shown.
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