Bipolar Disorders 2013 © 2013 John Wiley and Sons A/S

Published by Blackwell Publishing Ltd.

BIPOLAR DISORDERS

Review Article

Characteristics of patients diagnosed with

schizoaffective disorder compared with
schizophrenia and bipolar disorder
Pagel T, Baldessarini RJ, Franklin J, Baethge C. Characteristics of Tobias Pagela, Ross J Baldessarinib,c,
patients diagnosed with schizoaffective disorder compared with Jeremy Franklind and Christopher
schizophrenia and bipolar disorder. Baethgea,c
Bipolar Disord 2013: 00: 000–000. © 2013 John Wiley & Sons A/S. a
Department of Psychiatry and Psychotherapy,
Published by Blackwell Publishing Ltd. University of Cologne Medical School Cologne,
Germany, bDepartment of Psychiatry, Harvard
Objectives: Information on basic demographic and clinical Medical School, cInternational Consortium for
characteristics of schizoaffective disorder is sparse and subject to Psychotic and Bipolar Disorders Research,
sampling bias and low diagnostic reliability. In the present study we
McLean Division of Massachusetts General
aimed to: (i) estimate the demographic and clinical descriptors in Hospital, Boston, MA, USA, dInstitute of Medical
schizoaffective disorder patients and (ii) compare the findings with those
Statistics, Informatics, and Epidemiology,
with schizophrenia and bipolar disorder. University of Cologne Medical School Cologne,
Germany
Methods: To minimize sampling bias and low reliability, we
systematically reviewed studies that simultaneously compared
schizoaffective, schizophrenia, and bipolar disorder patients. We
estimated demographic, clinical, and psychometric characteristics based
on weighted pooling, and compared disorders by meta-analysis. We also
estimated whether schizoaffective disorder is closer to schizophrenia or
to bipolar disorder.

Results: We identified 50 studies that included 18312 patients. Most

characteristics of the 2684 schizoaffective disorder patients fell between
those of 4814 diagnosed with bipolar disorder and 10814 with
schizophrenia. However, the schizoaffective group had the highest
proportion of women (52%), had the youngest age at illness onset
(23.3  3.8 years), and had the highest standardized ratings of psychosis
and depression. Differences in pooled parameters between schizoaffective
versus schizophrenia and versus bipolar disorder subjects were similar.
Values for patients with schizoaffective disorders mostly were
intermediate between schizophrenia and bipolar disorder. However,
the majority of studies showed schizoaffective patients to be more like doi: 10.1111/bdi.12057
schizophrenia than bipolar disorder patients in seven out of nine
demographic and clinical categories as well as in five out of eight Key words: bipolar – meta-analysis –
psychometric measures. These results remained similar when we schizoaffective – schizophrenia
restricted the analyses to studies with psychotic bipolar disorder patients
only or to studies using the Diagnostic and Statistical Manual of Mental
Disorders (DSM)-IIIR and DSM-IV only. Corresponding author:
Christopher Baethge, M.D.
Conclusions: The present study provided estimates of important Klinik fu€r Psychiatrie und Psychotherapie
characteristics of schizoaffective disorder – as balanced as possible in Universita€t zu Ko€ln
summarizing the findings from observational studies as unbiased as Kerpener Straße 62
possible. The results did not support the hypothesis that schizoaffective Ko€ln 50937
disorder is primarily an affective disorder. The stronger resemblance of Germany
schizoaffective disorder to schizophrenia than to bipolar disorder needs Fax: +49-2234-7011-140
further investigation. E-mail: cbaethge@uni-koeln.de

1
Pagel et al.
From its introduction, the conceptualization and
nosological status of schizoaffective disorder have
been controversial (1–4). Concepts of schizoaffective
disorder have included markedly dissimilar views.
They include: (i) an early broad concept of acute
psychotic illnesses with prominent affective features,
and possible status as a separate disorder (5, 6); (ii)
being either a type of schizophrenia (7) or of major
affective disorder (1); (iii) a mixture of two distinct
but comorbid disorders (8); or (iv) as falling within
a spectrum of psychotic disorders (9), recalling the
19th century concept of Einheitspsychose (unitary
psychosis) (10, 11). Justification for the diagnostic
category schizoaffective disorder has been repeat-
edly called into question (12, 13). Indeed, Marneros
(14) aptly wrote that schizoaffective disorder is ‘a
nosological nuisance, but a clinical reality’.
Regardless of its theoretical and scientific status,
schizoaffective disorder is commonly considered
clinically. In a report by Olfson and co-authors
(15) on diagnoses among a large Medicaid sample,
schizoaffective disorder was diagnosed nearly half
as often as schizophrenia (42%). Criteria for the
diagnosis of schizoaffective disorder by the Inter-
national Classification of Diseases (ICD)-10 and
the Diagnostic and Statistical Manual of Mental
Disorders (DSM)-IV differ: DSM requires a period
of schizophrenia-like psychotic symptoms in the
absence of prominent mood symptoms, and so is
more similar to criteria for schizophrenia than
those of ICD-10 (16, 17).
The substantial prevalence of clinically diag-
nosed schizoaffective disorder notwithstanding, the
diagnosis appears to be particularly unreliable,
with Cohen’s j ranging between 0.08 and 0.63 in
six diagnostic studies (4).
Lack of conceptual consensus and low diagnos-
tic reliability may contribute to the paucity of epi-
demiological studies on the prevalence, course, and
other clinical characteristics of schizoaffective dis-
order. A rare exception is a Finnish study (18),
which estimated a lifetime prevalence of schizoaf-
fective disorder of 0.32% compared with a
2.7-times higher rate (0.87%) for schizophrenia. In
that report and in another small epidemiological
study (19), schizoaffective disorder was more pre-
valent in women than in men. Nevertheless, con-
trary to other, more reliable psychiatric diagnoses,
many basic and essential characteristics of schizo-
affective disorder, such as age at onset, longitudi-
nal course, and outcome are not available from
epidemiological studies.
Most information about the characteristics of
schizoaffective disorder patients has arisen from
informal studies of clinical samples uncontrolled
by comparisons with other disorders. Many of
2
these studies were based in specialized clinical units
for schizophrenia or for affective disorders. As
such, they were likely to be subject to recruitment
or conceptual biases arising from the primary
interests of the sites involved and local views of the
disorder as being more closely related either to
schizophrenia or major affective disorders. For
example, McGlashan and Williams (20) found
patients diagnosed with schizoaffective disorder
and schizophrenia in an institution for chronically,
severely mentally ill patients to be very similar,
whereas Angst and Preisig (21), based on a mood-
disorder research program, emphasized the resem-
blance of patients they diagnosed with schizoaffec-
tive disorder to those with major affective
disorders, particularly bipolar I disorder. A review
of maintenance therapy in schizoaffective disorder
(22) found that schizoaffective disorder patients
were reported to respond more favorably to anti-
psychotic agents (23) or to mood stabilizers (24),
depending on whether the studies included schi-
zoaffective disorder patients leaning towards either
affective of schizophrenic disorders.
Given the circumstances just reviewed, we aimed
to estimate information regarding the basic clinical
characteristics of schizoaffective disorder patients
drawn selectively from studies that directly com-
pared subjects diagnosed with schizoaffective dis-
order, schizophrenia, or bipolar disorder under
similar circumstances. This within-study compara-
tive approach represented an effort to limit the risk
of biasing findings in schizoaffective disorder sub-
jects toward either of the comparison disorders.
The present study was stimulated by a systematic
review by Cheniaux et al. (25). They found that
most demographic, clinical, psychometric, and bio-
logical measures among schizoaffective disorder
patients were intermediate between those identified
in subjects diagnosed with schizophrenia or with
bipolar disorder. However, Cheniaux and col-
leagues analyzed the data in a qualitative way and
did not focus on studies including all three diag-
nostic groups. Specific aims of the present study
were: (i) to estimate demographic and clinical
descriptors in schizoaffective disorder patients by
use of meta-analytical methods to pool data across
studies and (ii) to compare the findings with those
in schizophrenia and bipolar disorder subjects by
use of descriptive and inferential statistics.
Methods
Literature search
The present study was based on a systematic lit-
erature search. Relevant research literature until

2006 was based on that identified by Cheniaux
et al. (25), updated to 2010 using Medline and
PubMed Central databases via PubMed. Cheni-
aux and co-workers, in a search that also
included affective disorders other than bipolar
disorder, had listed 155 studies in their overview.
We tested all 155 studies for eligibility. However,
we carried out an additional literature search
using the search terms: [(schizoaffective or schizo-
affective) and (schizophr* or bipolar or bipolar
disorder or mani* or cyclothymi* or hypomania
or depress or affective)]. Searching was limited by
the following terms: clinical trial, meta-analysis,
randomized controlled trial, controlled clinical
trials, case report, classical article, clinical trial
(Phase I, II, III, or IV), comparative study, eval-
uation study, historical article, journal article,
multicenter study, twin study, validation study,
and publication dates from November 2006 to
April 2010.
Inclusion required that each study include three
groups of at least ten subjects per subgroup, diag-
nosed with schizoaffective disorder, schizophrenia,
and bipolar disorder, and that it provide at least
one quantifiable factor for comparison across diag-
noses. If more than one report was identified from
the same study, that with the highest N per para-
meter was included. All candidate reports (titles,
abstracts, full texts if necessary) were initially
screened by the first author (TP), with consultative
back-up by the last author (CB). This process iden-
tified a total of 920 reports [155 from Cheniaux
et al. (25) and 765 new items]. Of these, 250 met
screening criteria as relevant to schizoaffective dis-
order, and 670 were excluded. The main reason for
excluding studies was that they did not investigate
or report on all three diagnoses but only dealt with
schizoaffective disorder and either bipolar disorder
or schizophrenia, or that they included other affec-
tive disorders but not bipolar disorder. A final pool
of 50 reports meeting inclusion criteria was
reviewed in detail, and 200 were excluded (Fig. 1).
Identification
765 reports (2006–2010) 155 reports identified in
identified by PubMed search Cheniaux et al. 2008 (25)
Screening 95 reports included 670 reports excluded
Eligibility 250 reports for detailed assessment of inclusion/exclusion
Inclusion 50 reports included for analysis 200 reports excluded
Fig. 1. PRISMA flowchart of reports considered, and
excluded or included for analysis.
Characteristics of schizoaffective disorders
Data management and analysis
Data tabulated electronically included the refer-
ence and year of publication of each report, sub-
jects/study and per diagnosis, diagnostic criteria
employed, and frequencies or means [with stan-
dard deviations (SD)] of demographic and clinical
descriptive characteristics, by diagnostic group.
When multiple assessments or ratings were pro-
vided, only initial or baseline measures and only
total scores of ratings were included, with the
exception of the Scale for Assessment of Negative
Symptoms, which was sometimes reported with a
total score (SANS-1), or as the sum of mean sub-
scale scores (SANS-2). Data regarding diagnostic
subgroups with each primary diagnostic group
were pooled. We included only measures found in
at least two reports. Each parameter analyzed
was pooled within each diagnostic group, with
weighting by numbers of subjects. We used
random-effects meta-analytical modeling to com-
pare factors across diagnostic groups, based on
commercial software [RevMan 5.0 (Cochrane
IMS, London, UK)] and SPSS 19.0 (IBM-SPSS
Corp., Chicago, IL, USA).
To estimate demographic and clinical-course
data, measures of each parameter (for example,
age at onset and gender) in each diagnostic group
were pooled across studies, and weighted by num-
ber of patients. Such findings are not strictly com-
parable between diagnostic groups because of
differences in patient populations between studies
and varying proportions of each diagnostic group
among studies – they are susceptible to Simpson’s
paradox, the reversal of a finding by combining
groups.
In the second approach, we pooled data across
studies for each diagnostic group by random-
effects meta-analysis, to provide only within-study
comparisons to avoid biases just considered for the
first method. For dichotomous parameters, we
pooled odds ratios (ORs) by the Mantel–Haenszel
method, and for continuous parameters, we pooled
mean differences using the inverse variance
method.
As all studies in this field are observational, and
as larger observational studies are not necessarily
better than smaller ones, the weight assigned to
study size in meta-analyses may be misleading.
Therefore, in a third analysis, in order to assess the
differences between pairs of diagnostic groups,
each study was considered as a single contribution,
regardless of its size. We determined the number of
studies that, for different categories (such as gender
or age at onset), documented schizoaffective disor-
der to be closer to schizophrenia or to bipolar
3
Pagel et al.
disorder. To test such comparisons, we used two-
sided, exact binomial tests with a critical signifi-
cance level (a) of 0.05.
In sensitivity analyses, we restricted the calcula-
tions to studies that (i) had used DSM-IIIR and
DSM-IV only and (ii) had included psychotic bipo-
lar disorder patients only.
Results
The database
A total of 50 articles published between 1983 and
2009 were found to be suitable for analysis; the
reports that were included and excluded are
detailed in a flowchart (Fig. 1). Study basics are
provided in Table 1. Almost all (n = 47) studies
employed common diagnostic criteria, ranking:
DSM-IIIR 30%, DSM-IV 28%, Research Diag-
nostic Criteria (RDC) 22%, DSM-III 8%, ICD-9
2%, and ICD-10 2% (plus 8% involving more
than one diagnostic scheme).
Studies analyzed included a total of 18312
patient–subjects: 10814 (59.1%) diagnosed with
schizophrenia (mean: 216/study), 4814 (26.3%)
with bipolar disorder (96/study), and 2684
(14.7%) with schizoaffective disorder (54/study).
Studies varied in the proportions reporting on
demographic (49/50), illness course (25/50), and
psychometric (22/50) characteristics. A variety of
biological parameters were considered, but none
was investigated twice, and so all were excluded.
Estimates of demographic, clinical course, and psychometric
variables
The pooled average age of schizoaffective patients
was 42.7 years, or approximately four years youn-
ger than bipolar disorder and schizophrenia
patients, although only the difference from bipolar
disorder was statistically significant (Table 2).
Schizoaffective disorder patients also included sig-
nificantly more women than among schizophrenia
and bipolar disorder patients (respectively, 52%,
39%, 45%) (Table 2). Marital status and the pro-
portion of ethnic minorities (based on limited sam-
pling) were intermediate among schizoaffective
disorder subjects compared with the other diagno-
ses (Table 2).
Mean onset age, among other measures, varied
greatly among studies. Pooled onset age in schizo-
affective subjects was 23.3 years, significantly
lower than for bipolar disorder (26.1 years) and
higher than for schizophrenia (21.9 years)
(Table 2). These comparisons are also illustrated
as the results of meta-analyses comparing schizoaf-
4
fective subjects with those diagnosed with bipolar
disorder (Fig. 2A) or schizophrenia (Fig. 2B).
Adequate numbers of studies were found to sup-
port comparisons across diagnoses in ratings on
nine psychometric measures (Table 2), ranging
from n = 9 for the Brief Psychiatric Rating Scale
(BPRS) to n = 2 for the sum of subscale scores on
SANS-2. Two measures differed among diagnoses,
and significantly between schizoaffective and bipo-
lar disorder patients: BPRS score (mainly rating
psychotic features) and Wechsler IQ score, and
both were highest in schizoaffective disorder
patients (Table 2). SANS-1 (subscale means) and
depression ratings (Hamilton Depression Rating
Scale) were also highest among schizoaffective dis-
order patients. All other psychometric scores were
intermediate in schizoaffective disorder patients
between the comparison diagnoses, except that
Clinical Global Impression (CGI) scores were
identical among schizoaffective and bipolar disor-
der subjects, and almost equal to schizophrenia
patients (Table 2). For details of the comprehen-
sive meta-analytical results, please refer to the
Forest plots in Appendix S1 (See Supplementary
material).
Similarity of schizoaffective disorder to either schizophrenia
or bipolar disorder
Among pooled variables of schizoaffective patients
(Table 2), ten were more similar to schizophrenia
and ten to bipolar disorder. However, when vari-
ables were compared on the study level, variables
of schizoaffective disorder patients were slightly
more often closer to the results of samples of
patients with schizophrenia than of samples with
bipolar disorder patients: among demographic and
clinical variables 76 versus 74 comparisons
(p = 0.93) (Table 3), for psychometric tests 24 ver-
sus ten comparisons (p = 0.024) (Table 3). When
those comparisons were aggregated to variables
(e.g., all comparisons regarding age at onset),
demographical/clinical variables showed more sim-
ilarity to schizophrenia in seven out of nine vari-
ables (p = 0.18), and the results of psychometric
tests were also closer to those for schizophrenia
(five out of seven, with two variables showing a
similar distance to both control disorders,
p = 0.063) (Table 3).
Sensitivity analyses
Neither of the analyses changed the overall picture:
When the analysis was limited to studies employing
DSM-IIIR and DSM-IV (n = 30 studies), only
four out of nine demographic/clinical variables
 Characteristics of schizoaffective disorders

Table 1. Basic characteristics of all studies included (n = 50)

Subjects (n)

Study (Ref. no.) Country Sites Diagnosis All SAD SZ BD

Rieder et al. 1983 (29) USA Multiple RDC 62 15 28 19

Hubain et al. 1986 (30) Belgium Single Various 53 10 22 21
Holzmann et al. 1986 (31) USA Multiple Various 85 22 43 20
Williams & McGlashan McGlashan 1987 (32) USA Single DSM-III 298 87 188 23
Ragin & Oltmanns 1987 (33) USA Single RDC 36 12 12 12
Kiriike et al. 1988 (34) Japan Single RDC 46 10 27 9
Maj 1989 (35) Italy Single RDC 88 38 25 25
Bellack et al. 1989 (36)a USA Single DSM-IIIR 103 16 58 29
Silverstein et al. 1990 (37) USA Single RDC 48 13 23 12
Mcelroy et al. 1991 (38) USA Single DSM-III 78 25 39 14
Kitamura & Suga 1991 (39) Japan Multiple RDC 105 24 57 24
Pope & Yurgelun-Todd 1993 (40) USA Multiple DSM-III 77 39 12 26
Maier et al. 1993 (41) Germany Single RDC 341 115 146 80
Sharma et al. 1994 (42) USA Single RDC 51 13 30 8
Banov et al. 1994 (43) USA Single DSM-IIIR 173 81 40 52
Amador et al. 1994 (44) USA Multiple DSM-IIIR 310 49 221 40
Van Os et al. 1995 (45) GB Multiple RDC 174 24 79 71
Lewine et al. 1995 (46) USA Multiple DSM-IV 148 20 108 20
Haywood et al. 1995 (47) USA Multiple RDC 112 33 56 23
Verdoux et al. 1996 (48) France Multiple DSM-IIIR 92 14 38 40
Mitrushina et al. 1996 (49) USA Multiple DSM-IIIR 56 18 21 17
Fennig et al. 1996 (50) USA Multiple DSM-IIIR 110 17 46 47
Ricca et al. 1997 (51) Italy Single DSM-IIIR 72 15 28 29
Boutros et al. 1997 (52) Usa Single DSM-IIIR 57 19 22 16
Atre-Vaidya & Taylor 1997 (53) USA Single DSM-IV 66 13 13 40
Radomsky et al. 1999 (54) USA Single DSM-IIIR 733 159 454 120
Weiler et al. 2000 (55) USA Single DSM-III 135 14 81 40
Pini et al. 2001 (56) Italy Single DSM-IIIR 206 24 29 153
Benabarre et al. 2001 (57) Spain Single RDC 138 34 37 67
Reichenberg et al. 2002 (58) USA Single Various 635 31 536 68
Regenold et al. 2002 (59) USA Single DSM-IV 414 114 144 156
Pini et al. 2002 (60) Italy Single DSM-IIIR 156 32 46 78
Ciaparelli et al. 2003 (61) Italy Single DSM-IIIR 101 30 34 37
Averill et al. 2004 (62) USA Single DSM-IV 480 92 207 181
Nardi et al. 2005 (63) Brasil Single DSM-IV 173 61 55 57
Jacquet et al. 2005 (64) France Multiple DSM-IIIR 320 63 188 69
Glahn et al. 2006 (65)a USA Single DSM-IV 56 15 15 26
Richardson et al. 2007 (66) USA Single DSM-IIIR 240 59 154 27
Martin et al. 2007 (67) USA Multiple DSM-IV 87 18 29 40
Kilbourne et al. 2007 (68) USA Multiple ICD-9 7529 632 4721 2176
Ciapparelli et al. 2007 (69) Italy Single DSM-IV 98 19 23 56
van Winkel et al. 2008 (70) Belgium Single DSM-IV 707 92 503 112
Szoke et al. 2008 (71) France Multiple DSM-IV 166 26 48 92
Radonic et al. 2008 (72) Croatia Single Various 45 15 15 15
Walterfang et al. 2009 (73) Australia Single DSM-IIIR 67 15 30 22
Reichenberg et al. 2009 (74) USA Multiple DSM-IV 187 15 94 78
Ongur et al. 2009 (75) USA Single DSM-IV 233 61 80 92
Lencz et al. 2009 (76) USA Single DSM-IV 349 61 211 77
Ledda et al. 2009 (77) Italy Single DSM-IV 41 11 17 13
Lambert et al. 2009 (78) Germany Single ICD-10 2175 249 1681 245
Totals 15 multiple 18312 2684 10814 4814
(50 reports) 1983–2009 35 single

BD = bipolar disorder; DSM = Diagnostic and Statistical Manual of Mental Disorders; ICD = International Classification of Diseases;
RDC = Research Diagnostic Criteria; SAD = schizoaffective disorder; SZ = schizophrenia.
a
Reported attempts at matching patients.

5
Pagel et al.

Table 2. Comparison of characteristics in schizoaffective (SAD) versus schizophrenia (SZ) and versus bipolar disorder (BD) patients, based on
meta-analyses to provide pooled values and meta-analytical mean differences

SAD SAD
versus versus
Cases (n) SZ SAD BD SZ p-value BD p-value

Characteristics Pooled values Meta-analytical mean differences

Demographic and clinical

Age, years, mean (SD)
Onset 2464 21.9  2.9 23.3  3.8 26.1  4.9 0.78 0.22 2.91 0.0004
Current 15872 46.9  9.6 42.7  9.4 46.7  8.6 0.0 1.00 3.10 <0.0001
Education, years 1105 12.1  0.8 12.3  1.0 13.3  0.9 0.39 0.16 0.92 0.0006
Gender (%) 10285 0.57 <0.0001 1.03 <0.69
Men 61 48 55
Women 39 52 45
Ethnic origin (%)
Caucasian 2788 47 52 60 1.25 0.23 0.52 <0.0001
African-American 9565 32 25 13 0.52 <0.0001 1.50 <0.04
Martial status (%)
Currently married 970 12 37 44 3.24 0.03 0.59 0.13
Ever married 1522 25 34 41 1.61 0.03 0.63 0.02
Years of illness, 1444 11.1  2.5 13.3  3.4 11.5  3.3 1.77 0.03 2.10 0.04
mean (SD)
Hospitalizations/person, 2260 5.3  4.9 3.7  1.6 3.1  1.0 1.36 0.74 0.84 0.15
mean (SD)
Age at first hospitalization, 1173 21.3  1.2 23.7  2.1 24.8  4.1 1.49 0.38 1.25 0.42
years, mean (SD)
Psychometric, mean (SD)
BPRS 862 43.0  8.2 45.6  7.0 37.8  5.2 0.50 0.62 3.85 <0.0001
CGI 2374 5.0  0.2 5.1  0.2 5.1  0.1 0.14 0.22 0.15 0.19
GAF 1635 43.4  18.9 38.6  16.1 34.9  13.6 2.15 0.003 0.77 0.76
GAS 487 35.6  6.5 40.0  8.1 45.5  14.1 3.00 0.03 6.01 0.11
HDRS 479 13.3  4.9 20.3  5.5 10.8  5.9 4.71 0.03 7.01 0.01
SANS-1 (subscore mean) 404 2.9  2.2 3.3  2.2 0.9  0.5 0.63 0.03 0.85 0.02
SANS-2 (subscore sum) 276 55.8  2.8 47.9  7.9 27.5  4.0 7.66 0.15 22.7 0.07
SAPS 294 1.6  1.8 1.5  0.7 0.6  0.4 0.03 0.94 0.32 0.12
WAIS-IQ 741 102.4  8.8 105.5  10.0 103.7  8.8 0.64 0.75 7.31 0.001

Continuous measures are presented as mean  standard deviation (SD), categorical variables as percentages. Note that comparisons
of SAD versus SZ or BD are based on meta-analytical mean differences (to avoid Simpson’s paradox), not on pooled mean differences.
BPRS = Brief Psychiatric Rating Scale; CGI = Clinical Global Impression; GAF = Global Assessment of Functioning; GAS = Global
Assessment Scale; HDRS = Hamilton Depression Rating Scale; SANS = Scale for Assessment of Negative Symptoms; SAPS = Scale
for Assessment of Positive Symptoms; WAIS-IQ = Wechsler Adult Intelligence Scale-Intelligence Quotient.

were closer to bipolar disorder, and only two out
of nine closer to schizophrenia (for three out of
nine variables, we counted an equal number of
studies leaning in either direction). With regard to
psychometric scales, however, four out of seven
variables were closer to schizophrenia and none of
seven was closer to bipolar disorder (three out of
seven showed no difference). When we looked at
the pooled means of psychometric scales, the
resemblance of the values of schizoaffective disor-
der patients to those of schizophrenia patients was
not more pronounced (Table 4).
In the second sensitivity analysis (psychotic
bipolar patients only, n = 17 studies), the majority
of studies showed the scores of psychometric vari-
ables in schizoaffective disorder patients to have a
closer proximity to those of schizophrenia patients
(six out of seven variables, no difference in 1). With
6
regard to demographic/clinical variables, three out
of seven were closer to schizophrenia, two out of
seven to bipolar disorder (in two out of seven, no
difference) (Table 4).
Discussion
The present study considered only reports in which
schizoaffective disorder, schizophrenia, and bipo-
lar disorder patients were compared directly under
similar circumstances – an approach aimed at lim-
iting sampling bias. We estimated basic demo-
graphic, clinical, and psychometric parameters for
schizoaffective disorder and compared them with
the results from schizophrenia and bipolar disorder
patients evaluated simultaneously. Therefore, we
believe that the results presented are as balanced as
possible in summarizing observational studies.
 Characteristics of schizoaffective disorders

Kiriike et al. 1988

Maier et al. 1993
Amador et al. 1994
Banov et al. 1994
Verdoux et al. 1996
Atre-Vaidya & Taylor 1997
Ricca et al. 1997
Benabarre et al. 2001
Ciapparelli et al. 2003
Pini et al. 2004
Nardi et al. 2005
Glahn et al. 2006
Ciapparelli et al. 2007
Radonic et al. 2008
Ledda et al. 2009
Walterfang et al. 2009

A B
–25 –20 –15 –10 –5 0 5 10 –10 –5 0 5 10
Pooled mean difference
[ Schizoaffective lower]

Fig. 2. Examples of results from meta-analyses of reports on age at onset comparing (A) schizoaffective versus bipolar disorder
patients and (B) schizoaffective versus schizophrenia. Every study included patients with all three disorders. Onset age is significantly
younger in schizoaffective versus bipolar disorder patients: mean difference = 2.91 [confidence interval (CI): 4.52 to 1.29 years];
z = 3.53, p = 0.004; heterogeneity: (I2 = 77%, v2 = 64.05, p < 0.00001), but not versus schizophrenia cases: mean difference = 0.78
(CI: 0.46 to 2.01 years); z = 1.23, p = 0.22; heterogeneity: (I2 = 68%, v2 = 46.61, p < 0.0001).

In most categories, including a series of ratings
with standard psychometric scales, pooled mea-
sures for schizoaffective disorder patients were
intermediate between, or not significantly different
from, measures in comparison with subjects diag-
nosed with schizophrenia or bipolar disorder.
Notably, statistically significant exceptions were
that schizoaffective disorder patients had the high-
est proportion of women and the youngest
reported onset age of all three disorders. In addi-
tion, in terms of the numbers of studies, the find-
ings for schizoaffective disorder patients were more
similar to those for schizophrenia than to those for
bipolar disorder.
Two important epidemiological investigations of
schizoaffective disorder also found an excess of
women over men patients, and found more cases
meeting the diagnostic criteria for schizophrenia
(18, 19) and bipolar disorder (19) than for schizo-
affective disorder.
Overall, considering the pooled data, the present
findings do not support the hypothesis that schizo-
affective disorder is closer to schizophrenia or to
bipolar disorder. The numerical values of many
identified parameters in schizoaffective disorder
and their degree of similarity to findings in the
comparison groups fell between, or differed little
from, those in schizophrenia and in bipolar disor-
der patients (Table 2). However, in terms of the
numbers of studies, the findings for schizoaffective
disorder patients tended to be somewhat closer to
those for patients with schizophrenia than to those
for patients with bipolar disorder. Therefore, our
results do not support the hypothesis that schizoaf-
fective disorder is an affective illness. It remains
unclear, however, whether our findings reflect the
nature of the disorder or whether they are simply
an artifact of current diagnostic criteria.
Although some variables describe the course of
the illness, such as the number of hospitalizations,
more reflect cross-sectional aspects – namely, most
of the psychopathology scores. The course of
schizoaffective disorder may be more similar to
that of bipolar disorder than to that of schizophre-
nia. Therefore, an analysis of course variables may
produce different results.
Limitations
Some comparisons between diagnoses may have
been distorted by unbalanced statistical power
across the diagnoses, for which the numbers of
patient-subjects ranked: schizophrenia > bipolar
disorder > schizoaffective disorder. Therefore, it is
more likely to find differences from schizophrenia
than from bipolar disorder. In addition, the num-
bers of studies and of subjects for some measures
were small, and the results of most meta-analytical
comparisons of schizoaffective disorder with either
comparison group were still of considerable heter-
ogeneity (e.g., see Fig. 2), even after restricting the
comparisons to studies that simultaneously investi-
gated all three disorders. Sources of heterogeneity
may include the limited number of reports identi-
fied that met our inclusion criteria, and particularly
limited efforts to match subgroups within most
7
Pagel et al.

Table 3. Resemblance of measures in schizoaffective disorder (SAD) phrenia than to affective disorders, including
patients versus those diagnosed with schizophrenia (SZ) or bipolar dis- DSM-IIIR and DSM-IV criteria. In the same vein,
order (BD) in the same studies
it is conceivable that the differences from bipolar
SAD closer disorder will be smaller once comparisons are
to (n) restricted to patients with psychotic bipolar disor-
der, as has been found in a similar study that
Measures Comparisons (n) SZ BD
aimed at comparing the heterogeneity (as mea-
Demographic and clinical factors sured by the standard deviation) of schizoaffective
Current age 38 22 16 disorder with that of schizophrenia and bipolar
Proportion of men 39 12 27 disorder (27). In that study, we found that the het-
Onset age 18 10 8
Proportion of 13 6 7
erogeneity of schizoaffective disorder was, contrary
African-Americans to our expectations, no greater than that of schizo-
Marital status 11 6 5 phrenia and bipolar disorder but rather slightly
Years of education 10 6 4 smaller, and more similar to that of schizophrenia.
Years of illness 8 6 2 However, when we carried out sensitivity analy-
Hospitalizations 9 5 4
First-hospitalization age 4 3 1
ses and restricted the studies analyzed to those that
Sum 150 76 74 had employed DSM-IIIR and DSM-IV only or, in
Variables with majority of studies closer to 7 2 a second analysis, to studies including psychotic
either disorder bipolar disorder patients, the larger picture
Psychometric ratings remained the same. If anything, contrary to our
BPRS 8 5 3
WAIS-IQ 6 6 0
expectations, in DSM-IIIR and DSM-IV studies
GAF 5 3 2 the results of schizoaffective disorder samples were
GAS 4 2 2 slightly closer to those of bipolar disorder. The
HDRS 4 4 0 results of both sensitivity analyses indicate that the
SANS 5 3 2 diagnostic system used is probably less important
SAPS 2 1 1
Sum 34 24 10
than one would think. This interpretation is in line
Variables with majority of studies closer to 5 0 with the finding that psychiatrists base their diag-
either disorder nosis on diagnostic stereotypes rather than on
diagnostic criteria such as DSM-IV (28).
The table shows the number and percentage of comparisons for
each item in which measures among SAD patients were quanti-
tatively more similar to SZ or to BD patients. Note that findings Conclusions
are not independent but inter-correlated. BPRS = Brief Psychiat-
ric Rating Scale; GAF = Global Assessment of Functioning; The present study pooled data from individual
GAS = Global Assessment Scale; HDRS = Hamilton Depression studies designed to compare patients diagnosed
Rating Scale; SANS = Scale for Assessment of Negative Symp- with schizoaffective, schizophrenia, and bipolar
toms; SAPS = Scale for Assessment of Positive Symptoms;
WAIS-IQ = Wechsler Adult Intelligence Scale-Intelligence
disorders under similar circumstances. We believe
Quotient. that the value of this study is twofold: firstly, it pre-
sents a systematic and comprehensive estimation
of important illness variables in schizoaffective dis-
studies (with only two studies attempting to match order – for example, gender ratio, age at onset, and
samples). In addition, we deliberately avoided number of episodes. Secondly, by using these esti-
making comparisons of schizoaffective disorder mates to determine the position of schizoaffective
with major depressive disorder, even though many disorder in relation to schizophrenia and bipolar
cases of major depression are recurrent and some disorder, the study adds to the discussion about
show psychotic features, although to a lesser extent the nosological position of schizoaffective disorder.
than in bipolar disorder (26). The findings indicate some, often minor, differ-
Given the limitations of the present meta-analy- ences among the diagnostic groups in the numeri-
sis and of the reports included, the findings cal values of a large sampling of demographic,
reported must be considered with caution. It is, clinical, and psychometric measures. The findings
however, the largest quantitative study of this type support the view that schizoaffective disorder,
to date. Nevertheless, there is a need for epidemio- as currently defined, lies between, or shares fea-
logical studies of schizoaffective disorder to repli- tures of both, schizophrenia and bipolar disorder.
cate the demographic and clinical characteristics However, the long-standing controversies remain
found in the present study. open to discussion about whether schizoaffective
Some modern diagnostic systems define schizo- disorder is a separate, intermediate syndrome; lies
affective disorder as being more related to schizo- on a continuum of psychotic conditions; or may be
8

Table 4. Different demographic/clinical and psychometric variables with a closer proximity of schizoaffective disorder (SAD) patients to either schizo-
phrenia (SZ) or bipolar disorder (BD)a
Sample of studies Variables
Studies using all diagnostic Demographic/clinical variables
systems (n = 50) Psychometric variables
Studies using DSM-IIIR and Demographic/clinical variables
DSM-IV only (n = 30) Psychometric variables
Studies including psychotic Demographic/clinical variables
BD patients only (n = 17) Psychometric variables
a
For every variable, proximity was determined by counting the number of studies indicating a closer resemblance to SZ or BD (see
Table 3). For example, for psychometric variables, in studies using DSM-IIIR and DSM-IV only, the majority of studies showed the values
of SAD patients to be closer to those of SZ patients with regard to four psychometric variables (i.e., psychometric tests such as the Brief
Psychiatric Rating Scale or the Scale for Assessment of Negative Symptoms). However, for no psychometric test did a majority of stud-
ies indicate SAD patients’ results to be closer to those of BD patients than to those of SZ patients. For three psychometric tests, the num-
ber of studies leaning toward either disorder was equal.
a reflection of the lack of specificity of many crite-
ria for affective and non-affective psychotic disor-
ders. The present study adds balanced estimates of
important demographic and clinical variables char-
acterizing this enigmatic nosological concept. In
addition, our results indicate that schizoaffective
disorder may be closer to schizophrenia than to
bipolar disorder.
Acknowledgements
We gratefully acknowledge the assistance of Dr. Elie Cheniaux
of the Institute of Psychiatry, Federal University (Rio de
Janeiro, Brazil) in providing bibliographic references from her
review of schizoaffective disorder. This report is a component
of the doctoral dissertation of Tobias Pagel. The work was
supported, in part, by a grant from the Bruce J. Anderson
Foundation and the McLean Private Donors Psychiatric
Research Fund (RJB).
Disclosures
None of the authors or any immediate family member has
financial relationships with industrial or other commercial enti-
ties that might present the potential for conflicts of interest in
the material presented.
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Supporting Information
Additional Supporting Information may be found in the online
version of this article:
Appendix S1. Forest plots of meta-analyses. BP = bipolar dis-
order; S = schizophrenia; SAD = schizoaffective disorder.
11