Schizoaffective Disorder 2011

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Schizoaffective Disorder
LESLIE CITROME
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Schizoaffective Disorder
A Review of Current Research Themes and Pharmacological
Management
Joshua T. Kantrowitz
1,2
and Leslie Citrome
3
1 Schizophrenia Research Center, Nathan S. Kline Institute for Psychiatric Research, Orangeburg,
New York, USA
2 Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, New York, USA
3 Department of Psychiatry, New York University School of Medicine, New York, New York, USA
Contents
Abstract................................................................................. 317
1. History and Diagnostic Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
2. Diagnostic Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
3. Current Research Themes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
3.1 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
3.2 Neurocognition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
3.2.1 Comparisons of Schizoaffective Disorder with Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . 322
3.2.2 Comparisons of Schizoaffective Disorder with Bipolar Disorder . . . . . . . . . . . . . . . . . . . . . . 324
3.3 Basic Sensory Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
4. Medical Co-Morbidities and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
4.1 Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
4.2 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
5. Pharmacological Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
5.1 Monotherapy with Antipsychotics or Mood Stabilizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
5.2 Combination Treatment with Antipsychotics, Mood Stabilizers and/or Antidepressants . . . . . . . 327
6. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Abstract Despite a clear recognition of the existence of patients with co-morbid
psychotic and mood symptoms, many studies conclude that schizoaffective
disorder as a distinct diagnosis does not exist. Regardless of one’s opinion on
schizoaffective disorder, psychiatrists remain dependent on phenomenolog-
ical descriptions for diagnosing psychiatric disorders, and these phenom-
enological criteria are also used for clinical trial entry. On the other hand,
many psychiatrists prescribe for specific target symptoms and do not always
rigidly follow diagnostic systems and, moreover, there have been very few
trials that have specifically studied schizoaffective disorder.
Despite recent intriguing work in epidemiology, genetics, neurocognition
and electrophysiology, the diagnosis of schizoaffective disorder remains con-
troversial. Taken together, these studies suggest that even if schizoaffective
disorder exists as a separate diagnosis, it may not be useful clinically due to
considerable variation in the general use of this term. It is possible that diagnostic
criteria in the future will include genetic, imaging and electrophysiological
REVIEW ARTICLE CNS Drugs 2011; 25 (4): 317-331
1172-7047/11/0004-0317/$49.95/0
ª2011 Adis Data Information BV. All rights reserved.

components, and that this will allow for better differentiation of disease states
among the heterogeneous pool of patients currently believed to have schizo-
phrenia, schizoaffective disorder or bipolar disorder.
Although it is likely that most, if not all, antipsychotics are effective for
schizoaffective disorder, given recent regulatory approval of a specific anti-
psychotic agent for the acute treatment of schizoaffective disorder, greater
attention is now being focused on the entity of schizoaffective disorder and
potential treatment decisions. However, based on the limited extant evidence,
it is not yet possible to make definitive treatment recommendations for schizo-
affective disorder. Additional clinical trials that include other antipsychotics,
mood stabilizers and antidepressants are desirable and necessary before clear
and comprehensive evidence-based treatment recommendations can be made.
Few psychotic disorders are as controversial as
schizoaffective disorder. As currently formulated
in the DSM-IV-TR,
[1]
the fundamental feature of
schizoaffective disorder is a continuous period of
illness during which criteria for a major mood
disorder (e.g. a major depressive episode, a manic
episode or a mixed episode) coincide with the es-
sential features of schizophrenia. Although mood
symptoms must represent a prominent part of the
illness episode, there must be psychotic symptoms
(delusions or hallucinations) without prominent
mood symptoms for at least 2 weeks.
No one denies that patients with co-morbid
psychotic and mood symptoms exist. Neverthe-
less, as reviewed in section 2, many researchers
conclude that schizoaffective disorder does not
exist as a distinct diagnosis. There is a lack of con-
sensus regarding whether the disease represents
a distinct clinical entity, if the symptomatology
represents the presence of a co-occurrence of two
distinct mental disorders in a single patient, or
if the disease represents a state in the psychotic
continuum that extends from bipolar to schizo-
phrenia. There are several extant reviews that
argue for and against the legitimacy of schizo-
affective disorder.
[2-4]
Regardless of one’s opinion on schizoaffective
disorder, psychiatrists remain dependent on phe-
nomenological descriptions for diagnosing psy-
chiatric disorders, and these phenomenological
criteria are also used for clinical trial entry. On
the other hand, many psychiatrists prescribe for
specific target symptoms and do not always rig-
idly follow diagnostic systems and, moreover, as
detailed in the section on pharmacological treat-
ment (section 5), there have been very few trials that
have specifically studied schizoaffective disorder.
This review focuses primarily on the current
research themes of schizoaffective disorder, and
begins by tracing the history and diagnostic criteria
of the schizoaffective diagnosis, and then proceeds
to reviewing diagnostic reliability, and preliminary
findings in genetics, medical co-morbidities, neuro-
cognitive functioning and early sensory processing,
before concluding with a review of pharmacologi-
cal treatment studies. PubMed was searched up to
June 2010 using the keywords ‘schizoaffective dis-
order’ for all English-language articles. In addition,
we examined the reference lists of review articles for
other reports of interest that may have been missed
by our initial search. Since the primary focus of this
review is to educate the reader on current research
themes, we placed a particular focus on research
published since 2006.
1. History and Diagnostic Criteria
In his landmark 1919 work,
[5]
Kraepelin di-
vided psychotic and mood disorders into distinct
nosological entities. This division continues to
be useful in determining the course of mental
illnesses. Even at the time, however, it was rec-
ognized that there were instances where the major
mental illnesses could not be so easily subdivided.
In 1933, Dr Jacob Kasanin coined the term
‘schizoaffective psychosis’ based on a case series
of nine patients.
[6]
This group was distinguished
by an acute onset of illness, prominent manic
318 Kantrowitz & Citrome
ª2011 Adis Data Information BV. All rights reserved. CNS Drugs 2011; 25 (4)

and/or depressive symptomatology, active social
and pre-morbid personalities, and relatively brief
periods of psychosis lasting weeks to a few months
and good recoveries. In the US, schizoaffective
disorder did not appear as a separate diagnosis
with operationalized criteria until DSM-III-R in
1987.
[7]
Current diagnostic criteria for schizoaffective
disorder in DSM-IV-TR emphasize the need for
concurrent mood and psychotic symptoms (see
pages 319–23 in DSM-IV-TR
[1]
). According to
DSM-IV-TR, schizoaffective disorder is defined
as a period of uninterrupted illness that includes
psychotic and mood symptoms. More specifi-
cally, Criterion A states that, at some point in
their illness, schizoaffective disorder patients must
meet criteria for a major mood episode (i.e. a
major depressive, manic or mixed episode) co-
existing with symptoms that meet criterion A for
schizophrenia (i.e. delusions, hallucinations, grossly
disorganized behaviour, catatonic behaviour or
negative symptoms). Criterion B states that,
during the same episode that met criterion A,
delusions or hallucinations persisted for at least
2 weeks without prominent mood symptoms, and
Criterion C specifies that the mood symptoms
must be present for a substantial portion of the
total duration of the illness. Criterion C exists
to minimize the over-diagnosis of schizoaffective
disorder in a psychotic patient with limited con-
current mood symptoms. Schizoaffective disorder
may be further subdivided into two subtypes:
bipolar type, if a manic episode or mixed episode
is part of the presentation, and a depressive type,
if only major depressive episodes are part of the
presentation.
Other diagnostic schemes for schizoaffective
disorder exist, including the Research Diagnostic
Criteria (RDC)
[8]
and the International Classifi-
cation of Diseases (10th Edition) [ICD-10]
[9]
(table I). Similar to other diagnostic schemes,
RDC includes two main subtypes, manic and
depressed, but also argues for additional sub-
divisions, such as acute versus chronic, mainly
schizophrenic and mainly affective, for each sub-
type. ICD-10 differs from DSM-IV primarily by
requiring specific types of delusions or comment-
ing auditory hallucinations, and being somewhat
looser on requiring simultaneous psychotic and
mood symptoms. Regardless of which set of di-
agnostic criteria is used, the duration criteria for
both the mood and psychotic subcriteria can be
difficult to assess. More so than for other psy-
chiatric disorders, schizoaffective disorder requires
access to longitudinal clinical data, sometimes
over several years.
2. Diagnostic Uncertainty
Although the DSM-IV field trials
[13]
suggested
good reliability for the diagnosis of schizoaffec-
tive disorder, more recent trials have found a lack
of consensus. This can be summarized by a recent
meta-analysis,
[14]
which failed to find a clear dis-
tinction between schizoaffective and schizophrenia
or major depressive disorder in demographic char-
acteristics, symptoms, neuroimaging examinations,
response to treatment, illness course and family
morbidity. These findings are consistent with sev-
eral reports published since this particular meta-
analysis was undertaken. In a study by a group
from Denmark,
[15]
59 patients with hospital dis-
charge diagnoses of schizoaffective disorder were
re-reviewed using explicit criteria, with no pa-
tients meeting DSM-IV-TR criteria and only six
patients meeting ICD-10 criteria. The majority of
these patients were better characterized by schizo-
phrenia (n =22) or a primary affective illness
(n =6). In a strongly worded conclusion, the au-
thors called for a moratorium on the clinical use
of the diagnosis of schizoaffective disorder. This
was supported by an analysis of the 2.5 million
person Denmark registry.
[16]
In this large anal-
ysis, a large degree of co-morbidity was found
between schizophrenia, bipolar and schizoaffec-
tive disorders. Taken together, these studies sug-
gest that, even if schizoaffective disorder exists
as a separate diagnosis, it may not be clinically
useful due to considerable variation in the general
use of this term.
While it is often stated that the prognosis for
a patient with schizoaffective disorder is inter-
mediate between that of chronic schizophrenia and
that of bipolar disorder, several recent studies
[17,18]
have not revealed any clear distinctions between
these three disorders in terms of longitudinal
Schizoaffective Disorder: Research Themes and Pharmacological Management 319
ª2011 Adis Data Information BV. All rights reserved. CNS Drugs 2011; 25 (4)

Table I. Diagnostic criteria for schizoaffective disorder
Source Criteria
DSM-III
[10]
Included as a psychotic disorder not otherwise classified. Retained without diagnostic criteria for those instances in
which the clinician is unable to make a differential diagnosis with any degree of certainty between Affective Disorder
and either Schizophreniform Disorder or Schizophrenia
DSM-III-R
[7]
A. A disturbance during which, at some time, there is either a Major Depressive or a Manic Syndrome concurrent
with symptoms that meet criterion A for Schizophrenia
B. During an episode of the disturbance, there have been delusions or hallucinations for at least 2 weeks,
but no prominent mood symptoms
C. Schizophrenia has been ruled out, i.e. the duration of all episodes of a mood syndrome has not been brief relative
to the total duration of the psychotic disturbance
D. It cannot be established that an organic factor initiated and maintained the disturbance
Subtypes: Bipolar (current or previous Manic Syndrome) or Depressive (no current or previous Manic Syndrome)
DSM-IV
[11]
and
DSM-IV-TR
[1]
A. An uninterrupted period of illness during which, at some time, there is either a Major Depressive Episode, a Manic
Episode or a Mixed Episode concurrent with symptoms that meet Criterion A for Schizophrenia
Note: The Major Depressive Episode must include Criterion A1: depressed mood
B. During the same period of illness, there have been delusions or hallucinations for at least 2 weeks in the absence
of prominent mood symptoms
C. Symptoms that meet criteria for a mood episode are present for a substantial portion of the total duration of the active
and residual periods of the illness
D. The disturbance is not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication)
or a general medical condition
Subtypes: Bipolar, if the disturbance includes a Manic or a Mixed Episode (or a Manic or a Mixed Episode and Major
Depressive Episodes); Depressive, if the disturbance only includes Major Depressive Episodes
ICD-9
[12]a
A psychosis in which pronounced manic or depressive features are intermingled with schizophrenic features and which
tends towards remission without permanent defect, but which is prone to recur. The diagnosis should be made only
when both the affective and schizophrenic symptoms are pronounced
ICD-10
[9]a
G1. The disorder meets the criteria for one of the affective disorders of moderate or severe degree, as specified for
each category
G2. Symptoms from at least one of the groups listed below must be clearly present for most of the time during a period
of at least 2 weeks (these groups are almost the same as for schizophrenia):
1. thought echo, thought insertion or withdrawal, thought broadcasting
2. delusions of control, influence or passivity, clearly referred to body or limb movements or specific thoughts,
actions or sensations
3. hallucinatory voices giving a running commentary on the patient’s behaviour or discussing the patient among
themselves, or other types of hallucinatory voices coming from some part of the body
4. persistent delusions of other kinds that are culturally inappropriate and completely impossible, but not merely
grandiose or persecutory, e.g. has visited other worlds, can control the clouds by breathing in and out, can
communicate with plants or animals without speaking
5. grossly irrelevant or incoherent speech, or frequent use of neologisms
6. intermittent but frequent appearance of some forms of catatonic behaviour, such as posturing, waxy flexibility
and negativism
G3. Criteria G1 and G2 above must be met within the same episode of the disorder, and concurrently for at least part
of the episode. Symptoms from both G1 and G2 must be prominent in the clinical picture
G4. The disorder is not attributable to organic mental disorder, or to psychoactive substance-related intoxication,
dependence or withdrawal
RDC
[8]
An episode of illness that fulfils the criteria for a full depressive or manic syndrome but also has at least one of the
symptoms suggesting Schizophrenia. Signs of the illness have lasted at least 1 week from the onset of a noticeable
change in the patient’s usual condition. The affective syndrome overlaps temporally to some degree with the active
period of schizophrenia-like symptoms
a Although ICD-9 and -10 are also available in modified versions, noted as ‘Clinical Modification’ (CM), these versions have not resulted in
any textual changes to the criteria for schizoaffective disorder.
ICD-9 =International Classification of Diseases (9th Edition);ICD-10 =International Classification of Diseases (10th Edition);RDC =Research
Diagnostic Criteria.
320 Kantrowitz & Citrome
ª2011 Adis Data Information BV. All rights reserved. CNS Drugs 2011; 25 (4)