Short Report
Psychopathology 2016;49:14
DOI: 10.1159/000443837
Schizo-Obsessive Disorder: A Brief
Report of Neuroimaging Findings
LuigiAttademo a FrancescoBernardini a RobertoQuartesan a,b
a
School of Psychiatry and b Division of Psychiatry, Department of Medicine, University of Perugia, Perugia, Italy
Key Words
Schizo-obsessive disorder Imaging Neuroimaging Brief
report
Abstract
Background: The term schizo-obsessive disorder was
coined to describe schizophrenia (SCZ) patients who are also
affected by obsessive-compulsive symptoms (OCS) or also
meet the criteria for obsessive-compulsive disorder (OCD).
Several studies have investigated the clinical and epidemio-
logical features of OCS/OCD in SCZ, but the neuroimaging
literature is sparse. The aim of this brief report is to describe
some of the most important neuroimaging findings regard-
ing schizo-obsessive disorder. Methods: A literature search
of the PubMed electronic database was conducted up to
July 25, 2015. Search terms included schizo-obsessive com-
bined with the names of specific neuroimaging techniques.
Results: Neuroimaging studies suggest that there may be a
specific pattern of neuroanatomic dysfunction in schizo-ob-
sessive patients, but the number of studies is limited and
conclusions are preliminary because reports are of an explor-
atory nature. Conclusions: Further neurobiological research
is needed to definitely determine whether schizo-obsessive
disorder might have unique neuroanatomical and function-
al alterations. 2016 S. Karger AG, Basel
2016 S. Karger AG, Basel
02544962/16/04910001$39.50/0
E-Mail karger@karger.com
www.karger.com/psp
Received: July 28, 2015
Accepted after revision: January 7, 2016
Published online: February 24, 2016
Introduction
Schizophrenia (SCZ) and obsessive-compulsive disor-
der (OCD) are described as distinct diseases in contem-
porary psychiatric nomenclature, but these disorders
seem to have notable areas of overlap and have a complex
association on the psychopathological level [1]. Obses-
sive-compulsive symptoms (OCS) are common and clin-
ically significant phenomena in SCZ patients [2]. Epide-
miological studies reported that 2.564% and 037.5% of
SCZ patients experience OCS or have OCD, respectively
[3]. The lifetime prevalence is usually estimated to be be-
tween 1 and 1.5% for SCZ and to be between 2 and 3% for
OCD, therefore the co-occurrence of OCS/OCD and SCZ
cannot be explained by mere chance [4]. The term schizo-
obsessive disorder was coined to describe SCZ patients
who are also affected by OCS or also meet the criteria for
OCD [5, 6]. However, whether this putative schizo-obses-
sive subtype of the SCZ population represents a true di-
agnostic entity is still a matter of debate; in particular,
whether this co-occurrence is a mere comorbidity or rep-
resents a separate diagnostic entity remains controversial
[4]. In fact, although a number of studies have investi-
gated the clinical characteristics and the epidemiological
features of OCS/OCD in SCZ, neurobiology researches
are rather limited and the neuroimaging literature is
198.143.32.65 - 3/4/2016 7:29:46 PM
Luigi Attademo
University of Pittsburgh
School of Psychiatry, University of Perugia
Piazzale Lucio Severi, Edificio Ellisse (8 piano), SantAndrea delle Fratte
Downloaded by:
IT06132 Perugia (Italy)
E-Mail luigi.attademo@hotmail.it
sparse [4]. Neuroanatomy independent and compara-
tive studies of OCD and SCZ prevail on researches at-
tempting to identify the neurobiological aspects of the
putative schizo-obsessive disorder [7]. Neuroimaging
studies in OCD patients revealed abnormalities in the
cortical-striatal-thalamic-cortical circuitry (orbitofron-
tal/cingulate cortex, caudate nucleus, globus pallidus,
dorsal thalamus). Neuroimaging studies in SCZ patients
demonstrated abnormalities in brain regions such as the
prefrontal cortex, basal ganglia, thalamus and cerebel-
lum, and hypothesized a dysfunctional prefrontal-tha-
lamic-cerebellar-prefrontal circuitry [4]. The consider-
able overlap in the neurocircuitry and specific anatomical
structures implicated in each disorder may account for
symptom coexpression in the schizo-obsessive subgroup
of patients. In this brief report, we describe some of the
most important neuroimaging findings regarding this co-
morbid subgroup. The authors hope that this paper may
stimulate further empirical research to investigate on the
possible unique imaging patterns specific to a putative
schizo-obsessive subtype.
Methods
For this report, a literature search of the PubMed electronic
database was conducted by the first author up to July 25, 2015.
Search terms included schizo-obsessive combined with imaging
or neuroimaging or computed axial tomography or CAT or caudate nucleus in SCZ seems to be corroborated by the
computed tomography or CT or diffuse optical imaging or precipitation of OCS by lesions to this structure in OCD
event-related optical signal or magnetic resonance imaging or
MRI or functional magnetic resonance imaging or fMRI or
magnetoencephalography or positron emission tomography or
PET or single-photon emission computed tomography or
SPECT. As a result, a total of 9 studies were found, specifically 4
original research reports [2, 810], 4 review articles [1114] and 1
clinical case report [15]. One [9] of the above-mentioned original
research articles was discarded as unrelated to the topic. In addi-
tion to our PubMed search, another 4 relevant neuroimaging stud-
ies in schizo-obsessive disorder (all original research reports) were
also included in this report, based on our knowledge of the subject
[1619]. All articles were written in the English language.
Results
Main Findings from Structural Imaging Studies
In 1998, Iida et al. [18] conducted an MRI study which
identified a significant enlargement of the anterior horn
of the lateral ventricle and of the third ventricle in the
schizo-obsessive group (n = 11), in comparison with the
SCZ group (n = 12). Another MRI study, conducted in
2000 by Aoyama et al. [17], found significantly reduced
2 Psychopathology 2016;49:14
DOI: 10.1159/000443837
volumes of the left hippocampus, frontal lobes and ante-
rior horn of the lateral and third ventricles in the schizo-
obsessive group (n = 15) compared to the SCZ group
(n = 17) and healthy controls (HC; n = 19); an inverse cor-
relation between illness duration and frontal lobe size was
also found in schizo-obsessive patients but not in SCZ
patients.
Main Findings from Functional Imaging Studies
In 1998, Levine et al. [19] conducted an fMRI study
in a group of schizo-obsessive patients (n = 11) and
found a significant negative correlation between OCS
severity and activation of the left dorsolateral prefrontal
cortex (DLPFC). In this study, fMRI was performed to
analyze data from the left DLPFC during a word fluency
verbal paradigm. In 2003, Gross-Isseroff et al. [14] pub-
lished a comprehensive review of independent and com-
parative structural and functional neuroimaging studies
of OCD and SCZ in order to find a neuroimaging com-
munality between the two disorders. The authors re-
ported some controversial findings: (a) there are some
functional and structural similarities between the neu-
roanatomical regions implicated in OCD and SCZ;
(b) there is a partial overlap of findings between OCD
and SCZ in the caudate nucleus and anterior cingulated
gyrus; (c) no overlap has been found in thalamic struc-
tures, and (d) the evidence of a reduced volume of the
patients. In a review published in 2008 by Zink et al.
[12], the findings were that OCS and psychotic disorders
showed a variety of overlapping alterations in fMRI of
frontocortical areas, such as a deficient frontocortical
activation. More recently, Bleich-Cohen and colleagues
published a number of articles dedicated to the charac-
terization of schizo-obsessive patients using fMRI tech-
niques. In 2011, Bleich-Cohen et al. [15] reported the
psychopathological and fMRI characteristics of an SCZ
patient who presented auditory hallucinations, musical
in content and obsessive in form. The fMRI (performed
while the patient experienced obsessive musical halluci-
nations) revealed an increased activation of the inferior
and middle frontal gyri bilaterally, left DLPFC, right or-
bitofrontal cortex (OFC) and right middle temporal gy-
rus. In particular, an increased activation of the right
auditory associated cortex and striatal regions, primar-
ily the head of the left caudate, was shown. These acti-
vated brain areas are regions consistently implicated in
the pathophysiology of OCD. A 2014 fMRI study [10]
compared alterations in brain activation and functional
198.143.32.65 - 3/4/2016 7:29:46 PM
Attademo/Bernardini/Quartesan
University of Pittsburgh
Downloaded by:
connectivity underlying a working memory deficit in a
sample of 16 schizo-obsessive patients, 17 SCZ patients
and 20 HC. While applying fMRI, the subjects per-
formed the N-back working memory task. Working
memory-related activation in the right DLPFC and the
right caudate nucleus, brain areas relevant to SCZ and
OCD, and functional connectivity were analyzed. The
schizo-obsessive group exhibited brain activation pat-
terns remarkably similar to those of their pure SCZ
counterparts: these two groups exhibited a similar re-
duction in activation in the right DLPFC and right cau-
date as well as decreased functional connectivity com-
pared to the HC. To further examine possible differenc-
es between the schizo-obsessive group and the pure SCZ
group in a data-driven manner, a whole brain search for
activation clusters of cognitive load was performed dur-
ing the N-back working memory task using a multivox-
el pattern analysis approach termed searchlight-based
feature extraction [8]. The searchlight-based feature ex-
traction successfully classified the two groups with 91%
accuracy based on activations in the right intraparietal
sulcus, which further correlated with reduced symptom
severity among schizo-obsessive patients. Furthermore,
Bleich-Cohen et al. [2] used fMRI to investigate region-
al activation and language lateralization in the left and
right inferior frontal gyrus and interhemispheric func-
tional connectivity during a language task of auditory
verb generation in 14 schizo-obsessive patients com-
pared with 17 pure SCZ patients, 13 OCD patients and
14 HC. While OCD patients were indistinguishable
from HC, a similarly reduced lateralization in the infe-
rior frontal gyrus and diminished interhemispheric
functional connectivity were noted in the schizo-obses-
sive and SCZ groups, reporting no differences between
schizo-obsessive and SCZ patients. Another recent fMRI
study, conducted by Schirmbeck et al. [16], utilized re-
sponse inhibition and N-back working memory para-
digms to evaluate the effects of second-generation anti-
psychotics on the neural mechanisms related to OCS in
SCZ patients. The investigators stratified patients in two
groups: group I, SCZ patients (n = 21) treated with clo-
zapine or olanzapine, and group II, SCZ patients (n =
19) treated with amisulpride or aripiprazole. Frequency
and severity of OCS were significantly higher in group
I, which also showed significantly increased activation
in the OFC during response inhibition. In the authors
opinion, an increased activation of OFC associated with
the antipsychotic treatment might be a pathogenic
mechanism in the development of second-generation
antipsychotic-induced OCS in SCZ patients.
Neuroimaging Findings in
Schizo-Obsessive Disorder
Discussion
In terms of neuroimaging findings, although a large
number of studies analyzed the (structural and function-
al) neural mechanisms involved in SCZ and OCD sepa-
rately, still only a few studies investigated these mecha-
nisms in the putative schizo-obsessive disorder [4]. Nev-
ertheless, the findings of this report seem to offer
biological evidence in favor of the argument that, at least
in some cases, OCS are not completely independent from
SCZ. The analyzed neuroimaging studies seem to suggest
the presence of specific neuroanatomical abnormalities
in the comorbid schizo-obsessive group that may differ
from what is observed in the individual disorders (i.e.
SCZ and OCD). Furthermore, studies suggest greater
neuroanatomical dysfunction in the comorbid group.
Structural imaging studies found reduced volumes of the
left hippocampus and frontal lobes, as well as alterations
of the anterior horn of the lateral and third ventricles, in
the schizo-obsessive group. Functional imaging studies
found relevant abnormalities especially in the frontal ar-
eas (DLPFC, OFC, frontal gyrus) and caudate nucleus in
the schizo-obsessive group. Whether these findings re-
flect a specific pattern of dysfunction unique to this co-
morbid group or a severer form of SCZ with greater brain
dysfunction is, however, mostly unclear. Moreover, a
neuropsychological profile of schizo-obsessive disorder
has been investigated, with inconsistent findings when
comparing it to that of SCZ and OCD [4]. Also method-
ological limitations of current studies should be noted,
for example small sample size, cross-sectional design,
comparison with HC not always conducted, and pres-
ence of confounding factors such as antipsychotic and/
or selective serotonin reuptake inhibitor treatment. In-
vestigation of the schizo-obsessive neurobiology is still in
its infancy, but several studies on the neurobiological
mechanisms underlying a schizo-obsessive disorder are
emerging [20], with frontal lobe dysfunction and basal
ganglion dysfunction appearing to be the most relevant
[4]. Certainly, the question warrants further study. Fur-
ther longitudinal neurobiological studies with larger
samples are necessary to definitely clarify whether SCZ
with OCS/OCD might have unique neuroanatomical
and functional alterations. In particular, forthcoming
longitudinal, large-scaled neuroimaging studies, possi-
bly starting with at-risk mental state patients in the over-
lap group, are strongly required to determine whether
specific structural and functional abnormalities unique
to this putative subtype are present. Moreover, the devel-
opment of promising and more sensitive neuroimaging
198.143.32.65 - 3/4/2016 7:29:46 PM
Psychopathology 2016;49:14 3
University of Pittsburgh
DOI: 10.1159/000443837
Downloaded by:
techniques (with better spatial and temporal resolutions)
could allow more accurate measurements of the neuro-
logical abnormalities in SCZ and OCD, hoping that nov-
el multimodal neuroimaging techniques can be applied
to overcome the limitations of the present imaging mo-
dalities [21]. A deeper knowledge of the neuropsycho-
logical profile of schizo-obsessive disorder is needed too,
in order to drive future research on this subject in the
administration of alternative cognitive tests. Finally, the
same association between SCZ and OCD remains poorly
understood and must be deeply investigated. Therefore,
further neurobiological and genetic investigations focus-
ing specifically on the comorbid schizo-obsessive group
are essential to elucidate the nature of this proposed di-
agnostic entity.
Disclosure Statement
The authors report no conflict of interests.

References
1 Attademo L, Bernardini F, Paolini E, Quarte-
san R: History and conceptual problems of the
relationship between obsessions and halluci-
nations. Harv Rev Psychiatry 2015;23:1927.
2 Bleich-Cohen M, Poyurovsky M, Hendler T,
Weizman R, Sharon H: Does co-morbid ob-
sessive-compulsive disorder modify the ab-
normal language processing in schizophrenia
patients? An FMRI study. Front Hum Neuro-
sci 2014;8:560.
3 Cunill R, Castells X: Schizo-obsessive disor-
der; in Ritsner MS (ed): Handbook of Schizo-
phrenia Spectrum Disorders. London,
Springer, 2011, vol 2: Phenotypic and endo-
phenotypic presentations, pp 403448.
4 Rao NP, Venkatasubramanian G: Obsessive-
compulsive symptoms in schizophrenia: neu-
rophysiological and neuroimaging findings;
in De Haan L, Schirmbeck F, Zink M (eds):
Obsessive-Compulsive Symptoms in Schizo-
phrenia. New York, Springer International
Publishing, 2015, pp 135146.
5 Hwang MY, Hollander E: Schizo-obsessive
disorders. Psychiatr Ann 1993;23:396401.
6 Zohar J: Is there room for a new diagnostic
subtype: the schizoobsessive subtype? CNS
Spectr 1997;2:4950.
7 Fras-Ibez A, Palma-Sevillano C, Farriols-
Hernando N: Comorbidity between obses-
sive-compulsive disorder and schizophrenia:
prevalence, explanatory theories, and noso-
logical status (in Spanish). Actas Esp Psiquiatr
2014;42:2838.
8 Bleich-Cohen M, Jamshy S, Sharon H, Weiz-
man R, Intrator N, Poyurovsky M, Hendler T:
Machine learning fMRI classifier delineates
subgroups of schizophrenia patients.
Schizophr Res 2014;160:196200.
9 Fras A, Palma C, Farriols N, Salvador A,
Bonet J, Bernldez I: Psychopathology and
quality of life among patients with comorbid-
ity between schizophrenia spectrum disorder
and obsessive-compulsive disorder: no evi-
dence for a schizo-obsessive subtype. Compr
Psychiatry 2014;55:11651173.
10 Bleich-Cohen M, Hendler T, Weizman R,
Faragian S, Weizman A, Poyurovsky M:
Working memory dysfunction in schizophre-
nia patients with obsessive-compulsive symp-
toms: an fMRI study. Eur Psychiatry 2014;29:
160166.
11 Poyurovsky M, Zohar J, Glick I, Koran LM,
Weizman R, Tandon R, Weizman A: Obses-
sive-compulsive symptoms in schizophrenia:
implications for future psychiatric classifica-
tions. Compr Psychiatry 2012;53:480483.
12 Zink M, Englisch S, Dressing H: Neurobiol-
ogy confirms psychopathology. On the antag-
onism of psychosis and obsessive-compulsive
syndromes. Psychopathology 2008; 41: 279
285.
13 Bottas A, Cooke RG, Richter MA: Comorbid-
ity and pathophysiology of obsessive-com-
pulsive disorder in schizophrenia: is there ev-
idence for a schizo-obsessive subtype of
schizophrenia? J Psychiatry Neurosci 2005;
30:187193.
14 Gross-Isseroff R, Hermesh H, Zohar J, Weiz-
man A: Neuroimaging communality between
schizophrenia and obsessive compulsive dis-
order: a putative basis for schizo-obsessive
disorder? World J Biol Psychiatry 2003; 4:
129134.
15 Bleich-Cohen M, Hendler T, Pashinian A,
Faragian S, Poyurovsky M: Obsessive musical
hallucinations in a schizophrenia patient:
psychopathological and fMRI characteristics.
CNS Spectr 2011;16:153156.
16 Schirmbeck F, Mier D, Esslinger C, Rausch F,
Englisch S, Eifler S, Meyer-Lindenberg A,
Kirsch P, Zink M: Increased orbitofrontal
cortex activation associated with pro-obses-
sive antipsychotic treatment in patients with
schizophrenia. J Psychiatry Neurosci 2015;40:
8999.
17 Aoyama F, Iida J, Inoue M, Iwasaka H, Saki-
yama S, Hata K, Kishimoto T: Brain imaging
in childhood- and adolescence-onset schizo-
phrenia associated with obsessive-compul-
sive symptoms. Acta Psychiatr Scand 2000;
102:3237.
18 Iida J, Matsumura K, Aoyama F, Iwasaka H,
Hirao F, Sakiyama S, Kishimoto T: Cerebral
MRI findings in childhood-onset schizophre-
nia: comparison of patients with prodromal
obsessive-compulsive symptoms and those
without symptoms. Rec Prog Child Adolesc
Psychiatry 1998;2:7583.
19 Levine JB, Gruber SA, Baird AA, Yurgelun-
Todd D: Obsessive-compulsive disorder
among schizophrenic patients: an exploratory
study using functional magnetic resonance
imaging data. Compr Psychiatry 1998; 39:
308311.
20 Poyurovsky M: Schizo-Obsessive Disorder.
New York, Cambridge University Press, 2013.
21 Kim MS, Ha TH, Kwon JS: Neurological ab-
normalities in schizophrenia and obsessive-
compulsive disorder. Curr Opin Psychiatry
2004;17:215220.
198.143.32.65 - 3/4/2016 7:29:46 PM

4 Psychopathology 2016;49:14 Attademo/Bernardini/Quartesan

University of Pittsburgh

DOI: 10.1159/000443837
Downloaded by: