REVIEW ARTICLE

Obsessive–compulsive disorder comorbid with schizophrenia and bipolar

disorder
Lavanya P. Sharma, Y. C. Janardhan Reddy
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

ABSTRACT
Downloaded from http://journals.lww.com/indianjpsychiatry by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 03/12/2022

Obsessive Compulsive Disorder (OCD) and Obsessive Compulsive Symptoms (OCS) are known to be highly comorbid
with bipolar disorder and schizophrenia. Comorbid OCD/OCS influences the course of schizophrenia and bipolar
disorder. There is also some evidence to suggest that a diagnosis of OCD may be associated with elevated risk for later
development of psychosis and bipolar disorder. Comorbid OCD/OCS is associated with a greater severity of schizophrenia
phenotype and poorer prognosis. In addition, certain atypical antipsychotics, clozapine in particular are known to induce
or worsen OCS in schizophrenia. OCD when comorbid with bipolar disorder mostly runs an episodic course with
worsening and improvement of OCD/OCS in depressive and in manic/hypomanic phases respectively. There is limited
systematic data on the treatment of OCD in schizophrenia and bipolar disorder. When OCD presents in the context of
schizophrenia, management may include treatment with atypical antipsychotics with limited serotonergic properties,
changing the antipsychotic, reduction in the dose of the antipsychotic, addition of cognitive-behavior therapy (CBT), or
a specific serotonin reuptake inhibitor (SSRI). When OCD is comorbid with bipolar disorder, mood stabilization is the
priority. CBT may be preferred over SSRIs to treat OCD/OCS that persist in between the mood episodes because SSRIs
may induce a switch or worsen the course of bipolar disorder. SSRIs when indicated have to be used judiciously under
the cover of adequate mood stabilization.

Key words: Antipsychotic-induced obsessive-compulsive symptoms, bipolar disorder, obsessive-compulsive disorder,

obsessive-compulsive symptoms, schizo-obsessive disorder, schizophrenia

INTRODUCTION This article attempts to review the extant data on these

Obsessive–compulsive disorder (OCD), anxiety disorders,
and depression are known to be highly comorbid with each
other,[1] but the comorbidity of OCD with schizophrenia and
bipolar disorder (BD) is understudied. Treatment of OCD in
the context of schizophrenia and BD is highly challenging.
Address for correspondence: Dr. Y. C. Janardhan Reddy,
Department of Psychiatry, National Institute of Mental
Health and Neurosciences, Hosur Road, Bengaluru ‑ 560 029,
Karnataka, India.
E‑mail: ycjreddy@gmail.com
Access this article online
Quick Response Code
Website:
complex comorbidities.
METHODS
In this paper, we review the extant literature on this comorbidity
until August 2018 using the PubMed and the Google
Scholar. The key words used were: ‘obsessive-compulsive
disorder’, ‘obsessive-compulsive symptoms’, linked with
‘psychosis’, ‘schizophrenia’, ‘at risk mental states’ and ‘bipolar
disorder’. We also searched for ‘antipsychotic-induced
This is an open access journal, and articles are distributed under the terms of
the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License,
which allows others to remix, tweak, and build upon the work non-commercially,
as long as appropriate credit is given and the new creations are licensed under
the identical terms.

www.indianjpsychiatry.org For reprints contact: reprints@medknow.com

DOI:
How to cite this article: Sharma LP, Reddy YC.
Obsessive–compulsive disorder comorbid with schizophrenia
10.4103/psychiatry.IndianJPsychiatry_527_18
and bipolar disorder. Indian J Psychiatry 2019;61:S140-8.

S140 © 2019 Indian Journal of Psychiatry | Published by Wolters Kluwer ‑ Medknow

 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
obsessive-compulsive symptoms’. References of interest were
further identified by going through the references reported
in the accessed articles. The two authors reviewed the
articles for clinical, epidemiological, genetic, neurobiological,
neuropsychological and treatment aspects. The search was
limited to English language articles only.
OBSESSIVE-COMPULSIVE SYMPTOMS
IN SUBJECTS AT HIGH-RISK FOR
SCHIZOPHRENIA
Obsessive–compulsive symptoms (OCS) are frequently
observed during the course of schizophrenia. OCS/OCD
can manifest in those at ultra‑high risk for psychosis,
during prodromal psychotic state, in the first episode of
schizophrenia, during the course of chronic schizophrenia
and after treatment with atypical antipsychotics.[2] The
occurrence of OCS can range anywhere between 5% and
30%.[3] Although OCS are also common in the general
population and in those with other psychiatric disorders,[4,5]
those at ultra‑high risk for psychosis appear to have a higher
frequency of OCS than the general population.
OCS are more likely to be present among males, in those
with insidious onset and long duration of attenuated
psychosis, more negative symptoms,[6] and in the presence
of depression[3] and suicidality,[7] although their presence
and severity may not predict transition to frank psychosis.[8]
Individuals with OCS and at ultra‑high risk for psychosis
had poorer psychosocial functioning than those without[9,10]
but interestingly were found to perform better on tests
of neurocognitive functioning when compared to those
without.[7]
The common symptoms in those at risk for psychosis
are aggressive obsessions, checking compulsions, and
hoarding.[3,11] One study also found duration of subthreshold
psychosis to be longer in those with OCS (15.6 months vs.
6.2 months)[11] with the highest frequency of OCS in those
with a family history of psychosis.[11]
Because of these distinct differences, it has been
hypothesized that individuals at ultra‑high risk for psychosis
with OCS may constitute a separate phenotype.
OBSESSIVE–COMPULSIVE DISORDER IN THE
CONTEXT OF SCHIZOPHRENIA
Prevalence of obsessive–compulsive disorder in
schizophrenia
Some of the founders of modern psychiatry (Westphal,
Mayer‑Gross, Bleuler) clearly identified OCS in
schizophrenia and deemed them a feature of the
disorder’s prodromal or active phases, but initially, they
were thought to occur in a minority of schizophrenia
patients only (1%–3.5%) and were considered to be a
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019
protective factor.[12] However, in one of the early reports,
Fenton and McGlashan reported a high prevalence
of OCS in schizophrenia patients (12.9%), along with
a poorer outcome for those with OCS.[13] The term
“schizo‑obsessive disorder” was suggested in order to
draw attention to those schizophrenia patients with
clinically significant OCS.[14] Recent meta‑analyses have
shown that up to 30% of patients with schizophrenia
report OCS[15] and 12%–14% of them meet diagnostic
criteria for OCD.[1,15] A study from our center reported OCS
in 24% of 200 hospitalized patients with schizophrenia,
of which 19% had the Diagnostic and Statistical Manual of
Mental Disorders‑IV (DSM‑IV) OCD.[16]
OCS in schizophrenia are not merely a result of chronic illness
or due to antipsychotic treatment, since a high prevalence
rate (OCS, from 2.7% to 37%; OCD, from 1.5% to 30%)
reported in individuals at ultra‑high risk for psychosis, in
the prodromal phase of schizophrenia, and in first‑episode
drug‑naive schizophrenia patients is considerably higher
than in the general population.[9] In a study from our center,
65% had developed OCS before antipsychotic use.[16]
Obsessive–compulsive disorder as a risk factor for
schizophrenia
It is unclear if a diagnosis of OCD confers a risk for later
development of psychosis, but there is some evidence to
suggest that OCS may enhance the risk of psychosis.[17‑19]
In a study based on Danish registers, prior diagnosis of
OCD was associated with an increased risk of developing
schizophrenia (incidence rate ratio [IRR] = 6.90; 95%
confidence interval [CI], 6.25–7.60) and schizophrenia
spectrum disorders (IRR = 5.77; 95% CI, 5.33–6.22) later
in life.[18] Similarly, children of parents with OCD had an
increased risk of schizophrenia (IRR = 4.31; 95% CI, 2.72–6.43)
and schizophrenia spectrum disorders (IRR = 3.10; 95% CI,
2.17–4.27). The results were significant even after adjusting
for family history of psychiatric disorders and the patient’s
psychiatric history.[18]
A Swedish registry‑based longitudinal cohort and
multi‑generational family study found that patients with
OCD had a 12–13 times higher risk of having a comorbid
diagnosis of schizophrenia, BD, and schizoaffective disorder
compared with individuals without OCD.[19] Longitudinal
analyses showed that individuals first diagnosed with
OCD had a 3‑fold higher risk of receiving a later diagnosis
of schizophrenia compared with individuals without OCD
during the follow‑up period. Similarly, when rates of OCD
in primary psychotic disorders were studied, patients first
diagnosed with schizophrenia and schizoaffective disorder
had a 7 and a 5 times higher risk of receiving a later diagnosis
of OCD, respectively, compared with individuals without
schizophrenia. The risk of later development of OCD was
only marginally reduced when the use of second‑generation
antipsychotics (SGAs) was corrected for.[19]
S141
 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
Clinical characteristics, onset and course
Schizophrenia and OCD are characterized by similar gender
distribution, age of onset, and earlier age of onset in men.
OCS may present across the life span in adolescent, adult,
and elderly patients with schizophrenia.[20,21] Studies have
shown that in a majority of patients with comorbid OCD and
schizophrenia, OCS precede initial psychotic symptoms in
about 40% of patients, may succeed psychosis in 40%, and
occur concurrently with psychotic symptoms in around
20%.[16] In a 5‑year follow‑up of 172 patients admitted with
first‑episode schizophrenia and related disorders, 49% had no
OCS anytime during the course, 15% had OCS only during the
first assessment, 13% had persistent OCS, 7% developed OCS
subsequently, and 16% had intermittent OCS, suggesting that
the course of OCS is variable.[10] The presence of comorbid
OCD was associated with more severe depression, impaired
social functioning, and worse premorbid functioning.[10]
The phenomenology of OCS in schizo‑obsessive disorder
is similar to that in primary OCD patients and is typically
moderate to severe.[22‑25] One study reported good insight
into OCS in 85% of the patients, a rate comparable to that
in primary OCD,[26] but in an Indian study, less than a half
had good insight (46%).[16] Effect of OCS on the clinical
phenotype of schizophrenia is unclear. Findings are
conflicting, but most studies report an earlier age at onset
of psychosis, longer duration of illness, greater positive
and negative symptoms, more depressive symptoms and
suicide attempts, increased rates of hospitalization, poorer
neurocognitive performance, decreased likelihood of
being employed or married, lower quality of life, greater
disability, and overall poorer prognosis.[27‑29] However, two
cross‑sectional studies from our center have reported lesser
positive symptoms, lower score on anergia and higher
score on depression, higher comorbidity with Axis II and
anxiety disorders, somewhat lesser disability, better QOL,
and greater family loading for OCD.[16,25] In one study,
patients with schizo‑obsessive disorder tend to have a
different pattern of comorbidity from schizophrenia, with
a preferential aggregation of body dysmorphic disorder,
eating disorders, and tic disorders but not of major
depressive, substance abuse, or anxiety disorders.[30]
Family history
Both OCD and schizophrenia show familial aggregation.
Relatives of patients with schizo‑obsessive disorder and
schizophrenia, both have a higher risk of schizophrenia
spectrum disorders (9.4%, 7.5%) than community‑based
controls (0.75%), comparable to the average risk for
schizophrenia in first‑degree relatives in family studies of
schizophrenia (6%–9%).[31]
When compared with first degree relatives of schizophrenia
probands, relatives of schizo‑obsessive probands had
a significantly higher morbid risk for schizo‑obsessive
disorder, obsessive–compulsive personality disorder,
S142
and (at a trend level) an increased rate of OCD, with no
between‑group differences in the rate of schizophrenia
spectrum disorders.[32] In an Indian study of 200 participants
with schizophrenia, those with OCS/OCD had a significantly
greater family loading for OCD than those without.[16] Cederlöf
et  al., in their Swedish National Registry Study (2014),
reported that first‑degree relatives of probands with OCD
had a significantly increased risk for schizophrenia (relative
risk [RR]: 1.9), schizoaffective (RR: 1.5), and BD (RR: 1.7).[19]
Biological markers
The neurobiological underpinnings of OCS in schizophrenia
patients are not definitively known, but preliminary reports
suggest a distinct neuroanatomical profile. Imaging studies
have identified significantly reduced volumes of the left
hippocampus, frontal lobes, and anterior horn of the lateral
and third ventricles in a small group of schizo‑obsessive
patients compared with schizophrenia patients.[33] Patients
with schizo‑obsessive disorder in the prodromal phase had a
greater ventricle‑brain ratio than patients with pure OCD.[34]
A functional magnetic resonance imaging study found a
significant negative correlation between the severity of
OCS and activation of the left  dorso-lateral prefrontal
cortex (DLPFC), similar to the pattern seen in schizophrenia
patients.[35]
A neurophysiological study using event‑related potentials
(ERPs) during a discriminative response task found a distinct
ERP pattern, with abnormally increased target activation
and reduced P300 amplitude in the schizo‑obsessive
patients compared to that in patients with schizophrenia
and OCD.[36] Studies that have examined patterns of brain
activation during cognitive tasks in schizophrenia and
schizo‑obsessive participants have elicited similar reduction
in activation in the right DLPFC and right caudate, as well
as decreased functional connectivity during performance
of the N‑back task compared to healthy controls; these
patterns seem to be unrelated to severity of symptoms.[37]
Similarly, impaired language processing, tested by auditory
verb generation tasks, found comparable patterns of
lateralization in the inferior frontal gyrus and diminished
inter‑hemispheric functional connectivity in schizophrenia
and schizo‑obsessive subgroups.[38] There is preliminary
evidence to suggest that changes in orbitofrontal
cortex (OFC) activation may be significantly associated with
the severity of obsessions, with increased OFC activation
during performance of a Go‑No Go task in patients with
schizo‑obsessive disorder.[39]
Several studies report greater soft neurological signs and
neuropsychological deficits (abstraction and executive
function) in schizophrenia patients with OCS/OCD than in
those without OCS/OCD and in those with primary OCD.[40]
However, a meta‑analysis found impairment only in abstract
reasoning with no impairment in executive functions.[41] We
examined the neuropsychological profile of schizophrenia
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019
 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
with and without OCD with a comprehensive battery of tests
of attention, executive functions, and memory but found no
differences between the two groups.[42] It appears that there
are no consistent neuropsychological impairments typical
of schizo‑obsessive disorder; however, larger studies
with uniform methodology may be needed to further our
understanding of this area.
Is schizo‑obsessive disorder a subtype of schizophrenia?
Based on high rates of OCS/OCD in schizophrenia,
somewhat unique clinical profile (albeit with conflicting
findings), poorer prognosis, and preliminary neuroimaging
and neuropsychological data, some researchers have
proposed schizo‑obsessive disorder as a distinct
subtype of schizophrenia that needs further study.[43]
Accordingly, diagnostic criteria have been proposed for
schizo‑obsessive disorder with emphasis on the presence
of typical DSM OCD symptoms for a substantial portion
of the total duration of illness that are either time
consuming, distressing, interfering, or causing significant
impairment of functioning.[43] If OCS are related to
psychotic experiences, the presence of additional typical
OCS is required for a diagnosis. In addition, OCS should
not be secondary to antipsychotic drugs, substance abuse,
or an organic factor.
ANTIPSYCHOTIC‑INDUCED OBSESSIVE–
COMPULSIVE SYMPTOMS
SGAs such as clozapine, risperidone, and olanzapine, in
particular, are implicated in the de novo emergence and
exacerbation of OCS in patients with schizophrenia.[44]
First‑generation antipsychotics (FGAs) are not generally
implicated in the development of OCS, with the exception
of a rare case report of OCS induced by haloperidol.[45]
Clozapine is most frequently associated with exacerbation
of or de novo emergence of OCS in schizophrenia,[44,46,47]
although there are few contrary reports.[48,49] A review
estimated the frequency of de novo emergence of and
worsening of preexisting OCS to be 20%–28% and 10%–18%,
respectively, in those treated with clozapine.[44]
OCS usually manifest within the first few weeks of initiation
of treatment with a SGA,[50,51] whereas with clozapine, OCS
emerge gradually over the first 12 months or so.[9] There
seems to be some relation between dose of risperidone
and emergence of OCS with lower doses being effective
in augmenting the action of selective serotonin reuptake
inhibitors (SSRIs) in treating OCD[52] and higher doses
causing emergence of OCS.[53]
Arguments supporting the induction of OCS by SGAs include
increased prevalence of OCS after approval of SGAs, higher
rates of OCS in those with chronic schizophrenia treated
with SGAs especially with clozapine, marked differences in
the rates of OCS between those treated with FGAs and SGAs,
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019
OCS manifesting for the first time after initiating treatment
with SGAs, correlation of OCS severity with dose, duration
and serum levels of clozapine,[54,55] and improvement in
OCS after reduction in the dose of clozapine or change of
drug.[46,54‑57]
Predominant anti‑serotonergic profile (both 5‑HT2A
and 5‑HT2C receptor antagonism) of certain SGAs such
as clozapine and risperidone is hypothesized to be
responsible for inducing OCS.[39,58] Drugs with predominant
dopaminergic blockade such as amisulpride and
aripiprazole are not associated with induction of OCS. For
clozapine, anti‑serotonergic profile combined with low
anti‑dopaminergic potency and enhanced glutamatergic
transmission could explain OCS.[59] Chronic use of clozapine
is also known to downregulate hypersensitive 5‑HT2C
receptors. Polymorphisms of the SLC1A1, BDNF, DLGAP3,
and GRIN2B and interactions between these genes may also
confer susceptibility to clozapine‑induced OCS.[60‑62] Some
authors suggest that schizophrenia patients with OCS
might have genetic vulnerabilities to both schizophrenia
and OCD, with some common environmental factors
triggering the expression of both OCD and schizophrenia
genes.[63]
MANAGEMENT OF OBSESSIVE–COMPULSIVE
SYMPTOMS/OBSESSIVE–COMPULSIVE
DISORDER IN SCHIZOPHRENIA
Although OCD is a common comorbidity in schizophrenia,
there is limited literature on its treatment. There is
some evidence that monotherapy with SGAs such as
olanzapine[53,64] and ziprasidone[65] may help in alleviation
of both psychotic and OCS in preexisting OCS in
schizophrenia. Antipsychotics such as amisulpride and
aripiprazole which have negligible serotonergic properties
also appear to be somewhat useful in treating OCS in
schizophrenia.[46,66]
Because of the clinical similarity of OCS in schizophrenia
and in primary OCD, attempts have been made to
examine the efficacy of SSRIs and clomipramine. The APA
guidelines recommend the use of SSRIs in combination
with antipsychotics for the treatment of schizophrenia
with OCS/OCD.[67] SSRIs seem to be beneficial,[68] especially
escitalopram at 20 mg/day,[69] but not in all cases.
Addition of fluvoxamine[70] and clomipramine[71] has been
associated with worsening of psychosis. When adding
an SSRI or clomipramine to an antipsychotic regimen,
pharmacokinetic interactions, particularly between
clozapine and certain SSRIs, need to be kept in mind to
avoid side effects such as seizures and sudden elevation
in clozapine levels.
There are limited systematic data on the efficacy of
cognitive behavioral therapy (CBT) in treating OCS/
S143
 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
OCD in schizophrenia. Reviews of case reports and case
series suggest that CBT may be effective, but this needs
confirmation in well‑designed studies.[72] The APA also
recommends a trial of CBT in those with schizophrenia and
OCD who do not respond to adding an SSRI or change of
antipsychotic.[67]
Treatment of SGA‑induced OCS/OCD involves reduction of
antipsychotic dose (e.g., reduction of dose of clozapine if
feasible), change to another antipsychotic with minimal
influence on serotonergic systems such as aripiprazole,
amisulpride, or haloperidol,[55] addition of aripiprazole,[73]
and addition of SSRI[69] and CBT.[74]
OBSESSIVE–COMPULSIVE DISORDER WITH
BIPOLAR DISORDER
OCD and BD are highly comorbid with each other. It is
not clear whether this high comorbidity represents the
frequent occurrence of two independent diseases or
whether it represents the occurrence of symptoms of one
kind (e.g., OCD symptoms) in a different disease (i.e., BD).
Mayer‑Gross and colleagues in their influential textbook
on psychiatry stated the following: “Compulsive symptoms
are quite common in manic depressive psychoses, especially in
depressions. From time to time one sees the rare cases of recurrent
endogenous obsessional neuroses. These people who, in time of
health, show no noteworthy obsessional traits, but who have
phases in which compulsive symptoms appear out of the blue
and rapidly mount up to complete incapacitation. Nevertheless,
these illnesses remit and relapse in very much the same way as
cyclothymic illnesses, may show just as much regularity of timing,
and are probably to be included, from the etiological point of
view, in the manic‑depressive disorders.”[75]
Prevalence
Three population‑based studies conducted in Italy and the
USA reported lifetime prevalence rates of comorbid OCD in
BD patients ranging between 11.1% and 21%.[76] A systematic
review and meta‑analysis reported a pooled prevalence of
OCD in 17% (95% CI, 12.7%–22.4%) of BD patients, which was
comparable to the pooled prevalence of BD in 18% of OCD
patients (18.35%, 95% CI, 13.2%–24.8%).[77] The prevalence
of OCD was greater in BD children and adolescents than
in adults (24.2% vs. 13.5%) and in population‑based studies
rather than in hospital‑based studies (22.2% vs. 13.2%).
Pooled prevalence of BD‑I and BD‑II in OCD has been
reported to be 3.9% (95% CI, 2.4–6.4) and 13.5% (95% CI,
9.3–19.3), respectively, and pooled prevalence of OCD
in BD‑I to be 21.7% (95% CI 4.8–60.3).[78] A study from
our center reported the presence of OCD in 35% of 80
participants with remitted BD.[79] Another recent study
from our center reported OCS and OCD in 4% and 8% of the
396 hospitalized BD patients, respectively, suggesting that
rates are probably higher in remitted than in symptomatic
patients.[80] However, BD comorbidity in 171 patients with a
S144
primary diagnosis of OCD recruited from our specialty OCD
clinic has been relatively low (4%),[81] when compared with
the rates reported in systematic reviews.[77,82]
Obsessive–compulsive disorder as a risk factor for bipolar
disorder
A Swedish multigenerational registry study found that, in
individuals with BD, the risk of a later diagnosis of OCD
was approximately 1.2 times higher, with a median time
between diagnoses of 1.1 years (IR = 2.0). The risks were
generally higher among inpatients with OCD.[19] The risk
of receiving a diagnosis of BD after an initial diagnosis of
OCD (RR 13.7) was much greater than the risk of receiving
a diagnosis of OCD after an initial diagnosis of BD (RR: 1.2).
The association between antidepressant use and switch
to mania in patients with BD is well known. The risk of
receiving a diagnosis of BD after an initial diagnosis of OCD
was substantially reduced, but not eliminated, when the
use of SSRIs (but not other antidepressants) was controlled
for, which indicates that the presence of OCD may be an
independent risk factor for the later development of BD.[19]
Clinical characteristics, onset and course
Studies on the phenomenology of OCS in OCD‑BD have
shown inconsistent results. However, the presence of BD
comorbidity has been associated with greater incidence
of obsessions of sexual, religious, aggressive, symmetry,
and hoarding‑related themes and ordering/arranging and
hoarding compulsions.[83] Contamination obsessions and
washing compulsions have also been associated with
OCD‑BD;[84] however, the converse has also been
reported.[85,86] A review of 18 studies found no conclusive
evidence that BD‑OCD had more severe OCS.[83] However,
insight into OCD was found to be poorer in those with
comorbidity.[87,88]
OCD is more likely to manifest during mixed mania and
depressive episodes.[89,90] Patients with OCD‑BD tended
to have a greater number of depressive episodes than BD
alone.[91,92]
In the Epidemiologic Catchment Area (ECA) study database,
OCD‑BD patients had statistically significant higher lifetime
rates of death wishes and suicidal thoughts when compared
with non‑OCD‑BD patients,[93] which was confirmed by
subsequent studies.[88,94,95] OCD also was associated with
a 2.4‑fold increase in the odds of suicidal ideation among
BD adolescents.[96] A large hospital‑based study found
that BD‑OCD patients were more likely to be diagnosed
with substance and alcohol use disorders, panic disorder,
agoraphobia, posttraumatic stress disorder, and eating
disorders than noncomorbid patients.[97] One report showed
a positive association between BD‑OCD comorbidity and
sedatives, nicotine, alcohol, and coffee use.[98] The ECA
study confirmed the higher rate of drug abuse in OCD‑BD
participants than in noncomorbid participants (37.1% vs.
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019
 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
28.2%).[93] Higher rates of attention‑deficit/hyperactivity
disorder and oppositional defiant disorder and lower rates
of generalized anxiety disorder have been reported in
BD‑OCD patients as compared to noncomorbid patients.[99]
A single study from Italy assessed Axis II comorbidities and
reported higher rates of at least one Cluster A personality
disorder, at least one Cluster B personality disorder,
and narcissistic and antisocial personality disorder in
participants with OCD‑BD than in those without OCD
comorbidity.[100] Comorbid OCD‑BD has consistently been
associated with poorer functioning and lower quality of life
when compared with those with either OCD or BD alone.
The mean of number of hospitalizations in BD‑OCD patients
is also reported to be significantly higher than in those
without comorbidity.[83]
The course of OCD in the context of BD has been
predominantly described as being episodic,[85,88,101‑104]
although exceptions (a continuous, chronic course of OCD)
have also been described.[91,105] A study reported episodic
course of OCD to be more common in BD type II than in BD
type I.[102] In contrast, two studies found a chronic course
of affective episodes with residual symptoms in those with
OCD‑BD.[91,105] There is evidence that SSRIs cause more
mania/hypomania in BD‑OCD patients than in noncomorbid
patients.[83] OCS are reported to worsen during depression
and remit/improve in manic/hypomanic phases.[83,85,88]
With regard to onset of symptoms, studies report either
BD‑OCD beginning concomitantly,[98] with BD‑OCD cycling
together,[106] OCD preceding BD onset,[85] or onset of
depressive episodes before the onset of OCD.[107]
Family history
Studies of patients with OCD/OCS‑BD have shown family
loading for mood disorders,[85,98,108] as well as higher family
loading for OCD.[80] A family history of mood disorders has
been reported to be more frequent in patients with episodic
course of OCD than in those with chronic OCD.[102] However,
a community‑based study found no statistically significant
differences in family history for OCD, depression, and
mania in patients with OCD‑BD, when compared with OCD
comorbid with other anxiety disorders.[95]
Biological markers
There is scant literature on biological correlates of
OCD‑BD comorbidity. A study reported higher 5‑HTT
binding potential in OCD‑BD participants as compared
to non‑OCD‑BD in the insula, posterior cingulate cortex,
subgenual anterior cingulate cortex, and in the dorsal
cingulate cortex.[109]
Treatment
Challenges in managing comorbid OCD‑BD revolve around
the risk of SSRIs causing manic switch or worsening the
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019
course of BD. In addition, there are no systematic data on
the efficacy of CBT or SSRIs in treating OCD when comorbid
with BD.
A study examining treatment outcomes in OCD‑BD found
that clomipramine and, to a lesser extent, SRIs were
associated with a higher rate of manic switches versus
noncomorbid patients. BD‑OCD patients not on mood
stabilizers presented with more frequent mania when
compared with non‑BD‑OCD patients.[98]
Clinicians may encounter three clinical scenarios. If OCD is
confined to mood episodes only as is often the case, mood
stabilization is a priority and SSRIs may be avoided.[83] If
subclinical OCS persists in the inter‑episodic period, CBT
along with mood adequate stabilization may be preferred
over SSRIs if OCS are distressing and interfering. Clinically
significant OCD in between the episodes also needs to be
treated with CBT first and if CBT is ineffective or not feasible,
an SSRI may be used under the cover of mood stabilizers
and/or atypical antipsychotics with close supervision to
prevent a switch and cycle acceleration.[83,110]
CONCLUSIONS
OCD is a common comorbid condition in those with
schizophrenia and BD. There is some evidence that a
diagnosis of OCD may be associated with a higher risk for
later development of both schizophrenia and BD, but the
nature of the relationship with these disorders is still unclear.
It is, however, evident that episodic OCD may be primarily a
mood disorder and therefore treatment of OCD confined to
mood episodes primarily involves mood stabilization with
mood stabilizers and atypical antipsychotics. SSRIs have
to be used judiciously when treating OCD comorbid with
BD. OCD in schizophrenia may respond to SSRIs and CBT,
but there is very limited literature on treating comorbid
OCD in patients with schizophrenia. OCD arising de novo
or worsening of preexisting OCD following treatment with
atypical antipsychotics (clozapine in particular) is well
recognized. More research is needed to understand the
complex relationship between these comorbidities.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Achim AM, Maziade M, Raymond E, Olivier D, Mérette C, Roy MA, et al.
How prevalent are anxiety disorders in schizophrenia? A meta‑analysis and
critical review on a significant association. Schizophr Bull 2011;37:811‑21.
2. Sterk  B, Lankreijer  K, Linszen  DH, de Haan  L. Obsessive‑compulsive
symptoms in first episode psychosis and in subjects at ultra high risk for
developing psychosis; onset and relationship to psychotic symptoms. Aust
N Z J Psychiatry 2011;45:400‑6.
S145
 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
3. Mariné R, Creus  M, Solé M, Cabezas Á, Algora  MJ, Moreno  I, et al.
Clinical correlates of obsessive‑compulsive symptom dimensions in
at‑risk mental states and psychotic disorders at early stages. Psychiatry
Res 2015;228:363‑7.
4. Snorrason  I, Lee  HJ, de Wit  S, Woods  DW. Are nonclinical
obsessive‑compulsive symptoms associated with bias toward habits?
Psychiatry Res 2016;241:221‑3.
5. Fullana MA, Mataix‑Cols D, Caspi A, Harrington H, Grisham JR, Moffitt TE,
et al. Obsessions and compulsions in the community: Prevalence,
interference, help‑seeking, developmental stability, and co‑occurring
psychiatric conditions. Am J Psychiatry 2009;166:329‑36.
6. Iida J, Iwasaka H, Hirao F, Hashino K, Matsumura K, Tahara K, et al. Clinical
features of childhood‑onset schizophrenia with obsessive‑compulsive
symptoms during the prodromal phase. Psychiatry Clin Neurosci
1995;49:201‑7.
7. Hur  JW, Shin  NY, Jang  JH, Shim  G, Park  HY, Hwang  JY, et al. Clinical
and neurocognitive profiles of subjects at high risk for psychosis with
and without obsessive‑compulsive symptoms. Aust N Z J Psychiatry
2012;46:161‑9.
8. McAusland  L, Buchy  L, Cadenhead  KS, Cannon  TD, Cornblatt  BA,
Heinssen R, et al. Anxiety in youth at clinical high risk for psychosis. Early
Interv Psychiatry 2017;11:480‑7.
9. Zink M, Schirmbeck F, Rausch F, Eifler S, Elkin H, Solojenkina X, et al.
Obsessive‑compulsive symptoms in at‑risk mental states for psychosis:
Associations with clinical impairment and cognitive function. Acta Psychiatr
Scand 2014;130:214‑26.
10. de Haan  L, Sterk  B, Wouters  L, Linszen  DH. The 5‑year course of
obsessive‑compulsive symptoms and obsessive‑compulsive disorder
in first‑episode schizophrenia and related disorders. Schizophr Bull
2013;39:151‑60.
11. Soyata  AZ, Akışık S, İnhanlı D, Noyan  H, Üçok A. Relationship of
obsessive‑compulsive symptoms to clinical variables and cognitive
functions in individuals at ultra high risk for psychosis. Psychiatry Res
2018;261:332‑7.
12. Rosen I. The clinical significance of obsessions in schizophrenia. J Ment
Sci 1957;103:773‑85.
13. Fenton  WS, McGlashan  TH. The prognostic significance of
obsessive‑compulsive symptoms in schizophrenia. Am J Psychiatry
1986;143:437‑41.
14. Hollander E, Rosen J. OC Spectrum Disorders: The Impulsive and
Schizo-Obsessive Clusters. CNS Spectrums 1999;4(S3):16-21.
15. Swets M, Dekker J, van Emmerik‑van Oortmerssen K, Smid GE, Smit F,
de Haan L, et al. The obsessive compulsive spectrum in schizophrenia, a
meta‑analysis and meta‑regression exploring prevalence rates. Schizophr
Res 2014;152:458‑68.
16. Devi S, Rao NP, Badamath S, Chandrashekhar CR, Janardhan Reddy YC.
Prevalence and clinical correlates of obsessive‑compulsive disorder in
schizophrenia. Compr Psychiatry 2015;56:141‑8.
17. Van Dael  F, van Os  J, de Graaf  R, ten Have  M, Krabbendam  L,
Myin‑Germeys I, et al. Can obsessions drive you mad? Longitudinal
evidence that obsessive‑compulsive symptoms worsen the outcome of
early psychotic experiences. Acta Psychiatr Scand 2011;123:136‑46.
18. Meier  SM, Petersen  L, Pedersen  MG, Arendt  MC, Nielsen  PR,
Mattheisen M, et al. Obsessive‑compulsive disorder as a risk factor for
schizophrenia: A nationwide study. JAMA Psychiatry 2014;71:1215‑21.
19. Cederlöf M, Lichtenstein  P, Larsson  H, Boman  M, Rück C,
Landén M, et al. Obsessive‑compulsive disorder, psychosis, and bipolarity:
A Longitudinal cohort and multigenerational family study. Schizophr Bull
2015;41:1076‑83.
20. Rabe‑Jabłońska J. Obsessive‑compulsive disorders in adolescents with
diagnosed schizophrenia. Psychiatr Pol 2001;35:47‑57.
21. Poyurovsky M, Bergman J, Weizman R. Obsessive‑compulsive disorder
in elderly schizophrenia patients. J Psychiatr Res 2006;40:189‑91.
22. Kim  SW, Jeong  BO, Kim  JM, Shin  IS, Hwang  MY, Paul Amminger  G,
et al. Associations of obsessive‑compulsive symptoms with clinical and
neurocognitive features in schizophrenia according to stage of illness.
Psychiatry Res 2015;226:368‑75.
23. Faragian S, Pashinian A, Fuchs C, Poyurovsky M. Obsessive‑compulsive
symptom dimensions in schizophrenia patients with comorbid
obsessive‑compulsive disorder. Prog Neuropsychopharmacol Biol
Psychiatry 2009;33:1009‑12.
24. Devulapalli KK, Welge JA, Nasrallah HA. Temporal sequence of clinical
manifestation in schizophrenia with co‑morbid OCD: Review and
meta‑analysis. Psychiatry Res 2008;161:105‑8.
25. Rajkumar RP, Reddy YC, Kandavel T. Clinical profile of “schizo‑obsessive”
disorder: A comparative study. Compr Psychiatry 2008;49:262‑8.
26. Poyurovsky  M, Faragian  S, Kleinman‑Balush  V, Pashinian  A, Kurs  R,
Fuchs C, et al. Awareness of illness and insight into obsessive‑compulsive
symptoms in schizophrenia patients with obsessive‑compulsive disorder.
J Nerv Ment Dis 2007;195:765‑8.
S146
27. Byerly  M, Goodman  W, Acholonu  W, Bugno  R, Rush  AJ. Obsessive
compulsive symptoms in schizophrenia: Frequency and clinical features.
Schizophr Res 2005;76:309‑16.
28. Lysaker  PH, Whitney  KA. Obsessive‑compulsive symptoms in
schizophrenia: Prevalence, correlates and treatment. Expert Rev
Neurother 2009;9:99‑107.
29. Hwang MY, Kim SW, Yum SY, Opler LA. Management of schizophrenia with
obsessive‑compulsive features. Psychiatr Clin North Am 2009;32:835‑51.
30. Poyurovsky M, Fuchs C, Faragian S, Kriss V, Weisman G, Pashinian A,
et al. Preferential aggregation of obsessive‑compulsive spectrum
disorders in schizophrenia patients with obsessive‑compulsive disorder.
Can J Psychiatry 2006;51:746‑54.
31. Sullivan  PF, Kendler  KS, Neale  MC. Schizophrenia as a complex trait:
Evidence from a meta‑analysis of twin studies. Arch Gen Psychiatry
2003;60:1187‑92.
32. Poyurovsky M, Kriss V, Weisman G, Faragian S, Schneidman M, Fuchs C,
et al. Familial aggregation of schizophrenia‑spectrum disorders and
obsessive‑compulsive associated disorders in schizophrenia probands
with and without OCD. Am J Med Genet B Neuropsychiatr Genet
2005;133B: 31‑6.
33. Aoyama  F, Iida  J, Inoue  M, Iwasaka  H, Sakiyama  S, Hata  K, et al.
Brain imaging in childhood‑  and adolescence‑onset schizophrenia
associated with obsessive‑compulsive symptoms. Acta Psychiatr Scand
2000;102:32‑7.
34. Kurokawa  K, Nakamura  K, Sumiyoshi  T, Hagino  H, Yotsutsuji  T,
Yamashita  I, et al. Ventricular enlargement in schizophrenia spectrum
patients with prodromal symptoms of obsessive‑compulsive disorder.
Psychiatry Res 2000;99:83‑91.
35. 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;39:308‑11.
36. Pallanti  S, Castellini  G, Chamberlain  SR, Quercioli  L, Zaccara  G,
Fineberg  NA, et al. Cognitive event‑related potentials differentiate
schizophrenia with obsessive‑compulsive disorder  (schizo‑OCD)
from OCD and schizophrenia without OC symptoms. Psychiatry Res
2009;170:52‑60.
37. Bleich‑Cohen  M, Hendler  T, Weizman  R, Faragian  S, Weizman  A,
Poyurovsky M, et al. Working memory dysfunction in schizophrenia
patients with obsessive‑compulsive symptoms: An fMRI study. Eur
Psychiatry 2014;29:160‑6.
38. Bleich‑Cohen M, Poyurovsky M, Hendler T, Weizman R, Sharon H. Does
co‑morbid obsessive‑compulsive disorder modify the abnormal language
processing in schizophrenia patients? An FMRI study. Front Hum Neurosci
2014;8:560.
39. Schirmbeck F, Mier D, Esslinger C, Rausch F, Englisch S, Eifler S, et al.
Increased orbitofrontal cortex activation associated with “pro‑obsessive”
antipsychotic treatment in patients with schizophrenia. J  Psychiatry
Neurosci 2015;40:89‑99.
40. Patel DD, Laws KR, Padhi A, Farrow JM, Mukhopadhaya K, Krishnaiah R,
et al. The neuropsychology of the schizo‑obsessive subtype of
schizophrenia: A new analysis. Psychol Med 2010;40:921‑33.
41. Cunill R, Huerta‑Ramos E, Castells X. The effect of obsessive‑compulsive
symptomatology on executive functions in schizophrenia: A  systematic
review and meta‑analysis. Psychiatry Res 2013;210:21‑8.
42. Kazhungil F, Kumar KJ, Viswanath B, Shankar RG, Kandavel T, Math SB,
et al. Neuropsychological profile of schizophrenia with and without
obsessive compulsive disorder. Asian J Psychiatr 2017;29:30‑4.
43. Poyurovsky M, Zohar J, Glick I, Koran LM, Weizman R, Tandon R, et al.
Obsessive‑compulsive symptoms in schizophrenia: Implications for future
psychiatric classifications. Compr Psychiatry 2012;53:480‑3.
44. Fonseka  TM, Richter  MA, Müller DJ. Second generation
antipsychotic‑induced obsessive‑compulsive symptoms in schizophrenia:
A review of the experimental literature. Curr Psychiatry Rep 2014;16:510.
45. Sa  AR, Hounie  AG, Sampaio  AS, Arrais  J, Miguel  EC, Elkis  H, et al.
Obsessive‑compulsive symptoms and disorder in patients with
schizophrenia treated with clozapine or haloperidol. Compr Psychiatry
2009;50:437‑42.
46. Schirmbeck  F, Rausch  F, Englisch  S, Eifler  S, Esslinger  C,
Meyer‑Lindenberg A, et al. Differential effects of antipsychotic agents on
obsessive‑compulsive symptoms in schizophrenia: A  longitudinal study.
J Psychopharmacol 2013;27:349‑57.
47. Schirmbeck F, Esslinger C, Rausch F, Englisch S, Meyer‑Lindenberg A,
Zink  M, et al. Antiserotonergic antipsychotics are associated with
obsessive‑compulsive symptoms in schizophrenia. Psychol Med
2011;41:2361‑73.
48. Mukhopadhaya  K, Krishnaiah  R, Taye  T, Nigam  A, Bailey  AJ,
Sivakumaran T, et al. Obsessive‑compulsive disorder in UK
clozapine‑treated schizophrenia and schizoaffective disorder: A cause for
clinical concern. J Psychopharmacol 2009;23:6‑13.
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019
 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
49. Bleakley S, Brown D, Taylor D. Does clozapine cause or worsen obsessive
compulsive symptoms? An analysis and literature review. Ther Adv
Psychopharmacol 2011;1:181‑8.
50. Lykouras  L, Alevizos  B, Michalopoulou  P, Rabavilas  A.
Obsessive‑compulsive symptoms induced by atypical antipsychotics.
A  review of the reported cases. Prog Neuropsychopharmacol Biol
Psychiatry 2003;27:333‑46.
51. Mahendran  R, Liew  E, Subramaniam  M. De novo emergence of
obsessive‑compulsive symptoms with atypical antipsychotics in Asian
patients with schizophrenia or schizoaffective disorder: A  retrospective,
cross‑sectional study. J Clin Psychiatry 2007;68:542‑5.
52. Dold  M, Aigner  M, Lanzenberger  R, Kasper  S. Antipsychotic
augmentation of serotonin reuptake inhibitors in treatment‑resistant
obsessive‑compulsive disorder: An update meta‑analysis of double‑blind,
randomized, placebo‑controlled trials. Int J Neuropsychopharmacol
2015;18. pii: pyv047.
53. van Nimwegen L, de Haan L, van Beveren N, Laan W, van den Brink W,
Linszen  D, et al. Obsessive‑compulsive symptoms in a randomized,
double‑blind study with olanzapine or risperidone in young patients with
early psychosis. J Clin Psychopharmacol 2008;28:214‑8.
54. Schirmbeck  F, Zink  M. Clozapine‑induced obsessive‑compulsive
symptoms in schizophrenia: A  critical review. Curr Neuropharmacol
2012;10:88‑95.
55. Zink  M. Comorbid obsessive‑compulsive symptoms in schizophrenia:
Insight into pathomechanisms facilitates treatment. Adv Med
2014;2014:317980.
56. Gahr M, Rehbaum K, Connemann BJ. Clozapine‑associated development
of second‑onset obsessive compulsive symptoms in schizophrenia: Impact
of clozapine serum levels and fluvoxamine add‑on. Pharmacopsychiatry
2014;47:118‑20.
57. Grover S, Hazari N, Chakrabarti S, Avasthi A. Relationship of obsessive
compulsive symptoms/disorder with clozapine: A  retrospective
study from a multispeciality tertiary care centre. Asian J Psychiatr
2015;15:56‑61.
58. Grillault Laroche D, Gaillard A. Induced obsessive compulsive symptoms
(OCS) in schizophrenia patients under atypical 2 antipsychotics (AAPs):
Review and hypotheses. Psychiatry Res 2016;246:119‑28.
59. López-Gil X, Artigas F, Adell A. Unraveling monoamine receptors involved
in the action of typical and atypical antipsychotics on glutamatergic
and serotonergic transmission in prefrontal cortex. Curr Pharm Des
2010;16:502-15.
60. Cai J, Zhang W, Yi Z, Lu W, Wu Z, Chen J, et al. Influence of polymorphisms
in genes SLC1A1, GRIN2B, and GRIK2 on clozapine‑induced
obsessive‑compulsive symptoms. Psychopharmacology  (Berl)
2013;230:49‑55.
61. Ryu S, Oh S, Cho EY, Nam HJ, Yoo JH, Park T, et al. Interaction between
genetic variants of DLGAP3 and SLC1A1 affecting the risk of atypical
antipsychotics‑induced obsessive‑compulsive symptoms. Am J Med
Genet B Neuropsychiatr Genet 2011;156B:949‑59.
62. Zink  M, Englisch  S, Schmitt  A. Antipsychotic treatment modulates
glutamate transport and NMDA receptor expression. Eur Arch Psychiatry
Clin Neurosci 2014;264 Suppl 1:S67‑82.
63. Hong KS. Gene–Environment Interactions in the Pathogenesis of
Obsessive–Compulsive Symptoms in Schizophrenia. In: Obsessive-Compulsive
Symptoms in Schizophrenia. De Haan L, Schirmbeck F, Zink M, editors.
Springer International Publishing, Switzerland; 2015. p. 115-33.
64. Poyurovsky  M, Dorfman‑Etrog  P, Hermesh  H, Munitz  H, Tollefson  GD,
Weizman  A, et al. Beneficial effect of olanzapine in schizophrenic
patients with obsessive‑compulsive symptoms. Int Clin Psychopharmacol
2000;15:169‑73.
65. Juven‑Wetzler  A, Fostick  L, Cwikel‑Hamzany  S, Balaban  E, Zohar  J.
Treatment with ziprasidone for schizophrenia patients with OCD. Eur
Neuropsychopharmacol 2014;24:1454‑62.
66. Englisch  S, Esslinger  C, Inta  D, Weinbrenner A, Peus  V, Gutschalk A,
et al. Clozapine‑induced obsessive‑compulsive syndromes improve in
combination with aripiprazole. Clin Neuropharmacol 2009;32:227‑9.
67. Koran LM, Gregory Hanna CL, Hollander E, Nestadt G, Simpson HB.
Practice Guideline for the Treatment of Patients with Obsessive‑Compulsive
Disorder WORK GROUP ON OBSESSIVE‑COMPULSIVE DISORDER;
2010. Available from: http//www.psych.org/psych_pract/treatg/pg/prac_
guide.cfm. [Last accessed on 2018 Sep 18].
68. Ongür D, Goff  DC. Obsessive‑compulsive symptoms in schizophrenia:
Associated clinical features, cognitive function and medication status.
Schizophr Res 2005;75:349‑62.
69. Stryjer  R, Dambinsky  Y, Timinsky  I, Green  T, Kotler  M, Weizman  A,
et al. Escitalopram in the treatment of patients with schizophrenia and
obsessive‑compulsive disorder: An open‑label, prospective study. Int Clin
Psychopharmacol 2013;28:96‑8.
70. Poyurovsky  M, Isakov  V, Hromnikov  S, Modai  I, Rauchberger  B,
Schneidman M, et al. Fluvoxamine treatment of obsessive‑compulsive
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019
symptoms in schizophrenic patients: An add‑on open study. Int Clin
Psychopharmacol 1999;14:95‑100.
71. Poyurovsky M, Weizman A, Weizman R. Obsessive‑compulsive disorder
in schizophrenia: Clinical characteristics and treatment. CNS Drugs
2004;18:989‑1010.
72. Schirmbeck  F, Zink  M. Cognitive behavioural therapy for
obsessive‑compulsive symptoms in schizophrenia. Cogn Behav Therap
2013;6:e7.
73. Schönfelder S, Schirmbeck F, Waltereit R, Englisch S, Zink M. Aripiprazole
improves olanzapine‑associated obsessive compulsive symptoms in
schizophrenia. Clin Neuropharmacol 2011;34:256‑7.
74. Tundo A, Necci R. Cognitive‑behavioural therapy for obsessive‑compulsive
disorder co‑occurring with psychosis: Systematic review of evidence.
World J Psychiatry 2016;6:449‑55.
75. Mayer-Gross W, Slater E, Roth M. Clinical Psychiatry. 3rd  ed. London:
Elsevier Health Sciences; 1969.
76. Simon NM, Otto MW, Wisniewski SR, Fossey M, Sagduyu K, Frank E,
et al. Anxiety disorder comorbidity in bipolar disorder patients:
Data from the first 500 participants in the systematic treatment
enhancement program for bipolar disorder (STEP‑BD). Am J Psychiatry
2004;161:2222‑9.
77. Amerio  A, Stubbs  B, Odone  A, Tonna  M, Marchesi  C, Ghaemi  SN,
et al. The prevalence and predictors of comorbid bipolar disorder and
obsessive‑compulsive disorder: A systematic review and meta‑analysis.
J Affect Disord 2015;186:99‑109.
78. Amerio A, Stubbs B, Odone A, Tonna M, Marchesi C, Nassir Ghaemi S,
et al. Bipolar I and II disorders; A systematic review and meta‑analysis on
differences in comorbid obsessive‑compulsive disorder. Iran J Psychiatry
Behav Sci 2016;10:e3604.
79. Zutshi A, Reddy YC, Thennarasu  K, Chandrashekhar  CR. Comorbidity
of anxiety disorders in patients with remitted bipolar disorder. Eur Arch
Psychiatry Clin Neurosci 2006;256:428‑36.
80. Shashidhara  M, Sushma  BR, Viswanath  B, Math  SB, Janardhan
Reddy  YC. Comorbid obsessive compulsive disorder in patients with
bipolar‑I disorder. J Affect Disord 2015;174:367‑71.
81. Saraf G, Paul I, Viswanath B, Narayanaswamy JC, Math SB, Reddy YC,
et al. Bipolar disorder comorbidity in patients with a primary diagnosis of
OCD. Int J Psychiatry Clin Pract 2017;21:70‑4.
82. Amerio A, Tonna  M, Odone A, Ghaemi  SN. Comorbid bipolar disorder
and obsessive‑compulsive disorder: An old debate renewed. Psychiatry
Investig 2016;13:370‑1.
83. Amerio A, Odone A, Liapis CC, Ghaemi SN. Diagnostic validity of comorbid
bipolar disorder and obsessive‑compulsive disorder: A systematic review.
Acta Psychiatr Scand 2014;129:343‑58.
84. Issler  CK, Amaral  JA, Tamada  RS, Schwartzmann  AM, Shavitt  RG,
Miguel EC, et al. Clinical expression of obsessive‑compulsive disorder in
women with bipolar disorder. Braz J Psychiatr 2005;27:139‑42.
85. Zutshi  A, Kamath  P, Reddy  YC. Bipolar and nonbipolar
obsessive‑compulsive disorder: A clinical exploration. Compr Psychiatry
2007;48:245‑51.
86. Shabani  A, Alizadeh  A. The specific pattern of obsessive‑compulsive
symptoms in patients with bipolar disorder. Journal of Research in Medical
Sciences 2008;13:48-54.
87. Marazziti  D, Dell’Osso  L, Di Nasso  E, Pfanner  C, Presta  S, Mungai  F,
et al. Insight in obsessive‑compulsive disorder: A  study of an Italian
sample. Eur Psychiatry 2002;17:407‑10.
88. Mahasuar  R, Janardhan Reddy  YC, Math  SB. Obsessive‑compulsive
disorder with and without bipolar disorder. Psychiatry Clin Neurosci
2011;65:423‑33.
89. McElroy  SL, Strakowski  SM, Keck PE Jr. Tugrul  KL, West  SA,
Lonczak HS, et al. Differences and similarities in mixed and pure mania.
Compr Psychiatry 1995;36:187‑94.
90. Dell’Osso  L, Pini  S, Tundo A, Sarno  N, Musetti  L, Cassano  GB, et al.
Clinical characteristics of mania, mixed mania, and bipolar depression
with psychotic features. Compr Psychiatry 2000;41:242‑7.
91. Issler CK, Monkul ES, Amaral JA, Tamada RS, Shavitt RG, Miguel EC,
et al. Bipolar disorder and comorbid obsessive‑compulsive disorder is
associated with higher rates of anxiety and impulse control disorders.
Acta Neuropsychiatr 2010;22:81‑6.
92. Goes FS, McCusker MG, Bienvenu OJ, Mackinnon DF, Mondimore FM,
Schweizer  B, et al. Co‑morbid anxiety disorders in bipolar disorder
and major depression: Familial aggregation and clinical characteristics
of co‑morbid panic disorder, social phobia, specific phobia and
obsessive‑compulsive disorder. Psychol Med 2012;42:1449‑59.
93. Chen YW, Dilsaver SC. Comorbidity for obsessive‑compulsive disorder in
bipolar and unipolar disorders. Psychiatry Res 1995;59:57‑64.
94. Hantouche  EG, Kochman  F, Demonfaucon  C, Barrot  I, Millet  B,
Lancrenon S, et al. Bipolar obsessive‑compulsive disorder: Confirmation
of results of the “ABC‑OCD” survey in 2 populations of patient members
versus non‑members of an association. Encephale 2002;28:21‑8.
S147
 Sharma and Reddy: OCD in schizophrenia and bipolar disorder
95. Angst  J, Gamma  A, Endrass  J, Hantouche  E, Goodwin  R, Ajdacic  V,
et al. Obsessive‑compulsive syndromes and disorders: Significance of
comorbidity with bipolar and anxiety syndromes. Eur Arch Psychiatry Clin
Neurosci 2005;255:65‑71.
96. Dilsaver  SC, Akiskal  HS, Akiskal  KK, Benazzi  F. Dose‑response
relationship between number of comorbid anxiety disorders in adolescent
bipolar/unipolar disorders, and psychosis, suicidality, substance abuse
and familiality. J Affect Disord 2006;96:249‑58.
97. Timpano  KR, Rubenstein  LM, Murphy  DL. Phenomenological features
and clinical impact of affective disorders in OCD: A focus on the bipolar
disorder and OCD connection. Depress Anxiety 2012;29:226‑33.
98. Perugi  G, Toni  C, Frare  F, Travierso  MC, Hantouche  E, Akiskal  HS,
et al. Obsessive‑compulsive‑bipolar comorbidity: A  systematic
exploration of clinical features and treatment outcome. J Clin Psychiatry
2002;63:1129‑34.
99. Masi  G, Millepiedi  S, Perugi  G, Pfanner  C, Berloffa  S, Pari  C, et al.
A naturalistic exploratory study of the impact of demographic, phenotypic
and comorbid features in pediatric obsessive‑compulsive disorder.
Psychopathology 2010;43:69‑78.
100. Maina G, Albert U, Pessina E, Bogetto F. Bipolar obsessive‑compulsive
disorder and personality disorders. Bipolar Disord 2007;9:722‑9.
101. Tükel R, Meteris H, Koyuncu A, Tecer A, Yazici O. The clinical impact of
mood disorder comorbidity on obsessive‑compulsive disorder. Eur Arch
Psychiatry Clin Neurosci 2006;256:240‑5.
102. Perugi G, Akiskal HS, Gemignani A, Pfanner C, Presta S, Milanfranchi A,
et al. Episodic course in obsessive‑compulsive disorder. Eur Arch
Psychiatry Clin Neurosci 1998;248:240‑4.
S148
103. Perugi G, Akiskal HS, Pfanner C, Presta S, Gemignani A, Milanfranchi A,
et al. The clinical impact of bipolar and unipolar affective comorbidity on
obsessive‑compulsive disorder. J Affect Disord 1997;46:15‑23.
104. Amerio A, Tonna M, Odone A, Stubbs B, Ghaemi SN. Course of illness
in comorbid bipolar disorder and obsessive‑compulsive disorder patients.
Asian J Psychiatr 2016;20:12‑4.
105. Koyuncu  A, Tükel R, Ozyildirim  I, Meteris  H, Yazici  O. Impact of
obsessive‑compulsive disorder comorbidity on the sociodemographic
and clinical features of patients with bipolar disorder. Compr Psychiatry
2010;51:293‑7.
106. Strakowski SM, Sax KW, McElroy SL, Keck PE Jr., Hawkins JM, West SA,
et al. Course of psychiatric and substance abuse syndromes co‑occurring
with bipolar disorder after a first psychiatric hospitalization. J  Clin
Psychiatry 1998;59:465‑71.
107. Ortiz A, Bradler K, Slaney C, Garnham J, Ruzickova M, O’Donovan C,
et al. An admixture analysis of the age at index episodes in bipolar
disorder. Psychiatry Res 2011;188:34‑9.
108. Amerio A, Tonna M, Odone A, Stubbs B, Ghaemi SN. Heredity in comorbid
bipolar disorder and obsessive‑compulsive disorder patients. Shanghai
Arch Psychiatry 2015;27:307‑10.
109. Cannon DM, Ichise M, Fromm SJ, Nugent AC, Rollis D, Gandhi SK, et al.
Serotonin transporter binding in bipolar disorder assessed using [11C] DASB
and positron emission tomography. Biol Psychiatry 2006;60:207‑17.
110. Amerio A, Odone A, Marchesi C, Ghaemi SN. Do antidepressant‑induced
manic episodes in obsessive‑compulsive disorder patients represent
the clinical expression of an underlying bipolarity? Aust N Z J Psychiatry
2014;48:957.
Indian Journal of Psychiatry, Volume 61 (Supplement 1), January 2019