| Abstract|| |
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.
Keywords: Antipsychotic-induced obsessive-compulsive symptoms, bipolar disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, schizo-obsessive disorder, schizophrenia
|How to cite this article:|
Sharma LP, Reddy Y C. Obsessive–compulsive disorder comorbid with schizophrenia and bipolar disorder. Indian J Psychiatry 2019;61, Suppl S1:140-8
| Introduction|| |
Obsessive–compulsive disorder (OCD), anxiety disorders, and depression are known to be highly comorbid with each other, 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. This article attempts to review the extant data on these 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 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. The occurrence of OCS can range anywhere between 5% and 30%. Although OCS are also common in the general population and in those with other psychiatric disorders,, 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, and in the presence of depression and suicidality, although their presence and severity may not predict transition to frank psychosis. Individuals with OCS and at ultra-high risk for psychosis had poorer psychosocial functioning than those without, but interestingly were found to perform better on tests of neurocognitive functioning when compared to those without.
The common symptoms in those at risk for psychosis are aggressive obsessions, checking compulsions, and hoarding., One study also found duration of subthreshold psychosis to be longer in those with OCS (15.6 months vs. 6.2 months) with the highest frequency of OCS in those with a family history of psychosis.
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 protective factor. 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. The term “schizo-obsessive disorder” was suggested in order to draw attention to those schizophrenia patients with clinically significant OCS. Recent meta-analyses have shown that up to 30% of patients with schizophrenia report OCS and 12%–14% of them meet diagnostic criteria for OCD., 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.
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. In a study from our center, 65% had developed OCS before antipsychotic use.
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.,, 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. 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.
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. 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.
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., 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%. 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. The presence of comorbid OCD was associated with more severe depression, impaired social functioning, and worse premorbid functioning.
The phenomenology of OCS in schizo-obsessive disorder is similar to that in primary OCD patients and is typically moderate to severe.,,, One study reported good insight into OCS in 85% of the patients, a rate comparable to that in primary OCD, but in an Indian study, less than a half had good insight (46%). 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.,, 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., 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.
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%).
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, and (at a trend level) an increased rate of OCD, with no between-group differences in the rate of schizophrenia spectrum disorders. In an Indian study of 200 participants with schizophrenia, those with OCS/OCD had a significantly greater family loading for OCD than those without. 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).
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. Patients with schizo-obsessive disorder in the prodromal phase had a greater ventricle-brain ratio than patients with pure OCD. 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.
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. 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. 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. 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.
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. However, a meta-analysis found impairment only in abstract reasoning with no impairment in executive functions. We examined the neuropsychological profile of schizophrenia with and without OCD with a comprehensive battery of tests of attention, executive functions, and memory but found no differences between the two groups. 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. 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. 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. 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. Clozapine is most frequently associated with exacerbation of or de novo emergence of OCS in schizophrenia,,, although there are few contrary reports., 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.
OCS usually manifest within the first few weeks of initiation of treatment with a SGA,, whereas with clozapine, OCS emerge gradually over the first 12 months or so. 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 and higher doses causing emergence of OCS.
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, OCS manifesting for the first time after initiating treatment with SGAs, correlation of OCS severity with dose, duration and serum levels of clozapine,, and improvement in OCS after reduction in the dose of clozapine or change of drug.,,,,
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., 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. 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.,, 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.
| 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, and ziprasidone 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.,
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. SSRIs seem to be beneficial, especially escitalopram at 20 mg/day, but not in all cases. Addition of fluvoxamine and clomipramine 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/OCD in schizophrenia. Reviews of case reports and case series suggest that CBT may be effective, but this needs confirmation in well-designed studies. 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.
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, addition of aripiprazole, and addition of SSRI and CBT.
| 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.”
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%. 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%). 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). A study from our center reported the presence of OCD in 35% of 80 participants with remitted BD. 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. However, BD comorbidity in 171 patients with a primary diagnosis of OCD recruited from our specialty OCD clinic has been relatively low (4%), when compared with the rates reported in systematic reviews.,
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. 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.
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. Contamination obsessions and washing compulsions have also been associated with OCD-BD; however, the converse has also been reported., A review of 18 studies found no conclusive evidence that BD-OCD had more severe OCS. However, insight into OCD was found to be poorer in those with comorbidity.,
OCD is more likely to manifest during mixed mania and depressive episodes., Patients with OCD-BD tended to have a greater number of depressive episodes than BD alone.,
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, which was confirmed by subsequent studies.,, OCD also was associated with a 2.4-fold increase in the odds of suicidal ideation among BD adolescents. 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. One report showed a positive association between BD-OCD comorbidity and sedatives, nicotine, alcohol, and coffee use. The ECA study confirmed the higher rate of drug abuse in OCD-BD participants than in noncomorbid participants (37.1% vs. 28.2%). 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.
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. 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.
The course of OCD in the context of BD has been predominantly described as being episodic,,,,,, although exceptions (a continuous, chronic course of OCD) have also been described., A study reported episodic course of OCD to be more common in BD type II than in BD type I. In contrast, two studies found a chronic course of affective episodes with residual symptoms in those with OCD-BD., There is evidence that SSRIs cause more mania/hypomania in BD-OCD patients than in noncomorbid patients. OCS are reported to worsen during depression and remit/improve in manic/hypomanic phases.,,
With regard to onset of symptoms, studies report either BD-OCD beginning concomitantly, with BD-OCD cycling together, OCD preceding BD onset, or onset of depressive episodes before the onset of OCD.
Studies of patients with OCD/OCS-BD have shown family loading for mood disorders,,, as well as higher family loading for OCD. 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. 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.
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.
Challenges in managing comorbid OCD-BD revolve around the risk of SSRIs causing manic switch or worsening the 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.
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. 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.,
| 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.
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Conflicts of interest
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Dr. Y C Janardhan Reddy
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None