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A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis
Journal of Psychiatric Research 45 (2011) 1140e1145
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A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis Leonardo F. Fontenelle a, b, c, *,1, Ashleigh Lin a, d, Christos Pantelis a, Stephen J. Wood a, e, Barnaby Nelson d, Alison R. Yung d a
Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Australia Anxiety and Depression Research Program, Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Brazil Department of Psychiatry and Mental Health, Institute of Community Health, Universidade Federal Fluminense, Brazil d Orygen Youth Health Research Centre and Centre for Youth Mental Health, University of Melbourne, Australia e School of Psychology, University of Birmingham, UK b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 8 November 2010 Received in revised form 20 February 2011 Accepted 3 March 2011
Background: We evaluated whether (1) a diagnosis of obsessive-compulsive disorder (OCD) at baseline, or (2) the persistence, remission or emergence of de novo OCD at follow-up, were associated with the development of different psychotic disorders in a cohort of individuals at ultra-high risk (UHR) for psychosis. Methods: Patients were assessed for OCD at baseline and after a mean of 7.4 years follow-up and classified into: (i) Non-OCD group - patients without OCD both at baseline and follow-up (n ¼ 269; 86.2%), (ii) Incident OCD group - patients without OCD at baseline but with OCD at follow-up (n ¼ 17; 5.4%), (iii) Remitting OCD group - patients with OCD at baseline but without OCD at follow-up (n ¼ 20; 6.4%), (iv) Persistent OCD group - patients with OCD both at baseline and at follow-up (n ¼ 6; 1.9%). Rates of different DSM-IV psychotic disorders at follow-up were compared across these groups. Results: Patients who displayed remitting OCD were not related to the development of any DSM-IV psychotic disorder. A diagnosis of incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders not otherwise specified (PDNOS), and greater baseline severity of general psychopathology, alogia, and avolitionapathy. Two of the six patients (40%) with persistent OCD developed schizophrenia, while only 12.5%, 5.0%, and 9.7% of incident, remitting, and non-OCD groups, respectively, exhibited the same condition at follow-up. Rates of antipsychotic use in the previous two years were not significantly different between the groups. Conclusions: Our findings suggest that, in a cohort of individuals at UHR for psychosis, remission of OCD does not increase the risk of psychosis, while de novo OCD was associated with development of mood disorders with psychotic features and PDNOS. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Obsessive-compulsive disorder Psychosis Comorbidity Follow-up studies
1. Introduction Observations of patients with obsessive-compulsive disorder (OCD) indicate that the incidence of schizophrenia is low (de Haan et al., 2009), even after long-term follow-up (Pollitt, 1957; Kringlen, 1965; Lo, 1967). In contrast, obsessive-compulsive symptoms (OCS) are noted more commonly at various stages of psychosis and
* Corresponding author. Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, 161 Barry Street, Carlton South, Victoria 3053, Australia. E-mail address: [email protected] (L.F. Fontenelle). 1 Present address: Rua Visconde de Pirajá, 547, Sala 719, Ipanema, Rio de Janeiro, CEP 22410-003, Brazil. Tel./fax: þ55 21 22394919. 0022-3956/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2011.03.005
schizophrenia (Lysaker et al., 2009), although their impact on the outcome is still unclear. Early theorists have argued OCD might prevent the development of “malignant schizophrenia”, retard the “personality disintegration” associated with schizophrenia, or even herald remission of schizophrenic illness (Bottas et al., 2005). In fact, while some studies have suggested that schizophrenia patients with OCD (or OCS) may exhibit less severity of formal thought disorder and affective blunting (Poyurovsky et al., 1999), fewer negative symptoms (Tibbo et al., 2000; de Haan et al., 2005), and greater global functioning (Tibbo et al., 2000), a recent metaanalysis of cross-sectional studies suggested that OCS were associated with greater severity of global, positive and negative psychotic symptoms (Cunill et al., 2009). Thus, it remains unclear whether OCS/OCD bears any relationship to the emergence of
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psychosis and schizophrenia, or whether the two disorders are independent. In order to assess this relationship, longitudinal studies from early psychosis that examine the relationship to longterm outcome are needed. To date, there is only one study in a pre-psychotic sample of young people at ultra-high risk (UHR) for developing psychosis. Niendam et al. (2009) reported that, although UHR individuals with OCS exhibited greater levels of depression, suicidality, and positive and negative symptoms, baseline OCD (14% of their sample) was associated with a statistical trend towards lower rates of conversion to psychosis over the follow-up period. Further, while self-reported OCS remained temporally stable among UHR individuals who did not convert to psychosis, OCS declined among those UHR individuals who did develop psychosis. However, this analysis relied on self-reported symptoms and it remains unclear whether persistence, remission, or de novo OCD over time are associated with changes that contribute to conversion to psychosis. In this long-term longitudinal study of the UHR for psychosis cohort at the Personal Assessment and Crisis Evaluation (PACE) Clinic, we evaluated whether a diagnosis of OCD at baseline and the persistence, remission or emergence of de novo OCD are associated with the development of different psychotic disorders at follow-up. We predicted that increased transition to psychosis would be seen among UHR individuals who do not show OCD at baseline or at the follow-up, or who remit from OCD at follow-up.
2. Methods 2.1. Participants and procedure The sample consisted of 312 individuals (55.1% female) recruited consecutively on admission to the PACE Clinic at Orygen Youth Health in Melbourne, Australia between 1994 and 2005. At baseline, all were assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) (Yung et al., 2005) and met criteria for UHR for psychosis. These criteria are the attenuated positive symptoms, brief limited intermittent psychotic symptoms, and/or have vulnerability for psychotic illness, all of which must be accompanied by a deterioration in functioning. UHR individuals were aged 15e25 years at baseline and had no prior psychotic episode (treated or untreated). Detailed criteria for the identification of the UHR group are described elsewhere (Yung et al., 2005) and are summarized in Table 1.
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The CAARMS also includes a screening section for OCD symptoms, comprising questions on whether patients have distressing or intrusive thoughts, forced repetitive behaviors, rituals/superstitions, need to do things a certain way, or checking compulsions. Along with other symptoms dimensions, OCD symptoms are rated on [1] a 6-point severity (or interference) scale (0 ¼ never/absent to 6 ¼ extreme), [2] a 6-point frequency and duration scale (0 ¼ absent to 6 ¼ continuous), and [3] its relationship with substance abuse (0 ¼ not in relation, 1 ¼ sometimes in relation, and 2 ¼ only in relation to substance abuse). Participants were followed-up between 2007 and 2009. A tracking system based on a previously documented system used at Orygen (Henry et al., 2007) was implemented to locate and recontact participants in this cohort. The mean age of the sample at baseline was 18.8 (SD ¼ 3.2) and at follow-up assessment was 26.1 (SD ¼ 5.04) years old. The mean time to follow-up was 7.4 years (SD ¼ 3.2, range ¼ 2.4e14.8). All participants provided written informed consent in accordance with guidelines provided by the local mental health service research and ethics committee. This research was conducted in accordance with the Declaration of Helsinki.
2.2. Measures Additional measures of psychiatric symptoms at both baseline and follow-up assessments were the Structured Clinical Interview for DSM-IV (SCID; First et al., 2002), the Brief Psychiatric Rating Scale (BPRS) (McGorry et al., 1988), and the Scale for Assessment of Negative Symptoms (SANS) (Andreasen, 1982). A proportion of the participants were also assessed on the Hamilton Rating Scale for Anxiety (HARS) (Hamilton, 1959) and Hamilton Rating Scale for Depression (HRSD) (Hamilton, 1960). Diagnostic decisions followed the guidelines provided by the SCID/DSM-IV-TR, such that whenever another Axis I disorder was present (including a psychotic disorder), the patient was diagnosed with OCD only if the content of the obsessions or compulsions was not restricted to it. At both assessments, the functioning and disability of participants was determined using the Quality of Life Scale (QLS) (Heinrichs et al., 1984). The Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999) or an abbreviated form of the Wechsler Adult Intelligence ScaleRevised (WAIS-R) (Weschler, 1981) were used to estimate current IQ at baseline and follow-up.
Table 1 PACE Ultra-High Risk criteria: (1) must be aged between 15 and 25 years, (2) have been referred to a specialized service for help, and (3) meet the criteria for one or more of the following three groups. Group 1: Attenuated positive psychotic symptoms
Group 2: Brief limited intermittent psychotic symptoms
Group 3: Trait and state risk factors
Adapted from Yung et al. (2005).
Presence of at least one of the following symptoms: ideas of reference, odd beliefs or magical thinking, perceptual disturbance, paranoid ideation, odd thinking and speech, odd behavior and appearance Frequency of symptoms: at least several times a week Recency of symptoms: present within the last year Duration of symptoms: present for at least 1 week and no longer than 5 years Transient psychotic symptoms. Presence of at least one of the following: ideas of reference, magical thinking, perceptual disturbance, paranoid ideation, odd thinking or speech Duration of episode: less than 1 week Frequency of symptoms: at least several times per week Symptoms resolve spontaneously Recency of symptoms: must have occurred within the last year Schizotypal personality disorder in the identified individual, or a first-degree relative with a psychotic disorder Significant decline in mental state or functioning, maintained for at least 1 month and not longer than 5 years This decline in functioning must have occurred within the past year
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2.3. Study groups 1. Baseline OCD: All individuals who had a lifetime history of OCD at the first assessment (baseline). a) Persistent OCD group: Subjects who had both a lifetime history of OCD at the first assessment (baseline) and displayed OCD between the first and the second assessment (follow-up). b) Remitting OCD group: Subjects who had a lifetime history of OCD at the first assessment (baseline) but did not display OCD between the first and the second evaluation (followup). 2. Incident OCD (or de novo OCD): Subjects who did not have a lifetime history of OCD at the first assessment (baseline) but displayed OCD somewhere between the first and the second assessment (follow-up). 3. Non-OCD group: Subjects who had no lifetime history of OCD, either at the first assessment (baseline) or between the first and the second assessment (follow-up).
2.4. Statistical analysis Continuous variables were described as means (standard deviation, SD) and categorical variables as absolute (n) and relative (%) values. Comparisons between two groups were made with Chisquare (c2) tests and independent samples t-tests or ManneWhitney tests according to the normality of distribution. Comparisons between four groups were made using c2 and KruskalleWallis tests. At this point, the standard level of significance was .05. Post hoc c2 or ManneWhitney tests with Bonferroni’s correction followed significant differences. 3. Results We found that 8.1% (32 of 396) and 8.0% (25 of 314) of our UHR subjects had a diagnosis of OCD at baseline and at follow-up, respectively. Six subjects who had OCD at baseline but were lost to follow-up, and two individuals who had a diagnosis of OCD at follow-up and were not assessed for OCD at baseline were excluded from subsequent analysis, leaving 312 to be classified as incident OCD (n ¼ 17, 5.4%), persistent OCD (n ¼ 6, 1.9%), remitting OCD (n ¼ 20, 6.4%), or non-OCD (n ¼ 269, 86.2%). A total of 57 (18.2% of 312) patients fulfilled criteria for at least one psychotic disorder at follow-up: 31 (9.9%) developed schizophrenia, 1 (.3%) schizoaffective disorder, 1 (.3%) delusional disorder, 5 (1.6%) substance induced psychotic disorder, 13 (4.1%) psychotic disorder not otherwise specified (PDNOS), 4 (1.3%) bipolar disorder with psychotic features, and 6 (1.9%) major depression with psychotic features. The specific prevalence rates of OCD (including incident, persistent, and remitting cases) among UHR individuals who developed psychosis was 24.5% (n ¼ 14) for any psychotic disorder, 16.1% (n ¼ 5) in schizophrenia, 0% in schizoaffective disorder, 100% (n ¼ 1) in delusional disorder, 0% in substance induced psychotic disorder, 46.1% (n ¼ 6) in PDNOS, and 28.5% (n ¼ 4) in mood disorders with psychotic features, i.e. 50.0% (n ¼ 2) in bipolar disorders with psychotic features, and 33.3% (n ¼ 2) in major depressive disorder with psychotic features. At baseline, available CAARMS OCD symptoms subscale scores lead to predictable results, i.e. remitting OCD (n ¼ 13) had greater severity at baseline than incident OCD (n ¼ 8; p ¼ .005) and the non-OCD group (n ¼ 197; p < .001), and greater frequency/duration of OCD symptoms than the non-OCD group (p < .001). Incident OCD and non-OCD groups were not significantly different both in severity (p ¼ .89) and frequency/duration (p ¼ .75) of baseline OCD
symptoms. Only one patient with persisting OCD had baseline CAARMS OCD values, thus not allowing us to compare groups in terms of baseline severity, frequency, and duration of OCD. A comparison between the four groups according to the CAARMS OCD symptoms subscale scores at follow-up also generated results in the expected direction. Persistent (n ¼ 4) and incident OCD (n ¼ 15) had both greater severity (p < .001 each) and frequency/ duration (p ¼ .005 and p < .001, respectively) of OCD symptoms than non-OCD group (n ¼ 241). Persistent OCD had greater severity (p ¼ .006) of OCD symptoms than remitting OCD group (n ¼ 16) and incident OCD had both greater severity (p ¼ .001) and frequency/ duration (p ¼ .001) of OCD symptoms than remitting OCD group. Persisting OCD did not differ from incident OCD in terms of severity (p ¼ .02, non-significant after Bonferroni’s correction) and frequency/duration (p ¼ .83) of OCD symptoms. Remitting OCD group did not differ from non-OCD group in terms of severity (p ¼ .04; non-significant after Bonferroni’s correction) and frequency/duration (p ¼ .13) of OCD symptoms. There were no significant differences between UHR subjects with and without OCD at baseline, either in terms of clinical aspects or transition to different psychotic disorders (Table 2). However, as seen in Table 3, incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders NOS, and greater baseline severity of general psychopathology, alogia, and avolition-apathy. Two out of 6 (40%) patients with persisting OCD received a diagnosis of schizophrenia at follow-up, although this rate was not significantly different from those reported in other groups. 4. Discussion In this long-term follow-up study of subjects at ultra-high risk for the development of psychosis, 5.4% developed incident OCD, 1.9% exhibited persistent OCD, and 6.4% displayed remitting OCD. Further, we found that around 8.0% of our UHR individuals exhibited OCD as a comorbidity either at baseline or at follow-up. Although this rate is more than 3 times greater than the prevalence of OCD described in the general population (Faravelli et al., 2004), it is much lower than our OCD rates among the total number of UHR individuals (22.4%) who developed psychosis. This suggests that the transition to psychosis, rather than the high risk status, is associated with greater rates of OCD. Lower rates of OCD among UHR individuals can also be considered consistent with the findings from a meta-analysis showing a positive correlation between the severity of global, positive, and negative symptoms and severity of OCS in patients with schizophrenia (Cunill et al., 2009). The fact that the prevalence of OCD at baseline (8.1%) remained relatively stable at the follow-up (8.0%) did not reflect a great number of persistent cases. In fact, remitted (n ¼ 20) and incident (n ¼ 17) OCD patients outnumbered persistent cases (n ¼ 6) in our sample. Accordingly, this pattern of OCD symptoms’ fluctuation was already reported in epidemiological studies (Nelson and Rice, 1997) and was critical in allowing us to examine a dynamic relationship between OCD and psychosis and testing our hypothesis of a relative antagonism between both states. Consistent with Niendam et al. (2009), we were unable to find significant differences between UHR individuals with and without baseline OCD in terms of psychopathology (BPRS, SANS, HDRS, and HARS scores), quality of life, and conversion rates to different DSMIV psychotic disorders. While some studies of patients with schizophrenia reported similar results (Berman and pappas, 1997; Poyurovsky et al., 2001; Craig et al., 2002; Byerly et al., 2005; Sevincok et al., 2007), the fact that UHR individuals, by definition,
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Table 2 Comparison between baseline features and follow-up conversion rates between UHR patients with and without OCD.
Age Gender (female) IQ BPRS Psychotic subscale Total SANS Affective flattening Alogia Avolition-apathy Anhedonia-Asociality Attention Total HARS HDRS QLS DSM-IV-TR Psychotic disorders at follow-up Schizophrenia Schizoaffective disorder Delusional disorder Substance induced psychotic disorder Psychotic disorder NOS Bipolar disorder with psychotic features Major depression with psychotic features Mood disorders with psychotic features Any psychotic disorder
Presence of OCD at baseline
Absence of OCD at baseline
Test results
19.3 (3.1) 16 (61.%) 101.7 (13.3)
19.9 (3.3) 158 (54.9%) 98.0 (14.0)
t ¼ .4; df ¼ 372; p ¼ .64 c2 ¼ .43; df ¼ 1; p ¼ .51 t ¼ 1.4; df ¼ 330; p ¼ .15
9.6 (2.5) 45.6 (7.4)
9.5 (2.9) 47.3 (9.6)
t ¼ .81; df ¼ 392; p ¼ .93 t ¼ .98; df ¼ 392; p ¼ .32
5.1 (4.7) 1.4 (1.5) 3.5 (2.7) 7.2 (5.2) 1.2 (1.5) 18.5 (11.0) 15.3 (7.0) 18.6 (6.7) 75.4 (26.2)
5.5 (5.4) 2.4 (2.5) 4.1 (3.0) 6.0 (4.5) 1.8 (2.0) 19.8 (12.9) 15.3 (8.3) 18.9 (10.1) 76.0 (20.5)
t ¼ 3.6; df ¼ 393; p ¼ .67 ManneWhitneys’s p ¼ .86 t ¼ .95; df ¼ 393; p ¼ .34 t ¼ 1.4; df ¼ 393; p ¼ .14 ManneWhitneys’s p ¼ .63 t ¼ .57; df ¼ 393; p ¼ .57 t ¼ .002; df ¼ 175; p ¼ .99 t ¼ .18; df ¼ 26.8; p ¼ .85 t ¼ .14; df ¼ 389; p ¼ .88
4 0 0 0 2 0 0 0 5
34 (12.1%) 1 (.4%) 1 (.4%) 6 (2.2%) 15 (5.4%) 5 (1.8%) 5 (1.8%) 10 (3.6%) 64 (22.2%)
Fisher’s exact p ¼ .54 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ .64 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 c2 ¼ .12; df ¼ 1; p ¼ .72
(15.4%) (.0%) (.0%) (.0%) (7.7%) (.0%) (.0%) (.0%) (19.2%)
IQeIntelligence quotient; BPRSeBrief Psychiatric Rating Scale; SANSeScale for the Assessment of Negative Symptoms; HARSeHamilton Rating Scale for Anxiety; HDRSeHamilton Rating Scale for Depression; QLSeQuality of Life Scale; DSM-IV-TReDiagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision.
exhibit lower levels of psychopathology than patients with schizophrenia may have lessened the potential differences between patients with and without OCD. Alternatively, the lack of significance between groups could suggest that OCD may be an intrinsic
dimension of the at-risk state, free of additional impairments in psychopathological or quality of life spheres. The diagnosis of a psychotic disorder at follow-up was greater among UHR individuals who exhibited incident OCD, including
Table 3 Comparison between baseline features and follow-up conversion rates between UHR patients with different OCD outcomes. Incident OCD (n ¼ 17)
Persistent OCD (n ¼ 6)
Age 18.2 (2.8) 18.6 (3.2) Gender (female) 10 (62.5%) 3 (50%) Intelligence quotient 91.0 (14.9) 107.0 (17.0) Brief Psychiatric Rating Scale Psychotic subscale 10.2 (2.8) 7.8 (2.4) 39.3 (5.6) * Total 51.0 (7.1) * Scale for the Assessment of Negative Symptoms Affective flattening 5.3 (5.8) 3.6 (4.8) .1 (.40) * Alogia 3.4 (3.2) * 1.3 (1.2) * Avolition-apathy 5.6 (3.1) * Anhedonia-Asociality 6.6 (5.0) 8.1 (5.8) Attention 2.0 (1.9) .6 (1.6) Total 23 (12.8) 14.0 (9.8) Hamilton Rating Scale for Anxiety 21.8 (9.7) 14.2 (4.5) Hamilton Rating Scale for Depression 27.1 (11.2) 16 (.70) Quality of Life Scale 68.6 (19.6) 87.6 (13.6) Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. Psychotic Schizophrenia 2 (12.5%) 2 (40.0%) Schizoaffective disorder 0 (.0%) 0 (.0%) Delusional disorder 1 (6.7%) 0 (.0%) Substance induced psychotic disorder 0 (.0%) 0 (.0%) 0 (.0%) Psychotic disorder NOS 5 (31.3%)z Bipolar disorder with psychotic features 2 (13.3%) 0 (.0%) Major depression with psychotic features 2 (13.3%) 0 (.0%) 0 (.0%) Mood disorder w/psychotic features 4 (26.7%)z yz 2 (40.0%) Any Psychotic disorder 10 (62.5%) Any psychotropic at the entire period 10 (66.7%) 4 (80.0%) Antipsychotics at the entire period 7 (46.7%) 2 (50%) Any psychotropic two years before follow-up 9 (64.3%) 3 (75%) Antipsychotics two years before follow-up 5 (35.7%) 1 (25%)
Remitting OCD (n ¼ 20)
Non-OCD group (n ¼ 269)
Test results
19.5 (3.4) 8 (40.0%) 99.7 (12.1)
18.8 (3.2) 123 (45/7%) 98.3 (13.7)
KruskalleWallis’ p ¼ .71 c2 ¼ .98; df ¼ 3; p ¼ .80 KruskalleWallis’ p ¼ .14
10.3 (2.6) 47.3 (7.3)
9.3 (3.0) 47.2 (9.8)
KruskalleWallis’ p ¼ .20 KruskalleWallis’ p ¼ .03
5.1 (4.9) 5.6 (5.5) 1.4 (1.5) 2.3 (2.5) 4.5 (2.7) 3.9 (3.0) 6.8 (5.1) 5.9 (4.5) 1.3 (1.6) 1.7 (2.0) 19.3 (11.0) 19.6 (12.9) 17.1 (6.8) 15.2 (8.5) 20.3 (7.4) 18.3 (10.0) 71.8 (30.8) 78.5 (23.5) disorders at follow-up 1 (5.0%) 26 (9.7%) 0 (.0%) 1 (.4%) 0 (.0%) 0 (.0%) 0 (.0%) 5 (1.9%) 1 (5.0%) 7 (2.6%)z 0 (.0%) 2 (.7%) 0 (.0%) 4 (1.5%) 0 (.0%) 6 (2.2%)z y 2 (10.0%) 43 (16.0%)z 10 (66.7%) 140 (55.3%) 1 (5.9%) 47 (18.6%) 8 (53.3%) 95 (42.8%) 1 (6.7%) 34 (15.4%)
KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’
p¼ p¼ p¼ p¼ p¼ p¼ p¼ p¼ p¼
.78 .01 .01 .68 .23 .51 .28 .05 .11
c2 ¼ 5.7; df ¼ 3; p ¼ .12 c2 ¼ .15; df ¼ 3; p ¼ .98 c2 ¼ 19.6; df ¼ 3; p < .001 c2 ¼ .75; df ¼ 3; p ¼ .86 c2 ¼ 31.1; df ¼ 3; p < .001 c2 ¼ 18.0; df ¼ 3; p < .001 c2 ¼ 11.0; df ¼ 3; p ¼ .01 c2 ¼ 28.0; df ¼ 3; p < .001 c2 ¼ 24.2; df ¼ 3; p < .001 c2 ¼ 2.0; df ¼ 3; p ¼ .58 c2 ¼ 10.2; df ¼ 3; p ¼ .02 c2 ¼ 4.4; df ¼ 3; p ¼ .22 c2 ¼ 5.2; df ¼ 3; p ¼ .20
Note: 0-OCD vs. OCDeOCD: *p .008; 0-OCD vs. OCD-0: yp .008; 0-OCD vs. 0-0: zp .008. IQeIntelligence quotient; BPRSeBrief Psychiatric Rating Scale; SANSeScale for the Assessment of Negative Symptoms; HARSeHamilton Rating Scale for Anxiety; HDRSeHamilton Rating Scale for Depression; QLS: Quality of Life Scale; DSM-IV-TReDiagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision.
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higher rates of psychotic disorders NOS and mood disorders with psychotic features. The finding that de novo OCD was particularly likely to result in non-schizophrenic psychoses is consistent with early observations suggesting that delusions can arise in the course of OCD but do not necessarily signify a diagnosis of schizophrenia (Insel and Akiskal, 1986). Rather, these delusions may represent reactive, affective, or paranoid psychoses that are generally transient (Insel and Akiskal, 1986), and may be responsive to treatment with antidepressants. For example, it is interesting to note that 14 out of 25 patients with poor insight OCD recovered insight into their OCS after six months of combined treatment with serotonin reuptake inhibitors and cognitive behavioral therapy, with concomitant improvement of obsessive-compulsive and depressive symptoms (Matsunaga et al., 2002). Although it is tempting to suggest that patients with incident OCD are particularly prone to develop major depression with psychosis, we cannot exclude, at the present moment, the opposite phenomenon (as suggested by Gittleson, 1966). Alternatively, it could be argued that the association between incident OCD and non-schizophrenia psychoses could be ascribed to the fact that patients from this group reported greater use of antipsychotics during the two years before the follow-up assessments. In fact, the ability of some antipsychotics, particularly the atypicals, to generate de novo OCS, has been well documented in the literature (for a review, see (Lykouras et al., 2003). Nevertheless, it should be emphasized that the differences between the groups in terms of rates of antipsychotic use during the previous two years failed to reach statistical significance and that in no case was OCD judged by the examiners as being related to any substance use on the SCID or on the OCD subscale of the CAARMS. Regardless of the specific reason for these findings, the fact that the incident OCD group reported greater severity of general psychopathology, alogia and avolition-apathy at baseline suggests that UHR individuals with prominent negative symptoms may be particularly prone to develop late-onset primary or druginduced OCD. We have shown that a diagnosis of OCD at baseline did not predict conversion to DSM-IV psychotic disorders. Nevertheless, two (40%) out of six cases with early-onset persistent OCD had developed schizophrenia at follow-up. Studies with larger numbers will be required to examine this further. Accordingly, we could only speculate about the clinical significance of these results. For example, persistent OCD could lead to schizophrenia through exposure to chronic stress (Takahashi et al., 2009), or continual dysfunction in anatomical regions that are shared by both conditions, including the basal ganglia, thalamus, anterior cingulum, orbitofrontal cortex and regions of the temporal cortex (Bottas et al., 2005). Based on a correlation analysis, Guillem et al. (2009) suggested that delusions and obsessions, and auditory hallucinations and compulsions might share similar pathophysiological mechanisms in patients with schizophrenia. The results need to be interpreted in light of several limitations of this study. Firstly, despite assessing a large sample of UHR individuals, we could identify only a small percentage of persisting OCD cases. Indeed, a greater number of individuals showing OCD both at baseline and follow-up would help us to reach definitive conclusions regarding the role of persistent OCD and the future development of schizophrenia. Secondly, many potentially relevant OCD features were not assessed. In that sense, it would have been interesting to evaluate whether severity or type of symptom dimensions differ between patients showing persistent, remitting, or de novo OCD and whether patients showing a particular OCD phenotype were at greater risk for psychosis. Finally, we were unable to compare the rates of typical vs. atypical antipsychotic use across different groups of OCD patients. Therefore, we cannot
exclude the possibility that the use of atypical antipsychotics was more common among UHR patients that showed de novo OCD, something that could provide a better explanation for the finding of relating mood disorders with psychotic features to that group of late-onset OCD. Role of funding source This manuscript “A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis” was supported by the Colonial Foundation and a National Health and Medical Research Council (NHMRC) Program Grant (# 566529). None of the funding agencies had any role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Contributors A/Prof. Leonardo F. Fontenelle and Prof. Christos Pantelis developed the study hypothesis. A/Prof. Leonardo F. Fontenelle managed the literature searches, performed the statistical analyses and wrote the first draft of the manuscript. Dr. Ashleigh Lin assisted with data analysis and editing of the manuscript. Prof. Alison R. Yung, A/Prof. Stephen J. Wood, and Dr. Barnaby Nelson designed the study, wrote the protocol, and edited the manuscript. All authors have contributed to and approved the final manuscript. Conflict of interest statement A/Prof. Leonardo F. Fontenelle has received travel expense reimbursement from Solvay and has acted as a consultant to Lundbeck. Prof. Chris Pantelis has acted as a consultant for Pfizer and received research grants and acted as a consultant for JanssenCilag, Eli Lilly, Hospira (Mayne), and Astra Zeneca. All other authors declare that they have no conflicts of interest Acknowledements A/Prof. Leonardo F. Fontenelle was supported by an Endeavour Research Fellowship (postdoctoral research) from the Department of Education, Employment and Workplace Relations (Australia), and Bolsa de Produtividade em Pesquisa, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil); Dr. Ashleigh Lin was supported by an NHMRC program grant; Prof. Christos Pantelis was supported by an NHMRC Senior Principal Research Fellowship and NHMRC Program Grants; A/Prof. Stephen J. Wood was supported by an NHMRC Clinical Career Development Award and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award; Dr. Barnaby Nelson was supported by a Ronald Griffith Fellowship and a NARSAD Young Investigator Award; Prof. Alison R. Yung was supported by an NHMRC Senior Research Fellowship. References Andreasen NC. Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 1982;39:784e8. Berman I, Pappas D. Bermam S. Obsessive-compulsive symptoms in schizophrenia: are they manifestations of a distinct subclass of schizophrenia disorders. CNS Spectrum 1997;2:45e8. Bottas A, Cooke RG, Richter MA. Comorbidity and pathophysiology of obsessivecompulsive disorder in schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia? Journal of Psychiatry and Neuroscience 2005;30:187e93. Byerly M, Goodman W, Acholonu W, Bugno R, Rush AJ. Obsessive compulsive symptoms in schizophrenia: frequency and clinical features. Schizophrenia Research 2005;76:309e16.
L.F. Fontenelle et al. / Journal of Psychiatric Research 45 (2011) 1140e1145 Craig T, Hwang MY, Bromet EJ. Obsessive-compulsive and panic symptoms in patients with first-admission psychosis. American Journal of Psychiatry 2002;159:592e8. Cunill R, Castells X, Simeon D. Relationships between obsessive-compulsive symptomatology and severity of psychosis in schizophrenia: a systematic review and meta-analysis. Journal of Clinical Psychiatry 2009;70:70e82. de Haan L, Dudek-Hodge C, Verhoeven Y, Denys D. Prevalence of psychotic disorders in patients with obsessive-compulsive disorder. CNS Spectrum 2009;14:415e7. de Haan L, Hoogenboom B, Beuk N, van Amelsvoort T, Linszen D. Obsessivecompulsive symptoms and positive, negative, and depressive symptoms in patients with recent-onset schizophrenic disorders. Canadian Journal of Psychiatry 2005;50:519e24. Faravelli C, Abrardi L, Bartolozzi D, Cecchi C, Cosci F, D’Adamo D, et al. The Sesto Fiorentino study: background, methods and preliminary results. Lifetime prevalence of psychiatric disorders in an Italian community sample using clinical interviewers. Psychotherapy and Psychosomatics 2004;73:216e25. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical Interview for DSM-IV-TR Axis I disorders. Research Version, Patient Edition. (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute; 2002. Gittleson NL. Depressive psychosis in the obsessional neurotic. British Journal of Psychiatry 1966;112:883e7. Guillem F, Satterthwaite J, Pampoulova T, Stip E. Relationship between psychotic and obsessive compulsive symptoms in schizophrenia. Schizophrenia Research 2009;115:358e62. Hamilton M. The assessment of anxiety states by rating. British Journal of Medical Psychology 1959;32:50e5. Hamilton M. A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 1960;23:56e62. Heinrichs DW, Hanlon TE, Carpenter Jr WT. The Quality of life scale: an instrument for rating the schizophrenic deficit syndrome. Schizophrenia Bulletin 1984;10:388e98. Henry LP, Harris MG, Amminger GP, Yuen HP, Harrigan SM, Lambert M, et al. Early psychosis prevention and intervention centre long-term follow-up study of first-episode psychosis: methodology and baseline characteristics. Early Intervention in Psychiatry 2007;1:49e60. Insel TR, Akiskal HS. Obsessive-compulsive disorder with psychotic features: a phenomenologic analysis. American Journal of Psychiatry 1986;143:1527e33. Kringlen E. Obsessional neurotics: a long-term follow-Up. British Journal of Psychiatry 1965;111:709e22. Lo WH. A follow-up study of obsessional neurotics in Hong Kong Chinese. British Journal of Psychiatry 1967;113:823e32. Lykouras L, Alevizos B, Michalopoulou P, Rabavilas A. Obsessive-compulsive symptoms induced by atypical antipsychotics. A review of the reported cases.
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Progress in Neuropsychopharmacology and Biological Psychiatry 2003;27:333e46. Lysaker PH, Whitney KA, Davis LW. Associations of executive function with concurrent and prospective reports of obsessive-compulsive symptoms in schizophrenia. Journal of Neuropsychiatry and Clinical Neurosciences 2009;21:38e42. Matsunaga H, Kiriike N, Matsui T, Oya K, Iwasaki Y, Koshimune K, et al. Obsessivecompulsive disorder with poor insight. Comprehensive Psychiatry 2002;43:150e7. McGorry PD, Goodwin RJ, Stuart GW. The development, use, and reliability of the brief psychiatric rating scale (nursing modification)ean assessment procedure for the nursing team in clinical and research settings. Comprehensive Psychiatry 1988;29:575e87. Nelson E, Rice J. Stability of diagnosis of obsessive-compulsive disorder in the epidemiologic catchment area study. American Journal of Psychiatry 1997;154:826e31. Niendam TA, Berzak J, Cannon TD, Bearden CE. Obsessive compulsive symptoms in the psychosis prodrome: correlates of clinical and functional outcome. Schizophrenia Research 2009;108:170e5. Pollitt J. Natural history of obsessional states; a study of 150 cases. British Medical Journal 1957;1:194e8. Poyurovsky M, Fuchs C, Weizman A. Obsessive-compulsive disorder in patients with first-episode schizophrenia. American Journal of Psychiatry 1999;156:1998e2000. Poyurovsky M, Hramenkov S, Isakov V, Rauchverger B, Modai I, Schneidman M, et al. Obsessive-compulsive disorder in hospitalized patients with chronic schizophrenia. Psychiatry Research 2001;102:49e57. Sevincok L, Akoglu A, Kokcu F. Suicidality in schizophrenic patients with and without obsessive-compulsive disorder. Schizophrenia Research 2007;90:198e202. Takahashi T, Suzuki M, Velakoulis D, Lorenzetti V, Soulsby B, Zhou SY, et al. Increased pituitary volume in schizophrenia spectrum disorders. Schizophrenia Research 2009;108:114e21. Tibbo P, Kroetsch M, Chue P, Warneke L. Obsessive-compulsive disorder in schizophrenia. Journal of Psychiatric Research 2000;34:139e46. Wechsler D. Wechsler abbreviated scale of intelligence. San Antonio, Texas: The Psychological Corporation; 1999. San Antonio. Weschler D. Manual for the Wechsler adult intelligence scaledrevised. New York: Psychological Corporation; 1981. Yung AR, Yuen HP, McGorry PD, Phillips LJ, Kelly D, Dell’Olio M, et al. Mapping the onset of psychosis: the comprehensive assessment of atrisk mental states. Australian and New Zealand Journal of Psychiatry 2005;39:964e71.
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Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/psychires
A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis Leonardo F. Fontenelle a, b, c, *,1, Ashleigh Lin a, d, Christos Pantelis a, Stephen J. Wood a, e, Barnaby Nelson d, Alison R. Yung d a
Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Australia Anxiety and Depression Research Program, Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Brazil Department of Psychiatry and Mental Health, Institute of Community Health, Universidade Federal Fluminense, Brazil d Orygen Youth Health Research Centre and Centre for Youth Mental Health, University of Melbourne, Australia e School of Psychology, University of Birmingham, UK b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 8 November 2010 Received in revised form 20 February 2011 Accepted 3 March 2011
Background: We evaluated whether (1) a diagnosis of obsessive-compulsive disorder (OCD) at baseline, or (2) the persistence, remission or emergence of de novo OCD at follow-up, were associated with the development of different psychotic disorders in a cohort of individuals at ultra-high risk (UHR) for psychosis. Methods: Patients were assessed for OCD at baseline and after a mean of 7.4 years follow-up and classified into: (i) Non-OCD group - patients without OCD both at baseline and follow-up (n ¼ 269; 86.2%), (ii) Incident OCD group - patients without OCD at baseline but with OCD at follow-up (n ¼ 17; 5.4%), (iii) Remitting OCD group - patients with OCD at baseline but without OCD at follow-up (n ¼ 20; 6.4%), (iv) Persistent OCD group - patients with OCD both at baseline and at follow-up (n ¼ 6; 1.9%). Rates of different DSM-IV psychotic disorders at follow-up were compared across these groups. Results: Patients who displayed remitting OCD were not related to the development of any DSM-IV psychotic disorder. A diagnosis of incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders not otherwise specified (PDNOS), and greater baseline severity of general psychopathology, alogia, and avolitionapathy. Two of the six patients (40%) with persistent OCD developed schizophrenia, while only 12.5%, 5.0%, and 9.7% of incident, remitting, and non-OCD groups, respectively, exhibited the same condition at follow-up. Rates of antipsychotic use in the previous two years were not significantly different between the groups. Conclusions: Our findings suggest that, in a cohort of individuals at UHR for psychosis, remission of OCD does not increase the risk of psychosis, while de novo OCD was associated with development of mood disorders with psychotic features and PDNOS. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Obsessive-compulsive disorder Psychosis Comorbidity Follow-up studies
1. Introduction Observations of patients with obsessive-compulsive disorder (OCD) indicate that the incidence of schizophrenia is low (de Haan et al., 2009), even after long-term follow-up (Pollitt, 1957; Kringlen, 1965; Lo, 1967). In contrast, obsessive-compulsive symptoms (OCS) are noted more commonly at various stages of psychosis and
* Corresponding author. Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, 161 Barry Street, Carlton South, Victoria 3053, Australia. E-mail address: [email protected] (L.F. Fontenelle). 1 Present address: Rua Visconde de Pirajá, 547, Sala 719, Ipanema, Rio de Janeiro, CEP 22410-003, Brazil. Tel./fax: þ55 21 22394919. 0022-3956/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2011.03.005
schizophrenia (Lysaker et al., 2009), although their impact on the outcome is still unclear. Early theorists have argued OCD might prevent the development of “malignant schizophrenia”, retard the “personality disintegration” associated with schizophrenia, or even herald remission of schizophrenic illness (Bottas et al., 2005). In fact, while some studies have suggested that schizophrenia patients with OCD (or OCS) may exhibit less severity of formal thought disorder and affective blunting (Poyurovsky et al., 1999), fewer negative symptoms (Tibbo et al., 2000; de Haan et al., 2005), and greater global functioning (Tibbo et al., 2000), a recent metaanalysis of cross-sectional studies suggested that OCS were associated with greater severity of global, positive and negative psychotic symptoms (Cunill et al., 2009). Thus, it remains unclear whether OCS/OCD bears any relationship to the emergence of
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psychosis and schizophrenia, or whether the two disorders are independent. In order to assess this relationship, longitudinal studies from early psychosis that examine the relationship to longterm outcome are needed. To date, there is only one study in a pre-psychotic sample of young people at ultra-high risk (UHR) for developing psychosis. Niendam et al. (2009) reported that, although UHR individuals with OCS exhibited greater levels of depression, suicidality, and positive and negative symptoms, baseline OCD (14% of their sample) was associated with a statistical trend towards lower rates of conversion to psychosis over the follow-up period. Further, while self-reported OCS remained temporally stable among UHR individuals who did not convert to psychosis, OCS declined among those UHR individuals who did develop psychosis. However, this analysis relied on self-reported symptoms and it remains unclear whether persistence, remission, or de novo OCD over time are associated with changes that contribute to conversion to psychosis. In this long-term longitudinal study of the UHR for psychosis cohort at the Personal Assessment and Crisis Evaluation (PACE) Clinic, we evaluated whether a diagnosis of OCD at baseline and the persistence, remission or emergence of de novo OCD are associated with the development of different psychotic disorders at follow-up. We predicted that increased transition to psychosis would be seen among UHR individuals who do not show OCD at baseline or at the follow-up, or who remit from OCD at follow-up.
2. Methods 2.1. Participants and procedure The sample consisted of 312 individuals (55.1% female) recruited consecutively on admission to the PACE Clinic at Orygen Youth Health in Melbourne, Australia between 1994 and 2005. At baseline, all were assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) (Yung et al., 2005) and met criteria for UHR for psychosis. These criteria are the attenuated positive symptoms, brief limited intermittent psychotic symptoms, and/or have vulnerability for psychotic illness, all of which must be accompanied by a deterioration in functioning. UHR individuals were aged 15e25 years at baseline and had no prior psychotic episode (treated or untreated). Detailed criteria for the identification of the UHR group are described elsewhere (Yung et al., 2005) and are summarized in Table 1.
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The CAARMS also includes a screening section for OCD symptoms, comprising questions on whether patients have distressing or intrusive thoughts, forced repetitive behaviors, rituals/superstitions, need to do things a certain way, or checking compulsions. Along with other symptoms dimensions, OCD symptoms are rated on [1] a 6-point severity (or interference) scale (0 ¼ never/absent to 6 ¼ extreme), [2] a 6-point frequency and duration scale (0 ¼ absent to 6 ¼ continuous), and [3] its relationship with substance abuse (0 ¼ not in relation, 1 ¼ sometimes in relation, and 2 ¼ only in relation to substance abuse). Participants were followed-up between 2007 and 2009. A tracking system based on a previously documented system used at Orygen (Henry et al., 2007) was implemented to locate and recontact participants in this cohort. The mean age of the sample at baseline was 18.8 (SD ¼ 3.2) and at follow-up assessment was 26.1 (SD ¼ 5.04) years old. The mean time to follow-up was 7.4 years (SD ¼ 3.2, range ¼ 2.4e14.8). All participants provided written informed consent in accordance with guidelines provided by the local mental health service research and ethics committee. This research was conducted in accordance with the Declaration of Helsinki.
2.2. Measures Additional measures of psychiatric symptoms at both baseline and follow-up assessments were the Structured Clinical Interview for DSM-IV (SCID; First et al., 2002), the Brief Psychiatric Rating Scale (BPRS) (McGorry et al., 1988), and the Scale for Assessment of Negative Symptoms (SANS) (Andreasen, 1982). A proportion of the participants were also assessed on the Hamilton Rating Scale for Anxiety (HARS) (Hamilton, 1959) and Hamilton Rating Scale for Depression (HRSD) (Hamilton, 1960). Diagnostic decisions followed the guidelines provided by the SCID/DSM-IV-TR, such that whenever another Axis I disorder was present (including a psychotic disorder), the patient was diagnosed with OCD only if the content of the obsessions or compulsions was not restricted to it. At both assessments, the functioning and disability of participants was determined using the Quality of Life Scale (QLS) (Heinrichs et al., 1984). The Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999) or an abbreviated form of the Wechsler Adult Intelligence ScaleRevised (WAIS-R) (Weschler, 1981) were used to estimate current IQ at baseline and follow-up.
Table 1 PACE Ultra-High Risk criteria: (1) must be aged between 15 and 25 years, (2) have been referred to a specialized service for help, and (3) meet the criteria for one or more of the following three groups. Group 1: Attenuated positive psychotic symptoms
Group 2: Brief limited intermittent psychotic symptoms
Group 3: Trait and state risk factors
Adapted from Yung et al. (2005).
Presence of at least one of the following symptoms: ideas of reference, odd beliefs or magical thinking, perceptual disturbance, paranoid ideation, odd thinking and speech, odd behavior and appearance Frequency of symptoms: at least several times a week Recency of symptoms: present within the last year Duration of symptoms: present for at least 1 week and no longer than 5 years Transient psychotic symptoms. Presence of at least one of the following: ideas of reference, magical thinking, perceptual disturbance, paranoid ideation, odd thinking or speech Duration of episode: less than 1 week Frequency of symptoms: at least several times per week Symptoms resolve spontaneously Recency of symptoms: must have occurred within the last year Schizotypal personality disorder in the identified individual, or a first-degree relative with a psychotic disorder Significant decline in mental state or functioning, maintained for at least 1 month and not longer than 5 years This decline in functioning must have occurred within the past year
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2.3. Study groups 1. Baseline OCD: All individuals who had a lifetime history of OCD at the first assessment (baseline). a) Persistent OCD group: Subjects who had both a lifetime history of OCD at the first assessment (baseline) and displayed OCD between the first and the second assessment (follow-up). b) Remitting OCD group: Subjects who had a lifetime history of OCD at the first assessment (baseline) but did not display OCD between the first and the second evaluation (followup). 2. Incident OCD (or de novo OCD): Subjects who did not have a lifetime history of OCD at the first assessment (baseline) but displayed OCD somewhere between the first and the second assessment (follow-up). 3. Non-OCD group: Subjects who had no lifetime history of OCD, either at the first assessment (baseline) or between the first and the second assessment (follow-up).
2.4. Statistical analysis Continuous variables were described as means (standard deviation, SD) and categorical variables as absolute (n) and relative (%) values. Comparisons between two groups were made with Chisquare (c2) tests and independent samples t-tests or ManneWhitney tests according to the normality of distribution. Comparisons between four groups were made using c2 and KruskalleWallis tests. At this point, the standard level of significance was .05. Post hoc c2 or ManneWhitney tests with Bonferroni’s correction followed significant differences. 3. Results We found that 8.1% (32 of 396) and 8.0% (25 of 314) of our UHR subjects had a diagnosis of OCD at baseline and at follow-up, respectively. Six subjects who had OCD at baseline but were lost to follow-up, and two individuals who had a diagnosis of OCD at follow-up and were not assessed for OCD at baseline were excluded from subsequent analysis, leaving 312 to be classified as incident OCD (n ¼ 17, 5.4%), persistent OCD (n ¼ 6, 1.9%), remitting OCD (n ¼ 20, 6.4%), or non-OCD (n ¼ 269, 86.2%). A total of 57 (18.2% of 312) patients fulfilled criteria for at least one psychotic disorder at follow-up: 31 (9.9%) developed schizophrenia, 1 (.3%) schizoaffective disorder, 1 (.3%) delusional disorder, 5 (1.6%) substance induced psychotic disorder, 13 (4.1%) psychotic disorder not otherwise specified (PDNOS), 4 (1.3%) bipolar disorder with psychotic features, and 6 (1.9%) major depression with psychotic features. The specific prevalence rates of OCD (including incident, persistent, and remitting cases) among UHR individuals who developed psychosis was 24.5% (n ¼ 14) for any psychotic disorder, 16.1% (n ¼ 5) in schizophrenia, 0% in schizoaffective disorder, 100% (n ¼ 1) in delusional disorder, 0% in substance induced psychotic disorder, 46.1% (n ¼ 6) in PDNOS, and 28.5% (n ¼ 4) in mood disorders with psychotic features, i.e. 50.0% (n ¼ 2) in bipolar disorders with psychotic features, and 33.3% (n ¼ 2) in major depressive disorder with psychotic features. At baseline, available CAARMS OCD symptoms subscale scores lead to predictable results, i.e. remitting OCD (n ¼ 13) had greater severity at baseline than incident OCD (n ¼ 8; p ¼ .005) and the non-OCD group (n ¼ 197; p < .001), and greater frequency/duration of OCD symptoms than the non-OCD group (p < .001). Incident OCD and non-OCD groups were not significantly different both in severity (p ¼ .89) and frequency/duration (p ¼ .75) of baseline OCD
symptoms. Only one patient with persisting OCD had baseline CAARMS OCD values, thus not allowing us to compare groups in terms of baseline severity, frequency, and duration of OCD. A comparison between the four groups according to the CAARMS OCD symptoms subscale scores at follow-up also generated results in the expected direction. Persistent (n ¼ 4) and incident OCD (n ¼ 15) had both greater severity (p < .001 each) and frequency/ duration (p ¼ .005 and p < .001, respectively) of OCD symptoms than non-OCD group (n ¼ 241). Persistent OCD had greater severity (p ¼ .006) of OCD symptoms than remitting OCD group (n ¼ 16) and incident OCD had both greater severity (p ¼ .001) and frequency/ duration (p ¼ .001) of OCD symptoms than remitting OCD group. Persisting OCD did not differ from incident OCD in terms of severity (p ¼ .02, non-significant after Bonferroni’s correction) and frequency/duration (p ¼ .83) of OCD symptoms. Remitting OCD group did not differ from non-OCD group in terms of severity (p ¼ .04; non-significant after Bonferroni’s correction) and frequency/duration (p ¼ .13) of OCD symptoms. There were no significant differences between UHR subjects with and without OCD at baseline, either in terms of clinical aspects or transition to different psychotic disorders (Table 2). However, as seen in Table 3, incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders NOS, and greater baseline severity of general psychopathology, alogia, and avolition-apathy. Two out of 6 (40%) patients with persisting OCD received a diagnosis of schizophrenia at follow-up, although this rate was not significantly different from those reported in other groups. 4. Discussion In this long-term follow-up study of subjects at ultra-high risk for the development of psychosis, 5.4% developed incident OCD, 1.9% exhibited persistent OCD, and 6.4% displayed remitting OCD. Further, we found that around 8.0% of our UHR individuals exhibited OCD as a comorbidity either at baseline or at follow-up. Although this rate is more than 3 times greater than the prevalence of OCD described in the general population (Faravelli et al., 2004), it is much lower than our OCD rates among the total number of UHR individuals (22.4%) who developed psychosis. This suggests that the transition to psychosis, rather than the high risk status, is associated with greater rates of OCD. Lower rates of OCD among UHR individuals can also be considered consistent with the findings from a meta-analysis showing a positive correlation between the severity of global, positive, and negative symptoms and severity of OCS in patients with schizophrenia (Cunill et al., 2009). The fact that the prevalence of OCD at baseline (8.1%) remained relatively stable at the follow-up (8.0%) did not reflect a great number of persistent cases. In fact, remitted (n ¼ 20) and incident (n ¼ 17) OCD patients outnumbered persistent cases (n ¼ 6) in our sample. Accordingly, this pattern of OCD symptoms’ fluctuation was already reported in epidemiological studies (Nelson and Rice, 1997) and was critical in allowing us to examine a dynamic relationship between OCD and psychosis and testing our hypothesis of a relative antagonism between both states. Consistent with Niendam et al. (2009), we were unable to find significant differences between UHR individuals with and without baseline OCD in terms of psychopathology (BPRS, SANS, HDRS, and HARS scores), quality of life, and conversion rates to different DSMIV psychotic disorders. While some studies of patients with schizophrenia reported similar results (Berman and pappas, 1997; Poyurovsky et al., 2001; Craig et al., 2002; Byerly et al., 2005; Sevincok et al., 2007), the fact that UHR individuals, by definition,
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Table 2 Comparison between baseline features and follow-up conversion rates between UHR patients with and without OCD.
Age Gender (female) IQ BPRS Psychotic subscale Total SANS Affective flattening Alogia Avolition-apathy Anhedonia-Asociality Attention Total HARS HDRS QLS DSM-IV-TR Psychotic disorders at follow-up Schizophrenia Schizoaffective disorder Delusional disorder Substance induced psychotic disorder Psychotic disorder NOS Bipolar disorder with psychotic features Major depression with psychotic features Mood disorders with psychotic features Any psychotic disorder
Presence of OCD at baseline
Absence of OCD at baseline
Test results
19.3 (3.1) 16 (61.%) 101.7 (13.3)
19.9 (3.3) 158 (54.9%) 98.0 (14.0)
t ¼ .4; df ¼ 372; p ¼ .64 c2 ¼ .43; df ¼ 1; p ¼ .51 t ¼ 1.4; df ¼ 330; p ¼ .15
9.6 (2.5) 45.6 (7.4)
9.5 (2.9) 47.3 (9.6)
t ¼ .81; df ¼ 392; p ¼ .93 t ¼ .98; df ¼ 392; p ¼ .32
5.1 (4.7) 1.4 (1.5) 3.5 (2.7) 7.2 (5.2) 1.2 (1.5) 18.5 (11.0) 15.3 (7.0) 18.6 (6.7) 75.4 (26.2)
5.5 (5.4) 2.4 (2.5) 4.1 (3.0) 6.0 (4.5) 1.8 (2.0) 19.8 (12.9) 15.3 (8.3) 18.9 (10.1) 76.0 (20.5)
t ¼ 3.6; df ¼ 393; p ¼ .67 ManneWhitneys’s p ¼ .86 t ¼ .95; df ¼ 393; p ¼ .34 t ¼ 1.4; df ¼ 393; p ¼ .14 ManneWhitneys’s p ¼ .63 t ¼ .57; df ¼ 393; p ¼ .57 t ¼ .002; df ¼ 175; p ¼ .99 t ¼ .18; df ¼ 26.8; p ¼ .85 t ¼ .14; df ¼ 389; p ¼ .88
4 0 0 0 2 0 0 0 5
34 (12.1%) 1 (.4%) 1 (.4%) 6 (2.2%) 15 (5.4%) 5 (1.8%) 5 (1.8%) 10 (3.6%) 64 (22.2%)
Fisher’s exact p ¼ .54 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ .64 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 Fisher’s exact p ¼ 1.0 c2 ¼ .12; df ¼ 1; p ¼ .72
(15.4%) (.0%) (.0%) (.0%) (7.7%) (.0%) (.0%) (.0%) (19.2%)
IQeIntelligence quotient; BPRSeBrief Psychiatric Rating Scale; SANSeScale for the Assessment of Negative Symptoms; HARSeHamilton Rating Scale for Anxiety; HDRSeHamilton Rating Scale for Depression; QLSeQuality of Life Scale; DSM-IV-TReDiagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision.
exhibit lower levels of psychopathology than patients with schizophrenia may have lessened the potential differences between patients with and without OCD. Alternatively, the lack of significance between groups could suggest that OCD may be an intrinsic
dimension of the at-risk state, free of additional impairments in psychopathological or quality of life spheres. The diagnosis of a psychotic disorder at follow-up was greater among UHR individuals who exhibited incident OCD, including
Table 3 Comparison between baseline features and follow-up conversion rates between UHR patients with different OCD outcomes. Incident OCD (n ¼ 17)
Persistent OCD (n ¼ 6)
Age 18.2 (2.8) 18.6 (3.2) Gender (female) 10 (62.5%) 3 (50%) Intelligence quotient 91.0 (14.9) 107.0 (17.0) Brief Psychiatric Rating Scale Psychotic subscale 10.2 (2.8) 7.8 (2.4) 39.3 (5.6) * Total 51.0 (7.1) * Scale for the Assessment of Negative Symptoms Affective flattening 5.3 (5.8) 3.6 (4.8) .1 (.40) * Alogia 3.4 (3.2) * 1.3 (1.2) * Avolition-apathy 5.6 (3.1) * Anhedonia-Asociality 6.6 (5.0) 8.1 (5.8) Attention 2.0 (1.9) .6 (1.6) Total 23 (12.8) 14.0 (9.8) Hamilton Rating Scale for Anxiety 21.8 (9.7) 14.2 (4.5) Hamilton Rating Scale for Depression 27.1 (11.2) 16 (.70) Quality of Life Scale 68.6 (19.6) 87.6 (13.6) Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. Psychotic Schizophrenia 2 (12.5%) 2 (40.0%) Schizoaffective disorder 0 (.0%) 0 (.0%) Delusional disorder 1 (6.7%) 0 (.0%) Substance induced psychotic disorder 0 (.0%) 0 (.0%) 0 (.0%) Psychotic disorder NOS 5 (31.3%)z Bipolar disorder with psychotic features 2 (13.3%) 0 (.0%) Major depression with psychotic features 2 (13.3%) 0 (.0%) 0 (.0%) Mood disorder w/psychotic features 4 (26.7%)z yz 2 (40.0%) Any Psychotic disorder 10 (62.5%) Any psychotropic at the entire period 10 (66.7%) 4 (80.0%) Antipsychotics at the entire period 7 (46.7%) 2 (50%) Any psychotropic two years before follow-up 9 (64.3%) 3 (75%) Antipsychotics two years before follow-up 5 (35.7%) 1 (25%)
Remitting OCD (n ¼ 20)
Non-OCD group (n ¼ 269)
Test results
19.5 (3.4) 8 (40.0%) 99.7 (12.1)
18.8 (3.2) 123 (45/7%) 98.3 (13.7)
KruskalleWallis’ p ¼ .71 c2 ¼ .98; df ¼ 3; p ¼ .80 KruskalleWallis’ p ¼ .14
10.3 (2.6) 47.3 (7.3)
9.3 (3.0) 47.2 (9.8)
KruskalleWallis’ p ¼ .20 KruskalleWallis’ p ¼ .03
5.1 (4.9) 5.6 (5.5) 1.4 (1.5) 2.3 (2.5) 4.5 (2.7) 3.9 (3.0) 6.8 (5.1) 5.9 (4.5) 1.3 (1.6) 1.7 (2.0) 19.3 (11.0) 19.6 (12.9) 17.1 (6.8) 15.2 (8.5) 20.3 (7.4) 18.3 (10.0) 71.8 (30.8) 78.5 (23.5) disorders at follow-up 1 (5.0%) 26 (9.7%) 0 (.0%) 1 (.4%) 0 (.0%) 0 (.0%) 0 (.0%) 5 (1.9%) 1 (5.0%) 7 (2.6%)z 0 (.0%) 2 (.7%) 0 (.0%) 4 (1.5%) 0 (.0%) 6 (2.2%)z y 2 (10.0%) 43 (16.0%)z 10 (66.7%) 140 (55.3%) 1 (5.9%) 47 (18.6%) 8 (53.3%) 95 (42.8%) 1 (6.7%) 34 (15.4%)
KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’ KruskalleWallis’
p¼ p¼ p¼ p¼ p¼ p¼ p¼ p¼ p¼
.78 .01 .01 .68 .23 .51 .28 .05 .11
c2 ¼ 5.7; df ¼ 3; p ¼ .12 c2 ¼ .15; df ¼ 3; p ¼ .98 c2 ¼ 19.6; df ¼ 3; p < .001 c2 ¼ .75; df ¼ 3; p ¼ .86 c2 ¼ 31.1; df ¼ 3; p < .001 c2 ¼ 18.0; df ¼ 3; p < .001 c2 ¼ 11.0; df ¼ 3; p ¼ .01 c2 ¼ 28.0; df ¼ 3; p < .001 c2 ¼ 24.2; df ¼ 3; p < .001 c2 ¼ 2.0; df ¼ 3; p ¼ .58 c2 ¼ 10.2; df ¼ 3; p ¼ .02 c2 ¼ 4.4; df ¼ 3; p ¼ .22 c2 ¼ 5.2; df ¼ 3; p ¼ .20
Note: 0-OCD vs. OCDeOCD: *p .008; 0-OCD vs. OCD-0: yp .008; 0-OCD vs. 0-0: zp .008. IQeIntelligence quotient; BPRSeBrief Psychiatric Rating Scale; SANSeScale for the Assessment of Negative Symptoms; HARSeHamilton Rating Scale for Anxiety; HDRSeHamilton Rating Scale for Depression; QLS: Quality of Life Scale; DSM-IV-TReDiagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision.
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higher rates of psychotic disorders NOS and mood disorders with psychotic features. The finding that de novo OCD was particularly likely to result in non-schizophrenic psychoses is consistent with early observations suggesting that delusions can arise in the course of OCD but do not necessarily signify a diagnosis of schizophrenia (Insel and Akiskal, 1986). Rather, these delusions may represent reactive, affective, or paranoid psychoses that are generally transient (Insel and Akiskal, 1986), and may be responsive to treatment with antidepressants. For example, it is interesting to note that 14 out of 25 patients with poor insight OCD recovered insight into their OCS after six months of combined treatment with serotonin reuptake inhibitors and cognitive behavioral therapy, with concomitant improvement of obsessive-compulsive and depressive symptoms (Matsunaga et al., 2002). Although it is tempting to suggest that patients with incident OCD are particularly prone to develop major depression with psychosis, we cannot exclude, at the present moment, the opposite phenomenon (as suggested by Gittleson, 1966). Alternatively, it could be argued that the association between incident OCD and non-schizophrenia psychoses could be ascribed to the fact that patients from this group reported greater use of antipsychotics during the two years before the follow-up assessments. In fact, the ability of some antipsychotics, particularly the atypicals, to generate de novo OCS, has been well documented in the literature (for a review, see (Lykouras et al., 2003). Nevertheless, it should be emphasized that the differences between the groups in terms of rates of antipsychotic use during the previous two years failed to reach statistical significance and that in no case was OCD judged by the examiners as being related to any substance use on the SCID or on the OCD subscale of the CAARMS. Regardless of the specific reason for these findings, the fact that the incident OCD group reported greater severity of general psychopathology, alogia and avolition-apathy at baseline suggests that UHR individuals with prominent negative symptoms may be particularly prone to develop late-onset primary or druginduced OCD. We have shown that a diagnosis of OCD at baseline did not predict conversion to DSM-IV psychotic disorders. Nevertheless, two (40%) out of six cases with early-onset persistent OCD had developed schizophrenia at follow-up. Studies with larger numbers will be required to examine this further. Accordingly, we could only speculate about the clinical significance of these results. For example, persistent OCD could lead to schizophrenia through exposure to chronic stress (Takahashi et al., 2009), or continual dysfunction in anatomical regions that are shared by both conditions, including the basal ganglia, thalamus, anterior cingulum, orbitofrontal cortex and regions of the temporal cortex (Bottas et al., 2005). Based on a correlation analysis, Guillem et al. (2009) suggested that delusions and obsessions, and auditory hallucinations and compulsions might share similar pathophysiological mechanisms in patients with schizophrenia. The results need to be interpreted in light of several limitations of this study. Firstly, despite assessing a large sample of UHR individuals, we could identify only a small percentage of persisting OCD cases. Indeed, a greater number of individuals showing OCD both at baseline and follow-up would help us to reach definitive conclusions regarding the role of persistent OCD and the future development of schizophrenia. Secondly, many potentially relevant OCD features were not assessed. In that sense, it would have been interesting to evaluate whether severity or type of symptom dimensions differ between patients showing persistent, remitting, or de novo OCD and whether patients showing a particular OCD phenotype were at greater risk for psychosis. Finally, we were unable to compare the rates of typical vs. atypical antipsychotic use across different groups of OCD patients. Therefore, we cannot
exclude the possibility that the use of atypical antipsychotics was more common among UHR patients that showed de novo OCD, something that could provide a better explanation for the finding of relating mood disorders with psychotic features to that group of late-onset OCD. Role of funding source This manuscript “A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis” was supported by the Colonial Foundation and a National Health and Medical Research Council (NHMRC) Program Grant (# 566529). None of the funding agencies had any role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Contributors A/Prof. Leonardo F. Fontenelle and Prof. Christos Pantelis developed the study hypothesis. A/Prof. Leonardo F. Fontenelle managed the literature searches, performed the statistical analyses and wrote the first draft of the manuscript. Dr. Ashleigh Lin assisted with data analysis and editing of the manuscript. Prof. Alison R. Yung, A/Prof. Stephen J. Wood, and Dr. Barnaby Nelson designed the study, wrote the protocol, and edited the manuscript. All authors have contributed to and approved the final manuscript. Conflict of interest statement A/Prof. Leonardo F. Fontenelle has received travel expense reimbursement from Solvay and has acted as a consultant to Lundbeck. Prof. Chris Pantelis has acted as a consultant for Pfizer and received research grants and acted as a consultant for JanssenCilag, Eli Lilly, Hospira (Mayne), and Astra Zeneca. All other authors declare that they have no conflicts of interest Acknowledements A/Prof. Leonardo F. Fontenelle was supported by an Endeavour Research Fellowship (postdoctoral research) from the Department of Education, Employment and Workplace Relations (Australia), and Bolsa de Produtividade em Pesquisa, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil); Dr. Ashleigh Lin was supported by an NHMRC program grant; Prof. Christos Pantelis was supported by an NHMRC Senior Principal Research Fellowship and NHMRC Program Grants; A/Prof. Stephen J. Wood was supported by an NHMRC Clinical Career Development Award and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award; Dr. Barnaby Nelson was supported by a Ronald Griffith Fellowship and a NARSAD Young Investigator Award; Prof. Alison R. Yung was supported by an NHMRC Senior Research Fellowship. References Andreasen NC. Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 1982;39:784e8. Berman I, Pappas D. Bermam S. Obsessive-compulsive symptoms in schizophrenia: are they manifestations of a distinct subclass of schizophrenia disorders. CNS Spectrum 1997;2:45e8. Bottas A, Cooke RG, Richter MA. Comorbidity and pathophysiology of obsessivecompulsive disorder in schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia? Journal of Psychiatry and Neuroscience 2005;30:187e93. Byerly M, Goodman W, Acholonu W, Bugno R, Rush AJ. Obsessive compulsive symptoms in schizophrenia: frequency and clinical features. Schizophrenia Research 2005;76:309e16.
L.F. Fontenelle et al. / Journal of Psychiatric Research 45 (2011) 1140e1145 Craig T, Hwang MY, Bromet EJ. Obsessive-compulsive and panic symptoms in patients with first-admission psychosis. American Journal of Psychiatry 2002;159:592e8. Cunill R, Castells X, Simeon D. Relationships between obsessive-compulsive symptomatology and severity of psychosis in schizophrenia: a systematic review and meta-analysis. Journal of Clinical Psychiatry 2009;70:70e82. de Haan L, Dudek-Hodge C, Verhoeven Y, Denys D. Prevalence of psychotic disorders in patients with obsessive-compulsive disorder. CNS Spectrum 2009;14:415e7. de Haan L, Hoogenboom B, Beuk N, van Amelsvoort T, Linszen D. Obsessivecompulsive symptoms and positive, negative, and depressive symptoms in patients with recent-onset schizophrenic disorders. Canadian Journal of Psychiatry 2005;50:519e24. Faravelli C, Abrardi L, Bartolozzi D, Cecchi C, Cosci F, D’Adamo D, et al. The Sesto Fiorentino study: background, methods and preliminary results. Lifetime prevalence of psychiatric disorders in an Italian community sample using clinical interviewers. Psychotherapy and Psychosomatics 2004;73:216e25. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical Interview for DSM-IV-TR Axis I disorders. Research Version, Patient Edition. (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute; 2002. Gittleson NL. Depressive psychosis in the obsessional neurotic. British Journal of Psychiatry 1966;112:883e7. Guillem F, Satterthwaite J, Pampoulova T, Stip E. Relationship between psychotic and obsessive compulsive symptoms in schizophrenia. Schizophrenia Research 2009;115:358e62. Hamilton M. The assessment of anxiety states by rating. British Journal of Medical Psychology 1959;32:50e5. Hamilton M. A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 1960;23:56e62. Heinrichs DW, Hanlon TE, Carpenter Jr WT. The Quality of life scale: an instrument for rating the schizophrenic deficit syndrome. Schizophrenia Bulletin 1984;10:388e98. Henry LP, Harris MG, Amminger GP, Yuen HP, Harrigan SM, Lambert M, et al. Early psychosis prevention and intervention centre long-term follow-up study of first-episode psychosis: methodology and baseline characteristics. Early Intervention in Psychiatry 2007;1:49e60. Insel TR, Akiskal HS. Obsessive-compulsive disorder with psychotic features: a phenomenologic analysis. American Journal of Psychiatry 1986;143:1527e33. Kringlen E. Obsessional neurotics: a long-term follow-Up. British Journal of Psychiatry 1965;111:709e22. Lo WH. A follow-up study of obsessional neurotics in Hong Kong Chinese. British Journal of Psychiatry 1967;113:823e32. Lykouras L, Alevizos B, Michalopoulou P, Rabavilas A. Obsessive-compulsive symptoms induced by atypical antipsychotics. A review of the reported cases.
1145
Progress in Neuropsychopharmacology and Biological Psychiatry 2003;27:333e46. Lysaker PH, Whitney KA, Davis LW. Associations of executive function with concurrent and prospective reports of obsessive-compulsive symptoms in schizophrenia. Journal of Neuropsychiatry and Clinical Neurosciences 2009;21:38e42. Matsunaga H, Kiriike N, Matsui T, Oya K, Iwasaki Y, Koshimune K, et al. Obsessivecompulsive disorder with poor insight. Comprehensive Psychiatry 2002;43:150e7. McGorry PD, Goodwin RJ, Stuart GW. The development, use, and reliability of the brief psychiatric rating scale (nursing modification)ean assessment procedure for the nursing team in clinical and research settings. Comprehensive Psychiatry 1988;29:575e87. Nelson E, Rice J. Stability of diagnosis of obsessive-compulsive disorder in the epidemiologic catchment area study. American Journal of Psychiatry 1997;154:826e31. Niendam TA, Berzak J, Cannon TD, Bearden CE. Obsessive compulsive symptoms in the psychosis prodrome: correlates of clinical and functional outcome. Schizophrenia Research 2009;108:170e5. Pollitt J. Natural history of obsessional states; a study of 150 cases. British Medical Journal 1957;1:194e8. Poyurovsky M, Fuchs C, Weizman A. Obsessive-compulsive disorder in patients with first-episode schizophrenia. American Journal of Psychiatry 1999;156:1998e2000. Poyurovsky M, Hramenkov S, Isakov V, Rauchverger B, Modai I, Schneidman M, et al. Obsessive-compulsive disorder in hospitalized patients with chronic schizophrenia. Psychiatry Research 2001;102:49e57. Sevincok L, Akoglu A, Kokcu F. Suicidality in schizophrenic patients with and without obsessive-compulsive disorder. Schizophrenia Research 2007;90:198e202. Takahashi T, Suzuki M, Velakoulis D, Lorenzetti V, Soulsby B, Zhou SY, et al. Increased pituitary volume in schizophrenia spectrum disorders. Schizophrenia Research 2009;108:114e21. Tibbo P, Kroetsch M, Chue P, Warneke L. Obsessive-compulsive disorder in schizophrenia. Journal of Psychiatric Research 2000;34:139e46. Wechsler D. Wechsler abbreviated scale of intelligence. San Antonio, Texas: The Psychological Corporation; 1999. San Antonio. Weschler D. Manual for the Wechsler adult intelligence scaledrevised. New York: Psychological Corporation; 1981. Yung AR, Yuen HP, McGorry PD, Phillips LJ, Kelly D, Dell’Olio M, et al. Mapping the onset of psychosis: the comprehensive assessment of atrisk mental states. Australian and New Zealand Journal of Psychiatry 2005;39:964e71.