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Chronic tics and Tourette syndrome in patients with obsessive–compulsive disorder
JOURNAL OF PSYCHIATRIC RESEARCH
Journal of Psychiatric Research 40 (2006) 487–493
www.elsevier.com/locate/jpsychires
Chronic tics and Tourette syndrome in patients with obsessive–compulsive disorder Juliana B. Diniz a,*, Maria Conceic¸a˜o Rosario-Campos a,b, Ana Gabriela Hounie a, Mariana Curi a, Roseli Gedanke Shavitt a, Antonio Carlos Lopes a, Euripedes C. Miguel a
a
Department of Psychiatry, University of Sa˜o Paulo Medical School, R Dr Ovideo Pires de Campos, 785, 4°. andar/sala 3, Sa˜o Paulo, SP 05403-010, Brazil b Department of Psychiatry, Bahia Federal University, Sa˜o Paulo, SP, Brazil Received 22 June 2005; received in revised form 6 August 2005; accepted 20 September 2005
Abstract Tourette syndrome (TS) and chronic motor/vocal tics (CMVT) are both common disorders in patients with obsessive compulsive disorder (OCD). However, there have been few studies evaluating the differences between the OCD with TS and OCD with CMVT subgroups. This study was conducted in order to further investigate possible differences between the expression of the OCD phenotype in OCD with TS and that seen in OCD with CMVT. One hundred and fifty-nine outpatients referred to an OCD research program were evaluated using the following instruments: the Structured Clinical Interview for DSM-IV; the Yale-Brown Obsessive Compulsive Scale; the Yale Global Tic Severity Scale; and the USP-HARVARD Repetitive Behaviors Interview. Patients were divided into three groups: OCD patients without tics (OCD TICS, n = 98), OCD patients with chronic motor or vocal tics (OCD + CMVT, n = 31) and OCD patients with TS (OCD + TS, n = 30). OCD + CMVT patients were similar to OCD + TS patients regarding the frequency of intrusive sounds, repeating behaviors, counting and tic-like compulsions (in both cases more frequent than in OCD TICS patients). For age at obsessive–compulsive (OC) symptom onset, sensory phenomena score, number of comorbidities, frequency of somatic obsessions, bodily sensations and just-right perceptions, OCD + CMVT patients tended to be in between the other two groups. Our results suggest that there are qualitative and quantitative differences in the phenotypic expression of tic disorders in OCD patients, depending on whether the subject has TS or only CMVT. Ó 2005 Elsevier Ltd. All rights reserved. Keywords: Tourette syndrome; Obsessive–compulsive disorder; Tic disorders; Psychopathology; Comorbidity
1. Introduction Even though the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Classification of Diseases (ICD-10) define obsessive– compulsive disorder (OCD) as a unitary nosological *
Corresponding author. Present address: Obsessive Compulsive Disorder Project, Institute of Psychiatry of the Clinics Hospital of the University of Sa˜o Paulo, R Dr Ovidio Pires de Campos 785, 05403010, Sa˜o Paulo, SP, Brazil. Tel.: +55 11 30696972; fax: +55 11 30697895. E-mail address: [email protected] (J.B. Diniz). 0022-3956/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2005.09.002
entity, recent research has indicated that OCD is in fact a heterogeneous disorder, with a variety of putative clinical phenotypes. So far, the best-described OCD subgroup is composed of OCD patients with a lifetime history of tic disorders. Many studies have reported that the tic-related OCD subgroup presents specific clinical, comorbidity, neurobiological, genetic and treatment response patterns. For instance, clinical studies have reported that tic-related OCD patients have an earlier age of onset (Miguel et al., 1997; Rosario-Campos et al., 2001; Holzer et al., 1994; Leckman et al., 1995), are more fre-
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quently males (Holzer et al., 1994; Leckman et al., 1995), and present higher frequencies of some obsessive–compulsive symptoms (OCSs), such as intrusive violent and sexual images or thoughts, hoarding, counting rituals and tic-like compulsions (Swerdlow et al., 1999; Zohar et al., 1997; Cath et al., 2000; Holzer et al., 1994). Similarly, tic-related OCD has been associated with higher frequencies of sensory phenomena preceding or accompanying their compulsions (Miguel et al., 1997, 2000; Leckman et al., 1994). Regarding the presence of comorbid disorders, some studies have reported that patients with tic-related OCD present higher rates of trichotillomania, body dysmorphic disorder (BDD), mood disorders, social phobia, other anxiety disorders and attention deficit hyperactivity disorder when compared to patients with non-ticrelated OCD (Petter et al., 1998; Coffey et al., 1998). The association between TS and OCD has received additional support from genetic studies, which have shown not only higher rates of OCS and OCD in relatives of TS patients (Pauls et al., 1986; Comings and Comings, 1987; Robertson et al., 1988; Eapen et al., 1993), but also higher rates of tics or TS in first-degree relatives of OCD patients (Leonard et al., 1992; Pauls et al., 1995; Rosario-Campos et al., 2005). In summary, the impact of a comorbid tic disorder on the phenotypic expression of OCD has been extensively described. On the other hand, very few studies have investigated whether a comorbid diagnosis of TS would affect the expression of OCD differently than would one of CMVT. Most previous studies have only compared OCD with TS to OCD without TS (De Groot et al., 1994; Miguel et al., 1997; Petter et al., 1998; Cath et al., 2000, 2001), or OCD with tic disorders to OCD without tic disorders (including either CMVT or TS) (Holzer et al., 1994; Leckman et al., 1995; Zohar et al., 1997). As an exception, Swerdlow et al. (1999) compared patients with OCD alone to OCD patients with CMVT and OCD patients with TS. Patients with OCD and CMVT presented more severe OCD than did patients with OCD plus TS or patients with OCD alone. Religious obsessions, cleaning/washing and counting compulsions, intrusive sounds/images and tic-like compulsions were more common in the OCD with CMVT group than in the OCD with TS group. That study, however, did not evaluate other clinical variables such as psychiatric comorbidity and other psychopathological characteristics (e.g., sensory phenomena, specific subjective sensations preceding repetitive behaviors such as just-right perceptions) preceding repetitive behaviors. The present study was designed in order to further investigate possible phenomenological differences in the OCD phenotype according to the presence of TS or CMVT. Therefore, we designed a study to compare OCD patients with no history of tic disorders to patients
with OCD and CMVT and patients with OCD and TS using a bigger sample and with a very comprehensive psychopathological evaluation.
2. Methods 2.1. Subjects One hundred sixty-eight consecutive outpatients referred to an OCD research program between 1996 and 2001 were assessed. Referrals came from a university hospital (n = 96) and two private facilities (n = 72). The inclusion criterion was a DSM-IV diagnosis of OCD. Exclusion criteria were history of previous brain trauma (n = 1), refusal to complete interview assessment (n = 2), comorbid diagnosis of schizophrenia (n = 3) and history of a transient tic disorder (n = 3). The remaining patients (n = 159) were divided into three groups: OCD patients without tics (OCD TICS, n = 98); OCD patients with chronic motor or vocal tics (OCD + CMVT, n = 31); and OCD patients with TS (OCD + TS, n = 30). This sample has already been described previously elsewhere (Diniz et al., 2004). This study was approved by the Medical Ethics Committee of the Institute of Psychiatry from University of Sa˜o Paulo Medical School. All patients gave written informed consent after the study had been thoroughly described and assurance had been given that their decision to participate in the study would not interfere in any way with their clinical treatment. Interviewers were experienced psychologists and psychiatrists from the OC Spectrum Disorder Project of the Department of Psychiatry of the University of Sa˜o Paulo Medical School. Each interview was reviewed by the first author and each diagnosis was made according to a best estimate procedure (Leckman et al., 1982) given by two psychiatrists (ECM and RGS) experienced in the evaluation of OCD and TS. 2.2. Clinical assessment Age of onset of OCS was defined as the earliest age that the patient remembered having OCS. When possible, a family member was also interviewed about the age of onset. These data on age at onset were retrospectively assessed by direct interview with the patient as described elsewhere (Rosario-Campos et al., 2001). The presence and severity of OCS and tics were determined by checklists and rating scales of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (Goodman et al., 1989a,b) and the Yale Global Tic Severity Scale (YGTSS) (Leckman et al., 1989), respectively. Subjects with ‘‘tic-like’’ compulsions were defined as patients who referred the need to perform a behavior similar to a tic in order to relieve the distress and/or anx-
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iety caused by an obsession or those who endorsed at least one of the following Y-BOCS symptom items: ‘‘the need to touch, tap or rub’’ and ‘‘rituals involving blinking or staring’’ (Rosario-Campos et al., 2001). ‘‘Sensory phenomena’’ were defined as local or generalized bodily sensations occurring before the patient performs repetitive behaviors (e.g. rituals, compulsions or tics) and mental sensations such as general uncomfortable, feelings or perceptions occurring before or while the patient performs repetitive behaviors (Miguel et al., 2000). Examples of sensory phenomena include the need to perform a behavior until the patient feels ‘‘just right’’ (Leckman et al., 1994), a need for energy release, a feeling of incompleteness, an urge to perform a behavior and generalized feelings of inner tension or pressure. Some OCD patients report that compulsions are preceded by sensory phenomena rather than obsessions; others present either obsessions or sensory phenomena preceding their compulsions, and some present only obsessions preceding their repetitive behaviors (Miguel et al., 2000). The presence and severity of sensory phenomena preceding or accompanying OCS and/or CMVT were assessed through the USP-HARVARD Repetitive Behaviors Interview (Miguel et al., 1995). The significance of sensory phenomena is defined using the following scale: 0 = the patient never had any sensory phenomena preceding his or her repetitive behaviors; 1 = the patient had at least one experience involving sensory phenomena preceding his or her repetitive behavior, but is not currently experiencing such phenomena; 2 = the patient currently presents sensory phenomena, but these phenomena are less pronounced in frequency and intensity than the current obsessions, fear or preoccupations; 3 = the patient currently presents sensory phenomena and these phenomena are more pronounced in frequency and intensity than the current obsessions, fear or preoccupations; 4 = the patient currently presents only sensory phenomena preceding his or her repetitive behavior and does not currently experience any obsessions, fear or preoccupation before performing repetitive behaviors. Of the original sample of 159 patients, 137 completed the USP-HARVARD Repetitive Behaviors Interview with the help of an experienced psychologist or psychiatrist. The other 22 patients did not complete this interview for various reasons and were excluded from the analyses regarding sensory phenomena. Psychiatric axis I comorbid disorders were assessed by the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1995), supplemented with additional modules based on DSM-IV criteria for TS, CMVT, trichotillomania, kleptomania, compulsive gambling and pyromania (data available upon request). Nine patients younger than 16 years old were interviewed using the Schedule for Affective Disorders and
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Schizophrenia Epidemiological version (Orvaschel and Puig-Antich, 1987), administered to a parent and child. Current and lifetime diagnoses were included in the analyses. Sub-threshold diagnoses were not included. 2.3. Statistical analyses Statistical analyses were performed using the Statistical Package for the Social Sciences, v. 11.0. The three groups were compared using ANOVA for continuous variables and PearsonÕs v2 test for categorical variables. In order to evaluate which group was different from the other two in each analysis, the Tukey test was used for continuous variables and partition chi-square for categorical variables. Variables presenting statistically significant differences between and among groups in the univariate analysis were included in a polytomic forward stepwise logistic regression (McCullagh and Nelder, 1996) in order to identify the variables most significantly associated with the differences among the three groups. The logit link function was used considering OCD TICS as the reference group. In other words, the response variables of the logistic model were defined as the logit of the probability of being from the OCD + TS group, divided by the probability of being from the OCD TICS group, and as the logit of the probability of being from the OCD + CMVT group, divided by the probability of being from the OCD TICS group. For all variables, the probability of F to enter the regression equations was set at 60.05; and the probability of F to remove was set at P0.10. A two-tailed p value < 0.10 was considered significant for the univariate analyses and a p value < 0.05 for the multivariate analyses.
3. Results Fifty-nine percent (n = 95) of all patients studied were male and 41% (n = 66) were female. Their age ranged from 12 to 59 years (mean age = 30 ± 10). Patients presented a mean age at OC symptoms onset of 13.2 ± 8.7 years ranging from 4 to 46 years. The mean illness duration in our sample was 16.3 ± 9.6 years ranging from 1 to 46 years. Mean YBOCS score for obsessions was 13.1 ± 3.6 and for compulsions 13.5 ± 3.8. The three groups differed according to mean age at interview (mean age OCD TICS = 31 ± 10, OCD + CMVT = 28 ± 9, OCD + TS = 25 ± 9; p = 0.010). Patients with OCD + CMVT presented a mean age at interview that was not statistically different from that of OCD + TS or OCD TICS patients but tended to be more similar to that of OCD + TS patients than that of OCD TICS patients (p = 0.23 and p= 0.13, respectively).
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Mean age at OCS onset was statistically different between and among the three groups (OCD TICS = 15 ± 10; OCD + CMVT = 12 ± 8; OCD + TS = 9 ± 3; p = 0.002). Patients with OCD + TS presented an earlier age at onset of OCS than did OCD TICS patients. Patients with OCD + CMVT presented a mean age at onset of OCS intermediate to OCD + TS and OCD TICS (p = 0.05 and p = 0.10, respectively). As expected, OCD + TS patients presented higher tic severity scores and earlier age at tic onset than did OCD + CMVT patients (mean YGTSS score for OCD + TS = 41 ± 26 vs. 15 ± 13 for OCD + CMVT; p < 0.001 and mean age at tic onset for OCD + TS = 9 ± 3 vs. 12 ± 6 for OCD + CMVT; p = 0.006). The current OCD severity measured by the YBOCS score was similar in all three groups (mean total YBOCS score = 26 ± 6 for OCD TICS, 27 ± 7 for OCD + CMVT and 27 ± 7 for OCD + TS). Significant data on obsessive–compulsive symptoms, sensory phenomena and psychiatric disorders are shown in Tables 1–3 respectively. Table 1 Obsessive–compulsive symptoms in patients with OCD OCD Religious obsessions Somatic obsessions Hoarding Repeating behaviors Intrusive sounds Counting compulsions Tic-like compulsions
52.0% 49.0% 37.2% 63.3% 37.1% 37.8% 42.9%
The demographic and clinical characteristics of the 22 patients who did not complete the USP-HARVARD Repetitive Behaviors Interview were not different from those of the group of 137 patients that completed this interview. 3.1. Multivariate analysis The presence of repeating behaviors (p = 0.015) was selected by the logistic regression as the one variable associated with the occurrence of CMVT in OCD patients. Likewise, four variables were found to correlate strongly with TS in OCD patients: early age at onset of OCS; somatic obsessions; energy release; and bipolar disorder (p = 0.041; p = 0.022; p = 0.002; and p = 0.042, respectively). The odds ratios are not shown, since they were associated with very broad 95% confidence intervals (95% CIs), demonstrating that the polytomic logistic regression model identified the major variables associated with TS
TICS, OCD + CMVT and OCD + TS
TICS, n = 98
OCD + CMVT, n = 31
(51) (48) (32) (62) (36) (37) (42)
71.0% 61.3% 45.2% 83.9% 61.3% 56.7% 61.3%
a
(22) (19) (14) (26)a (19)a (17)a (19)a
OCD + TS, n = 30 60.0% 76.7% 66.7% 83.3% 56.7% 56.7% 76.7%
b
(18) (23)a (20)a (25)a (17)a (17)a (23)a
p 0.061 0.023 0.004 0.023 0.025 0.054 0.003
OCD: obsessive compulsive disorder; OCD TICS: OCD alone; OCD + CMVT: OCD with chronic motor or vocal tics; OCD + TS: OCD with Tourette syndrome. a Significant difference when compared to OCD TICS. b Significant difference when compared to OCD + CMVT. Table 2 Sensory phenomena in OCD
TICS, OCD + CMVT and OCD + TS patients OCD
Sensory phenomena score Energy release Just-right perceptions Bodily sensations
TICS, n = 84
1.8 ± 1.2 22.4% (19) 48.8% (42) 29.4% (25)
OCD + CMVT, n = 26
OCD + TS, n = 27
p
2.0 ± 1.2 22.2% (6) 59.3% (16) 48.1% (13)
2.4 ± 0.9a 51.9% (14)a 77.8% (21)a 51.9% (14)a
0.062 0.009 0.029 0.048
OCD: obsessive compulsive disorder; OCD TICS: OCD alone; OCD + CMVT: OCD with chronic motor or vocal tics; OCD + TS: OCD with Tourette syndrome. a Significant difference when compared to OCD TICS. Table 3 Psychiatric comorbidity in OCD + TS, OCD + CMVT and OCD OCD Number of comorbidities other than tics Bipolar disorder Body dysmorphic disorder
TICS patients
TICS, n = 98
2.3 ± 1.7 7.2% (7) 15.3% (15)
OCD + CMVT, n = 31
OCD + TS, n = 30
p
2.7 ± 2.0 56.5% (2) 13.3% (4)
3.3 ± 2.2a 20.7% (6)ab 37.9% (11)ab
0.049 0.077 0.016
OCD: obsessive compulsive disorder; OCD TICS: OCD alone; OCD + CMVT: OCD with chronic motor or vocal tics; OCD + TS: OCD with Tourette syndrome. a Significant difference when compared to OCD TICS. b Significant difference when compared to OCD + CMVT.
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and CMVT but was unable to quantify them. In other words, the variables chosen by the logistic model might be the most closely associated with TS and CMVT in this group of OCD patients, but, in this model, it is not clear how much these variables influence the relationship that OCD has with TS and CMVT. Comparison between estimated coefficients in polytomic logistic regressions for TS and CMVT logits was not performed because the selected variables were not the same.
4. Discussion By using a very comprehensive phenomenological evaluation, this study was able to show that there are phenotypic differences in OCD patients according to the presence of TS or CMVT. Patients with OCD + CMVT present clinical characteristics that are intermediate between those of OCD + TS and OCD TICS patients. OCD + TS patients were better characterized by an earlier age at onset of OCS, presence of bipolar disorder, and sensory phenomena preceding repetitive behaviors (energy release), whereas the presence of repeating behaviors better characterized CMVT in OCD. There were no significant differences in the YBOCS scores between and among the three groups. Other authors have also found that OCD severity is unrelated to comorbid CMVT or TS (Leckman et al., 1995; Cath et al., 2000, 2001; Petter et al., 1998; Zohar et al., 1997). Therefore, although tic-related OCD is phenomenologically different from non-tic-related OCD, this difference does not influence the severity of OCS as measured by our current scales. Our results suggest that hoarding and somatic obsessions are associated with OCD + TS. Previous studies have also reported higher frequencies of hoarding behaviors (Leckman et al., 1995) and ‘‘concern with a body part or appearance’’ (Petter et al., 1998) in OCD patients with TS than in those with OCD TICS. Hoarding is considered a separate OCD symptom dimension by factor analyses (Leckman et al., 1997; Mataix-Cols et al., 1999; Summerfeldt et al., 1999) and has been associated with increased psychiatric comorbidity (Mataix-Cols et al., 1999; Frost et al., 2000), poor response to treatment (Mataix-Cols et al., 1999; Black et al., 1998) and the presence of specific genetic markers (Zhang et al., 2002). One can hypothesize that the association of TS with hoarding may be related to a putative ‘‘genetic’’ OCD subtype or susceptibility genes since both are related to earlier OCD onset (Millet et al., 2004; Diniz et al., 2004; Geller et al., 2001; RosarioCampos et al., 2001) and familial aggregation (Grados et al., 2001; Zhang et al., 2002). Sensory phenomena consisting of mental or bodily sensations preceding the compulsions in the absence of any thought, fear or worry were first described in TS
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patients (Leckman et al., 1994; Eapen et al., 1994). Energy release, ‘‘just-right’’ perceptions and other mental sensations are types of sensory phenomena that have been reported, both here and in previous studies (Miguel et al., 2000), as being more frequent in OCD + TS patients than in patients with OCD alone. In the present study, patients with OCD + CMVT were intermediate between OCD + TS and OCD TICS regarding frequency of and scores for sensory phenomena. These subjective experiences may prove useful in subtyping OCD. In addition to TS, BDD is the psychiatric disorder with more evidence of being part of the OCD spectrum (McElroy et al., 1994; Jaisoorya et al., 2003). Moreover, it has been suggested that there is a genetic association between BDD and OCD (Bienvenu et al., 2000). We found BDD to be more frequent in the OCD + TS group. Considering these findings, it is possible to speculate that the relationship between BDD and TS is also associated with genetic and familial vulnerability. It is interesting to note that somatic obsessions, as well as concern with body and appearance, are also related to a diagnosis of BDD, which has also been associated with TS in other studies (Coffey et al., 1998; Sverd et al., 1997). Another psychiatric comorbidity also found to be associated with TS in our study was bipolar disorder, a finding that also replicates those of previous studies (Coffey et al., 1998; Kerbeshian et al., 1995). However, it is of note that comorbid bipolar disorder in TS patients has been also associated with a higher prevalence of OCD (Berthier et al., 1998). Both genetic and neurochemical mechanisms have been implicated in the interconnectedness of bipolar disorder, TS and OCD (Berthier et al., 1998; Kerbeshian et al., 1995). In an attempt to explain the interrelationships among these disorders, it has been postulated that they constitute a spectrum of hereditary neuropsychiatric disorders (Comings and Comings, 1992). Since recent genetic studies have been unsuccessful in identifying the most likely mode of transmission of OCD, the hypothesis that genes are added to produce a cumulative quantitative effect seems plausible. Therefore, from a quantitative point of view, we could speculate that different loadings of susceptibility genes would predispose to different possible OCD manifestations accompanied by tics. For instance, there could be several thresholds that, when reached, increase the risk for a specific phenotype, such as OCD or OCD + TS, whereas patients with OCD + CMVT fall in between (Kelsoe, 2003; Hounie et al., in press). In this model, the degree of genetic loading would be higher for the disorders at the end of the OCD TS spectrum. Supporting this hypothesis, in our study we found an earlier age at onset of OCS in the TS pole of this spectrum (the CMVT group was intermediate), and the earlier age at onset, the higher the genetic load in OCD (RosarioCampos et al., 2005). Some of our findings, however,
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were specific related to the CMVT group. Therefore, it is likely that a hypothetical model including both the qualitative aspects (explaining the presence of different expression of OCS and comorbid disorders) and quantitative aspects (explaining the magnitude of the expression of specific features such age at onset and presence of sensory phenomena within each group) in interaction with the environment may provide the most plausible explanation for the variability of the tic-related OCD phenotype.
lo (FAPESP), grant 99/13005-1 to Dr. Diniz, 9901548-0 to Dr. Shavitt, 99/15013-9 to Dr. Hounie and 99/122057 to Dr Miguel; from the Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq) grant 521369/96 to Dr Miguel; from the Tourette Syndrome Association, as well as from the Obsessive–Compulsive Foundation, to Dr. Rosario-Campos.
References 5. Limitations Some limitations of this study should be taken into account. Since the sample consisted of patients referred to a specialty clinic, the subjects assessed could be more severely impaired and present a higher number of comorbidities, thus precluding the extrapolation of our findings to community samples. We relied on retrospective assessment of diagnoses and ages at onset, which may limit the accuracy of our data. Multiple comparisons were performed with no statistical correction, which may have diminished the statistical accuracy, although some of our results persisted after multivariate analyses. Other disorders such as attention deficit hyperactivity disorder and separation anxiety disorder were not investigated in this study.
6. Conclusions This study describes specific phenotypic features associated with OCD, whether with or without CMVT or TS. These findings support the idea that OCD + CMVT may be an intermediate phenotype between OCD alone and OCD + TS. One possible explanation for this differential clinical expression is that it reflects differences in the number and quality of the genes involved in the tic disorder spectrum phenotype. These findings may be consistent with an additive quantitative genetic model for the final expression of the tic component associated with OCD. Future studies dissecting the phenotype into less complex components may furnish important tools for the identification of susceptibility genes for OCD. In addition, success in refining the characterization of OCD phenotypes is likely to lead to greater clarity concerning course, treatment strategies and outcome (Miguel et al., 2005).
Acknowledgements This paper was supported in part by grants from the Fundac¸a˜o de Amparo a` Pesquisa do Estado de Sa˜o Pau-
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Journal of Psychiatric Research 40 (2006) 487–493
www.elsevier.com/locate/jpsychires
Chronic tics and Tourette syndrome in patients with obsessive–compulsive disorder Juliana B. Diniz a,*, Maria Conceic¸a˜o Rosario-Campos a,b, Ana Gabriela Hounie a, Mariana Curi a, Roseli Gedanke Shavitt a, Antonio Carlos Lopes a, Euripedes C. Miguel a
a
Department of Psychiatry, University of Sa˜o Paulo Medical School, R Dr Ovideo Pires de Campos, 785, 4°. andar/sala 3, Sa˜o Paulo, SP 05403-010, Brazil b Department of Psychiatry, Bahia Federal University, Sa˜o Paulo, SP, Brazil Received 22 June 2005; received in revised form 6 August 2005; accepted 20 September 2005
Abstract Tourette syndrome (TS) and chronic motor/vocal tics (CMVT) are both common disorders in patients with obsessive compulsive disorder (OCD). However, there have been few studies evaluating the differences between the OCD with TS and OCD with CMVT subgroups. This study was conducted in order to further investigate possible differences between the expression of the OCD phenotype in OCD with TS and that seen in OCD with CMVT. One hundred and fifty-nine outpatients referred to an OCD research program were evaluated using the following instruments: the Structured Clinical Interview for DSM-IV; the Yale-Brown Obsessive Compulsive Scale; the Yale Global Tic Severity Scale; and the USP-HARVARD Repetitive Behaviors Interview. Patients were divided into three groups: OCD patients without tics (OCD TICS, n = 98), OCD patients with chronic motor or vocal tics (OCD + CMVT, n = 31) and OCD patients with TS (OCD + TS, n = 30). OCD + CMVT patients were similar to OCD + TS patients regarding the frequency of intrusive sounds, repeating behaviors, counting and tic-like compulsions (in both cases more frequent than in OCD TICS patients). For age at obsessive–compulsive (OC) symptom onset, sensory phenomena score, number of comorbidities, frequency of somatic obsessions, bodily sensations and just-right perceptions, OCD + CMVT patients tended to be in between the other two groups. Our results suggest that there are qualitative and quantitative differences in the phenotypic expression of tic disorders in OCD patients, depending on whether the subject has TS or only CMVT. Ó 2005 Elsevier Ltd. All rights reserved. Keywords: Tourette syndrome; Obsessive–compulsive disorder; Tic disorders; Psychopathology; Comorbidity
1. Introduction Even though the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Classification of Diseases (ICD-10) define obsessive– compulsive disorder (OCD) as a unitary nosological *
Corresponding author. Present address: Obsessive Compulsive Disorder Project, Institute of Psychiatry of the Clinics Hospital of the University of Sa˜o Paulo, R Dr Ovidio Pires de Campos 785, 05403010, Sa˜o Paulo, SP, Brazil. Tel.: +55 11 30696972; fax: +55 11 30697895. E-mail address: [email protected] (J.B. Diniz). 0022-3956/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2005.09.002
entity, recent research has indicated that OCD is in fact a heterogeneous disorder, with a variety of putative clinical phenotypes. So far, the best-described OCD subgroup is composed of OCD patients with a lifetime history of tic disorders. Many studies have reported that the tic-related OCD subgroup presents specific clinical, comorbidity, neurobiological, genetic and treatment response patterns. For instance, clinical studies have reported that tic-related OCD patients have an earlier age of onset (Miguel et al., 1997; Rosario-Campos et al., 2001; Holzer et al., 1994; Leckman et al., 1995), are more fre-
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quently males (Holzer et al., 1994; Leckman et al., 1995), and present higher frequencies of some obsessive–compulsive symptoms (OCSs), such as intrusive violent and sexual images or thoughts, hoarding, counting rituals and tic-like compulsions (Swerdlow et al., 1999; Zohar et al., 1997; Cath et al., 2000; Holzer et al., 1994). Similarly, tic-related OCD has been associated with higher frequencies of sensory phenomena preceding or accompanying their compulsions (Miguel et al., 1997, 2000; Leckman et al., 1994). Regarding the presence of comorbid disorders, some studies have reported that patients with tic-related OCD present higher rates of trichotillomania, body dysmorphic disorder (BDD), mood disorders, social phobia, other anxiety disorders and attention deficit hyperactivity disorder when compared to patients with non-ticrelated OCD (Petter et al., 1998; Coffey et al., 1998). The association between TS and OCD has received additional support from genetic studies, which have shown not only higher rates of OCS and OCD in relatives of TS patients (Pauls et al., 1986; Comings and Comings, 1987; Robertson et al., 1988; Eapen et al., 1993), but also higher rates of tics or TS in first-degree relatives of OCD patients (Leonard et al., 1992; Pauls et al., 1995; Rosario-Campos et al., 2005). In summary, the impact of a comorbid tic disorder on the phenotypic expression of OCD has been extensively described. On the other hand, very few studies have investigated whether a comorbid diagnosis of TS would affect the expression of OCD differently than would one of CMVT. Most previous studies have only compared OCD with TS to OCD without TS (De Groot et al., 1994; Miguel et al., 1997; Petter et al., 1998; Cath et al., 2000, 2001), or OCD with tic disorders to OCD without tic disorders (including either CMVT or TS) (Holzer et al., 1994; Leckman et al., 1995; Zohar et al., 1997). As an exception, Swerdlow et al. (1999) compared patients with OCD alone to OCD patients with CMVT and OCD patients with TS. Patients with OCD and CMVT presented more severe OCD than did patients with OCD plus TS or patients with OCD alone. Religious obsessions, cleaning/washing and counting compulsions, intrusive sounds/images and tic-like compulsions were more common in the OCD with CMVT group than in the OCD with TS group. That study, however, did not evaluate other clinical variables such as psychiatric comorbidity and other psychopathological characteristics (e.g., sensory phenomena, specific subjective sensations preceding repetitive behaviors such as just-right perceptions) preceding repetitive behaviors. The present study was designed in order to further investigate possible phenomenological differences in the OCD phenotype according to the presence of TS or CMVT. Therefore, we designed a study to compare OCD patients with no history of tic disorders to patients
with OCD and CMVT and patients with OCD and TS using a bigger sample and with a very comprehensive psychopathological evaluation.
2. Methods 2.1. Subjects One hundred sixty-eight consecutive outpatients referred to an OCD research program between 1996 and 2001 were assessed. Referrals came from a university hospital (n = 96) and two private facilities (n = 72). The inclusion criterion was a DSM-IV diagnosis of OCD. Exclusion criteria were history of previous brain trauma (n = 1), refusal to complete interview assessment (n = 2), comorbid diagnosis of schizophrenia (n = 3) and history of a transient tic disorder (n = 3). The remaining patients (n = 159) were divided into three groups: OCD patients without tics (OCD TICS, n = 98); OCD patients with chronic motor or vocal tics (OCD + CMVT, n = 31); and OCD patients with TS (OCD + TS, n = 30). This sample has already been described previously elsewhere (Diniz et al., 2004). This study was approved by the Medical Ethics Committee of the Institute of Psychiatry from University of Sa˜o Paulo Medical School. All patients gave written informed consent after the study had been thoroughly described and assurance had been given that their decision to participate in the study would not interfere in any way with their clinical treatment. Interviewers were experienced psychologists and psychiatrists from the OC Spectrum Disorder Project of the Department of Psychiatry of the University of Sa˜o Paulo Medical School. Each interview was reviewed by the first author and each diagnosis was made according to a best estimate procedure (Leckman et al., 1982) given by two psychiatrists (ECM and RGS) experienced in the evaluation of OCD and TS. 2.2. Clinical assessment Age of onset of OCS was defined as the earliest age that the patient remembered having OCS. When possible, a family member was also interviewed about the age of onset. These data on age at onset were retrospectively assessed by direct interview with the patient as described elsewhere (Rosario-Campos et al., 2001). The presence and severity of OCS and tics were determined by checklists and rating scales of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (Goodman et al., 1989a,b) and the Yale Global Tic Severity Scale (YGTSS) (Leckman et al., 1989), respectively. Subjects with ‘‘tic-like’’ compulsions were defined as patients who referred the need to perform a behavior similar to a tic in order to relieve the distress and/or anx-
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iety caused by an obsession or those who endorsed at least one of the following Y-BOCS symptom items: ‘‘the need to touch, tap or rub’’ and ‘‘rituals involving blinking or staring’’ (Rosario-Campos et al., 2001). ‘‘Sensory phenomena’’ were defined as local or generalized bodily sensations occurring before the patient performs repetitive behaviors (e.g. rituals, compulsions or tics) and mental sensations such as general uncomfortable, feelings or perceptions occurring before or while the patient performs repetitive behaviors (Miguel et al., 2000). Examples of sensory phenomena include the need to perform a behavior until the patient feels ‘‘just right’’ (Leckman et al., 1994), a need for energy release, a feeling of incompleteness, an urge to perform a behavior and generalized feelings of inner tension or pressure. Some OCD patients report that compulsions are preceded by sensory phenomena rather than obsessions; others present either obsessions or sensory phenomena preceding their compulsions, and some present only obsessions preceding their repetitive behaviors (Miguel et al., 2000). The presence and severity of sensory phenomena preceding or accompanying OCS and/or CMVT were assessed through the USP-HARVARD Repetitive Behaviors Interview (Miguel et al., 1995). The significance of sensory phenomena is defined using the following scale: 0 = the patient never had any sensory phenomena preceding his or her repetitive behaviors; 1 = the patient had at least one experience involving sensory phenomena preceding his or her repetitive behavior, but is not currently experiencing such phenomena; 2 = the patient currently presents sensory phenomena, but these phenomena are less pronounced in frequency and intensity than the current obsessions, fear or preoccupations; 3 = the patient currently presents sensory phenomena and these phenomena are more pronounced in frequency and intensity than the current obsessions, fear or preoccupations; 4 = the patient currently presents only sensory phenomena preceding his or her repetitive behavior and does not currently experience any obsessions, fear or preoccupation before performing repetitive behaviors. Of the original sample of 159 patients, 137 completed the USP-HARVARD Repetitive Behaviors Interview with the help of an experienced psychologist or psychiatrist. The other 22 patients did not complete this interview for various reasons and were excluded from the analyses regarding sensory phenomena. Psychiatric axis I comorbid disorders were assessed by the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1995), supplemented with additional modules based on DSM-IV criteria for TS, CMVT, trichotillomania, kleptomania, compulsive gambling and pyromania (data available upon request). Nine patients younger than 16 years old were interviewed using the Schedule for Affective Disorders and
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Schizophrenia Epidemiological version (Orvaschel and Puig-Antich, 1987), administered to a parent and child. Current and lifetime diagnoses were included in the analyses. Sub-threshold diagnoses were not included. 2.3. Statistical analyses Statistical analyses were performed using the Statistical Package for the Social Sciences, v. 11.0. The three groups were compared using ANOVA for continuous variables and PearsonÕs v2 test for categorical variables. In order to evaluate which group was different from the other two in each analysis, the Tukey test was used for continuous variables and partition chi-square for categorical variables. Variables presenting statistically significant differences between and among groups in the univariate analysis were included in a polytomic forward stepwise logistic regression (McCullagh and Nelder, 1996) in order to identify the variables most significantly associated with the differences among the three groups. The logit link function was used considering OCD TICS as the reference group. In other words, the response variables of the logistic model were defined as the logit of the probability of being from the OCD + TS group, divided by the probability of being from the OCD TICS group, and as the logit of the probability of being from the OCD + CMVT group, divided by the probability of being from the OCD TICS group. For all variables, the probability of F to enter the regression equations was set at 60.05; and the probability of F to remove was set at P0.10. A two-tailed p value < 0.10 was considered significant for the univariate analyses and a p value < 0.05 for the multivariate analyses.
3. Results Fifty-nine percent (n = 95) of all patients studied were male and 41% (n = 66) were female. Their age ranged from 12 to 59 years (mean age = 30 ± 10). Patients presented a mean age at OC symptoms onset of 13.2 ± 8.7 years ranging from 4 to 46 years. The mean illness duration in our sample was 16.3 ± 9.6 years ranging from 1 to 46 years. Mean YBOCS score for obsessions was 13.1 ± 3.6 and for compulsions 13.5 ± 3.8. The three groups differed according to mean age at interview (mean age OCD TICS = 31 ± 10, OCD + CMVT = 28 ± 9, OCD + TS = 25 ± 9; p = 0.010). Patients with OCD + CMVT presented a mean age at interview that was not statistically different from that of OCD + TS or OCD TICS patients but tended to be more similar to that of OCD + TS patients than that of OCD TICS patients (p = 0.23 and p= 0.13, respectively).
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Mean age at OCS onset was statistically different between and among the three groups (OCD TICS = 15 ± 10; OCD + CMVT = 12 ± 8; OCD + TS = 9 ± 3; p = 0.002). Patients with OCD + TS presented an earlier age at onset of OCS than did OCD TICS patients. Patients with OCD + CMVT presented a mean age at onset of OCS intermediate to OCD + TS and OCD TICS (p = 0.05 and p = 0.10, respectively). As expected, OCD + TS patients presented higher tic severity scores and earlier age at tic onset than did OCD + CMVT patients (mean YGTSS score for OCD + TS = 41 ± 26 vs. 15 ± 13 for OCD + CMVT; p < 0.001 and mean age at tic onset for OCD + TS = 9 ± 3 vs. 12 ± 6 for OCD + CMVT; p = 0.006). The current OCD severity measured by the YBOCS score was similar in all three groups (mean total YBOCS score = 26 ± 6 for OCD TICS, 27 ± 7 for OCD + CMVT and 27 ± 7 for OCD + TS). Significant data on obsessive–compulsive symptoms, sensory phenomena and psychiatric disorders are shown in Tables 1–3 respectively. Table 1 Obsessive–compulsive symptoms in patients with OCD OCD Religious obsessions Somatic obsessions Hoarding Repeating behaviors Intrusive sounds Counting compulsions Tic-like compulsions
52.0% 49.0% 37.2% 63.3% 37.1% 37.8% 42.9%
The demographic and clinical characteristics of the 22 patients who did not complete the USP-HARVARD Repetitive Behaviors Interview were not different from those of the group of 137 patients that completed this interview. 3.1. Multivariate analysis The presence of repeating behaviors (p = 0.015) was selected by the logistic regression as the one variable associated with the occurrence of CMVT in OCD patients. Likewise, four variables were found to correlate strongly with TS in OCD patients: early age at onset of OCS; somatic obsessions; energy release; and bipolar disorder (p = 0.041; p = 0.022; p = 0.002; and p = 0.042, respectively). The odds ratios are not shown, since they were associated with very broad 95% confidence intervals (95% CIs), demonstrating that the polytomic logistic regression model identified the major variables associated with TS
TICS, OCD + CMVT and OCD + TS
TICS, n = 98
OCD + CMVT, n = 31
(51) (48) (32) (62) (36) (37) (42)
71.0% 61.3% 45.2% 83.9% 61.3% 56.7% 61.3%
a
(22) (19) (14) (26)a (19)a (17)a (19)a
OCD + TS, n = 30 60.0% 76.7% 66.7% 83.3% 56.7% 56.7% 76.7%
b
(18) (23)a (20)a (25)a (17)a (17)a (23)a
p 0.061 0.023 0.004 0.023 0.025 0.054 0.003
OCD: obsessive compulsive disorder; OCD TICS: OCD alone; OCD + CMVT: OCD with chronic motor or vocal tics; OCD + TS: OCD with Tourette syndrome. a Significant difference when compared to OCD TICS. b Significant difference when compared to OCD + CMVT. Table 2 Sensory phenomena in OCD
TICS, OCD + CMVT and OCD + TS patients OCD
Sensory phenomena score Energy release Just-right perceptions Bodily sensations
TICS, n = 84
1.8 ± 1.2 22.4% (19) 48.8% (42) 29.4% (25)
OCD + CMVT, n = 26
OCD + TS, n = 27
p
2.0 ± 1.2 22.2% (6) 59.3% (16) 48.1% (13)
2.4 ± 0.9a 51.9% (14)a 77.8% (21)a 51.9% (14)a
0.062 0.009 0.029 0.048
OCD: obsessive compulsive disorder; OCD TICS: OCD alone; OCD + CMVT: OCD with chronic motor or vocal tics; OCD + TS: OCD with Tourette syndrome. a Significant difference when compared to OCD TICS. Table 3 Psychiatric comorbidity in OCD + TS, OCD + CMVT and OCD OCD Number of comorbidities other than tics Bipolar disorder Body dysmorphic disorder
TICS patients
TICS, n = 98
2.3 ± 1.7 7.2% (7) 15.3% (15)
OCD + CMVT, n = 31
OCD + TS, n = 30
p
2.7 ± 2.0 56.5% (2) 13.3% (4)
3.3 ± 2.2a 20.7% (6)ab 37.9% (11)ab
0.049 0.077 0.016
OCD: obsessive compulsive disorder; OCD TICS: OCD alone; OCD + CMVT: OCD with chronic motor or vocal tics; OCD + TS: OCD with Tourette syndrome. a Significant difference when compared to OCD TICS. b Significant difference when compared to OCD + CMVT.
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and CMVT but was unable to quantify them. In other words, the variables chosen by the logistic model might be the most closely associated with TS and CMVT in this group of OCD patients, but, in this model, it is not clear how much these variables influence the relationship that OCD has with TS and CMVT. Comparison between estimated coefficients in polytomic logistic regressions for TS and CMVT logits was not performed because the selected variables were not the same.
4. Discussion By using a very comprehensive phenomenological evaluation, this study was able to show that there are phenotypic differences in OCD patients according to the presence of TS or CMVT. Patients with OCD + CMVT present clinical characteristics that are intermediate between those of OCD + TS and OCD TICS patients. OCD + TS patients were better characterized by an earlier age at onset of OCS, presence of bipolar disorder, and sensory phenomena preceding repetitive behaviors (energy release), whereas the presence of repeating behaviors better characterized CMVT in OCD. There were no significant differences in the YBOCS scores between and among the three groups. Other authors have also found that OCD severity is unrelated to comorbid CMVT or TS (Leckman et al., 1995; Cath et al., 2000, 2001; Petter et al., 1998; Zohar et al., 1997). Therefore, although tic-related OCD is phenomenologically different from non-tic-related OCD, this difference does not influence the severity of OCS as measured by our current scales. Our results suggest that hoarding and somatic obsessions are associated with OCD + TS. Previous studies have also reported higher frequencies of hoarding behaviors (Leckman et al., 1995) and ‘‘concern with a body part or appearance’’ (Petter et al., 1998) in OCD patients with TS than in those with OCD TICS. Hoarding is considered a separate OCD symptom dimension by factor analyses (Leckman et al., 1997; Mataix-Cols et al., 1999; Summerfeldt et al., 1999) and has been associated with increased psychiatric comorbidity (Mataix-Cols et al., 1999; Frost et al., 2000), poor response to treatment (Mataix-Cols et al., 1999; Black et al., 1998) and the presence of specific genetic markers (Zhang et al., 2002). One can hypothesize that the association of TS with hoarding may be related to a putative ‘‘genetic’’ OCD subtype or susceptibility genes since both are related to earlier OCD onset (Millet et al., 2004; Diniz et al., 2004; Geller et al., 2001; RosarioCampos et al., 2001) and familial aggregation (Grados et al., 2001; Zhang et al., 2002). Sensory phenomena consisting of mental or bodily sensations preceding the compulsions in the absence of any thought, fear or worry were first described in TS
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patients (Leckman et al., 1994; Eapen et al., 1994). Energy release, ‘‘just-right’’ perceptions and other mental sensations are types of sensory phenomena that have been reported, both here and in previous studies (Miguel et al., 2000), as being more frequent in OCD + TS patients than in patients with OCD alone. In the present study, patients with OCD + CMVT were intermediate between OCD + TS and OCD TICS regarding frequency of and scores for sensory phenomena. These subjective experiences may prove useful in subtyping OCD. In addition to TS, BDD is the psychiatric disorder with more evidence of being part of the OCD spectrum (McElroy et al., 1994; Jaisoorya et al., 2003). Moreover, it has been suggested that there is a genetic association between BDD and OCD (Bienvenu et al., 2000). We found BDD to be more frequent in the OCD + TS group. Considering these findings, it is possible to speculate that the relationship between BDD and TS is also associated with genetic and familial vulnerability. It is interesting to note that somatic obsessions, as well as concern with body and appearance, are also related to a diagnosis of BDD, which has also been associated with TS in other studies (Coffey et al., 1998; Sverd et al., 1997). Another psychiatric comorbidity also found to be associated with TS in our study was bipolar disorder, a finding that also replicates those of previous studies (Coffey et al., 1998; Kerbeshian et al., 1995). However, it is of note that comorbid bipolar disorder in TS patients has been also associated with a higher prevalence of OCD (Berthier et al., 1998). Both genetic and neurochemical mechanisms have been implicated in the interconnectedness of bipolar disorder, TS and OCD (Berthier et al., 1998; Kerbeshian et al., 1995). In an attempt to explain the interrelationships among these disorders, it has been postulated that they constitute a spectrum of hereditary neuropsychiatric disorders (Comings and Comings, 1992). Since recent genetic studies have been unsuccessful in identifying the most likely mode of transmission of OCD, the hypothesis that genes are added to produce a cumulative quantitative effect seems plausible. Therefore, from a quantitative point of view, we could speculate that different loadings of susceptibility genes would predispose to different possible OCD manifestations accompanied by tics. For instance, there could be several thresholds that, when reached, increase the risk for a specific phenotype, such as OCD or OCD + TS, whereas patients with OCD + CMVT fall in between (Kelsoe, 2003; Hounie et al., in press). In this model, the degree of genetic loading would be higher for the disorders at the end of the OCD TS spectrum. Supporting this hypothesis, in our study we found an earlier age at onset of OCS in the TS pole of this spectrum (the CMVT group was intermediate), and the earlier age at onset, the higher the genetic load in OCD (RosarioCampos et al., 2005). Some of our findings, however,
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were specific related to the CMVT group. Therefore, it is likely that a hypothetical model including both the qualitative aspects (explaining the presence of different expression of OCS and comorbid disorders) and quantitative aspects (explaining the magnitude of the expression of specific features such age at onset and presence of sensory phenomena within each group) in interaction with the environment may provide the most plausible explanation for the variability of the tic-related OCD phenotype.
lo (FAPESP), grant 99/13005-1 to Dr. Diniz, 9901548-0 to Dr. Shavitt, 99/15013-9 to Dr. Hounie and 99/122057 to Dr Miguel; from the Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq) grant 521369/96 to Dr Miguel; from the Tourette Syndrome Association, as well as from the Obsessive–Compulsive Foundation, to Dr. Rosario-Campos.
References 5. Limitations Some limitations of this study should be taken into account. Since the sample consisted of patients referred to a specialty clinic, the subjects assessed could be more severely impaired and present a higher number of comorbidities, thus precluding the extrapolation of our findings to community samples. We relied on retrospective assessment of diagnoses and ages at onset, which may limit the accuracy of our data. Multiple comparisons were performed with no statistical correction, which may have diminished the statistical accuracy, although some of our results persisted after multivariate analyses. Other disorders such as attention deficit hyperactivity disorder and separation anxiety disorder were not investigated in this study.
6. Conclusions This study describes specific phenotypic features associated with OCD, whether with or without CMVT or TS. These findings support the idea that OCD + CMVT may be an intermediate phenotype between OCD alone and OCD + TS. One possible explanation for this differential clinical expression is that it reflects differences in the number and quality of the genes involved in the tic disorder spectrum phenotype. These findings may be consistent with an additive quantitative genetic model for the final expression of the tic component associated with OCD. Future studies dissecting the phenotype into less complex components may furnish important tools for the identification of susceptibility genes for OCD. In addition, success in refining the characterization of OCD phenotypes is likely to lead to greater clarity concerning course, treatment strategies and outcome (Miguel et al., 2005).
Acknowledgements This paper was supported in part by grants from the Fundac¸a˜o de Amparo a` Pesquisa do Estado de Sa˜o Pau-
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