Psychiatry Research 226 (2015) 156–161
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The impact of tics, obsessive–compulsive symptoms, and impulsivity on global functioning in Tourette syndrome Yukiko Kano a,n, Toshiaki Kono b, Natsumi Matsuda c, Maiko Nonaka d, Hitoshi Kuwabara e, Takafumi Shimada f, Kurie Shishikura g, Chizue Konno h, Masataka Ohta i a
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bukyo-ku, Tokyo 113-8655, Japan Department of Forensic Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan c Department of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan d Course of Clinical Psychology, Graduate School of Education, The University of Tokyo, Tokyo, Japan e Disability Services Office, The University of Tokyo, Tokyo, Japan f Division for Counseling and Support, The University of Tokyo, Tokyo, Japan g Komagino Hospital, Tokyo, Japan h Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan i Institute for Development of Mind and Behavior, Tokyo, Japan b
art ic l e i nf o
a b s t r a c t
Article history: Received 29 April 2014 Received in revised form 8 September 2014 Accepted 30 December 2014 Available online 7 January 2015
This study investigated the relationships between tics, obsessive–compulsive symptoms (OCS), and impulsivity, and their effects on global functioning in Japanese patients with Tourette syndrome (TS), using the dimensional approach for OCS. Fifty-three TS patients were assessed using the Yale Global Tic Severity Scale, the Dimensional Yale–Brown Obsessive–Compulsive Scale, the Impulsivity Rating Scale, and the Global Assessment of Functioning Scale. Although tic severity scores were significantly and positively correlated with OCS severity scores, impulsivity severity scores were not significantly correlated with either. The global functioning score was significantly and negatively correlated with tic and OCS severity scores. Of the 6 dimensional OCS scores, only aggression scores had a significant negative correlation with global functioning scores. A stepwise multiple regression analysis showed that only OCS severity scores were significantly associated with global functioning scores. Despite a moderate correlation between tic severity and OCS severity, the impact of OCS on global functioning was greater than that of tics. Of the OCS dimensions, only aggression had a significant impact on global functioning. Our findings suggest that it is important to examine OCS using a dimensional approach when analyzing global functioning in TS patients. & 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Obsessive-compulsive disorder (OCD) Dimensions Comorbidities
1. Introduction Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor tics and one or more vocal tics that persist for at least 1 year (American Psychiatric Association, 2013). The comorbidities of TS often include various psychiatric disorders such as obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). The prevalence of OCD among TS patients is estimated to be as high as 30%, and as much as 50% or more if sub-clinical cases are included (Hounie et al., 2006). Several studies have suggested that the severity of tics and the prevalence of self-injurious behavior (SIB) and impulsivity are higher among TS patients with OCD than those without OCD (Cardona et al., 2004; Kano et al., 2010b). n
Corresponding author. Tel./fax.: þ 81 3 5800 8664. E-mail address: [email protected] (Y. Kano).
http://dx.doi.org/10.1016/j.psychres.2014.12.041 0165-1781/& 2015 Elsevier Ireland Ltd. All rights reserved.
Impulsivity is a multifaceted construct, and is a core symptom of ADHD, which is frequently comorbid with TS as well as OCD (Freeman, 2007). Patients with TS can exhibit impulse-control problems such as rage attacks. Rage attacks are defined as discrete episodes of failure to resist aggressive impulses that result in serious assaultive acts or the destruction of property, wherein the degree of aggressiveness expressed is grossly out of proportion to any precipitating psychosocial stressors. Previous North American studies have indicated that the rage attacks in TS patients are associated with the presence of comorbidities including ADHD and OCD (Freeman, 2007; Budman et al., 2000). However, this association was not found in a study of Japanese TS patients (Kano et al., 2008) and remains to be confirmed. In addition, impulse control disorders characterized by significant difficulties in controlling urges to perform rewarding behavior were frequently found to be comorbid in adults with TS, and the most common one was intermittent explosive disorder whose main symptoms are rage attacks (Frank et al., 2011).
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Global functioning is impaired to a much greater degree in TS patients with comorbidities than in those without, and comorbid ADHD and OCD in particular have been associated with poorer global or psychosocial functioning (Gorman et al., 2010; Lebowitz et al., 2012; Pringsheim et al., 2009). Several studies have suggested that OCS may have a slightly greater effect than ADHD on the symptomatology of TS, including tics (Cardona et al., 2004; Kano et al., 2010b). All of these studies have focused on the overall impact of ADHD rather than impulsivity, including impulse control problems such as rage attacks. Therefore, it remains to be clarified how tics, OCS, and impulsivity collectively interfere with the global functioning of TS patients. When considering the impact of OCS on global functioning among TS patients, recent research findings indicate that a dimensional approach for examining OCS should be considered. Factor analytic studies using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) have suggested that OCS among patients with OCD can be divided into 3–5 dimensions, and genetic, neuroimaging, and treatment studies have supported the usefulness of this approach (Stewart et al., 2007; Bloch et al., 2008). In addition, a relationship has been found between comorbid tic disorders and the symmetry/ordering (Labad et al., 2008) and aggressive/checking (Nikolajsen et al., 2011) dimensions of OCS among OCD patients. Furthermore, research on OCS dimension phenotypes among TS families has indicated that both the aggression/checking and symmetry/ordering dimensions were correlated within families (Leckman et al., 2003). We investigated the relationships between tics, OCS, and impulsivity, and their effects on global functioning among Japanese TS patients. We formulated hypotheses focused on compulsivity and impulsivity, as they are important components of Obsessive–compulsive spectrum disorders including TS (Berlin and Hollander, 2014). Learning more about these relationships seems to be important for both understanding the pathogenesis and improving the treatment. We expected to find that OCS and impulsivity each affect global functioning independently, and also when combined with tics, and that the impact of OCS on global functioning is the same or greater than that of impulsivity. We also expected to find that the aggression and symmetry dimensions of OCS would have a greater effect on global functioning than other dimensions.
ordinal scales, and a total tics score is obtained by summing the individual scores (0–50). The current impairment due to tics was also assessed (0–50). The global severity score was determined (0–100) as the sum of the total tics score and the impairment score. Additionally, tics were assessed on the basis of clinical observations and a review of the patients' medical records. Clinicians carefully investigated both the current and historical presence of tics and related symptoms such as coprolalia, which refers to the utterance of social unacceptable words, and SIB, which is the deliberate, repetitive infliction of self-harm.
2. Methods
2.2.5. Medication and comorbidities Information on medication was collected from the patients' psychiatrists and the medical records. Comorbid OCD and ADHD were diagnosed on the basis of DSM-IV-TR criteria, as in the case of TS.
2.1. Subjects Subjects were recruited from a specialty clinic that treats people with TS and related disorders at the Department of Child Psychiatry of the University of Tokyo Hospital during the period from February 2005 to February 2010. Subjects were included if they had a Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Tourette's disorder (American Psychiatric Association, 2000). They were excluded if they had mental retardation, autistic disorder, or any neurological disorder that could interfere with the quality of the interviews. Diagnoses were made according to DSM-IV-TR criteria by expert child psychiatrists, with a high diagnostic concordance rate. This study was approved by the Institutional Review Board of the University of Tokyo Hospital. The subjects signed informed consent forms after the study was explained to them in detail and they were assured that the decision to participate in the study would not affect their treatment in any way. If the subjects were 19 years old or younger, written informed consent was obtained from parents. All interviews were conducted by psychologists who had in-depth knowledge of the instruments, clinical experience with TS, and no involvement with the treatment of the subjects, after training to ensure conformity of assessment.
2.2.2. Assessment of OCS Current OCS were evaluated using the Dimensional Y-BOCS (DY-BOCS), a rating scale developed for assessing the presence and severity of specific OCS dimensions (Rosario-Campos et al., 2006). According to the DY-BOCS, OCS were divided into six dimensions: (1) obsessions about harm due to injury, violence, aggression, or natural disasters, and related compulsions (aggression); (2) sexual and religious obsessions and related compulsions (sexual/religious); (3) obsessions and compulsions related to symmetry, ordering, counting, and arranging (symmetry); (4) contamination obsessions and cleaning compulsions (contamination); (5) obsessions and compulsions related to hoarding and collecting (hoarding); and (6) miscellaneous obsessions and compulsions (miscellaneous). The severity of each dimension was measured on three ordinal scales with six anchor points that focus on symptom frequency (0–5), the amount of distress caused (0–5), and the degree to which they interfered with functioning (0–5) during the week before examination. Global OCS severity was estimated via the same three ordinal scales. The overall level of current impairment due to OCS (0–15) was assessed for all patients. The total global score (0–30) was obtained by combining the sum (0–15) of the global severity scores for the frequency, distress, and interference, with the impairment scores (0–15). The Japanese version was designed using a rigorous methodology involving translation and back translation, and its validity and reliability were re-examined in a preliminary study (Kano et al., 2006).
2.2.3. Assessment of impulsivity Current impulsivity was evaluated using the Japanese version of the Impulsivity Rating Scale (IRS) (Lecrubier et al., 1995). The IRS is a semi-structured interviewbased scale of seven items with four anchor points (0–3). The sum of the seven scores represents the global score (0–21). The Japanese version was designed using a rigorous methodology involving translation and back translation, and the validity and reliability of the original version were established.
2.2.4. Assessment of global functioning Current global functioning was evaluated using the Global Assessment of Functioning (GAF) scale (American Psychiatric Association, 2000).
2.3. Data analysis Statistical analyses were performed using SPSS software version 18.0. To examine the interrelationships between the clinical indicators of tics, OCS, impulsivity, and global functioning, Pearson's correlation coefficients were calculated. A 0.05 level of significance was selected. To examine the effects of tics, OCS, and impulsivity on global functioning, stepwise multiple regression analyses were performed with the GAF score as the dependent variable. If the p-Value was less than 0.05, the corresponding independent variable was entered into the model, and if it exceeded 0.10, the corresponding independent variable was removed from the model. When an additional analysis, based on stratification by age, was performed, a t-test was used to compare the two groups with 0.05 as the significance level.
3. Results 2.2. Instruments 2.2.1. Assessment of tics The presence and severity of tics were evaluated for the current study using the Japanese version of the Yale Global Tic Severity Scale (YGTSS) (Leckman et al., 1989). This version has previously been proven valid and reliable (Inoko et al., 2006). On this scale, motor and vocal tics are evaluated separately (0–25) on five
Of the 68 patients invited to participate in this study, 58 agreed. Finally, 53 TS patients (40 men and 13 women) were included (age range, 5–43 years; mean ¼ 17.6; standard deviation (S.D.) ¼9.2). No significant difference in demographic findings was found between the 58 subjects who agreed to participate and the 10 who did not.
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Table 1 Demographic and clinical characteristics of the subjects (n¼ 53). Age, in years, mean (S.D.; range) Age at tic onset, years, mean (S.D.; range) Age on the first visit, years, mean (S.D.; range) Age at the worst ever period, years, mean (S.D.; range) Gender, male n (%) YGTSS scores: Total tic, mean (S.D.; range) Impairment, mean (S.D.; range) Global severity, mean (S.D.; range) DY-BOCS scores: Total OCS, mean (S.D.; range) Impairment, mean (S.D.; range) Global severity, mean (S.D.; range) Aggression, mean (S.D.; range) Sexual/religious, mean (S.D.; range) Symmetry, mean (S.D.; range) Contamination, mean (S.D.; range) Hoarding, mean (S.D.; range) Miscellaneous, mean (S.D.; range) IRS score, mean (S.D.; range) GAF score, mean (S.D.; range)
17.6 6.1 15.5 13.9 40
Table 2 Correlations between tics, OCS, impulsivity, and global functioning. (9.2; 5–43) (2.4; 2–12) (8.2; 5–38) (7.0; 5–34) (75)
26.5 (8.2; 0–45) 26.0 (10.3; 0–50) 52.5 (16.4; 0–85) 4.6 3.9 8.5 1.9 1.0 2.0 1.7 0.5 2.5 5.0 57.4
(3.8; 0–12) (3.6; 0–13) (7.3; 0–25) (3.0; 0–12) (2.4; 0–9) (2.9; 0–12) (3.3; 0–12) (1.5; 0–8) (3.4; 0–12) (3.6; 0–14) (9.7; 36–84)
YGTSS global severity YGTSS total 0.855nn tics YGTSS global severity DY-BOCS total OCS DY-BOCS global severity IRS
DY-BOCS total OCS
DY-BOCS IRS global severity
GAF
0.364nn
0.319n
0.231† 0.312n
0.302n
0.245†
0.115
0.441nn
0.981nn
0.187
0.422nn
0.245† 0.434nn
0.217
Pearson's correlation coefficients. † n
p o 0.1. p o 0.05. p o 0.01.
nn
Table 3 OCS dimensions and correlations with tics, impulsivity and global functioning.
3.1. Description of tics, OCS, impulsivity, global functioning, pharmacotherapy, and comorbidities
Correlation with OCS dimension YGTSS total tics
The age at onset of tics averaged 6.1 years (S.D. ¼ 2.4) (Table 1). The mean age on the first visit to the clinic was 15.5 years (S.D. ¼8.2). The mean age at which the episode of tics was the worst ever was 13.9 years (S.D. ¼ 7.0). Coprolalia was found in 13 subjects (25%) as a current symptom and in 26 subjects (49%) as a lifetime symptom. SIB was found in eight subjects (15%) as a current symptom and in 23 (43%) as a lifetime symptom. The mean current scores on the YGTSS were 26.5 (S.D. ¼8.2) for total tics, 26.0 (S.D. ¼10.3) for impairment due to tics, and 52.5 (S.D. ¼16.4) for global severity. Of the 53 subjects included in the study, 44 (83%) had current OCS. The mean current DY-BOCS scores were 4.6 (S.D. ¼3.8) for total OCS, 3.9 (S.D. ¼ 3.6) for impairment, and 8.5 (S.D. ¼7.3) for global severity. The miscellaneous dimension showed the highest mean DY-BOCS dimensional score of 2.5 (S.D. ¼3.4), followed by the symmetry dimension (mean ¼2.0; S.D. ¼2.9), and the aggression dimension (mean¼1.9; S.D.¼ 3.0). The mean IRS score was 5.0 (S.D. ¼3.6), and the mean GAF score was 57.4 (S.D. ¼9.7). Forty-four subjects (83%) were taking some kind of psychotropic drug, of which 40 were on antipsychotics (risperidone, 12 subjects; pimozide and haloperidol, nine subjects each). Other drugs were being used by 26 subjects (antidepressants, 13 subjects; clonidine, six subjects; anxiolytics, four subjects; mood stabilizers, four subjects). According to the DSM-IV-TR criteria, 15 (28%) subjects had comorbid OCD and 8 (15%) had comorbid ADHD as a lifetime diagnosis. 3.2. Correlations between tics, OCS, and impulsivity The YGTSS total tics scores were significantly and positively correlated with the DY-BOCS total OCS scores (r ¼0.364, p ¼0.007) (Table 2). In terms of global severity, including impairment due to tics and OCS, the correlation between the YGTSS and DY-BOCS scores did not reach statistical significance (r ¼0.245, p ¼0.077). IRS scores were not significantly correlated with either the YGTSS or DY-BOCS scores. When the correlations between the 6 DY-BOCS dimensional scores and the YGTSS and IRS scores were examined, the DY-BOCS
Aggression Sexual/religious Symmetry Contamination Hoarding Miscellaneous
n
0.318 0.368nn 0.356nn 0.189 0.177 0.212
YGTSS global severity
IRS
GAF
0.223 0.310n 0.319n 0.228 0.123 0.111
0.014 0.013 0.038 0.211 0.291n 0.111
0.297n 0.225 0.218 0.254† 0.075 0.239†
Pearson's correlation coefficients. †
p o 0.1. p o 0.05. nn p o 0.01. n
dimensional scores for aggression, sexual/religious, and symmetry dimensions were found to be significantly and positively correlated with the YGTSS total tics scores (r ¼0.318, 0.368, and 0.356, respectively), although the aggression dimension scores were not significantly correlated with the YGTSS global severity scores (r ¼0.223) (Table 3). When the correlation between the DY-BOCS dimensional scores and the IRS scores was examined, only the hoarding dimension scores were found to have a significant positive correlation (r ¼0.291). 3.3. Relationships between tics, OCS, and impulsivity, and global functioning 3.3.1. Correlation coefficients Although GAF scores were significantly and negatively correlated with YGTSS total tics scores (r ¼ 0.312, p ¼0.023) and DYBOCS total OCS scores (r ¼ 0.422, p ¼0.002), they were not significantly correlated with IRS scores (Table 2). Among the 6 DY-BOCS dimensional scores, only those of the aggression dimension had a significant negative correlation with GAF scores (r ¼ 0.297, p ¼0.031) (Table 3). 3.3.2. Multiple regression analysis When YGTSS total tics scores, DY-BOCS total OCS scores, and IRS scores were entered into the initial regression model as independent variables, the YGTSS and IRS scores had to be removed from the model, and only the DY-BOCS scores showed a significant association with GAF scores (B ¼ 1.083, t ¼ 3.324, p ¼0.002) (Table 4). When YGTSS global severity scores, DY-BOCS global
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Table 4 Impact of tics, OCS and impulsivity on global functioning (multiple regression analysis).
Model 1 DY-BOCS total OCS score Model 2 YGTSS global severity score DY-BOCS global severity score Model 3 YGTSS impairment score DY-BOCS impairment score Model 4 Dimensional score of “Aggression”
R2adj
B
β
t
1.083
0.422
3.324
0.002
0.212 0.463
0.356 0.346
2.933 2.852
0.005 0.006
0.403 1.064
0.424 0.397
3.744 3.509
o 0.001 0.001
0.960
0.297
2.219
0.031
p
0.162 0.279
0.337
0.070
B: regression coefficient, β: standardized regression coefficient, R2adj: adjusted multiple coefficient of determination.
severity scores, and IRS scores were entered into the initial regression model as independent variables, IRS scores had to be removed from the model, and YGTSS (B ¼ 0.212, t¼ 2.933, p ¼0.005) and DY-BOCS scores showed a significant association with GAF scores (B ¼ 0.463, t ¼ 2.852, p ¼0.006). When YGTSS total tic scores, YGTSS impairment scores, DY-BOCS total OCS scores, DY-BOCS impairment scores, and IRS scores were entered into the initial regression model as independent variables, YGTSS impairment (B¼ 0.403, t ¼ 3.744, p o0.001) and DY-BOCS impairment scores showed a significant association with GAF scores (B ¼ 1.064, t¼ 3.509, p ¼0.001). When the 6 DY-BOCS dimensional scores were entered into the initial regression model as independent variables, only the score for the aggression dimension remained in the model and was significantly associated with GAF scores (B ¼ 0.960, t ¼ 2.219, p ¼0.031). 3.4. Analysis based on stratification by age As the subjects' ages were widely distributed, and the severity of tics is thought to start declining by adulthood in a large proportion of TS patients, we divided them into two groups: 17 years old or younger (younger group; six girls and 27 boys) and 18 years old or older (older group; 7 women and 13 men). The younger and older group data were subjected to the same statistical analyses as those that were performed for the entire sample of subjects. 3.4.1. Description of tics, OCS, impulsivity, global functioning, and pharmacotherapy The mean age at tic onset, mean age at the first visit, and mean age during the worst-ever period were significantly higher for the older group than for the younger group. There was no significant difference between the two groups for any scores except the DYBOCS dimension scores. The aggression, symmetry, and miscellaneous dimension scores were significantly higher for the older group than the younger group (p ¼0.008, p ¼0.043, p ¼0.037, respectively). Twenty-five (76%) in the younger group and 19 (95%) in the older group were on medication. 3.4.2. Correlations between tics, OCS, and impulsivity For the younger group, there was a significant positive correlation between YGTSS total tics scores and DY-BOCS total OCS scores (r ¼ 0.426, p¼ 0.013). IRS scores were significantly correlated with YGTSS and DY-BOCS scores (r ¼0.504, p ¼0.003 for total tic scores; r ¼0.372, p ¼0.033 for YGTSS global severity scores; r ¼0.411, p ¼0.017 for OCS scores; r¼ 0.457, p ¼ 0.007 for DY-BOCS global severity scores). Of the 6 DY-BOCS dimensional scores, only those of the symmetry dimension were significantly correlated with YGTSS total tic scores and global severity scores (r ¼0.409,
p¼ 0.018; r ¼0.379, p ¼0.030, respectively). There was no significant correlation between dimensional scores and IRS scores. For the older group, there was no significant correlation between any scores. 3.4.3. Relationships between tics, OCS, and impulsivity with global functioning In the younger group, GAF scores were significantly and negatively correlated with DY-BOCS OCS scores, global severity scores (r ¼ 0.602, p o0.001; r¼ 0.614, p o0.001, respectively), and IRS scores (r ¼ 0.486, p ¼0.004). Among the 6 DY-BOCS dimensional scores, those of sexual/religious, symmetry, and miscellaneous dimensions were significantly and negatively correlated with GAF scores (r ¼ 0.384, p¼ 0.028; r ¼ 0.352, p¼ 0.044; r ¼ 0.404, p ¼0.020, respectively). In multiple regression analysis, when YGTSS total tics scores, DY-BOCS total OCS scores, and IRS scores were entered into the initial regression model as independent variables, only DY-BOCS scores showed a significant association with GAF scores (B ¼ 1.421, t¼ 4.193, po 0.001). When the 6 DY-BOCS dimensional scores were entered into the initial regression model as independent variables, the scores for the symmetry and miscellaneous dimensions remained in the model and had a significant association with GAF scores (B ¼ 1.203, t¼ 2.216, p ¼0.034; B ¼ 1.239, t¼ 2.559, p¼ 0.016, respectively). For the older group, GAF scores were significantly and negatively correlated with only YGTSS global severity scores (r ¼ 0.515, p ¼0.020). No other significant correlation was found.
4. Discussion Based on data from the 53 TS patients, we examined the following hypotheses: that tics, OCS, and impulsivity affect global functioning; that the impact of OCS on global functioning is the same or greater than that of impulsivity; and that the aggression and symmetry dimensions of OCS have the greatest influence on global functioning. We also examined the prevalence of comorbidities and the relationships between tics, OCS, and impulsivity. The prevalence of OCD and any OCS was 28% and 83%, respectively. This high prevalence was comparable to that found in previous studies (Hounie et al., 2006; Freeman, 2007). On the other hand, the prevalence of ADHD was 15%, which is lower than that in previous studies (Freeman, 2007). Compared to those without ADHD, TS patients with ADHD might have hesitated more about participating in this study, which takes time to complete. When the interrelationships between tics, OCS, and impulsivity were examined, tic and OCS severity were moderately related to each other and were relatively independent of impulsivity. These findings may be compatible with those of a previous study that did not find a significant difference in tic severity and comorbid OCD
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prevalence among TS patients with and without clinically significant aggressive symptoms (Kano et al., 2008). An examination of the impact of tics, OCS, and impulsivity on global functioning for all subjects showed that as the severity of tics and OCS increased, the global functioning of the patients worsened. Multiple regression analysis revealed that OCS had the greatest impact of all. The quantitative assessment of the symptomatology of TS conducted in this study seems to replicate findings from previous studies (Freeman, 2007): patients with TS and comorbidities have lower global functioning than those with TS alone. Our results are consistent both with our hypotheses and previous studies suggesting that comorbid OCS may have a greater effect on the symptomatology of TS than ADHD symptoms (Cardona et al., 2004; Kano et al., 2010b) and that OCS has more widespread effects on quality of life than ADHD (Eddy et al., 2012). However, several recent studies have suggested that both OCS and ADHD symptoms might be related to quality of life, psychosocial and educational problems, or psychosocial stress among children with TS (Lebowitz et al., 2012; Bernard et al., 2009; Debes et al., 2010). Even after selecting the subjects in this study with an age similar to those in the above-mentioned studies, OCS rather than impulsivity showed a significant impact on global functioning. On the basis of the YGTSS scores and the prevalence of coprolalia, the number of patients with severe tics was expected to be higher in this study than in other recent studies (Pringsheim et al., 2009; Bernard et al., 2009). As TS patients with comorbid OCD are characterized by more severe tics (Lebowitz et al., 2012), the impact of OCS may tend to be emphasized among TS patients in this study who had severe tics more frequently than subjects in other studies. Even with these considerations, our hypothesis that OCS have the most impact on global functioning was supported. Using the dimensional approach to study OCS for all subjects revealed that OCS in the aggression dimension produced the greatest impairment in global functioning, as indicated by the results of both the correlation analysis and the multiple regression analysis. The aggression dimension severity scores were not significantly correlated with either YGTSS global severity scores or IRS scores. Therefore, the impact of this dimension, which represents obsessions and related compulsions about harm as opposed to aggressiveness, might be relatively independent of tics and impulsivity. When the subjects were stratified by age, the strong impact of the aggression dimension was not evident. In the younger group, the symmetry dimension showed a significant impact on global functioning. In our previous study on TS patients, the difference between the worst ever and the current ratings for OCS dimensions was the smallest for the aggression dimension and was much lower than that for the symmetry dimension (Kano et al., 2010a). This finding suggests that the aggression dimension might have a sustained effect on global functioning throughout development and that the impact of the symmetry dimension might diminish over the course of development. A recent study of children and adolescents with OCD has indicated that high scores on the aggressive/checking dimension, derived from the Children's Yale–Brown Obsessive–Compulsive Scale (CY-BOCS), were associated with comorbid tic disorders (Nikolajsen et al., 2011). It has been suggested that the aggression dimension is not only associated with TS but also plays an important role in the global functioning of TS patients. This study has several limitations. Firstly, the number of the subjects was small, and they were recruited from a specialty clinic, resulting in referral bias. The subjects differed greatly in terms of age, tic severity, and pharmacotherapy. Although we analyzed the data according to age, the sample size of these subgroups may have been too small to justify the conclusions. In future research, we would like to conduct a study with a larger number of subjects,
wherein we can examine symptomatology and global functioning with the appropriate stratification for age and tic severity. The influence of current and lifetime pharmacotherapy should be examined. Secondly, as children and parents may be unlikely to share similar views about the impact of TS (Cavanna et al., 2013), more deliberate consideration about data from the younger group might be needed. Thirdly, further consideration regarding the assessment of impulsivity is necessary. The IRS is an interviewbased quantitative assessment tool that is applicable to a wide range of ages. Of the seven items in the IRS, irritability, aggressiveness, and control of responses are likely to relate more closely to impulse control problems such as rage attacks and SIB than the remaining items; however, the differentiation between them is arbitrary. Therefore, we used the IRS score by summing the seven items. ADHD symptoms such as inattention, hyperactivity, and impulsivity were not assessed independently. Impulsivity should be evaluated in future studies by focusing on impulse control problems as well as overall ADHD symptoms. Despite these limitations, to the best of our knowledge, ours is the first study to investigate the impact of tics, OCS, and impulsivity on global functioning using the dimensional approach for OCS among Japanese TS patients. The findings suggest the importance of the dimensional approach for correctly analyzing global functioning.
Acknowledgments The present study was partly supported by a Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H17004), Comprehensive Research on Disability, Health and Welfare (H20-006 and H22-004), Research Grant for Nervous and Mental Disorders (17A-2 and 20B-6), and an Intramural Research Grant (23-1) for Neurological and Psychiatric Disorders of NCNP, all from the Ministry of Health, Labour and Welfare, Japan. Further support was received from a Grant of Project Research from Kitasato University and Grant-in-Aid for Scientific Research on Innovative Areas Grant number 26118704.
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Kurlan, J.F., Leckman, J.F., 2012. Tourette syndrome in youth with and without obsessive compulsive disorder and attention deficit hyperactivity disorder. European Child and Adolescent Psychiatry 21, 451–457. Leckman, J.F., Riddle, M.A., Hardin, M.T., Ort, S.I., Swartz, K.L., Stevenson, J., Cohen, D.J., 1989. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. Journal of the American Academy of Child and Adolescent Psychiatry 28, 566–573. Leckman, J.F., Pauls, D.L., Zhang, H., Rosario-Campos, M.C., Katsovich, L., Kidd, K.K., Pakstis, A.J., Alsobrook, J.P., Robertson, M.M., McMahon, W.M., Walkup, J.T., van de Wetering, B.J., King, R.A., Cohen, D.J., 2003. Tourette Syndrome Assocation International Consortium for Genetics, 2003. Obsessive–compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette syndrome. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 116B, 60–68. Lecrubier, Y., Braconnier, A., Said, S., Payan, C., 1995. The impulsivity rating scale (IRS): preliminary results. European Psychiatry 10, 331–338. Nikolajsen, K.H., Nissen, J.B., Thomsen, P.H., 2011. Obsessive–compulsive disorder in children and adolescents. Symptom dimensions in a naturalistic setting. Nordic Journal of Psychiatry 65, 244–250. Pringsheim, T., Lang, A., Kurlan, R., Pearce, M., Sandor, P., 2009. Understanding disability in Tourette syndrome. Developmental Medicine and Child Neurology 51, 468–472. Rosario-Campos, M.C., Miguel, E.C., Quatrano, S., Chacon, P., Ferrao, Y., Findley, D., Katsovich, L., Scahill, L., King, R.A., Woody, S.R., Tolin, D., Hollander, E., Kano, Y., Leckman, J.F., 2006. The Dimensional Yale–Brown Obsessive–Compulsive Scale (DY-BOCS): an instrument for assessing obsessive–compulsive symptom dimensions. Molecular Psychiatry 11, 495–504. Stewart, S.E., Rosario, M.C., Brown, T.A., Carter, A.S., Leckman, J.F., Sukhodolsky, D., Katsovitch, L., King, R., Geller, D., Pauls, D.L., 2007. Principal components analysis of obsessive–compulsive disorder symptoms in children and adolescents. Biological Psychiatry 61, 285–291.
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The impact of tics, obsessive–compulsive symptoms, and impulsivity on global functioning in Tourette syndrome Yukiko Kano a,n, Toshiaki Kono b, Natsumi Matsuda c, Maiko Nonaka d, Hitoshi Kuwabara e, Takafumi Shimada f, Kurie Shishikura g, Chizue Konno h, Masataka Ohta i a
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bukyo-ku, Tokyo 113-8655, Japan Department of Forensic Psychiatry, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan c Department of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan d Course of Clinical Psychology, Graduate School of Education, The University of Tokyo, Tokyo, Japan e Disability Services Office, The University of Tokyo, Tokyo, Japan f Division for Counseling and Support, The University of Tokyo, Tokyo, Japan g Komagino Hospital, Tokyo, Japan h Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan i Institute for Development of Mind and Behavior, Tokyo, Japan b
art ic l e i nf o
a b s t r a c t
Article history: Received 29 April 2014 Received in revised form 8 September 2014 Accepted 30 December 2014 Available online 7 January 2015
This study investigated the relationships between tics, obsessive–compulsive symptoms (OCS), and impulsivity, and their effects on global functioning in Japanese patients with Tourette syndrome (TS), using the dimensional approach for OCS. Fifty-three TS patients were assessed using the Yale Global Tic Severity Scale, the Dimensional Yale–Brown Obsessive–Compulsive Scale, the Impulsivity Rating Scale, and the Global Assessment of Functioning Scale. Although tic severity scores were significantly and positively correlated with OCS severity scores, impulsivity severity scores were not significantly correlated with either. The global functioning score was significantly and negatively correlated with tic and OCS severity scores. Of the 6 dimensional OCS scores, only aggression scores had a significant negative correlation with global functioning scores. A stepwise multiple regression analysis showed that only OCS severity scores were significantly associated with global functioning scores. Despite a moderate correlation between tic severity and OCS severity, the impact of OCS on global functioning was greater than that of tics. Of the OCS dimensions, only aggression had a significant impact on global functioning. Our findings suggest that it is important to examine OCS using a dimensional approach when analyzing global functioning in TS patients. & 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Obsessive-compulsive disorder (OCD) Dimensions Comorbidities
1. Introduction Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor tics and one or more vocal tics that persist for at least 1 year (American Psychiatric Association, 2013). The comorbidities of TS often include various psychiatric disorders such as obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). The prevalence of OCD among TS patients is estimated to be as high as 30%, and as much as 50% or more if sub-clinical cases are included (Hounie et al., 2006). Several studies have suggested that the severity of tics and the prevalence of self-injurious behavior (SIB) and impulsivity are higher among TS patients with OCD than those without OCD (Cardona et al., 2004; Kano et al., 2010b). n
Corresponding author. Tel./fax.: þ 81 3 5800 8664. E-mail address: [email protected] (Y. Kano).
http://dx.doi.org/10.1016/j.psychres.2014.12.041 0165-1781/& 2015 Elsevier Ireland Ltd. All rights reserved.
Impulsivity is a multifaceted construct, and is a core symptom of ADHD, which is frequently comorbid with TS as well as OCD (Freeman, 2007). Patients with TS can exhibit impulse-control problems such as rage attacks. Rage attacks are defined as discrete episodes of failure to resist aggressive impulses that result in serious assaultive acts or the destruction of property, wherein the degree of aggressiveness expressed is grossly out of proportion to any precipitating psychosocial stressors. Previous North American studies have indicated that the rage attacks in TS patients are associated with the presence of comorbidities including ADHD and OCD (Freeman, 2007; Budman et al., 2000). However, this association was not found in a study of Japanese TS patients (Kano et al., 2008) and remains to be confirmed. In addition, impulse control disorders characterized by significant difficulties in controlling urges to perform rewarding behavior were frequently found to be comorbid in adults with TS, and the most common one was intermittent explosive disorder whose main symptoms are rage attacks (Frank et al., 2011).
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Global functioning is impaired to a much greater degree in TS patients with comorbidities than in those without, and comorbid ADHD and OCD in particular have been associated with poorer global or psychosocial functioning (Gorman et al., 2010; Lebowitz et al., 2012; Pringsheim et al., 2009). Several studies have suggested that OCS may have a slightly greater effect than ADHD on the symptomatology of TS, including tics (Cardona et al., 2004; Kano et al., 2010b). All of these studies have focused on the overall impact of ADHD rather than impulsivity, including impulse control problems such as rage attacks. Therefore, it remains to be clarified how tics, OCS, and impulsivity collectively interfere with the global functioning of TS patients. When considering the impact of OCS on global functioning among TS patients, recent research findings indicate that a dimensional approach for examining OCS should be considered. Factor analytic studies using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) have suggested that OCS among patients with OCD can be divided into 3–5 dimensions, and genetic, neuroimaging, and treatment studies have supported the usefulness of this approach (Stewart et al., 2007; Bloch et al., 2008). In addition, a relationship has been found between comorbid tic disorders and the symmetry/ordering (Labad et al., 2008) and aggressive/checking (Nikolajsen et al., 2011) dimensions of OCS among OCD patients. Furthermore, research on OCS dimension phenotypes among TS families has indicated that both the aggression/checking and symmetry/ordering dimensions were correlated within families (Leckman et al., 2003). We investigated the relationships between tics, OCS, and impulsivity, and their effects on global functioning among Japanese TS patients. We formulated hypotheses focused on compulsivity and impulsivity, as they are important components of Obsessive–compulsive spectrum disorders including TS (Berlin and Hollander, 2014). Learning more about these relationships seems to be important for both understanding the pathogenesis and improving the treatment. We expected to find that OCS and impulsivity each affect global functioning independently, and also when combined with tics, and that the impact of OCS on global functioning is the same or greater than that of impulsivity. We also expected to find that the aggression and symmetry dimensions of OCS would have a greater effect on global functioning than other dimensions.
ordinal scales, and a total tics score is obtained by summing the individual scores (0–50). The current impairment due to tics was also assessed (0–50). The global severity score was determined (0–100) as the sum of the total tics score and the impairment score. Additionally, tics were assessed on the basis of clinical observations and a review of the patients' medical records. Clinicians carefully investigated both the current and historical presence of tics and related symptoms such as coprolalia, which refers to the utterance of social unacceptable words, and SIB, which is the deliberate, repetitive infliction of self-harm.
2. Methods
2.2.5. Medication and comorbidities Information on medication was collected from the patients' psychiatrists and the medical records. Comorbid OCD and ADHD were diagnosed on the basis of DSM-IV-TR criteria, as in the case of TS.
2.1. Subjects Subjects were recruited from a specialty clinic that treats people with TS and related disorders at the Department of Child Psychiatry of the University of Tokyo Hospital during the period from February 2005 to February 2010. Subjects were included if they had a Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Tourette's disorder (American Psychiatric Association, 2000). They were excluded if they had mental retardation, autistic disorder, or any neurological disorder that could interfere with the quality of the interviews. Diagnoses were made according to DSM-IV-TR criteria by expert child psychiatrists, with a high diagnostic concordance rate. This study was approved by the Institutional Review Board of the University of Tokyo Hospital. The subjects signed informed consent forms after the study was explained to them in detail and they were assured that the decision to participate in the study would not affect their treatment in any way. If the subjects were 19 years old or younger, written informed consent was obtained from parents. All interviews were conducted by psychologists who had in-depth knowledge of the instruments, clinical experience with TS, and no involvement with the treatment of the subjects, after training to ensure conformity of assessment.
2.2.2. Assessment of OCS Current OCS were evaluated using the Dimensional Y-BOCS (DY-BOCS), a rating scale developed for assessing the presence and severity of specific OCS dimensions (Rosario-Campos et al., 2006). According to the DY-BOCS, OCS were divided into six dimensions: (1) obsessions about harm due to injury, violence, aggression, or natural disasters, and related compulsions (aggression); (2) sexual and religious obsessions and related compulsions (sexual/religious); (3) obsessions and compulsions related to symmetry, ordering, counting, and arranging (symmetry); (4) contamination obsessions and cleaning compulsions (contamination); (5) obsessions and compulsions related to hoarding and collecting (hoarding); and (6) miscellaneous obsessions and compulsions (miscellaneous). The severity of each dimension was measured on three ordinal scales with six anchor points that focus on symptom frequency (0–5), the amount of distress caused (0–5), and the degree to which they interfered with functioning (0–5) during the week before examination. Global OCS severity was estimated via the same three ordinal scales. The overall level of current impairment due to OCS (0–15) was assessed for all patients. The total global score (0–30) was obtained by combining the sum (0–15) of the global severity scores for the frequency, distress, and interference, with the impairment scores (0–15). The Japanese version was designed using a rigorous methodology involving translation and back translation, and its validity and reliability were re-examined in a preliminary study (Kano et al., 2006).
2.2.3. Assessment of impulsivity Current impulsivity was evaluated using the Japanese version of the Impulsivity Rating Scale (IRS) (Lecrubier et al., 1995). The IRS is a semi-structured interviewbased scale of seven items with four anchor points (0–3). The sum of the seven scores represents the global score (0–21). The Japanese version was designed using a rigorous methodology involving translation and back translation, and the validity and reliability of the original version were established.
2.2.4. Assessment of global functioning Current global functioning was evaluated using the Global Assessment of Functioning (GAF) scale (American Psychiatric Association, 2000).
2.3. Data analysis Statistical analyses were performed using SPSS software version 18.0. To examine the interrelationships between the clinical indicators of tics, OCS, impulsivity, and global functioning, Pearson's correlation coefficients were calculated. A 0.05 level of significance was selected. To examine the effects of tics, OCS, and impulsivity on global functioning, stepwise multiple regression analyses were performed with the GAF score as the dependent variable. If the p-Value was less than 0.05, the corresponding independent variable was entered into the model, and if it exceeded 0.10, the corresponding independent variable was removed from the model. When an additional analysis, based on stratification by age, was performed, a t-test was used to compare the two groups with 0.05 as the significance level.
3. Results 2.2. Instruments 2.2.1. Assessment of tics The presence and severity of tics were evaluated for the current study using the Japanese version of the Yale Global Tic Severity Scale (YGTSS) (Leckman et al., 1989). This version has previously been proven valid and reliable (Inoko et al., 2006). On this scale, motor and vocal tics are evaluated separately (0–25) on five
Of the 68 patients invited to participate in this study, 58 agreed. Finally, 53 TS patients (40 men and 13 women) were included (age range, 5–43 years; mean ¼ 17.6; standard deviation (S.D.) ¼9.2). No significant difference in demographic findings was found between the 58 subjects who agreed to participate and the 10 who did not.
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Table 1 Demographic and clinical characteristics of the subjects (n¼ 53). Age, in years, mean (S.D.; range) Age at tic onset, years, mean (S.D.; range) Age on the first visit, years, mean (S.D.; range) Age at the worst ever period, years, mean (S.D.; range) Gender, male n (%) YGTSS scores: Total tic, mean (S.D.; range) Impairment, mean (S.D.; range) Global severity, mean (S.D.; range) DY-BOCS scores: Total OCS, mean (S.D.; range) Impairment, mean (S.D.; range) Global severity, mean (S.D.; range) Aggression, mean (S.D.; range) Sexual/religious, mean (S.D.; range) Symmetry, mean (S.D.; range) Contamination, mean (S.D.; range) Hoarding, mean (S.D.; range) Miscellaneous, mean (S.D.; range) IRS score, mean (S.D.; range) GAF score, mean (S.D.; range)
17.6 6.1 15.5 13.9 40
Table 2 Correlations between tics, OCS, impulsivity, and global functioning. (9.2; 5–43) (2.4; 2–12) (8.2; 5–38) (7.0; 5–34) (75)
26.5 (8.2; 0–45) 26.0 (10.3; 0–50) 52.5 (16.4; 0–85) 4.6 3.9 8.5 1.9 1.0 2.0 1.7 0.5 2.5 5.0 57.4
(3.8; 0–12) (3.6; 0–13) (7.3; 0–25) (3.0; 0–12) (2.4; 0–9) (2.9; 0–12) (3.3; 0–12) (1.5; 0–8) (3.4; 0–12) (3.6; 0–14) (9.7; 36–84)
YGTSS global severity YGTSS total 0.855nn tics YGTSS global severity DY-BOCS total OCS DY-BOCS global severity IRS
DY-BOCS total OCS
DY-BOCS IRS global severity
GAF
0.364nn
0.319n
0.231† 0.312n
0.302n
0.245†
0.115
0.441nn
0.981nn
0.187
0.422nn
0.245† 0.434nn
0.217
Pearson's correlation coefficients. † n
p o 0.1. p o 0.05. p o 0.01.
nn
Table 3 OCS dimensions and correlations with tics, impulsivity and global functioning.
3.1. Description of tics, OCS, impulsivity, global functioning, pharmacotherapy, and comorbidities
Correlation with OCS dimension YGTSS total tics
The age at onset of tics averaged 6.1 years (S.D. ¼ 2.4) (Table 1). The mean age on the first visit to the clinic was 15.5 years (S.D. ¼8.2). The mean age at which the episode of tics was the worst ever was 13.9 years (S.D. ¼ 7.0). Coprolalia was found in 13 subjects (25%) as a current symptom and in 26 subjects (49%) as a lifetime symptom. SIB was found in eight subjects (15%) as a current symptom and in 23 (43%) as a lifetime symptom. The mean current scores on the YGTSS were 26.5 (S.D. ¼8.2) for total tics, 26.0 (S.D. ¼10.3) for impairment due to tics, and 52.5 (S.D. ¼16.4) for global severity. Of the 53 subjects included in the study, 44 (83%) had current OCS. The mean current DY-BOCS scores were 4.6 (S.D. ¼3.8) for total OCS, 3.9 (S.D. ¼ 3.6) for impairment, and 8.5 (S.D. ¼7.3) for global severity. The miscellaneous dimension showed the highest mean DY-BOCS dimensional score of 2.5 (S.D. ¼3.4), followed by the symmetry dimension (mean ¼2.0; S.D. ¼2.9), and the aggression dimension (mean¼1.9; S.D.¼ 3.0). The mean IRS score was 5.0 (S.D. ¼3.6), and the mean GAF score was 57.4 (S.D. ¼9.7). Forty-four subjects (83%) were taking some kind of psychotropic drug, of which 40 were on antipsychotics (risperidone, 12 subjects; pimozide and haloperidol, nine subjects each). Other drugs were being used by 26 subjects (antidepressants, 13 subjects; clonidine, six subjects; anxiolytics, four subjects; mood stabilizers, four subjects). According to the DSM-IV-TR criteria, 15 (28%) subjects had comorbid OCD and 8 (15%) had comorbid ADHD as a lifetime diagnosis. 3.2. Correlations between tics, OCS, and impulsivity The YGTSS total tics scores were significantly and positively correlated with the DY-BOCS total OCS scores (r ¼0.364, p ¼0.007) (Table 2). In terms of global severity, including impairment due to tics and OCS, the correlation between the YGTSS and DY-BOCS scores did not reach statistical significance (r ¼0.245, p ¼0.077). IRS scores were not significantly correlated with either the YGTSS or DY-BOCS scores. When the correlations between the 6 DY-BOCS dimensional scores and the YGTSS and IRS scores were examined, the DY-BOCS
Aggression Sexual/religious Symmetry Contamination Hoarding Miscellaneous
n
0.318 0.368nn 0.356nn 0.189 0.177 0.212
YGTSS global severity
IRS
GAF
0.223 0.310n 0.319n 0.228 0.123 0.111
0.014 0.013 0.038 0.211 0.291n 0.111
0.297n 0.225 0.218 0.254† 0.075 0.239†
Pearson's correlation coefficients. †
p o 0.1. p o 0.05. nn p o 0.01. n
dimensional scores for aggression, sexual/religious, and symmetry dimensions were found to be significantly and positively correlated with the YGTSS total tics scores (r ¼0.318, 0.368, and 0.356, respectively), although the aggression dimension scores were not significantly correlated with the YGTSS global severity scores (r ¼0.223) (Table 3). When the correlation between the DY-BOCS dimensional scores and the IRS scores was examined, only the hoarding dimension scores were found to have a significant positive correlation (r ¼0.291). 3.3. Relationships between tics, OCS, and impulsivity, and global functioning 3.3.1. Correlation coefficients Although GAF scores were significantly and negatively correlated with YGTSS total tics scores (r ¼ 0.312, p ¼0.023) and DYBOCS total OCS scores (r ¼ 0.422, p ¼0.002), they were not significantly correlated with IRS scores (Table 2). Among the 6 DY-BOCS dimensional scores, only those of the aggression dimension had a significant negative correlation with GAF scores (r ¼ 0.297, p ¼0.031) (Table 3). 3.3.2. Multiple regression analysis When YGTSS total tics scores, DY-BOCS total OCS scores, and IRS scores were entered into the initial regression model as independent variables, the YGTSS and IRS scores had to be removed from the model, and only the DY-BOCS scores showed a significant association with GAF scores (B ¼ 1.083, t ¼ 3.324, p ¼0.002) (Table 4). When YGTSS global severity scores, DY-BOCS global
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Table 4 Impact of tics, OCS and impulsivity on global functioning (multiple regression analysis).
Model 1 DY-BOCS total OCS score Model 2 YGTSS global severity score DY-BOCS global severity score Model 3 YGTSS impairment score DY-BOCS impairment score Model 4 Dimensional score of “Aggression”
R2adj
B
β
t
1.083
0.422
3.324
0.002
0.212 0.463
0.356 0.346
2.933 2.852
0.005 0.006
0.403 1.064
0.424 0.397
3.744 3.509
o 0.001 0.001
0.960
0.297
2.219
0.031
p
0.162 0.279
0.337
0.070
B: regression coefficient, β: standardized regression coefficient, R2adj: adjusted multiple coefficient of determination.
severity scores, and IRS scores were entered into the initial regression model as independent variables, IRS scores had to be removed from the model, and YGTSS (B ¼ 0.212, t¼ 2.933, p ¼0.005) and DY-BOCS scores showed a significant association with GAF scores (B ¼ 0.463, t ¼ 2.852, p ¼0.006). When YGTSS total tic scores, YGTSS impairment scores, DY-BOCS total OCS scores, DY-BOCS impairment scores, and IRS scores were entered into the initial regression model as independent variables, YGTSS impairment (B¼ 0.403, t ¼ 3.744, p o0.001) and DY-BOCS impairment scores showed a significant association with GAF scores (B ¼ 1.064, t¼ 3.509, p ¼0.001). When the 6 DY-BOCS dimensional scores were entered into the initial regression model as independent variables, only the score for the aggression dimension remained in the model and was significantly associated with GAF scores (B ¼ 0.960, t ¼ 2.219, p ¼0.031). 3.4. Analysis based on stratification by age As the subjects' ages were widely distributed, and the severity of tics is thought to start declining by adulthood in a large proportion of TS patients, we divided them into two groups: 17 years old or younger (younger group; six girls and 27 boys) and 18 years old or older (older group; 7 women and 13 men). The younger and older group data were subjected to the same statistical analyses as those that were performed for the entire sample of subjects. 3.4.1. Description of tics, OCS, impulsivity, global functioning, and pharmacotherapy The mean age at tic onset, mean age at the first visit, and mean age during the worst-ever period were significantly higher for the older group than for the younger group. There was no significant difference between the two groups for any scores except the DYBOCS dimension scores. The aggression, symmetry, and miscellaneous dimension scores were significantly higher for the older group than the younger group (p ¼0.008, p ¼0.043, p ¼0.037, respectively). Twenty-five (76%) in the younger group and 19 (95%) in the older group were on medication. 3.4.2. Correlations between tics, OCS, and impulsivity For the younger group, there was a significant positive correlation between YGTSS total tics scores and DY-BOCS total OCS scores (r ¼ 0.426, p¼ 0.013). IRS scores were significantly correlated with YGTSS and DY-BOCS scores (r ¼0.504, p ¼0.003 for total tic scores; r ¼0.372, p ¼0.033 for YGTSS global severity scores; r ¼0.411, p ¼0.017 for OCS scores; r¼ 0.457, p ¼ 0.007 for DY-BOCS global severity scores). Of the 6 DY-BOCS dimensional scores, only those of the symmetry dimension were significantly correlated with YGTSS total tic scores and global severity scores (r ¼0.409,
p¼ 0.018; r ¼0.379, p ¼0.030, respectively). There was no significant correlation between dimensional scores and IRS scores. For the older group, there was no significant correlation between any scores. 3.4.3. Relationships between tics, OCS, and impulsivity with global functioning In the younger group, GAF scores were significantly and negatively correlated with DY-BOCS OCS scores, global severity scores (r ¼ 0.602, p o0.001; r¼ 0.614, p o0.001, respectively), and IRS scores (r ¼ 0.486, p ¼0.004). Among the 6 DY-BOCS dimensional scores, those of sexual/religious, symmetry, and miscellaneous dimensions were significantly and negatively correlated with GAF scores (r ¼ 0.384, p¼ 0.028; r ¼ 0.352, p¼ 0.044; r ¼ 0.404, p ¼0.020, respectively). In multiple regression analysis, when YGTSS total tics scores, DY-BOCS total OCS scores, and IRS scores were entered into the initial regression model as independent variables, only DY-BOCS scores showed a significant association with GAF scores (B ¼ 1.421, t¼ 4.193, po 0.001). When the 6 DY-BOCS dimensional scores were entered into the initial regression model as independent variables, the scores for the symmetry and miscellaneous dimensions remained in the model and had a significant association with GAF scores (B ¼ 1.203, t¼ 2.216, p ¼0.034; B ¼ 1.239, t¼ 2.559, p¼ 0.016, respectively). For the older group, GAF scores were significantly and negatively correlated with only YGTSS global severity scores (r ¼ 0.515, p ¼0.020). No other significant correlation was found.
4. Discussion Based on data from the 53 TS patients, we examined the following hypotheses: that tics, OCS, and impulsivity affect global functioning; that the impact of OCS on global functioning is the same or greater than that of impulsivity; and that the aggression and symmetry dimensions of OCS have the greatest influence on global functioning. We also examined the prevalence of comorbidities and the relationships between tics, OCS, and impulsivity. The prevalence of OCD and any OCS was 28% and 83%, respectively. This high prevalence was comparable to that found in previous studies (Hounie et al., 2006; Freeman, 2007). On the other hand, the prevalence of ADHD was 15%, which is lower than that in previous studies (Freeman, 2007). Compared to those without ADHD, TS patients with ADHD might have hesitated more about participating in this study, which takes time to complete. When the interrelationships between tics, OCS, and impulsivity were examined, tic and OCS severity were moderately related to each other and were relatively independent of impulsivity. These findings may be compatible with those of a previous study that did not find a significant difference in tic severity and comorbid OCD
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prevalence among TS patients with and without clinically significant aggressive symptoms (Kano et al., 2008). An examination of the impact of tics, OCS, and impulsivity on global functioning for all subjects showed that as the severity of tics and OCS increased, the global functioning of the patients worsened. Multiple regression analysis revealed that OCS had the greatest impact of all. The quantitative assessment of the symptomatology of TS conducted in this study seems to replicate findings from previous studies (Freeman, 2007): patients with TS and comorbidities have lower global functioning than those with TS alone. Our results are consistent both with our hypotheses and previous studies suggesting that comorbid OCS may have a greater effect on the symptomatology of TS than ADHD symptoms (Cardona et al., 2004; Kano et al., 2010b) and that OCS has more widespread effects on quality of life than ADHD (Eddy et al., 2012). However, several recent studies have suggested that both OCS and ADHD symptoms might be related to quality of life, psychosocial and educational problems, or psychosocial stress among children with TS (Lebowitz et al., 2012; Bernard et al., 2009; Debes et al., 2010). Even after selecting the subjects in this study with an age similar to those in the above-mentioned studies, OCS rather than impulsivity showed a significant impact on global functioning. On the basis of the YGTSS scores and the prevalence of coprolalia, the number of patients with severe tics was expected to be higher in this study than in other recent studies (Pringsheim et al., 2009; Bernard et al., 2009). As TS patients with comorbid OCD are characterized by more severe tics (Lebowitz et al., 2012), the impact of OCS may tend to be emphasized among TS patients in this study who had severe tics more frequently than subjects in other studies. Even with these considerations, our hypothesis that OCS have the most impact on global functioning was supported. Using the dimensional approach to study OCS for all subjects revealed that OCS in the aggression dimension produced the greatest impairment in global functioning, as indicated by the results of both the correlation analysis and the multiple regression analysis. The aggression dimension severity scores were not significantly correlated with either YGTSS global severity scores or IRS scores. Therefore, the impact of this dimension, which represents obsessions and related compulsions about harm as opposed to aggressiveness, might be relatively independent of tics and impulsivity. When the subjects were stratified by age, the strong impact of the aggression dimension was not evident. In the younger group, the symmetry dimension showed a significant impact on global functioning. In our previous study on TS patients, the difference between the worst ever and the current ratings for OCS dimensions was the smallest for the aggression dimension and was much lower than that for the symmetry dimension (Kano et al., 2010a). This finding suggests that the aggression dimension might have a sustained effect on global functioning throughout development and that the impact of the symmetry dimension might diminish over the course of development. A recent study of children and adolescents with OCD has indicated that high scores on the aggressive/checking dimension, derived from the Children's Yale–Brown Obsessive–Compulsive Scale (CY-BOCS), were associated with comorbid tic disorders (Nikolajsen et al., 2011). It has been suggested that the aggression dimension is not only associated with TS but also plays an important role in the global functioning of TS patients. This study has several limitations. Firstly, the number of the subjects was small, and they were recruited from a specialty clinic, resulting in referral bias. The subjects differed greatly in terms of age, tic severity, and pharmacotherapy. Although we analyzed the data according to age, the sample size of these subgroups may have been too small to justify the conclusions. In future research, we would like to conduct a study with a larger number of subjects,
wherein we can examine symptomatology and global functioning with the appropriate stratification for age and tic severity. The influence of current and lifetime pharmacotherapy should be examined. Secondly, as children and parents may be unlikely to share similar views about the impact of TS (Cavanna et al., 2013), more deliberate consideration about data from the younger group might be needed. Thirdly, further consideration regarding the assessment of impulsivity is necessary. The IRS is an interviewbased quantitative assessment tool that is applicable to a wide range of ages. Of the seven items in the IRS, irritability, aggressiveness, and control of responses are likely to relate more closely to impulse control problems such as rage attacks and SIB than the remaining items; however, the differentiation between them is arbitrary. Therefore, we used the IRS score by summing the seven items. ADHD symptoms such as inattention, hyperactivity, and impulsivity were not assessed independently. Impulsivity should be evaluated in future studies by focusing on impulse control problems as well as overall ADHD symptoms. Despite these limitations, to the best of our knowledge, ours is the first study to investigate the impact of tics, OCS, and impulsivity on global functioning using the dimensional approach for OCS among Japanese TS patients. The findings suggest the importance of the dimensional approach for correctly analyzing global functioning.
Acknowledgments The present study was partly supported by a Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H17004), Comprehensive Research on Disability, Health and Welfare (H20-006 and H22-004), Research Grant for Nervous and Mental Disorders (17A-2 and 20B-6), and an Intramural Research Grant (23-1) for Neurological and Psychiatric Disorders of NCNP, all from the Ministry of Health, Labour and Welfare, Japan. Further support was received from a Grant of Project Research from Kitasato University and Grant-in-Aid for Scientific Research on Innovative Areas Grant number 26118704.
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