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Keywords:

  • dimensional approach;
  • neuropsychology;
  • obsessive–compulsive symptoms;
  • Tourette's syndrome;
  • Wisconsin Card Sorting Test

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

Aim:  Although inconsistencies in neuropsychological impairments in Tourette's syndrome (TS) have been discussed with respect to comorbid disorders, such as obsessive–compulsive disorder, few studies have focused on the specific dimensions of obsessive–compulsive symptoms (OCS) related to TS, such as aggression and symmetry. The aim of this study was to explore the impact of specific TS-related OCS on neuropsychological performance.

Methods:  A series of neuropsychological tasks examining attention and executive functioning were performed in groups of 33 TS participants and 18 healthy controls. The neuropsychological performance of TS with Aggression OCS (n = 11) were compared to TS without Aggression OCS (n = 22) and controls by using mancova controlling for age. In the same way as Aggression, we compared the performance of three groups by Symmetry: TS with Symmetry OCS (n = 14), TS without Symmetry OCS (n = 19) and controls.

Results:  TS participants with Aggression OCS tended to make more perseverative errors than those without. Global OCS severity and tic severity did not correlate with any neuropsychological performances. No significant differences were detected between TS participants with and without Symmetry OCS.

Conclusion:  Neuropsychological deficits in TS might be affected not by global OCS severity but by specific TS-related OCS.

TOURETTE'S SYNDROME (TS) is a chronic neurodevelopmental disorder with childhood onset characterized by motor tics and at least one vocal tic.1 Since TS is presumed to be related to dysfunction in frontal-striatal circuits,2 frontal dysfunctions in these circuits may lead to neuropsychological impairments.

However, the findings regarding cognitive impairments in TS are not unitary,3 which may be because of the heterogeneous characteristics of TS. Comorbidity is thought to be one of the factors contributing to such inconsistencies.4 Therefore, examining uncomplicated TS without comorbidities could be useful. It is suggested that uncomplicated TS is linked to mild impairments in certain inhibitory tasks.5 Although this approach has made a significant contribution, uncomplicated TS patients are rather rare (about 10%).3,6 This suggests that uncomplicated TS is only one of the subtypes of the disorder and does not explain TS as a whole. Ozonoff et al.4 suggested that a dimensional approach, such as those examining comorbidity or severity, might be more useful than a categorical approach.

Comorbid obsessive–compulsive symptoms (OCS) are commonly exhibited in TS: about 50% of those diagnosed with TS have prominent OCS.7 Also, OCS might affect neuropsychological aspects of TS.3,8,9 Numerous studies suggest that TS and obsessive–compulsive disorder (OCD) share a common dysfunction in frontal-striatal circuits,10 which is consistent with the idea that OCS and tics might be part of a spectrum.11 Therefore, we focused on the impact of OCS on neuropsychological performance.

OCS has distinctly heterogeneous clinical expressions. These clinically different symptoms were suggested to be associated with a distinct pattern of activation of neural regions.12 Therefore, different OCS contents should be associated with different aspects of neuropsychological deficits and some researches support this.13 Four symptom dimensions have been identified in factor analysis,14 two of which are associated with increased familial risk for OCD15 and TS.16 In those two dimensions associated with TS and OCD, the first dimension includes sexual and religious obsessions, and checking compulsions (which is labeled Aggression OCS in our study), and the second dimension includes symmetry and ordering obsessions and compulsions (which is labeled Symmetry OCS in our study). These symptoms are frequently observed in patients with TS.16,17 Therefore, we surmised that Aggression and Symmetry OCS must be related to TS and focused on the effect of these two types of OCS on neuropsychological tasks.

While few studies focused on neuropsychological aspects of Aggression and Symmetry OCS, some indicate indirectly that these two types of OCS might affect cognitive ability. Hartston and Swerdlow18 reported that abnormal performance patterns in visuospatial priming tasks were associated with these two types of OCS in OCD patients. Checking compulsions have also been examined with respect to impaired memory function19–21 and Milner-type errors on the Wisconsin Card Sorting Test (WCST).21 However, these studies did not focus on Aggression and Symmetry OCS separately. In addition, checking compulsions are inherently ambiguous and caused by different types of obsessions, including Aggression and Symmetry OCS.14,22 Therefore, we categorized checking compulsions according to the obsessions causing them.

As Aggression and Symmetry OCS are frequently seen in TS16,17 but have not been focused upon in previous research, an exploration of the effect of Aggression and Symmetry OCS on neuropsychological performance is warranted. Three neuropsychological tasks that examine executive functions and attention were utilized: the WCST, the Stroop Test, and the Continuous Performance Test (CPT).

The main purpose of this study was to investigate cognitive impairments in participants with TS with Aggression OCS and/or Symmetry OCS compared with TS participants without those OCS and with normal controls. We hypothesized that TS with Aggression OCS and/or Symmetry OCS would perform worse on some neuropsychological subsets than both TS without those OCS and normal controls.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

Subjects

Participants with TS (n = 33) were recruited from the outpatient clinic of the Department of Child Psychiatry at the University of Tokyo Hospital. All participants with TS met diagnostic criteria of the DSM-IV-TR for TS.1 Normal controls (n = 18) recruited were college students, hospital staff members, and their acquaintances and children. The exclusion criteria for all groups were neurological illness and alcohol/substance abuse or addiction. An additional exclusion criterion for the control group was a history of psychiatric disease. Participants with a full-scale intelligence quotient (IQ) < 70 on the Wechsler Intelligence Scale for Children-III23 or Wechsler Adult Intelligence Scale24 and outliers on neuropsychological tasks (mean scores ± 3SD) were excluded. The institutional ethics committee approved the study protocol. Written informed consent was obtained from adult subjects and the parents of participating children, and assent was obtained from the children. Five participants with TS had comorbid attention-deficit/hyperactivity disorder (ADHD) and seven participants with TS had comorbid OCD. These comorbid disorders were diagnosed by one of the authors, a well-trained child psychiatrist, according to DSM-IV-TR. Demographic and clinical characteristics of participants are shown in Table 1. Eight out of 33 patients had both Aggression and Symmetry OCS and 16 out of 33 had neither of them.

Table 1.  Clinical characteristics of patients with Tourette's syndrome (n = 33) and normal controls (n = 18)
 Tourette's syndromeNormal controlsStatisticsP
Mean ± SDMean ± SD
  • IQs of child TS participants and controls (age ≤ 15) were evaluated with the WISC-III. IQs of adolescent and adult TS participants and controls (age ≥ 16) were estimated by four subtests of the Wechsler Adult Intelligence Scale, except for one 16-year-old TS participant, who was evaluated with the WISC-III.

  • ADHD, attention-deficit/hyperactivity disorder; DY-BOCS, Dimensional Yale–Brown Obsessive–Compulsive Scale; NA, not applicable; OCD, obsessive–compulsive disorder; OCS, obsessive–compulsive symptoms; TS, Tourette's syndrome; WISC-III, Wechsler Intelligence Scale for Children; Y-BOCS, Yale–Brown Obsessive–Compulsive Scale; YGTSS, The Yale Global Tic Severity Scale.

Sex distribution (male: female)26:712:6χ2 = 0.900.34
Age (years)18.0 ± 9.315.4 ± 6.3t = −1.040.31
Full IQ score101.6 ± 14.3105.6 ± 7.8t = 1.110.27
Range74–14592–118  
YGTSS47.5 ± 15.3NA  
DY-BOCS6.7 ± 5.9NA  
Y-BOCS8.2 ± 7.8NA  
Duration of illness (years)8.8 ± 8.3NA  
Comorbidity    
 OCDn = 7 21%NA  
 ADHDn = 5 15%NA  
OCS    
 Harm, violence and aggressionn = 11 33%NA  
 Sexual and religiousn = 3 9%NA  
 Symmetry and countingn = 14 42%NA  
Medication at time of testing    
 Antidepressantn = 6 18%NA  
 Antipsychoticn = 25 76%NA  

Cognitive measures

WCST

The WCST measures abstraction and cognitive flexibility and has been found to be particularly sensitive to dorsolateral prefrontal cortex functioning.25 The WCST requires participants to discover criteria (color, shape, or number) based on feedback from the examiner. We calculated percentage of total errors made (TE), percentage of perseverative errors (PE), and percentage of cognitive level response (CLR: total number of consecutive correct responses in a sequence of three or more). The PE is thought to be linked to cognitive flexibility and the CLR suggests abstraction.26 Scores are reported as age-corrected t-scores based on published normative data, with higher scores indicating better performance.27

Stroop test

The Stroop test measures ability to inhibit the tendency to follow a dominant response.28 Two non-interference conditions were presented. Participants were first required to name the color of a series of circles (condition 1), then to name the color in which a series of non-color words were printed (condition 2), as quickly as possible. The interference trial was then presented. Participants were required to name the colors in which a series of color words were printed, instead of reading the words themselves (condition 3). Three interference scores were calculated: color–circle (response time of condition 1 subtracted from that of condition 3), color–non-color (response time of condition 2 subtracted from that of condition 3), color/circle (response time of condition 3 divided by that of condition 1).

CPT

Two conditions were presented: X task and AX task. X task required participants to respond to the number 7 while a series of numbers (1–9) were presented randomly. AX task required participants to respond to the number 7 only after the number 3.29 Two error types were calculated: omission (failed to respond to the target number) and commission (response to an irrelevant number). Omission errors are thought to be linked to poor attention, and commission errors, to impulsivity.

Clinical characteristics

Clinical characteristics in the analysis were age, duration of TS illness, tic severity measured by The Yale Global Tic Severity Scale (YGTSS),30 OCS severity, and OCS subtype. OCS severity and OCS subtypes were examined with the Dimensional Yale–Brown Obsessive–Compulsive Scale (DY-BOCS),22 a rating scale for assessing presence and severity of specific OCS dimensions. In the DY-BOCS, OCS are divided into six dimensions: aggression, sexual/religious, symmetry, contamination, hoarding, and miscellaneous. In the current study, we focused on three of the six dimensions, Aggression and Sexual/Religious dimensions for Aggression OCS, and Symmetry dimension for Symmetry OCS. We also used the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS)31 to measure OCD severity for 28 participants with TS. DY-BOCS and Y- BOCS correlated significantly (r = 0.78, P < 0.001).

Statistical analysis

Data were analyzed using spss version 18 (spss Inc, 2009, Chicago, IL, USA).

We first explored the effect of specific OCS on neuropsychological performance. We divided TS participants with Aggression OCS (n = 11) from those without Aggression OCS (n = 22). There were no significant differences in IQ, tic severity, or sex distribution between the two groups (P-values > 0.60). The TS with Aggression OCS group was older than the group without (TS with Aggression OCS, mean age = 23.4 years, SD = 11.0; TS without Aggression OCS, mean age = 15.1, SD = 7.2; P < 0.05), and had more severe global OCS scores on the DY-BOCS than the group without (TS with Aggression OCS, mean score = 11.3, SD = 5.2; TS without Aggression OCS, mean score = 5.0, SD = 5.5; P < 0.05). We then compared the performance of the three groups: TS with and without Aggression OCS and controls (n = 18). mancova was conducted using groups as the independent variable, age as covariate, and performance on neuropsychological subsets as dependent variables. We also conducted a similar mancova controlling for age between the three groups: TS with Symmetry OCS (n = 14), TS without Symmetry OCS (n = 19), and controls (n = 18). There were no significant differences in IQ, tic severity, or sex distribution between groups with and without Symmetry OCS (P-values > 0.27), but the TS with Symmetry OCS group were older than those without (TS with Symmetry OCS, mean age = 21.7 years, SD = 10.0; TS without Symmetry OCS, mean age = 14.7 years, SD = 7.6; P < 0.05), and had higher global OCS scores on the DY-BOCS than the group without (TS with Symmetry OCS, mean score = 9.5, SD = 5.8; TS without Symmetry OCS, mean score = 5.1, SD = 5.7; P < 0.05).

Next, we explored the effect of clinical characteristics on neuropsychological performance. Pearson's correlation coefficients were calculated between demographical/clinical characteristics and neuropsychological performance within TS participants or normal controls. After controlling their ages, we conducted partial correlation analysis between clinical characteristics and neuropsychological performance within TS participants.

P-values < 0.05 were considered significant for mancova and correlation analysis. P-values < 0.0083 were considered significant for multiple comparisons in order to avoid type I errors caused by multiple comparisons for three groups and conducting the mancova twice.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

Effects of specific OCS dimensions

Table 2 summarizes the group mean performance and statistical comparisons for each task.

Table 2.  Performance on neuropsychological subsets
 NC (n = 18)Agg − (n = 22)Agg + (n = 11)FPComparison
Mean ± SDMean ± SDMean ± SD
  1. Agg −, Tourette's syndrome participants without Aggression obsessive–compulsive symptoms; Agg +, Tourette's syndrome participants with Aggression obsessive–compulsive symptoms; CLR, conceptual level response rate; NC, normal controls; NS, not significant; PE, perseverative errors made; TE, total errors made.

TE56.9 ± 5.550.3 ± 8.742.0 ± 12.07.80.001NC >, Agg+
PE54.9 ± 6.250.3 ± 7.839.7 ± 9.99.90.001NC, Agg– > Agg+
CLR56.7 ± 5.350.1 ± 8.941.6 ± 11.58.40.001NC > Agg+
Color–circle5.9 ± 5.16.8 ± 4.48.8 ± 6.20.80.470NS
Color–non-color3.7 ± 4.13.5 ± 4.56.8 ± 5.11.00.359NS
Color/circle1.4 ± 0.41.5 ± 0.41.6 ± 0.40.70.495NS
Commission (X)0.7 ± 1.31.6 ± 3.51.1 ± 2.10.80.465NS
Omission (X)1.0 ± 1.94.0 ± 9.50.3 ± 0.51.20.324NS
Commission (AX)1.5 ± 1.52.4 ± 4.33.0 ± 5.22.20.126NS

Results of mancova controlling for age and comparing TS groups with and without Aggression OCS and controls showed the effect of group was significant (Wilks-λ = 0.49, F(18,78) = 1.9, P = 0.03). Comparison between groups showed that main effects of group on WCST were significant (TE: F(2,48) = 7.80, P = 0.001; PE: F(2,48) = 9.93, P < 0.001; CLR: F(2,48) = 8.38, P = 0.001). TS participants with Aggression OCS performed poorer than controls on t-scores of TE, PE, and CLR on the WCST (P < 0.001 for all) and performed poorer than TS participants without Aggression OCS on PE t-score on the WCST (P = 0.003). The effect sizes of difference between TS groups with and without Aggression OCS on three scores of WCST are d = 0.92(TE), d = 1.25(PE), and d = 0.95(CLR). No significant main effects of group were detected on CPT and Stroop test.

The second mancova with three groups of TS with and without Symmetry OCS and controls showed no significant main effects of groups (Wilks-λ = 0.63, F(18,78) = 1.1, P = 0.34). The effect sizes of difference between TS groups with and without Symmetry OCS on three scores of WCST were d = 0.36(TE), d = 0.54(PE), and d = 0.34(CLR).

Correlation analysis

Correlations between clinical characteristics and neuropsychological performance in TS participants are shown in Table 3.

Table 3.  Pearson's correlation coefficients between clinical and neuropsychological variables within TS participants
 AgeDuration of illnessYGTSSDY-BOCSY-BOCSAggressionSymmetry
OCSOCS
  • *

    P < 0.05.

  • CLR, conceptual level response rate; DY-BOCS, Dimensional Yale–Brown Obsessive–Compulsive Scale; OCS, obsessive–compulsive symptoms; PE, perseverative errors made; TE, total errors made; Y-BOCS, Yale–Brown Obsessive–Compulsive Scale; YGTSS, The Yale Global Tic Severity Scale.

TE−0.42*−0.45*−0.22−0.040.06−0.21−0.15
PE−0.36*−0.34−0.19−0.19−0.14−0.36*−0.30
CLR−0.42*−0.45*−0.15−0.050.09−0.22−0.16
Color-circle0.230.210.210.160.000.080.34
Color-non-color0.280.260.230.250.050.140.31
Color/circle0.190.180.220.13−0.07−0.010.31
Commission (X)−0.32−0.230.030.04−0.130.230.04
Omission (X)−0.35*−0.320.150.05−0.06−0.26−0.30
Commission (AX)−0.33−0.240.000.03−0.160.210.07

TS participants tended to perform worse on the WCST with advancing age (TE: r = −0.42, PE: r = −0.36, CLR: r = −0.42; d.f. = 31, P < 0.05 for all) and duration of illness (TE: r = −0.45, CLR: r = −0.45; d.f. = 31, P < 0.05 for both), whereas the controls' scores on the neuropsychological subsets did not correlate with their ages. In contrast, both TS participants and controls made fewer errors on CPT with advancing age as evidenced by negative correlations between age and omission errors on the X task on CPT in TS (r = −0.35, d.f. = 31, P < 0.05) and commission errors on the AX task on CPT in controls (r = −0.47, d.f. = 31, P < 0.05).

DY-BOCS severity score for aggression dimension negatively correlated significantly with PE t-scores on the WCST (r = −0.36, d.f. = 31, P < 0.05). No significant correlations were found between other clinical characteristics (YGTSS, DY-BOCS, and Y-BOCS) and neuropsychological subsets in TS participants (P > 0.10). After controlling their ages, correlation between DY-BOCS severity score for aggression dimension and PE t-scores on WCST was not significant.

ADHD effect

After five TS participants with ADHD were excluded, the same analysis on all experimental tasks was conducted. The main findings of the study did not change after this exclusion. TS participants with Aggression OCS performed worse than controls on TE, PE, and CLR on the WCST (P < 0.001 for all) and performed worse than TS participants without Aggression OCS on PE on the WCST (P = 0.006). Correlations between Aggression OCS and WCST PE score (r = −0.39, d.f. = 26, P < 0.05) and correlations between age and each WCST (TE: r = −0.49, PE: r = −0.48, CLR: r = −0.49; d.f. = 26, P < 0.01, for all) were also still significant.

Medication effect

After six TS participants taking antidepressants were excluded, the same analysis on all experimental tasks was conducted, which showed that the main findings of the study did not change after this exclusion. Also, after eight TS participants who were not taking antipsychotics were excluded, the main findings of the study did not change.

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

The main finding in the current study is that TS participants with Aggression OCS made more perseverative errors than controls and TS participants without Aggression OCS, while no differences in any neuropsychological subsets were seen between TS with and without Symmetry OCS. Total tic severity score and global OCS severity scores did not correlate with any neuropsychological performance.

The finding that tic severity scores did not correlate with WCST performance aligns with previous studies that reported intact performance on the WCST in TS.3,32 In this study, global OCS severity scores were not associated with impaired performance on the WCST in TS. Instead, TS participants with Aggression OCS made more perseverative errors on the WCST, indicating that it was not global OCS severity but specific OCS that were related to impaired set-shifting ability. The results of previous studies that examined cognitive flexibility in OCD and TS compared with normal controls are inconsistent.3,33 So far, these inconsistencies have been discussed in the context of OCS severity.9,33 The current study, however, suggested that these results were not due to global OCS severity, but to specific dimension OCS, especially Aggression OCS.

Whereas previous studies indicated that checking compulsions are related to impaired memory ability19–21 and cognitive flexibility21 in OCD, the current study indicated that Aggression OCS in TS is related to impaired cognitive flexibility, regardless of the presence of checking compulsions. Aggression OCS would have different characteristics from other OCS, both etiologically34 and clinically.35,36 For example, the violence/aggression-dimension OCS have been associated with early onset OCD.34 Also, aggressive obsessions were reported more frequently in OCD patients with major depression compared to those without major depression.35 Furthermore, TS patients with aggression-dimension OCS had lower Global Assessment of Functioning scores and higher frequencies of coprolalia.36 The current study supposed that these clinical difficulties related to Aggression OCS might be partly due to cognitive inflexibility. No significant effects of Symmetry were seen in the current study, which might suppose a closer connection between Aggression OCS and cognitive dysfunction than those with Symmetry OCS.

TS participants tended to perform worse on the WCST with advancing age and duration of illness, while no age effect was found in the control group. As Aggression OCS were more frequent in older TS participants, this difference between TS and controls might be partly due to Aggression OCS.

In contrast to WCST performance, there were no effects of groups on the Stroop test and CPT, indicating that TS participants in the current study had ordinary attention and impulse-control abilities and ordinary ability to inhibit dominant responses.

Although the current study has some important implications, several limitations must be considered.

First, only preliminary examinations of the validity and reliability of the Japanese version of the DY-BOCS were completed,36 although the Japanese version of the DY-BOCS had good criterion-related validity with Y-BOCS in the current study.

A second limitation is that there existed overlap between Aggression OCS and Symmetry OCS. As effect sizes of differences on mancova implied that Aggression OCS related more strongly to cognitive impairments on WCST than Symmetry OCS, an interaction effect of Aggression OCS and Symmetry OCS was not considered.

A third limitation relates to the small number of participants and wide age distribution. In particular, TS participants with Aggression OCS tended to be older than those without Aggression OCS. While the difference between TS with and without Aggression OCS was significant after controlling for the effect of age, further studies with larger samples and age-matched comparisons between TS with and without Aggression and/or Symmetry OCS are needed.

In summary, TS participants with Aggression OCS made more perseverative errors than TS without Aggression OCS, while no differences in any neuropsychological subsets were seen between TS with and without Symmetry OCS. This indicates that it would be fruitful to examine specific OCS related to TS in order to explore heterogeneous aspects of TS.

ACKNOWLEDGMENT

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES

The present study was partly supported by a Grant for Research on Psychiatric and Neurological Disease and Mental Health (H17-004), Comprehensive Research on Disability, Health and Welfare (H20-006), a Research Grant for Nervous and Mental Disorders (17A-2 and 20B-6), all from the Ministry of Health, Labour and Welfare, and Grant of Project Research from Kitasato University. There are no conflicts of interest to disclose.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. REFERENCES
  • 1
    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th Ed, Text Revision) (DSM-IV-TR). APA, Washington, DC, 2000.
  • 2
    Marsh R, Maia TV, Peterson BS. Functional disturbances within frontostriatal circuits across multiple childhood psychopathologies. Am. J. Psychiatry 2009; 166: 664674.
  • 3
    Eddy CM, Rizzo R, Cavanna AE. Neuropsychological aspects of Tourette syndrome: a review. J. Psychosom. Res. 2009; 67: 503513.
  • 4
    Ozonoff S, Strayer DL, McMahon WM, Filloux F. Inhibitory deficits in Tourette syndrome: a function of comorbidity and symptom severity. J. Child Psychol. Psychiatry 1998; 39: 11091118.
  • 5
    Channon S, Robertson MM, Orth M, Crawford S. Tourette's syndrome (TS): inhibitory performance in adults with uncomplicated TS. Neuropsychology 2009; 23: 359366.
  • 6
    Khalifa N, von Knorring AL. Tourette syndrome and other tic disorders in a total population of children: clinical assessment and background. Acta Paediatr. 2005; 94: 16081614.
  • 7
    Hounie AG, do Rosario-Campos MC, Diniz JB et al. Obsessive-compulsive disorder in Tourette syndrome. Adv. Neurol. 2006; 99: 2238.
  • 8
    Muller SV, Johannes S, Wieringa B et al. Disturbed monitoring and response inhibition in patients with Gilles de la Tourette Syndrome and co-morbid obsessive compulsive disorder. Behav. Neurol. 2003; 14: 2937.
  • 9
    Bornstein RA. Neuropsychological correlates of obsessive characteristics in Tourette syndrome. J. Neuropsychiatry Clin. Neurosci. 1991; 3: 157162.
  • 10
    Albin RL, Mink JW. Recent advances in Tourette syndrome research. Trends Neurosci. 2006; 29: 175182.
  • 11
    Hollander E, Kim S, Braun A, Simeon D, Zohar J. Cross-cutting issues and future directions for the OCD spectrum. Psychiatry Res. 2009; 170: 36.
  • 12
    Mataix-Cols D, Wooderson S, Lawrence N, Brammer MJ, Speckens A, Phillips ML. Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder. Arch. Gen. Psychiatry 2004; 61: 564576.
  • 13
    Nedeljkovic M, Kyrios M, Moulding R et al. Differences in neuropsychological performance between subtypes of obsessive-compulsive disorder. Aust. N. Z. J. Psychiatry 2009; 43: 216226.
  • 14
    Bloch MH, Landeros-Weisenberger A, Rosario MC, Pittenger C, Leckman JF. Meta-analysis of the symptom structure of obsessive-compulsive disorder. Am. J. Psychiatry 2008; 165: 15321542.
  • 15
    Alsobrook JP II, Leckman JF, Goodman WK, Rasmussen SA, Pauls DL. Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores. Am. J. Med. Genet. 1999; 88: 669675.
  • 16
    Leckman JF, Pauls DL, Zhang H et al. Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette syndrome. Am. J. Med. Genet. 2003; 116B: 6068.
  • 17
    Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. Brain 2000; 123: 425462.
  • 18
    Hartston HJ, Swerdlow NR. Visuospatial priming and stroop performance in patients with obsessive compulsive disorder. Neuropsychology 1999; 13: 447457.
  • 19
    Sher KJ, Frost RO, Kushner M, Crews TM, Alexander JE. Memory deficits in compulsive checkers: replication and extension in a clinical sample. Behav. Res. Ther. 1989; 27: 6569.
  • 20
    Sher KJ, Frost RO, Otto R. Cognitive deficits in compulsive checkers: an exploratory study. Behav. Res. Ther. 1983; 21: 357363.
  • 21
    Nakao T, Nakagawa A, Nakatani E et al. Working memory dysfunction in obsessive–compulsive disorder: a neuropsychological and functional MRI study. J. Psychiatr. Res. 2009; 43: 784791.
  • 22
    Rosario-Campos MC, Miguel EC, Quatrano S et al. The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS): an instrument for assessing obsessive-compulsive symptom dimensions. Mol. Psychiatry 2006; 11: 495504.
  • 23
    Japanese WISC-III Publication Committee. Nihonban WISC-III Chinou Kensahou (Japanese Wechsler Intelligence Scale for Children, 3rd Ed.). Nihon Bunka Kagakusha, Tokyo, 1998.
  • 24
    Shinagawa F, Kobayashi S, Fujita K, Maekawa H. Japanese Wechsler Adult Intelligence Scale-Revised. Nihon Bunka Kagakusha, Tokyo, 1990.
  • 25
    Lombardi WJ, Andreason PJ, Sirocco KY et al. Wisconsin Card Sorting Test performance following head injury: dorsolateral fronto-striatal circuit activity. J. Clin. Exp. Neuropsychol. 1999; 21: 216.
  • 26
    Everett J, Lavoie K, Gagnon JF, Gosselin N. Performance of patients with schizophrenia on the Wisconsin Card Sorting Test (WCST). J. Psychiatry Neurosci. 2001; 26: 123130.
  • 27
    Kongs SK, Thompson LL, Iverson GL, Heaton RK. WCST-64. PAR, Lutz, FL, 2000.
  • 28
    Golden CJ. Identification of brain disorders by the Stroop Color and Word Test. J. Clin. Psychol. 1976; 32: 654658.
  • 29
    Yamada S, Shirokizawa H, Sugano M et al. Effects of methylphenidate on the continuous performance test (CPT) of children with attention deficit-hyperactivity disorder. Jpn. J. Dev. Disabil. 2004; 26: 8591 (in Japanese).
  • 30
    Leckman JF, Riddle MA, Hardin MT et al. The Yale global tic severity scale: initial testing of a clinician-rated scale of tic severity. J. Am. Acad. Child Adolesc. Psychiatry 1989; 28: 566573.
  • 31
    Goodman WK, Price LH, Rasmussen SA et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch. Gen. Psychiatry 1989; 46: 10061011.
  • 32
    Bornstein RA, Yang V. Neurological performance in medicated and unmedicated patients with Tourette's disorder. Am. J. Psychiatry 2001; 148: 468471.
  • 33
    Chamberlain SR, Blackwell AD, Fineberg NA, Robbins TW, Sahakian BJ. The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. Neurosci. Biobehav. Rev. 2005; 29: 399419.
  • 34
    de Mathis MA, Diniz JB, Shavitt RG et al. Early onset obsessive-compulsive disorder with and without tics. CNS Spectr. 2009; 14: 362370.
  • 35
    Besiroglu L, Uguz F, Saglam M, Agargun MY, Cilli AS. Factors associated with major depressive disorder occurring after the onset of obsessive-compulsive disorder. J. Affect. Disord. 2007; 102: 7379.
  • 36
    Kano Y, Kono T, Shishikura K, Kuwabara H, Ohta M, do Rosario MC. Obsessive-compulsive symptom dimensions in Japanese Tourette syndrome subjects. CNS 2010; 15: 296303.