No announcement yet.

Study: Tourette Syndrome and Tic Severity Predictions

  • Filter
  • Time
  • Show
Clear All
new posts

  • Study: Tourette Syndrome and Tic Severity Predictions

    Blackwell Synergy

    Journal of Child Psychology and Psychiatry

    Volume 47 Page 551 - June 2006
    Volume 47 Issue 6

    Fine-motor skill deficits in childhood predict adulthood tic severity and global psychosocial functioning in Tourette's syndrome

    Michael H. Bloch1, Denis G. Sukhodolsky1, James F. Leckman1,2, Robert T. Schultz1,3

    Background: Most children with Tourette's syndrome (TS) experience a significant decline in tic symptoms during adolescence. Currently no clinical measures have been identified that can predict whose tic symptoms will persist into adulthood. Patients with TS have deficits on neuropsychological tests involving fine-motor coordination and visual-motor integration. We seek to determine if these neuropsychological tests are useful in predicting future symptom severity.

    Methods: Thirty-two children, aged 8?14, with TS underwent clinical evaluation and a focused neuropsychological testing battery consisting of the Purdue Pegboard, Beery Visual-Motor Integration (VMI) Test and the Rey-Osterreith Complex Figure Task (RCFT). A follow-up clinical assessment was performed on these children an average of 7.5 years later. Ordinal logistic regression analysis was used to correlate neuropsychological testing at Time 1 with tic severity, OCD severity and global psychosocial functioning at Time 2.

    Results: Poor performance with the dominant hand on the Purdue Pegboard test predicted worse adulthood tic severity and correlated with tic severity at the time of childhood assessment. Poor performance on the VMI and Purdue Pegboard tests (both dominant and non-dominant hand) also predicted worse adulthood global psychosocial functioning. None of the neuropsychological tests were useful in predicting the future course of OCD symptoms in TS patients.

    Conclusion: Fine motor skill deficits may be a predictor of future tic severity and global psychosocial function in children with TS. We hypothesize that performance on the Purdue Pegboard test may serve as a useful endophenotype in the study of TS and provide a rough measure of the degree of basal ganglia dysfunction present in TS patients.

    Tourette's syndrome (TS) is a childhood onset neuropsychiatric disorder that is characterized by the onset of both motor and vocal tics prior to the age of 18. Previous longitudinal studies of Tourette's syndrome have demonstrated that the tics of TS typically have an onset around the age of 5?6 and reach their worst-ever severity between the ages of 10?12 (Erenberg, Cruse, & Rothner, 1987; Leckman et al., 1998; Pappert, Goetz, Louis, Blasucci, & Leurgans, 2003). Approximately one-half to two-thirds of children with TS will then experience a substantial decrease or remission of tics during adolescence (Bloch et al., in press b; Leckman et al., 1998; Pappert et al., 2003). However, the continuation of tics into adulthood can have serious consequences that may include self-injurious tics and those that cause social unease, such as coprolalia (Erenberg et al., 1987). Furthermore, approximately one-third of these children diagnosed with TS will develop clinically significant symptoms of obsessive-compulsive disorder (OCD) by adulthood (Bloch et al., in press b). These OCD symptoms may, on average, have a greater effect on the adulthood psychosocial functioning of children diagnosed with TS than the tics themselves (Erenberg et al., 1987). In this study we seek to address whether neuropsychological testing can be used to predict adulthood symptom severity in patients with TS.

    Previous studies have consistently demonstrated that both children and adults with TS have deficits on visual-motor integration (VMI) tasks such as Bender-Gesalt Test and the Beery Visual-Motor Integration Test when compared to normative data or normal controls (Brookshire, Butler, Ewing-Cobbs, & Fletcher, 1994; Lucas, Kauffman, & Morris, 1982; Schultz et al., 1998; Shapiro, Shapiro, & Clarkin, 1974; Shapiro, Shapiro, Bruun, & Sweet, 1978). Additionally, fine-motor coordination deficits in TS subjects have been demonstrated on both the grooved pegboard and Purdue Pegboard tests (Bornstein, 1991a, 1991b; Bornstein & Yang, 1991; Hagin, Beecher, Pagano, & Kreeger, 1982; Schultz et al., 1998). These VMI and fine-motor skill deficits in the original TS literature helped pinpoint the caudate nucleus, basal ganglia and fronto-cortico-striatal circuits as the neuroanatomical region of interest in TS research (Schultz, Carter, Scahill, & Leckman, 1999).

    Neuropsychological deficits have also been found in comorbid disorders commonly associated with TS. Patients with ADHD have consistently demonstrated deficits of executive function (Barkley, Grodzinsky, & DuPaul, 1992). TS patients with comorbid ADHD have deficits on copying and long-term recall of the Rey-Osterreith Complex Figure (RCFT) and excutive function tasks such as the Trail-making Test, the Hayling Test and Wisconsin Card Sorting Test when compared to TS patients without comorbid ADHD (Channon, Pratt, & Robertson, 2003; Harris et al., 1995; Schuerholz, Baumgardner, Singer, Reiss, & Denckla, 1996; Yeates & Bornstein, 1994). In neuropsychological studies, TS patients with comorbid ADHD are frequently treated as a separate study population (compared to TS patients without comorbid disease) (Schultz et al., 1998). Furthermore, co-occurring ADHD is significantly associated with deficits in psychosocial functioning in children with TS and OCD (Sukhodolsky et al., 2003, 2005). For these reasons we excluded all TS subjects with comorbid ADHD from this follow-up sample.

    Neuropsychiatric testing of adults with OCD has consistently demonstrated deficiencies in visual memory tasks such as immediate and delayed recall of the RCFT (Boone, Ananth, & Philpott, 1991; Savage, Baer, & Keuthen, 1995; Schultz, Evans, & Wolff, 1999). In OCD patients, poor performance on this task has been linked to encoding and retrieval deficits (Savage et al., 1999) and also been associated with reduction in the size of the left anterior orbitofrontal cortex on structural MRI studies (Choi et al., 2004).

    OCD patients have also demonstrated consistent deficits on oculomotor tests of response inhibition. Both adults with OCD and psychotropic-na?ve, newly diagnosed, non-depressed children with OCD have demonstrated deficits on oculomotor tests of response inhibition, but not for delayed response time or event anticipation, when compared to normal controls (Tien, Pearlson, Machlin, Bylsma, & Hoehn-Saric, 1992; Rosenberg et al., 1997). Furthermore, the proportion of errors on oculomotor tests of response inhibition correlated with OCD severity in the psychotropic-na?ve children with OCD (Rosenberg et al., 1997). OCD patients have also demonstrated deficits of response inhibition on Go-No/Go tasks (Malloy, Rasmussen, Braden, & Haier, 1989; Bannon, Gonsalvez, Croft, & Boyce, 2002). TS patients with comorbid OCD have similarly demonstrated an increased number of commission errors on Go-No/Go tasks compared to normal controls (Muller et al., 2003). By contrast, these same deficits on Go-No/Go tasks have not been found in TS patients without comorbid OCD (Serrien, Orth, Evans, Lees, & Brown, 2005). However, to our knowledge, no studies have directly compared response inhibition in TS patients with and without comorbid OCD.

    Our a priori hypotheses were that poor childhood VMI and Purdue Pegboard performance will be associated with worse childhood tic severity and predict increased adulthood tic severity in children with TS. Furthermore, we predicted that childhood deficits on RCFT will be associated with increased future OCD symptom severity in children with TS. In a set of exploration analyses, we examined how these measures correlate with tic severity at the time of neuropsychological examination and predict adulthood global psychosocial functioning.


    The 32 subjects included in this study were previously evaluated at the Yale Child Study Center Tic Disorder Clinic, had previously participated in MRI imaging studies (Peterson et al., 2001, 2003) and neuropsychological studies (Schultz et al., 1998) in childhood and their follow-up data were reported on in previous longitudinal studies (Bloch et al., in press b; Bloch, Leckman, & Peterson, in press a). Eligible subjects had: 1) a previous diagnosis of TS, 2) an MRI scan and detailed neuropsychological evaluation performed prior to age 14 (Time 1), and 3) they were older than age 16 at follow-up (Time 2). Exclusionary criteria in these earlier studies included a history of prior seizure, head trauma with loss of consciousness, ongoing or past substance abuse or an IQ below 80. A comorbid diagnosis of ADHD at Time 1 was an additional exclusion factor. The high comorbidity rate of ADHD among TS patients has been cited as a factor clouding our current understanding of the neuropsychological profile of TS (Schultz, Carter, Scahill, & Leckman 1999), hence these subjects were excluded from analysis.

    The 32 subjects who completed the Time 2 follow-up component of our study elected to participate from an eligible sample of 41 evaluated at Time 1. Reasons for non-participation included subject refusal to participate (N =8 ) or inability to locate subjects (N = 1). Demographic measurements did not differ statistically significantly between participating and non-participating subjects as assessed during initial evaluation at Time 1 (Table 1).

    Interview procedure at Time 1

    Assessment at Time 1, when subjects were under age 14, included current and worst-ever measures using the Yale Global Tic Severity Scale (YGTSS) and Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) (Leckman et al., 1989; Scahill et al., 1997). The Schedule for Tourette and Other Behavioral Syndromes, which includes the Kiddie-Schedule for Affective Disorders and Schizophrenia Epidemiologic Present and Lifetime Version for diagnosis in children and more detailed sections on TS and OCD, was used to screen for comorbid psychiatric illnesses (Ambrosini, Metz, Prabucki, & Lee, 1989; Kaufman et al., 1997; Pauls & Hurst, 1996).

    Focused neuropsychological testing was performed in a uniform battery over the course of two sessions lasting on average two hours each. IQ testing was performed with the Kaufman Brief Intelligence Test (Naugle, Chelune, & Tucker, 1993). Visual Motor Integration was assessed with the Beery-Buktenica Visual Motor Integration Test (VMI) (Beery & Buktenica, 1989). Visual Memory was tested with the RCFT using the Taylor Scoring System (Rey, 1941; Osterreith, 1944). The copying and long-term delayed recall paradigms of the RCFT were specifically examined. Fine motor skill was tested using a timed peg-placing test, the Purdue Pegboard (Tiffen, 1968), using the procedures described previously (Schultz et al., 1998). No participants in this current sample had tics involving their hands that interfered directly with performance on this measure. Dominant, non-dominant and bimanual handed test conditions were administered to all subjects. A single RCFT test and a single VMI test were excluded from analysis due to poor subject effort on exam.

    Interview procedure at Time 2

    After providing written informed consent, subjects and their parents were interviewed by trained investigators at Time 2. Assessments included current and worst-ever YGTSS and CY-BOCS ratings. Overall psychosocial functioning was rated using the Global Assessment Scale (GAS) after the follow-up interview (Endicott, Spitzer, Fleiss, & Cohen, 1976). Screening for any comorbid psychiatric conditions was conducted with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-1). Additional assessment included a thorough medication history, specific inquiry about ADHD symptoms and age of worst-ever tic and OC symptoms. Eight clinical evaluations relied solely on information provided by a parent who lived in the same home as the research subject. Compensation was provided for participation.

    Data analysis

    All statistical procedures were performed using SPSS version 12.0. Histograms were generated to examine the distribution of YGTSS, CY-BOCS and GAS scores at Time 2. Given the large proportion of subjects with no current tic or obsessive-compulsive symptoms at Time 2, the data for YGTSS and Y-BOCS did not have a normal distribution. GAS ratings at follow-up, due to the high number of subjects with scores greater than 90, also did not have a normal distribution. These rating scales were transferred into ordinal groupings prior to hypothesis analysis in order to maintain important distinctions in symptom severity while also maintaining ordinal groups of roughly equal subject numbers. The ordinal groupings for YGTSS score (range: 0?50) at follow-up used in these analyses were 0 (N = 10), 1?9 (N = 9), 10?19 (N = 6), and >20 (N = 7). These ordinal grouping for YGTSS scores roughly correspond to absence of tics (YGTSS = 0), minimal tic symptoms (YGTSS: 1?9), mild tic symptoms (YGTSS: 11?19) and moderate-to-marked tic symptoms (YGTSS > 20). For CY-BOCS score (range: 0?40) at follow-up groupings for ordinal logistic regression were 0 (N = 1), 1?9 (N = 5), and >10 (N = 7). These ordinal groupings for CY-BOCS scores roughly correspond to absence of OCD symptoms (CY-BOCS = 0), subclinical OCD symptoms (CY-BOCS: 1?9) and OCD symptoms of clinical significance (CY-BOCS > 10). The ordinal groupings for GAS ratings were ≤70 (N = 6), 71?80 (N = 4), 81?90 (N = 10), 91?100 (N = 12).

    In SPSS 12.0 ordinal regression with a logit link was used in analysis. Ordinal groupings for YGTSS, CY-BOCS and GAS ratings were used as the dependent variable in analysis. Neuropsychological testing results that were converted into z-scores based on previously reported age and gender norms were used as the predictor variable in analysis (Beery & Buktenica, 1989; Lezak, 1995; Spreen & Strauss, 1991; Tiffen, 1968). For each model both the Pearson goodness-of-fit test and the test of parallel lines were checked for p > .05 to ensure the validity of our model (Kleinbaum & Klein, 2002). Additionally, for each of the continuous covariates the assumption of linearity was checked graphically by plotting the cumulative logits of the ordinal ratings against each covariate. Each plot demonstrated that the ordinal responses were linearly related to the covariates, thus validating the use of ordinal linear regression for this analysis (Bender & Grouven, 1997).

    For the correlations of neuropsychological testing results with current tic symptom severity at Time 1 a simple linear regression analysis was used since the distribution of this outcome variable is normal. OCD symptom severity at Time 1 was not analyzed in this current study given the small number of subjects with significant OCD symptoms at Time 1. The threshold for statistical significance was set at p < .05 to maximize hypothesis generation. All statistical analyses were two-tailed.

    All results were assessed carefully for the possible influence of medication use. Medication classes that were considered included use of any medication for tics, as well as alpha-2 agonists and neuroleptic use at Time 1. Any subject taking medications of interest was eliminated from the analysis and the β coefficient for the significant result recalculated. Only β coefficients outside the 95% confidence interval of the full study sample are reported as significant.

    At Time 1, when subjects were an average age of 11.4 ? 1.5 (mean ? SD), all subjects had previously received a diagnosis of TS. All of our subjects had previously experienced clinically significant tic symptoms (YGTSS ≥ 15). Twenty-four of the 32 subjects were experiencing clinically significant tic symptoms (YGTSS ≥ 15) at Time 1. Only 2 of the 32 subjects reported experiencing clinically significant OCD symptoms at Time 1 (CY-BOCS ≥ 10) although 9 had received a previous OCD diagnosis. Sixteen of the 32 subjects at Time 1 were taking medications to combat their tic symptoms. Eleven subjects were medicated with alpha-2 agonists (clonidine or guanfacine) and 6 were medicated with neuroleptics (5 ? typical, 1 ? atypical) at Time 1. Three subjects were additionally taking selective serotonin reuptake inhibitors (SSRI) for a history of OCD symptoms at Time 1.

    Despite having above average IQ scores, consistent with our prior report on a sample that included these cases (Schultz et al., 1998), subjects performed one-half to a whole standard deviation below the normative average data of normal control subjects on the visual-motor and fine motor tasks at Time 1. We observed a similar phenomenon in the data from those subjects who chose not to participate at follow-up. Among participating subjects higher full-scale IQ was associated with better performance on most of the tasks in our focused neuropsychological testing battery (Purdue Pegboard dominant-hand (Pearson correlation coefficient (r) = .38, p = .03), Purdue Pegboard bimanual (r = .42, p = .02), VMI (r = .56, p = .001) and RCFT long-term recall (r = .40, p = .03)). Demographic and neuropsychological testing data at Time 1 for participating and non-participating subjects is shown in Table 1.

    When subjects underwent follow-up clinical assessment an average of 7.4 years later, when subjects had an average age of 18.8 ? 1.7, 10 of the 32 subjects reported being completely free of tic symptoms at follow-up (YGTSS = 0). Average YGTSS at Time 2 was 8.9 ? 8.6 (median = 2), approximately half that of YGTSS score at Time 1 (19.5 ? 8.9). On the other hand, at Time 2, 11 of the 32 subjects had reported experiencing clinically significant OCD symptoms that had developed since interview at Time 1. Average CY-BOCS score at Time 2 for the 11 subjects with a history of clinically OCD symptoms was 11.4 ? 10.7 compared to at Time 1 when it was 4.9 ? 4.9 (median = 2).

    Tic severity

    Dominant (β = −.44, F = 7.1, t = −2.7, p = .012, R2 = .19) and non-dominant (β = −.51, F = 10.5, t = −3.2, p = .003, R2 = .26) hand, as well as bimanual (β = −.36, F = 4.4, t = −2.1, p = .045, R2 = .13) Purdue Pegboard scores were positively correlated with current tic severity at Time 1, the time of neuropsychological assessment. Consistent with our a priori hypotheses, deficits on dominant handed Purdue Pegboard (Parameter Estimate (PE) = −.53 (95%CI: (−1.1,−.02)), OR = .59, p = .04, Nagelerke R2 = .13) predicted worse tic severity at follow-up Time 2. Neither non-dominant handed (PE = −.63 (95%CI: (−1.3,.07)), OR = .53, p = .07) nor bimanual (PE = −.34 (95%CI: (−.84,.16)), OR = .71, p = .19) Purdue Pegboard performance at Time 1 predicted tic severity at Time 2. Contrary to our hypothesis, VMI performance did not correlate either with tic severity at Time 1 (β = −.07, F = .13, t = −.36, p = .72) or predict tic severity at Time 2 (PE = −.03 (95%CI: (−.61,.54)), OR = .97, p = .91).

    OCD severity

    Contrary to our a priori hypothesis, childhood performance on the Rey Complex Figure Task did not predict OCD symptom severity at Time 2. Performance on copying (PE = −.08 (95%CI: (−1.0,.85)), OR = .92, p = .87) and long-term recall (PE = .22 (95%CI: (−.66,1.1)), OR = 1.2, p = .62) on the RCFT at Time 1 did not predict OCD severity at Time 2. Purdue Pegboard (Dominant: (PE = −.16 (95%CI: (−.68,.36)), OR = .85, p = .56), Non-dominant: (PE = −.54 (95%CI: (−1.3,.27)), OR = .58, p = .19), Bimanual: (PE = −.06 (95%CI: (−.59,.4)), OR = .94, p = .63) and VMI (PE = .15 (95%CI: (−.47,.7)), OR = 1.2, p = .63)) performance similarly did not predict future OCD severity.

    Global psychosocial functioning

    Poor performance on the dominant (PE = .64 (95%CI: (.10,1.2)), OR = 1.9, p = .019, R2 = .1) and non-dominant (PE = .88 (95%CI: (.12,1.6)), OR = 2.4, p = .024, R2 = .1) Purdue Pegboard tasks predicted worse global psychosocial functioning at Time 2. Neither Bimanual Purdue Pegboard (PE = .41 (95%CI: (−.10,.92)), OR = 1.5, p = .12), VMI (PE = .46 (95%CI: (.17,1.1)), OR = 1.6, p = .15), nor performance on copying (PE = −.04 (95%CI: (−.86,.7)), OR = .96, p = .93) or long-term recall (PE = −.03 (95%CI: (−.81,.76)), OR = .97, p = .95) of the RCFT predicted global functioning at Time 2.

    Medication effects

    No significant medication effects were observed for use of dopamine receptor antagonists, alpha-2 agonists, or for use of any anti-tic medication at Time 1.

    This study, to our knowledge, represents the first attempt to explore the prognostic value of neuropsychological testing of fine motor skills in predicting future disease severity in any neuropsychiatric illness.

    We found that both the dominant and non-dominant handed deficits on a timed task involving the placement of 1 inch metal pegs into a vertically aligned set of holes (the Purdue Pegboard test) correlated with increased tic severity at the time of childhood neuropsychiatric testing. Additionally, deficits on the dominant handed Purdue Pegboard test predicted increased tic severity at follow-up in late adolescence, an average of 7.5 years after initial neuropsychological testing. Both dominant and non-dominant Purdue Pegboard deficits additionally predicted worse global psychosocial functioning at follow-up. Other neuropsychological measures tapping visual motor skill were not significant predictors of these outcomes, suggesting some specificity in the processes tapped by the Purdue Pegboard to these relationships, and negating any obvious relationship to explanations centered on participant motivation to perform well.

    These results from Purdue Pegboard testing are consistent with previous studies that have demonstrated deficits in fine-motor coordination tests such as the Purdue Pegboard in patients with TS (Bornstein, 1991a, 1991b; Bornstein & Yang, 1991; Hagin et al., 1982; Schultz et al., 1998). Purdue Pegboard performance deficiencies have been linked to poor social functioning in schizophrenia (Lehoux et al., 2002). There are at least two possible explanations for the ability of the Purdue Pegboard test to predict future tic and global psychosocial functioning in children with TS. First, poor Purdue Pegboard performance is a reflection of poor fine-motor skills in childhood. Fine-motor skill deficits make it difficult for these children to succeed in activities such as team sports, video games and musical instruments that are instrumental to building self-esteem and social relationships in these pivotal developmental years. This experience of success is of increased importance in children with TS because of the social stigma that all too often accompanies their tics. Second, poor Purdue Pegboard performance is a sign of deficits in complex, visually guided or coordinated movement that are likely mediated by circuits involving the basal ganglia (Schultz et al., 1998). Deficits on Purdue Pegboard testing have been associated with reduced putamen volumes in Parkinson's disease patients (Alegret et al., 2001) and basal ganglia hyperperfusion in 99mTc-hexamethyl propyleneamine oxime SPECT studies of patients with subclinical hepatic encephalopathy (Catafau et al., 2000). These findings are particularly of interest given the considerable evidence of basal ganglia abnormalities in TS patients. Reduced caudate volume has been previously demonstrated to be a morphological trait of Tourette's syndrome on structural MRI (Peterson et al., 2003). Additionally, reduced caudate volume on childhood MRI has been demonstrated to predict future tic severity (Bloch et al., in press a). We favor this hypothesis since it is able to explain not only the Purdue Pegboard test's ability to predict future tic severity and global psychosocial function but also its correlation with tic severity at the time of neuropsychological assessment.

    Deficits on Purdue Pegboard performance in patients with TS may also serve as a useful endophenotype in the study of the disorder.

    Endophenotypes are unseen, measurable components of psychiatric illness along the pathway between disease and genotype (Gottesman & Gould, 2003). Purdue Pegboard performance deficits have been associated with the diagnosis of TS (Bornstein, 1991a, 1991b; Bornstein & Yang, 1991; Hagin et al., 1982; Schultz et al., 1998), and now, in this study, associated with increased tic severity at follow-up in early adulthood 7.5 years later. It is important to note that Purdue Pegboard Performance is also highly correlated with tic severity at the time of childhood neuropsychological testing and is thus not significantly predictive of adulthood tic severity if childhood tic severity is controlled for in analysis. However, Purdue Pegboard performance was a more robust predictor of future adulthood tic severity than childhood tic severity in our study (Bloch et al., in press a). Tic severity in TS typically waxes and wanes dramatically over the short term and is dependent on environmental factors such as emotional excitement, stress, fatigue, sleepiness and temperature (Peterson & Leckman, 1998). By contrast, Purdue Pegboard performance remains relatively stable with time, as evidenced by a test?retest reliability of .8 when retested at a one-month interval in children of this age group (Smith & Hong, 2000). Therefore Purdue Pegboard performance may thus represent a more stable characteristic of the baseline neuropathology than current childhood tic severity itself. However, future study into the test?retest reliability of the Purdue Pegboard with time specifically in children with tics and into the hereditability of Purdue Pegboard performance is critical to determining the utility of this test as an endophenotype in the study of TS.

    The Beery?Buktenica VMI Test, however, was neither correlated with tic severity at the time of childhood neuropsychological assessment nor able to predict future tic symptom severity or global psychosocial functioning on follow-up assessment in early adulthood. VMI deficits in multiple previous studies have been demonstrated to be a neuropsychological testing correlate of a TS diagnosis (Brookshire et al., 1994; Lucas et al., 1982; Schultz et al., 1998; Shapiro et al., 1974, 1978). Our data supports this finding (the mean VMI z-score for our sample was ?.27), while still failing to demonstrate any ability of the VMI to predict future symptom severity in children with TS.

    Another important finding in this study was the inability of Rey?Osterreith Complex Figure copying or recall deficits to predict the development and severity of OCD symptoms in these children with TS.

    The later development of OC symptoms is a particularly common outcome in children with tic disorders, reportedly affecting a third to a half of these individuals (Bloch et al., in press a). Deficits on long-term and immediate recall of the RCFT as explained by impaired organizational strategies for figure memory has been consistently reported in the adult OCD literature (Boone et al., 1991; Choi et al., 2004; Savage et al., 1995, 1999).

    There are at least three possible explanations for our negative findings with regard to the RCFT.

    First, deficits on visual memory tasks such as the RCFT represent a late neuropsychological manifestation of prolonged OCD symptoms rather than an indicator of neurological predisposition to the illness. Neuropsychological testing of children with OCD has previously suggested that children do not share the deficits on neuropsychological testing found in adult subjects, although RCFT was not included in their test battery (Beers et al., 1999). Alternatively, it is possible that the deficits on RCFT observed in adult subjects are caused by secondary factors such as depression or prolonged SSRI use that are associated with, but independent of, prolonged OCD symptomatology (Schultz et al., 1999). In this case, the neural processes underlying RCFT deficits would be independent of those related to OCD pathogenesis. Studies that correlate degree of RCFT deficits with duration and severity of OCD symptoms and control for medication use and comorbid disease would definitively address this hypothesis. Additionally, obsessive-compulsive symptoms in patients with comorbid tic disorders may represent a distinct subtype of OCD without the hallmarks of the larger disease entity on neuropsychological testing. Tic-related OCD has been previously reported to involve a disproportionately high percentage of compulsions involving symmetry and exactness and touching and tapping rituals and obsessions involving fear of harm or sexual or violent imagery (Leckman et al., 1997). These characteristics of obsessions and compulsions in patients with tic-related OCD contrasts with adult-onset OCD patients, who more commonly experience contamination obsessions and cleaning compulsions (Leckman et al., 1997). Patients with tic-related OCD are also noted to have an earlier age of illness onset and be less responsive to selective-serotonin receptor inhibitor monotherapy than adult-onset OCD patients (King, Leckman, Scahill, & Cohen, 1999). Given that these subpopulations of OCD patients often appear clinically distinct and respond to medications differently, it would not be unexpected if their neuropsychological profiles differed. Studies examining profiles on neuropsychological testing of OCD patients with and without comorbid tics could help address this question.

    Although the RCFT in children with TS does not appear to be predictive of future OCD symptom severity, our previous analysis has suggested that full-scale IQ in childhood is. We have previously reported that childhood IQ as measured by the Kaufmann Brief Intelligence Test was predictive of OCD symptom severity an average of 7.6 years later (Bloch et al., in press a). In other prospective, longitudinal studies increased IQ has been associated with the diagnosis of OCD and predictive of an increase in OCD symptom severity between adolescence and adulthood (Peterson, Pine, Cohen, & Brook, 2001).

    Our current study has several limitations. It reports on a clinically referred population of children with TS whose overall illness severity and rates of comorbid illnesses are likely to be greater than in children who have TS in the general population. Furthermore, nearly one-quarter of eligible subjects did not participate in the follow-up evaluation. Although participating and non-participating subjects did not differ significantly in any demographic or clinical characteristics at the time of initial evaluation, we cannot exclude the possibility that self-selection bias affected our findings at follow-up. Third, one-half of the study sample was taking psychotropic medications at the time of neuropsychological testing. Although efforts were made to discern any effects medication use could have exerted on our results, this possibility cannot be entirely discounted. However, previous studies have demonstrated no influence of medication use on the neuropsychological testing results of patients with Tourette's syndrome (Bornstein & Yang, 1991; Schultz et al., 1998). Fourth, we excluded TS patients with comorbid ADHD from our study. Therefore our findings should not be generalized to apply to those children with TS who suffer from comorbid ADHD, although it should be mentioned that inclusion of TS patients with comorbid ADHD in our study sample did not affect the findings in this study in any appreciable way (data unreported).

    Despite these limitations our study is, to our knowledge, the first to address the potential prognostic role of focused neuropsychological testing in predicting future tic, OCD and global psychosocial functioning in children with TS. We found that Purdue Pegboard deficits predicted increased adulthood tic severity in children with TS although not with the predictive power of structural MRI measures (Bloch et al., in press a). Purdue Pegboard deficits were additionally significantly able to predict worse global psychosocial functioning at follow-up in adulthood and, when combined with previously significant clinical predictors (childhood tic severity), explained 29% variance at follow-up. Our results suggest that the Purdue Pegboard testing may be used in combination with other indices to help predict outcome in children with TS. Unlike our structural MRI findings, this test is available and economically realistic to all clinicians who treat patients with TS. Although we did not discover any useful tests or neuropsychological battery for predicting the future development or severity of OC symptoms in TS patients, our previous findings suggest that IQ may be a useful predictor of this outcome measure, with a higher childhood IQ suggesting a predisposition for the later development of OCD symptoms.


  • #2

    Thanks for that topic, I find it very interesting.
    sex filmy