The validity of instruments measuring tic severity in Tourette's syndrome.

By using four different scales that measure tic severity in Tourette's syndrome, three independent judges concurrently evaluated their validity and interjudge reliability in 20 affected individuals. The Yale Global Tic Severity Scale, Tourette's Syndrome Severity Scale, Tourette's Syndrome-Clinical Global Impression Scale, and the Hopkins Motor and Vocal Tic Scale were equally effective in determining overall severity and showed good interrater reliability. Both historical information and direct observation of the subject were shown to have a significant contribution towards the overall assessment of tic severity. With all instruments, tic symptom ratings were shown to be independent of those for either attention-deficit hyperactivity disorder or obsessive-compulsive disorder. A 67% incidence of behavioral problems and social difficulties was identified by the Child Behavior Checklist. Nevertheless, associations with tic severity were limited to areas showing interference with social relationships and school adjustments. These results extend the understanding of Tourette's syndrome severity scales and provide additional information necessary for the development of a unified rating scale.     

A factor analysis of tic symptoms in Gilles de la Tourette's syndrome

OBJECTIVE: Gilles de la Tourette's syndrome is a well-characterized disorder with clear DSM-IV criteria. However, the great deal of clinical variability across patients may represent an underlying etiologic complexity. Issues of phenotypic heterogeneity are particularly critical to current efforts at mapping genes involved in this syndrome. METHOD: Lifetime tic symptom data were obtained from direct structured interviews of 85 Tourette's disorder probands. Information on 29 tic symptoms was elicited. The probands' tic symptoms were grouped by using agglomerative hierarchical clustering, with no a priori assumptions concerning the relatedness of symptoms. Scores for the probands' symptom clusters were used as variables in a principal-component factor analysis. The relationships of the resulting factor scores to comorbidity in probands and recurrence risks in relatives were examined. In addition, intraclass correlations were calculated for within-family factor scores of 36 families. RESULTS: Four significant factors were identified: 1) aggressive phenomena (e.g., kicking, temper fits, argumentativeness), 2) purely motor and phonic tic symptoms, 3) compulsive phenomena (e.g., touching of others or objects, repetitive speech, throat clearing), and 4) tapping and absence of grunting. Analysis of the symptom loadings, comorbidity, recurrence risks, and within-family correlations indicate that these factors represent a valid structure with clinical and biological relevance. CONCLUSIONS: In this symptom-based factor analysis of Tourette's disorder, four factors accounted for 61% of the phenotypic symptom variance in Tourette's disorder probands and their first-degree relatives. Three of these factors may indicate the presence of heritable components of the Tourette's disorder phenotype.     

Anxiety disorders and tic severity in juveniles with Tourette's disorder

OBJECTIVE: It was hypothesized that comorbidity with anxiety disorders would predict tic severity in youths with Tourette's disorder (TD). METHOD: Subjects were 190 youths meeting DSM-III-R diagnostic criteria for TD who were consecutively referred to a pediatric psychopharmacology program between 1994 and 1997. Subjects were initially evaluated with a clinical interview and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version. Statistical analysis used t tests, chi 2 tests, and logistic regression analysis. RESULTS: One hundred thirty-four subjects were classified as mild/moderate and 56 as severe TD cases. No meaningful differences were found in socioeconomic status, gender distribution, or age at onset of TD between the 2 groups. The 2 groups could not be differentiated by the presence of comorbid mood or disruptive behavior disorders including attention-deficit hyperactivity disorder. Although obsessive-compulsive disorder (OCD) was overrepresented among the severe TD cases, the difference failed to reach statistical significance. Excluding social and simple phobias, all other anxiety disorders were more clearly overrepresented among subjects with severe TD; separation anxiety disorder most robustly predicted tic severity, irrespective of the presence of OCD or other anxiety disorders. CONCLUSION: Findings suggest that non-OCD anxiety disorders in general and separation anxiety disorder in particular may be significantly associated with tic severity in referred TD patients.     

Distinguishing illness severity from tic severity in children and adolescents with Tourette's disorder

OBJECTIVE: To examine whether tic severity, comorbid disorders, or both are associated with illness morbidity in youths with Tourette's disorder (TD). METHOD: Subjects were 156 consecutively referred youths (aged 5-20 years) who met DSM-III-R criteria for Tourette's disorder at a major academic medical center. All subjects were evaluated with a clinical interview by a child and adolescent psychiatrist and an assessment battery that included the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version. Statistical analysis used chi 2 and multivariate logistic regression. RESULTS: Nineteen (12%) of the 156 youths with TD required psychiatric hospitalization. Current age, TD severity, TD duration, obsessive-compulsive disorder, psychosis, major depression, bipolar disorder, panic disorder, and overanxious disorder were significant univariate predictors of psychiatric hospitalization (p < .01). While tic severity was marginally significant as a predictor of psychiatric hospitalization (p < .05), major depression (p < .016) and bipolar disorder (p < .001) were robust predictors of psychiatric hospitalization, even after statistical adjustment for collinearity and correction for all other variables assessed. CONCLUSION: The findings indicate that comorbid mood disorders are strongly associated with illness morbidity in youths with TD, highlighting the importance of attention to comorbidity in patients with TD.     

Pilot study of effect of emotional stimuli on tic severity in children with Tourette's syndrome.

To assess objectively the effects of emotional stimuli on the severity of tics and to determine if such effects were mediated by the autonomic nervous system, we carried out videotape ratings of tics and electrophysiological monitoring of heart beat and respiration on 4 children with Tourette's syndrome while they were watching a movie known to elicit emotional responses relevant to normal childhood events. Measured tic severity was highest during periods associated with anticipation, resolution of emotional changes, and lower concentration, lowest during periods of anger and happiness, and intermediate during periods of sadness and fear. Tic severity did not correlate with heart or respiratory rate. Thus, tics seem influenced differentially by various emotional states, but this effect does not seem to be autonomically mediated.     

Transient tic disorder and the spectrum of Tourette's syndrome

Transient tic disorder (TTD) has not generally been considered part of the spectrum of Tourette's syndrome (TS). We studied a large kindred affected by TS and identified two family members with TTD who are very likely obligate carriers of the TS gene. Our observations indicate that TTD is a possible expression of the TS gene and that individuals with TTD may transmit TS to their offspring.     

Disruptive behavior in children with Tourette's syndrome: association with ADHD comorbidity,tic severity,and functional impairment

OBJECTIVE: To examine the association of disruptive behavior with social, adaptive, and family functioning in Tourette's syndrome (TS) with and without comorbid attention-deficit/hyperactivity disorder (ADHD). METHOD: The sample included 207 children (144 boys and 63 girls) between the ages of 7 and 18 years. Forty-two children received a diagnosis of TS-only, 52 received a diagnosis of ADHD-only, 52 children had TS+ADHD, and there were 61 unaffected control children. Best-estimate DSM-IV diagnoses were assigned on the basis of structured interviews and clinical ratings. Dependent measures included parent and teacher ratings of disruptive behavior, parent ratings of social and family functioning, and the Vineland Adaptive Behavior Scales. RESULTS: Children with TS-only did not differ from unaffected controls on the parent ratings of aggression and delinquent behavior or on the teacher ratings of conduct problems. By contrast, children with TS+ADHD were rated significantly above unaffected controls and similar to children with ADHD-only on these indices of disruptive behavior. Hierarchical regression analyses revealed that aggression and delinquency scores added unique contributions to impairment in social and family functioning, controlling for age, gender, and diagnostic status. CONCLUSIONS: Comorbid ADHD is highly associated with disruptive behavior and functional impairment in children with TS. When disruptive behavior problems are present, there is an additional burden on children's social and family functioning.     

Cortisol levels are positively correlated with hippocampal N-acetylaspartate.

BACKGROUND: This study examined the relationship of hypothalamic-pituitary-adrenal measures and hippocampal N-acetylaspartate (NAA) in posttraumatic stress disorder (PTSD) patients and control subjects. METHODS: Eleven patients with combat-related PTSD and 11 control subjects were evaluated with magnetic resonance spectroscopy as well as by morning salivary cortisol samples before and after administration of low-dose dexamethasone (.5 mg). RESULTS: Left hippocampal NAA was strongly associated with both pre-dexamethasone cortisol levels (n = 22, r =.53, p =.013) and post-dexamethasone cortisol levels (n = 22, r =.63, p =.002). After accounting for clinical symptom severity and hippocampal volume, cortisol levels accounted for 21.9% of the variance (F = 5.6, p =.004) in left hippocampal NAA and 12.6% of the variance (F = 3.2, p =.035) in right hippocampal NAA. CONCLUSIONS: This study shows a positive relationship between cortisol levels and hippocampal NAA in subjects without hypercortisolemia. Within the range of values seen in our subjects, cortisol may have a trophic effect on the hippocampus.     

Saccadic performance characteristics and the behavioural neurology of Tourette's syndrome

OBJECTIVE: To better understand the neuropathological correlates of Tourette's syndrome (TS), measures of saccadic eye movement performance were examined among patients with TS. METHODS: A case-control design was used. Twenty one patients with DSM-IV TS (mean age 40.6 years (SD 11.0); 38% female) mainly recruited from UCSD Psychiatry Services, and a community based sample of 21 normal subjects (mean age 34.6 years (SD 13.4); 43% women) participated in this study. Participants were administered ocular motor tasks assessing visual fixation, and the generation of prosaccades, predictive saccades, and antisaccades. Saccadic reaction time, amplitude, duration, and mean and peak velocity were computed. Intrusive saccades during visual fixation and the proportion of correct antisaccade responses were also evaluated. RESULTS: The groups had similar visual fixation performance. Whereas patients with TS generated prosaccades with normal reaction times and amplitudes, their saccade durations were shorter and their mean velocities were higher than in normal subjects. During a prosaccade gap task, patients with TS exhibited an increased proportion of anticipatory saccades (RTs<90). The proportion of "express" saccades (90相似文献   

The influence of contextual factors on tic expression in Tourette's syndrome: a review

Symptoms of Tourette's syndrome vary in frequency and intensity. Although such variability may be the result of deficits in the underlying neurological system, tic expression can also be systematically impacted by contextual factors. This article reviews research on the impact of several contextual factors on tic expression and discusses implications for future research and treatment development.     

Impact of obsessive-compulsive symptoms in Tourette's syndrome on neuropsychological performance

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.     

Comorbid bipolar disorder in Tourette's syndrome responds to the nicotinic receptor antagonist mecamylamine (Inversine).

BACKGROUND: We have previously proposed that the therapeutic effect of transdermal nicotine in Tourette's syndrome may involve nicotinic receptor inactivation resulting from a prolonged continuous exposure to nicotine. In vitro studies with nicotine and preliminary positive experience with mecamylamine (Inversine), a nicotinic receptor antagonist, in the clinical treatment of Tourette's syndrome patients, further supports the receptor inactivation hypothesis. METHODS: We retrospectively documented an unexpected therapeutic response to mecamylamine (2.5-7.5 mg/day) in two Tourette's syndrome patients who were subsequently found to have comorbid bipolar disorder as defined by DSM-IV criteria. RESULTS: In patient 1, the mood-stabilizing effect of mecamylamine was noticed by the patient during the course of mecamylamine treatment and brought to our attention, whereas for patient 2, manic symptoms were only apparent clinically following cessation of mecamylamine treatment. CONCLUSIONS: The clinical observations presented here suggest that nicotinic antagonists might be potential therapeutic agents for the treatment of bipolar disorder. Double-blind, placebo-controlled studies are now necessary to investigate these observations under more rigorous conditions.     

Association between maternal smoking and increased symptom severity in Tourette's syndrome

OBJECTIVE: Substantial evidence suggests that both environmental and genetic factors contribute to the development and clinical expression of Tourette's syndrome. Although genetic studies of Tourette's syndrome are common, studies of environmental factors are relatively few and have not identified consistent risk factors across studies. This study examines in a large cohort of subjects (N=180) the relationship between prenatal/perinatal adverse events with Tourette's syndrome severity as determined by tic severity and rates of commonly comorbid disorders such as obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and self-injurious behavior. METHOD: Tic severity, OCD, ADHD, self-injurious behavior, and exposure to a variety of prenatal/perinatal events were systematically assessed in all subjects enrolled in three genetic studies of Tourette's syndrome. Using linear and logistic regression, a best-fit model was determined for each outcome of interest. RESULTS: Prenatal maternal smoking was strongly correlated with increased tic severity and with the presence of comorbid OCD in these Tourette's syndrome subjects. Other variables, such as paternal age and subject's birth weight, were significantly but less strongly associated with increased symptom severity. The authors found no association between symptom severity and hypoxia, forceps delivery, or hyperemesis during pregnancy, which have been previously identified as risk factors. CONCLUSIONS: This study identifies prenatal maternal smoking as a strong risk factor for increased symptom severity in Tourette's syndrome.     

Luteinizing hormone levels are positively correlated with plasma amyloid-beta protein levels in elderly men

Dysregulation of the hypothalamic pituitary gonadal (HPG) axis during aging has been associated with increased risk of cognitive decline and developing dementia. Compared to controls, men with Alzheimer's disease (AD) have been shown to have lower serum testosterone levels and higher serum luteinizing hormone (LH) levels. As serum free testosterone concentration is negatively correlated with LH in older men, the independent contributions of these hormones to the pathogenesis of AD warrants further clarification. To explore this notion, we measured plasma amyloid-beta (Abeta), serum testosterone, serum LH and other biochemical parameters in 40 cognitively normal elderly men. Multiple linear regression analysis revealed that serum LH concentration is the only parameter that significantly correlates with plasma Abeta levels in these men (r=0.5, p=0.041). These results suggest that increased serum LH concentration, rather than lower serum free testosterone, is associated with the accumulation of Abeta in plasma. Larger, longitudinal human studies are needed to determine the significance of LH in the pathogenesis of AD.     

Aggressive symptoms in children with tic disorders

Episodes of explosive anger and aggression are reported in patients with tic disorders and probably contribute to psychosocial stress and low quality of life. The source of these symptoms is controversial. The objective of the study was to study the relationship between tic disorders, their associated comorbidities, and aggressive behavior. The cohort included 47 children and adolescents (age 7–17 years) with Tourette syndrome or other chronic tic disorders attending a tertiary pediatric Tourette clinic. Associated psychopathology was assessed with the Yale Global Tic Severity Scale, Yale Brown Obsessive Compulsive Scale, Conners ADHD Rating Scale, Screen for Child Anxiety-Related Emotional Disorders, and Child Depression Inventory. Aggression was assessed with the Overt Aggression Scale and scores were compared with a group of 32 healthy age- and sex-matched children. There were no significant differences in aggression scores between the children with tic disorders and controls. Verbal aggression was the most prevalent type of aggression, found in 70% of the patients with tic disorders. The level of aggression was not correlated to tic severity. Comorbid attention-deficit hyperactivity disorder and obsessive–compulsive disorder increased the probability of aggressive behavior in patients with tic disorders. On regression analysis, the only significant predictor of aggression was the severity of attention-deficit hyperactivity disorder. This study suggests that there is no difference in aggressive behavior between children with tics without comorbidities and healthy children. It is possible that aggressive behavior in children with tic disorders is predominantly associated with comorbid attention-deficit hyperactivity disorder.

     

A case of Tourette's syndrome with symptoms of attention deficit disorder treated with desipramine

Therapy for Tourette's syndrome with tricyclic antidepressants has had varied results. Previous reports have not addressed the frequent association of symptoms of attention deficit disorder (ADD) with Tourette's syndrome or the plasma levels of tricyclic antidepressants. A boy with Tourette's syndrome and ADD-like symptoms was treated with desipramine, and all the symptoms improved. This drug may be effective therapy for patients with Tourette's syndrome and ADD-like symptoms.