The effects of comorbid obsessive-compulsive disorder and attention-deficit hyperactivity disorder on quality of life in tourette syndrome.

Tourette syndrome (TS) is a complex neuropsychiatric disorder affecting patients' quality of life (QoL). The authors compared QoL measures in young patients with "pure" TS (without comorbid conditions) versus those with TS+OCD (obsessive-compulsive disorder), TS+ADHD (attention-deficit hyperactivity disorder), or TS+OCD+ADHD. Age and scores on scales assessing tic severity, depression, anxiety, and behavioral problems were included as covariates. Young patients with both comorbidities exhibited significantly lower Total and Relationship Domain QoL scores, versus patients with pure TS. Across the whole sample, high ADHD-symptom scores were related to poorer QoL within the Self and Relationship domains, whereas high OCD symptom scores were associated with more widespread difficulties across the Self, Relationship, Environment, and General domains. Significant differences in QoL may be most likely when both comorbidities are present, and features of OCD and ADHD may have different impacts on QoL across individual domains.

Clinical correlates of quality of life in Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder involving tics, which is frequently accompanied by comorbid obsessive compulsive (OCD) or attention deficit hyperactivity disorder (ADHD). Individuals with TS often report poor quality of life (QoL) in comparison with the general population. This study investigated the clinical correlates of QoL in young people with TS using a self-report multidimensional QoL measure, and a range of clinical scales used to assess tic severity and the symptoms of anxiety, depression, OCD, ADHD and other emotional and behavioral symptoms. Symptoms of depression, OCD, and ADHD appeared to have a widespread negative impact on QoL, but poorer QoL was not associated with increased tic severity. Greater emotional and behavioral difficulties, including symptoms of OCD, were among the best predictors of poor QoL in young people with TS.

Cardiovascular safety of aripiprazole and pimozide in young patients with Tourette syndrome.

The pharmacotherapy for tic management in Tourette syndrome (TS) relies on neuroleptics, which have been associated with electrocardiographic abnormalities, including QTc interval prolongation. This study assessed the cardiovascular safety of the newer antipsychotic aripiprazole in comparison with the neuroleptic pimozide among young patients affected by TS. Fifty patients aged 6-18 years were assigned to either pimozide (n = 25; mean daily dose 4.4 mg/die) or aripiprazole (n = 25; 5.3 mg/die) treatment for up to 24 months. All patients underwent five serial cardiovascular assessments (baseline, 6, 12, 18 and 24 months). The group treated with pimozide showed significant changes in blood pressure (decreased), QT and QTc (both prolonged). The aripiprazole group showed changes from baseline to peak values in blood pressure (increased), whilst modifications in QT and QTc were not statistically significant. At equivalent doses, aripiprazole is characterised by a safer cardiovascular profile than pimozide, being associated with a lower frequency of QTc prolongation.

Premonitory Urges in Patients with Gilles de la Tourette Syndrome: An Italian Translation and a 7-Year Follow-up.

OBJECTIVE: Premonitory sensations or urges (PUs) are described as characteristic sensory phenomena preceding tics, which are often described as unpleasant. They occur in 90% of patients affected by Gilles de la Tourette Syndrome (GTS). They may be localized (around the area of tic) or generalized (covering a wide area of the body). The PUs can be measured by the Premonitory Urge for Tics Scale (PUTS). In this study we translated the PUTS scale into Italian and then assessed children and adolescents/young people (CYP) with GTS using the scale. METHODS: GTS patients were assessed at the initial interview and after 7 years to evaluate the PUs, and the correlations of the PUTS scores with tic severity, severity of comorbid disorders (obsessive-compulsive disorder [OCD], attention-deficit/hyperactivity disorder [ADHD]), and a variety of coexisting psychopathologies. RESULTS: A total of 95 patients were studied. We successfully translated the PUTS into Italian, and our results indicated that our translated version had good psychometric properties. Results demonstrated that the CYP had PUs at both interviews, but that older CYP were more consistent in reporting PUs than younger CYP (i.e., PUTS scores increased with age). We found no correlations between PUTS score and tic severity at either interview. We found a statistical significant correlation between PUTS score and obsessive-compulsive symptoms (OCS) at both interviews; Moreover both the PUTS and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores increased significantly, whereas the Yale Global Tic Severity Rating Scale (YGTSS) score decreased significantly. We found no relationships between PUTS scores and anxiety, depression, ADHD, and externalizing/internalizing behavioral scores. CONCLUSIONS: Our results suggest the the Italian translation of the PUTS has good psychometric properties. Although both younger (<10 years of age) and older CYP (≤ 10 years of age) reported PUs, the scores at the initial interview were statistically significantly lower than at follow-up. Moreover, in CYP >10 years of age, the PUs correlated with obsessions and compulsions (CY-BOCS scores).

Circulating miRNAs profiles in Tourette syndrome: molecular data and clinical implications.

BACKGROUND: Tourette Syndrome (TS) is a highly prevalent childhood neuropsychiatric disorder (about 1 %), characterized by multiple motor and one or more vocal tics. The syndrome is commonly associated to comorbid conditions (e.g., Attention Deficit Hyperactivity Disorder and Obsessive Compulsive Disorder), which considerably aggravate clinical symptoms and complicate diagnosis and treatment. To date, TS molecular bases are unknown and its molecular diagnosis is unfeasible. RESULTS: Due to their master role within cell networks and pathways both in physiology as in pathology, we sought to determine the transcriptome of circulating miRNAs in TS patients: by TaqMan Low Density Arrays, we profiled the expression in serum of 754 miRNAs in six TS patients and three unaffected controls (NCs) (discovery set). These data were validated by single TaqMan assays on serum from 52 TS patients and 15 NCs (validation set). Network and Gene-ontology analysis were performed by using Cytoscape and Babelomics server. We found that miR-429 is significantly underexpressed in TS patients with respect to NCs. Decreased serum levels of miR-429 allowed us to discriminate TS patients from NCs with 95 % of sensitivity and 42 % of specificity. Intriguingly, computational analysis of the network comprising miR-429 targets demonstrates their involvement in differentiation of midbrain and hindbrain and synaptic transmission. CONCLUSIONS: Our data open the way to further molecular characterization of TS and eventual identification of the corresponding genotypes. Circulating miR-429 may be immediately useful as sensitive molecular biomarker to support TS diagnosis, actually based only on DSM-V criteria.

Tourette syndrome and comorbid conditions: a spectrum of different severities and complexities.

To investigate clinical correlates of Tourette syndrome and to identify the impact of comorbidities, we retrospectively recruited 92 young people affected by Tourette syndrome compared with 102 healthy controls. Neuropsychological assessment included: Youth Quality of Life-Research, Multidimensional Anxiety Scale for Children, Children's Depression Inventory, and Conner's and Child Behavior Checklist; moreover, Tourette syndrome patients completed the Yale Global Tic Severity Rating Scale and the Yale-Brown Obsessive Compulsive Scale. Four clinical subgroups were identified: pure Tourette syndrome (49.8%), Tourette syndrome plus attention-deficit hyperactivity disorder (ADHD) (22.2%), Tourette syndrome plus obsessive-compulsive disorder (21.5%), and Tourette syndrome plus ADHD plus obsessive-compulsive disorder (6.5%). Our findings suggested that emotional lability appeared in all Tourette syndrome subgroups, independently from comorbidities, representing a clinical feature of Tourette syndrome itself. Moreover, our data suggested that all 4 clinical subgroups had higher statistically significant behavioral problems compared with the healthy controls (P = .000), whereas affective and anxiety symptoms were overrepresented in Tourette syndrome plus comorbidities subgroups. Finally, Tourette syndrome patients had a lower quality of life compared with the healthy controls. These differences were statistically significant between the pure Tourette syndrome subgroups and Tourette syndrome plus comorbidities subgroups, as well as Tourette syndrome plus comorbidities subgroups and healthy controls.

Tourette Syndrome and comorbid ADHD: current pharmacological treatment options.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is the most common co-morbid condition encountered in people with tics and Tourette Syndrome (TS). The co-occurrence of TS and ADHD is associated with a higher psychopathological, social and academic impairment and the management may represent a challenge for the clinicians. AIM: To review recent advances in management of patients with tic, Tourette Syndrome and comorbid Attention Deficit Hyperactivity Disorder. METHODS: We searched peer reviewed and original medical publications (PUBMED 1990-2012) and included randomized, double-blind, controlled trials related to pharmacological treatment for tic and TS used in children and adolescents with comorbid ADHD. "Tourette Syndrome" or "Tic" and "ADHD", were cross referenced with the words "pharmacological treatment", "α-agonist", "psychostimulants", "selective norepinephrine reuptake inhibitor", "antipsychotics". RESULTS: Three classes of drugs are currently used in the treatment of TS and comorbid ADHD: α-agonists (clonidine and guanfacine), stimulants (amphetamine enantiomers, methylphenidate enantiomers or slow release preparation), and selective norepinephrine reuptake inhibitor (atomoxetine). It has been recently suggested that in a few selected cases partial dopamine agonists (aripiprazole) could be useful. CONCLUSION: Level A of evidence supported the use of noradrenergic agents (clonidine). Reuptake inhibitors (atomoxetine) and stimulants (methylphenidate) could be, also used for the treatment of TS and comorbid ADHD. Taking into account the risk-benefit profile, clonidine could be used as the first line treatment. However only few studies meet rigorous quality criteria in terms of study design and methodology; most trials have low statistical power due to small sample size or short duration. Treatment should be "symptom targeted" and personalized for each patient.

Disease-specific quality of life in young patients with tourette syndrome.

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating "pure" Tourette syndrome from Tourette syndrome "plus" behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments.

The Gilles de la Tourette Syndrome-Quality of Life Scale for children and adolescents (C&A-GTS-QOL): development and validation of the Italian version.

BACKGROUND: Gilles de la Tourette syndrome (GTS) is a chronic childhood-onset neuropsychiatric disorder with a significant impact on patients' health-related quality of life (HR-QOL). Cavanna et al. (Neurology 2008; 71: 1410-1416) developed and validated the first disease-specific HR-QOL assessment tool for adults with GTS (Gilles de la Tourette Syndrome-Quality of Life Scale, GTS-QOL). This paper presents the translation, adaptation and validation of the GTS-QOL for young Italian patients with GTS. METHODS: A three-stage process involving 75 patients with GTS recruited through three Departments of Child and Adolescent Neuropsychiatry in Italy led to the development of a 27-item instrument (Gilles de la Tourette Syndrome-Quality of Life Scale in children and adolescents, C&A-GTS-QOL) for the assessment of HR-QOL through a clinician-rated interview for 6-12 year-olds and a self-report questionnaire for 13-18 year-olds. RESULTS: The C&A-GTS-QOL demonstrated satisfactory scaling assumptions and acceptability. Internal consistency reliability was high (Cronbach's alpha > 0.7) and validity was supported by interscale correlations (range 0.4-0.7), principal-component factor analysis and correlations with other rating scales and clinical variables. CONCLUSIONS: The present version of the C&A-GTS-QOL is the first disease-specific HR-QOL tool for Italian young patients with GTS, satisfying criteria for acceptability, reliability and validity.

Parent and self-report health-related quality of life measures in young patients with Tourette syndrome.

Tourette syndrome is a neurodevelopmental disorder characterized by tics and comorbid behavioral problems. This study compared child- and parent-reported quality of life and everyday functioning. We assessed 75 children with Tourette syndrome, of which 42 (56%) had comorbid conditions (obsessive-compulsive disorder = 25; attention-deficit hyperactivity disorder = 6; both comorbidities = 4). All patients completed psychometric instruments, including the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (child report) and the Child Tourette's Syndrome Impairment Scale (parent report). Data were compared for patients with pure Tourette syndrome, Tourette syndrome + obsessive-compulsive disorder, Tourette syndrome + attention-deficit hyperactivity disorder, and Tourette syndrome + both comorbidities. There were no group differences in quality of life. However, there were differences for total, school, and home activities impairment scores. Children and parents may not share similar views about the impact of Tourette syndrome on functioning. The measurement of health-related quality of life in Tourette syndrome is more complex in children than adults.

Long term clinical course of Tourette syndrome.

BACKGROUND: Recent studies using cluster analysis and factor analysis have suggested that Tourette Syndrome (TS) should no longer be considered a unitary condition. MATERIAL AND METHODS: We retrospectively studied the long term clinical course of 100 TS patients. The patients were assessed at the onset and after 10 years follow-up to evaluate the severity of tic, the Obsessive Compulsive Disorder (OCD), the Attention Deficit Hyperactivity Disorder (ADHD) and the presence of anxiety and depression, rage attacks, self injuries behavior. Moreover at the follow-up they completed an evaluation scale on quality of life to assess the impairment in everyday life after 10 years of illness. RESULTS: The "pure TS" clinical group (38 subjects) showed after 10 years follow-up that 58% carried on with the same clinical phenotype, whereas 42% changed in "TS+OCD" phenotype. Fifty-five percentage required pharmacological treatment. All the "TS+ADHD" clinical group (48 subjects) showed after 10 years follow-up a different clinical phenotype: 62% "TS pure" phenotype, 35% "TS+OCD" phenotype, 2% "TS+ADHD+OCD" phenotype. Sixty-five percentage of the subject required pharmacological treatment. The "TS+ADHD+OCD" clinical group (14 subjects) after 10 years follow-up showed that 14% carried on with the same clinical phenotype, whereas 8.3% presented "TS pure" phenotype and 92% presented "TS+OCD" phenotype. Seventy-one percentage were in need of therapy. With regards to quality of life, patients presented widespread impairment correlated to the presence of comorbid conditions. CONCLUSION: Our findings suggest that pure TS has quite a good long-term clinical course. By contrast, those who presented comorbid condition at the onset showed a more severe prognosis.

Metabolic effects of aripiprazole and pimozide in children with Tourette syndrome.

This study assessed the metabolic effects of aripiprazole and pimozide in pediatric Tourette syndrome, a neurodevelopmental condition characterized by multiple motor and phonic tics. Patients receiving aripiprazole (n = 25) or pimozide (n = 25) were compared with medication-free patients (n = 25). Body mass index, glycemia, triglyceridemia, and cholesterolemia were monitored at baseline and 12 and 24 months after commencing treatment. The aripiprazole group demonstrated significant increases in cholesterolemia. The pimozide group demonstrated significant increases in glycemia. Both groups demonstrated elevations in triglyceridemia not significantly different from those in unmedicated control subjects. The effect of aripiprazole on cholesterol was apparent after 12 months, but leveled off during year 2 of treatment. Longitudinal studies are required to evaluate the full extent of glycemic alterations with pimozide. Both agents appear relatively safe for use in pediatric Tourette syndrome. These findings will help guide medication selection in patients with specific medical vulnerabilities.