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Across a range of neurodevelopmental conditions, a diagnosis of attention deficit hyperactivity disorder (ADHD) has been shown to be associated with executive function impairment. However, the DSM-V emphasis upon viewing psychological characteristics as existing on a continuous distributed quantitative dimension has enabled the opportunity to consider the influence of sub-diagnostic or sub-referral levels of these psychological characteristics upon cognitive function. This study adopted a continuum approach to the consideration of this ADHD influence and examined the extent to which the difference in parental reported executive functions between children with Tourette syndrome (TS) or typically developing children could be mediated by a concurrent group difference in the possession of sub-referral levels of ADHD-like characteristics. A total of 146 children, 58 with reported TS diagnosis, participated. Parental report measures of ecological executive functioning, the Child Executive Functioning Inventory, and the Vanderbilt ADHD Diagnostic Parent Rating Scale were employed. The analyses with a full sample and a sub-referral sample revealed significant group differences in most of the key measures. In addition, these measures were highly correlated even when controlling for age and gender. A series of mediation analyses indicated that in all models, the ADHD-like measures significantly mediated the group difference in executive function. These results suggest that sub-referrals levels of ADHD-like characteristics continue to contribute to executive challenges in TS. Future intervention research targeting these executive functions should consider the presence of ADHD-like characteristics at sub-referral levels of possession.

Aim: To compare transcranial magnetic stimulation (TMS)-derived measures of primary motor cortex (M1) physiology between children with and without Tourette syndrome, and to dimensionally analyze TMS measures with Tourette syndrome-related symptom severity., Method: We used a cross-sectional experimental design. Sixty 8- to 12-year-old children participated (30 with Tourette syndrome: three females, mean age 10 years 10 months, standard deviation [SD] 1 year 3 months; 30 typically developing children: seven females, mean age 10 years 7 months, SD 1 year 3 months). In the group with Tourette syndrome, 15 (one female, mean age 10 years 11 months, SD 1 year 3 months) had comorbid attention-deficit/hyperactivity disorder (ADHD), rated with the Conners, Third Edition and the parent-reported ADHD rating scales. Tic severity was rated with the Yale Global Tic Severity Scale and urge severity with the Individualized Premonitory Urge for Tics Scale. M1 short-interval cortical inhibition (SICI) and intracortical facilitation were compared between diagnostic groups and, within the group with Tourette syndrome, correlated with symptom severity using linear mixed-effects models for repeated measures., Results: Accounting for ADHD, we found no difference in SICI or intracortical facilitation in those with Tourette syndrome versus typically developing children (p > 0.1). In the group with Tourette syndrome, reduced M1 SICI predicted greater total (p = 0.012) and global (p = 0.002) tic severity. There were no associations with urge severity (p > 0.5)., Interpretation: Reduced M1 SICI is robustly associated with increased tic, but not urge, severity., What This Paper Adds: Increased tic severity is associated with reduced motor cortex short-interval cortical inhibition (SICI). Children with Tourette syndrome with increased urge severity also show increased tic severity. However, reduced motor cortex SICI is associated with tic, but not urge, severity., (© 2023 Mac Keith Press.)

Objective: Among adults with Tourette syndrome, depression and anxiety symptoms are widely prevalent and consistently associated with poor quality of life. Important knowledge gaps remain regarding mood and anxiety dimensions of the adult Tourette syndrome phenotype. Taking a dimensional approach, this study sought to determine the prevalence, severity, and clinical correlates of depression and anxiety symptoms in a clinical sample of adults with Tourette syndrome and other chronic tic disorders., Methods: A retrospective chart review was conducted of all adults with a chronic tic disorder presenting to a tertiary care Tourette syndrome clinic between December 2020 and July 2022. Information extracted during chart review included data from scales administered as part of routine care: Quality of Life in Neurological Disorders (Neuro-QoL) Depression Short Form, Neuro-QoL Anxiety Short Form, Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale, Dimensional Obsessive-Compulsive Scale, and Yale Global Tic Severity Scale. Relationships between variables were examined by conducting between-group, correlation, and multivariable regression analyses., Results: Data from 120 adult patients with a chronic tic disorder (77 men and 43 women) were analyzed. Neuro-QoL Anxiety scores were elevated in 66% of the cohort; Neuro-QoL Depression scores were elevated in 26%. Neuro-QoL Anxiety scores were significantly higher than general population norms, whereas Neuro-QoL Depression scores were not. After adjustment for covariates, depressive and anxiety symptom severity scores were significantly associated with each other and with obsessive-compulsive disorder symptom severity but not with tic severity. Sex-based differences emerged in the analyses., Conclusions: Among adults with chronic tic disorder, anxiety symptoms were more prevalent and severe than depressive symptoms, co-occurring psychiatric symptoms were more tightly linked with each other than with tic severity, and sex-based differences were evident., Competing Interests: Dr. Isaacs has received grant funding from Teva Branded Pharmaceutical Products, Research and Development. Dr. Riordan has received an educational grant from Medtronic. The other authors report no financial relationships with commercial interests.

Background: Sleep problems are common in children with Tourette Syndrome (TS). However, research regarding their demographic and clinical profile is limited., Methods: We examined characteristics of 114 children aged five to 17 years with a lifetime diagnosis of TS and compared children with sleep disorder (n = 32) and without sleep disorder (n = 82). Parent report from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome provided demographics and clinical information, other diagnosed disorders, medication use, TS severity, and impairment., Results: More children with TS with sleep disorder were from households with lower parental education (P < 0.01) and poverty (P = 0.04); had other diagnoses (P = 0.03), including obsessive-compulsive disorder (P < 0.01), oppositional defiant disorder or conduct disorder (P < 0.01), attention-deficit/hyperactivity disorder (ADHD) (P = 0.02), and autism (P = 0.03); and had ever used TS medication (P = 0.01) than children with TS without sleep disorder. More children with TS with sleep disorder had severe TS symptoms (P <0.01), tic-related impairment (P<0.01), and severe ADHD symptoms (P < 0.01) compared with children with TS without sleep disorder., Conclusions: Findings suggest greater parent-reported impact and tic-related interference in children with TS with sleep disorder compared with TS without sleep disorder. Results underscore the importance of monitoring and intervention for TS exacerbations, other diagnosed disorders, and medication use, and consideration of socioeconomic context in sleep disorder management and prevention in children with TS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tourette's syndrome affects about 1% of the school-age population. Children and young people with the condition exhibit involuntary motor and vocal (also known as phonic) tics. Only 10% of those with Tourette's syndrome have coprolalia, which involves involuntary swearing and inappropriate language. Tourette's syndrome often presents with other conditions such as obsessive-compulsive disorder, autism and attention deficit hyperactivity disorder. Those affected by Tourette's syndrome may be able to manage the condition with little or no professional support, but some may need pharmacological and nonpharmacological input, particularly from mental health services. It is essential that peers, teachers, healthcare staff and members of the public are aware of Tourette's syndrome to ensure that children and young people living with the condition are supported well., Competing Interests: None declared, (© 2022 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Background: Oculogyric tics are identified in a substantial proportion of patients with Tourette syndrome (TS) and related tic-disorders. Nevertheless, studies assessing its frequency and clinical correlations are lacking., Materials and Methods: We reviewed video-recordings and clinical history of 201 patients with TS and chronic motor/phonic tic disorder, diagnosed according to DSM-5., Results: Oculogyric tics presented in 22.4% of our patients. Transient upward gaze was the most common phenomenology in patients with simple oculogyric tics; whereas eye-closure followed by upward and lateral deviations was the most commonly observed phenomenon in patients with combined oculogyric tics. Oculogyric tics have a median duration of 799 ms (range 299-34,500 ms). Patients with oculogyric tics were younger (P = 0.023) and had a higher frequency of cranial tics (P = 0.037) compared to those without oculogyric tics. No differences in tic severity, frequency of attention-deficit/hyperactivity disorder, obsessive-compulsive disorder or use of dopamine receptor antagonists were observed in patients with and without oculogyric tics., Conclusions: Oculogyric tics are a common phenomenology in chronic tic disorders. They are more common in younger patients with TS and are markers of other cranial tics, but not of TS severity or comorbid neuropsychiatric syndromes., (© 2022. The Author(s) under exclusive licence to Belgian Neurological Society.)

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements., (© 2021. The Author(s).)

Tourette syndrome (TS) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur, especially in children. Reduced inhibitory control abilities have been suggested as a shared phenotype across both conditions but its neural underpinnings remain unclear. Here, we tested the behavioral and electrophysiological correlates of inhibitory control in children with TS, ADHD, TS+ADHD, and typically developing controls (TDC). One hundred and thirty-eight children, aged 7-14 years, performed a Go/NoGo task during dense-array EEG recording. The sample included four groups: children with TS only (n = 47), TS+ADHD (n = 32), ADHD only (n = 22), and matched TDC (n = 35). Brain activity was assessed with the means of frontal midline theta oscillations, as well as the N200 and P300 components of the event-related potentials. Our analyses revealed that both groups with TS did not differ from other groups in terms of behavioral performance, frontal midline theta oscillations, and event-related potentials. Children with ADHD-only had worse Go/NoGo task performance, decreased NoGo frontal midline theta power, and delayed N200 and P300 latencies, compared to typically developing controls. In the current study, we found that children with TS or TS+ADHD do not show differences in EEG during a Go/NoGo task compared to typically developing children. Our findings however suggest that children with ADHD-only have a distinct electrophysiological profile during the Go/NoGo task as indexed by reduced frontal midline theta power and delayed N200 and P300 latencies., Competing Interests: Declaration of competing interest The authors have no biomedical financial interests or potential conflicts of interest to declare related to this present study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Insomnia is common in Tourette syndrome (TS) and chronic tic disorder (CTD), but precise prevalence estimates are lacking., Objective: In this Swedish register-based cohort study, we estimated the prevalence of insomnia in TS/CTD and quantified the magnitude of this association, accounting for familial confounders and relevant somatic and psychiatric comorbidities., Methods: Of 10,444,702 individuals living in Sweden during the period from 1997 to 2013, 5877 had a diagnosis of TS/CTD and were compared to unexposed individuals from the general population on the presence of insomnia using logistic regression models., Results: Individuals with TS/CTD had a period prevalence of insomnia of 32.16%, compared to 13.70% of the unexposed population. This translated into a 6.7-fold increased likelihood of insomnia in TS/CTD (odds ratio adjusted [aOR] for sex, birth year, birth country, and somatic disorders = 6.74; 95% confidence interval [CI], 6.37-7.15). A full sibling comparison, designed to adjust for shared familial factors, attenuated the estimates (aOR = 5.41; 95% CI, 4.65-6.30). When individuals with attention-deficit/hyperactivity disorder (ADHD) and pervasive developmental disorders were excluded, the association was also attenuated, whereas exclusion of other psychiatric comorbidities had minimal impact. Having persistent TS/CTD, comorbid ADHD, and taking ADHD medication greatly increased the likelihood of insomnia., Conclusions: Insomnia is significantly associated with TS/CTD, independently from somatic disorders, familial factors or psychiatric comorbidities, although familial factors, neurodevelopmental comorbidities, and ADHD/ADHD medication may explain part of the association. Insomnia should be routinely assessed and managed in TS/CTD, particularly in chronic patients and in those with comorbid ADHD. Other sleep disorders require further study. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Tourette syndrome (TS) and chronic motor/vocal tic disorder (CTD) are neurodevelopmental conditions defined by the occurrence of multiple tics. Besides the well-known association with attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), rage attacks (RA) represent common and detrimental symptoms for patients. Inorder to explore prevalence of RA in tic disorders, relation to tic severity/comorbidities and available treatments, we performed a systematic literature review based on PRISMA Guidelines. 32 studies published between January 2008 - December 2019 were deemed suitable for the analysis and provided a prevalence of 20-67 %. Most findings showed a direct correlation with tic severity and a significant impact on psychosocial functioning. Although apparently related to comorbid ADHD, RA also frequently occur as independent manifestations. Association with other comorbidities, such as OCD, impulse control and mood disorders has also been reported, not yet fully established. Behavioral interventions appear to be effective, whereas there is limited evidence concerning the efficacy of medication. In TS/CTD, RA may be regarded as a major comorbidity that requires clinical investigation in order to develop personalized treatments., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Tourette syndrome (TS) and persistent motor/vocal tic disorders are neurodevelopmental conditions characterised by the chronic presence of motor and/or vocal tics. Patients with TS often present with co-morbid disorders, especially attention-deficit and hyperactivity disorder (which tends to improve after childhood), and obsessive-compulsive disorder (which can persist in adulthood). We set out to explore pharmacotherapy for tics in adult patients with TS and persistent motor/vocal tic disorders, as well as its relationship with the presence of co-morbid conditions., Methods: We retrospectively reviewed the clinical characteristics and pharmacotherapy of 192 adult patients with TS (n = 187), persistent motor tic disorder (n = 3) and persistent vocal tic disorder (n = 2) attending a specialist clinic in the UK., Results: Anti-dopaminergic medications (n = 65) and alpha-2-agonists (n = 50) were the most commonly prescribed pharmacotherapy for tic management. A sub-group analysis revealed that co-morbid obsessive-compulsive disorder and sub-threshold obsessive-compulsive behaviours were significantly more common in patients treated with anti-dopaminergic medications than patients taking alpha-2-agonists (p = 0.013 and p = 0.047, respectively)., Conclusions: The use of pharmacotherapy options for tic management observed at a specialist clinic for adults with TS reflects guideline recommendations. We found that the presence of co-morbid obsessive-compulsive disorder/behaviours correlates with the choice of anti-dopaminergic medications over alpha-2-agonists, in line with available evidence on the efficacy of anti-dopaminergic medications for the treatment of specific tic-related behavioural symptoms.

Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple tics. In addition to common behavioral co-morbidities such as obsessive-compulsive disorder and attention-deficit and hyperactivity disorder, patients with TS can present with self-injurious behavior (SIB): deliberate, non-accidental, repetitive infliction of self-harm without suicidal intent. In order to determine the prevalence and clinical correlates of SIB in TS, we conducted a systematic literature review in accordance to the methodology described in the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies in Epidemiology. The literature search yielded 20 cohort studies that were suitable for quantitative synthesis. Combined results showed that SIB is present in 35 % of patients with TS. Obsessive-compulsive behaviors appear to be associated with SIB in patients with TS, and their presence should alert clinicians to the possible co-occurrence of SIB, particularly if the patient has multiple behavioral co-morbidities. Since the reviewed studies were methodologically heterogeneous and were conducted in specialist clinics, our findings cannot be generalized to patients with TS in the wider community., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Findings of executive functioning deficits in Tourette syndrome (TS) have so far been inconsistent, possibly due to methodological challenges of previous studies, such as the use of small sample sizes and not accounting for comorbid attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or medication use. We aimed to address these issues by examining several areas of executive functioning (response inhibition, attentional flexibility, cognitive control, and working memory) and psychomotor speed in 174 8-to-12-year-old children with TS [n = 34 without (TS-ADHD) and n = 26 with comorbid ADHD (TS+ADHD)], ADHD without tics (ADHD-TS; n = 54), and healthy controls (n = 60). We compared executive functioning measures and psychomotor speed between these groups and related these to ADHD severity across the whole sample, and tic severity across the TS groups. Children with TS+ADHD, but not TS-ADHD, made more errors on the cognitive control task than healthy children, while TS-ADHD had a slower psychomotor speed compared to healthy controls. The ADHD group showed impairment in cognitive control and working memory versus healthy controls. Moreover, higher ADHD severity was associated with poorer cognitive control and working memory across all groups; there was no relation between any of the executive functioning measures and tic severity. OCD severity or medication use did not influence our results. In conclusion, we found little evidence for executive function impairments inherent to TS. Executive function problems appear to manifest predominantly in relation to ADHD symptomatology, with both cross-disorder and unique features of neuropsychological functioning when cross-comparing TS and ADHD., Competing Interests: Declaration of Competing Interest Jan K. Buitelaar has been a consultant to/member of advisory board of/and/or speaker for Janssen Cilag BV, Eli Lilly, Lundbeck, Shire, Roche, Medice, Novartis, and Servier. He has received research support from Roche and Vifor. He is not an employee or a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, and royalties. The other authors have no conflict of interest to report., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Impaired habit-learning has been proposed to underlie the tic symptoms of Tourette syndrome (TS). However, accounts differ in terms of how habit-learning is altered in TS, with some authors proposing habit formation is impaired due to a deficient 'chunking' mechanism, and others proposing habit-learning is overactive and tics reflect hyperlearned behaviours. Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with TS and is known to affect cognitive function in young people with co-occurring TS and ADHD (TS + ADHD). It is unclear, however, how co-occurring ADHD symptoms affect habit-learning in TS. In this study, we investigated whether young people with TS would show deficient or hyperactive habit-learning, and assessed the effects of co-occurring ADHD symptoms on habit-learning in TS. Participants aged 9-17 years with TS (n = 18), TS + ADHD (n = 17), ADHD (n = 13), and typical development (n = 20) completed a motor sequence learning task to assess habit-learning. We used a 2 (TS-yes, TS-no) × 2 (ADHD-yes, ADHD-no) factorial analysis to test the effects of TS, ADHD, and their interaction on accuracy and reaction time indices of sequence learning. TS was associated with intact sequence learning, but a tendency for difficulty transitioning from sequenced to non-sequenced performance was suggestive of hyper-learning. ADHD was associated with significantly poorer accuracy during acquisition of the sequence, indicative of impaired habit-learning. There were no interactions between the TS and ADHD factors, indicating young people with TS + ADHD showed both TS- and ADHD-related atypicalities in habit-learning., (© 2018 The British Psychological Society.)

Objective: To examine (a) the quality of life (QOL) in children with Tourette's disorder (TD) and ADHD (TD + ADHD) compared with ADHD without tics (ADHD alone) and (b) the effects of the severity of tics, ADHD symptoms, comorbid diagnoses, and family functioning on QOL., Method: The assessments included the Kiddie-Schedule for Affective Disorders and Schizophrenia, Yale Global Tic Severity Scale, ADHD Rating Scale, Pediatric Quality of Life Inventory, and Family Assessment Device., Results: The TD + ADHD group had poorer psychosocial QOL. Agreement between child and parent ratings was higher in the TD + ADHD group, and children reported higher scores than their parents in both groups. Severity of tics and ADHD symptoms had stronger negative associations with parent-reported than child-reported QOL. Significant positive correlations were detected between QOL and family functioning in both groups., Conclusion: Children with TD + ADHD have lower QOL than their peers with ADHD alone. Family functioning seems to affect QOL in both groups.

Tourette syndrome is a chronic tic disorder characterized by motor and vocal tics. Comorbidities such as attention deficit hyperactivity disorder and obsessive compulsive disorder can be found. The overlap between neuroanatomical regions and neurotransmitter systems in the olfactory system and the pathophysiology of Tourette syndrome let us hypothesize altered olfactory performance in Tourette syndrome. The main objective of this study was to systematically assess olfactory functioning in subjects with Tourette syndrome and to compare it to healthy controls. We assessed 28 adults with Tourette syndrome (age 33.1±9.4 years, disease duration 23.7±9.7 years) and 28 healthy controls (age 32.9±9.0 years) matched in regard to age, sex, education and smoking habits. The "Sniffin Sticks" test battery was applied to assess odor threshold, discrimination, and identification. Additionally, the combined score of the odor threshold test, the odor discrimination test and the odor identification test of the "Sniffin Sticks" test battery was calculated. Although it was not the primary aim of this study, we assessed whether tics and comorbidity could contribute to olfactory alterations in adults with Tourette syndrome. Therefore, clinical scores were used to assess severity of tics and co-morbidity such as attention deficit hyperactivity disorder, obsessive compulsive disorder, anxiety and depression in subjects with Tourette syndrome. Pathology of the nasal cavities was excluded with rhinoendoscopy. Independent sample t-tests were applied to compare performance in olfactory tests. In the case of statistically significant differences (critical p-value: 0.05), multiple linear regression analysis was carried out to explore whether tic severity, social impairment, co-morbidity or medical treatment had an impact on the differences found. Descriptive values are reported as mean ± standard deviation. Tourette syndrome subjects showed lower combined scores (Tourette syndrome subjects 31.9 ± 5.1 versus healthy controls 35.0 ± 3.1; p = 0.007), odor identification scores (Tourette syndrome subjects 12.4 ± 2.0 versus healthy controls 13.7 ± 1.4; p = 0.008) and odor discrimination scores (Tourette syndrome subjects 12.1 ± 2.1 versus healthy controls 13.2 ± 1.6; p = 0.041) in comparison to healthy subjects, while there was no difference in odor threshold (Tourette syndrome subjects 7.3 ± 2.7 versus healthy controls 8.1 ± 2.2; p = 0.22). Seven out of 28 Tourette syndrome subjects (25%) scored in the range of the age- and sex-dependent combined score for hyposmia, while two of 28 healthy controls (7%) had a similar low combined score. None of the participants were found to have functional anosmia. Multiple linear regression analyses suggest that social impairment may a predictor for low combined score and odor identification score in Tourette syndrome subjects (p = 0.003). Compared to healthy controls, altered olfaction in adults with Tourette syndrome was found in this study. Normal odor threshold level but lower scores at tasks involving supra-threshold odor concentrations point towards a central-nervous alteration in the processing of olfactory information in Tourette syndrome., Competing Interests: The authors have declared that no competing interests exist.

Gilles de la Tourette syndrome is a chronic and complex tic disorder accompanied by specific behavioral problems in the majority of patients. With its multifaceted interplay between motion and emotion, this condition is a paradigmatic example of the science and art of clinical neuropsychiatry. This review article encompasses the clinical phenomenology of motor and vocal tics and associated sensory experiences (premonitory urges), as well as the behavioral spectrum of the most common comorbidities, including obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, affective symptoms, and impulsivity. Knowledge of the contributions of both tics and behavioral problems to patients' health-related quality of life across the lifespan should assist treating clinicians in formulating a targeted management plan. Although the exact pathophysiology of Gilles de la Tourette syndrome remains elusive, research into therapeutic interventions has expanded the range of available interventions across multiple domains. A thorough understanding of the neurology and psychiatry of this condition is of key importance to meet the needs of this patient population, from the formulation of an accurate diagnosis to the implementation of effective treatment strategies.

Procedural memory, which is rooted in the basal ganglia, plays an important role in the implicit learning of motor and cognitive skills. Few studies have examined procedural learning in either Tourette syndrome (TS) or Attention Deficit Hyperactivity Disorder (ADHD), despite basal ganglia abnormalities in both of these neurodevelopmental disorders. We aimed to assess procedural learning in children with TS (n=13), ADHD (n=22), and comorbid TS-ADHD (n=20), as well as in typically developing children (n=21). Procedural learning was measured with a well-studied implicit probabilistic sequence learning task, the alternating serial reaction time task. All four groups showed evidence of sequence learning, and moreover did not differ from each other in sequence learning. This result, from the first study to examine procedural memory across TS, ADHD and comorbid TS-ADHD, is consistent with previous findings of intact procedural learning of sequences in both TS and ADHD. In contrast, some studies have found impaired procedural learning of non-sequential probabilistic categories in TS. This suggests that sequence learning may be spared in TS and ADHD, while at least some other forms of learning in procedural memory are impaired, at least in TS. Our findings indicate that disorders associated with basal ganglia abnormalities do not necessarily show procedural learning deficits, and provide a possible path for more effective diagnostic tools, and educational and training programs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Tourette syndrome (TS) is a neuropsychiatric disorder involving motor and phonic tics. Inhibitory control is a key issue in TS, and many disruptive or impulsive behaviors might arise from inhibitory deficits. However, conflicting findings regarding TS patients' inhibitory performance in neuropsychological tasks have been reported throughout the literature. Therefore, this meta-analysis aimed to evaluate inhibitory control through neuropsychological tasks, and to analyze the factors modulating inhibitory deficits. To this end, a literature search was performed through MEDLINE and PsycINFO, to retrieve studies including neuropsychological tasks that assessed inhibitory control in TS patients. Of the 4020 studies identified, 61 were included in the meta-analysis, for a total of 1717 TS patients. Our analyses revealed a small to medium effect in favor of inhibitory deficits in TS patients. This effect was larger in TS+ADHD patients, but pure TS patients also showed some inhibitory deficits. Therefore, deficits in inhibitory control seem to be an inherent component of TS, and are exacerbated when ADHD is concomitant., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Tourette's disorder and attention-deficit/hyperactivity disorder often co-occur and have both been associated with structural variation of the basal ganglia. However, findings are inconsistent and comorbidity is often neglected., Methods: T1-weighted magnetic resonance images from children (n = 141, 8 to 12 years) with Tourette's disorder and/or attention-deficit/hyperactivity disorder and controls were processed with the Oxford Centre for Functional MRI [Magnetic resonance imaging] of the Brain (FMRIB) integrated registration and segmentation tool to determine basal ganglia nuclei volume and shape. Across all participants, basal ganglia nuclei volume and shape were estimated in relation to Tourette's disorder (categorical), attention-deficit/hyperactivity disorder severity (continuous across all participants), and their interaction., Results: The analysis revealed no differences in basal ganglia nuclei volumes or shape between children with and without Tourette's disorder, no association with attention-deficit/hyperactivity disorder severity, and no interaction between the two., Conclusion: We found no evidence that Tourette's disorder, attention-deficit/hyperactivity disorder severity, or a combination thereof are associated with structural variation of the basal ganglia in 8- to 12-year-old patients. © 2016 International Parkinson and Movement Disorder Society., (© 2016 International Parkinson and Movement Disorder Society.)

Efficient cognitive control is implicated in tic control in young people with Tourette syndrome (TS). Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with TS and is associated with impaired cognitive control. Young people with TS and ADHD (TS+ADHD) show poorer cognitive control performance than those with TS, but how co-occurring ADHD affects underlying neural activity is unknown. We investigated this issue by examining behavioural and event-related potential (ERP) correlates of cognitive control in young people with these conditions. Participants aged 9-17 with TS (n = 17), TS+ADHD (n = 17), ADHD (n = 11), and unaffected controls (n = 20) performed a visual Go/Nogo task during electroencephalography (EEG) recording. Behavioural performance measures (D-prime, RT, reaction time variability, post-error slowing) and ERP measures (N2, P3, error-related negativity (ERN), error positivity (Pe)) were analysed in a 2 (TS-yes, TS-no) × 2 (ADHD-yes, ADHD-no) factorial analysis to investigate the effects of TS, ADHD, and their interaction. The results of these analyses showed that ADHD was associated with poorer performance and reduced amplitude of all ERPs, reflecting widespread cognitive control impairments. Tourette syndrome was associated with slowed RTs, which might reflect a compensatory slowing of motor output to facilitate tic control. There was no interaction between the TS and ADHD factors for any behavioural or ERP measure, indicating the impairing effects of ADHD on behaviour and electrophysiological markers of cognitive control were present in TS+ADHD and that RT slowing associated with TS was unaffected by co-occurring ADHD symptoms., (© 2015 The British Psychological Society.)

Altered reinforcement learning is implicated in the causes of Tourette syndrome (TS) and attention-deficit/hyperactivity disorder (ADHD). TS and ADHD frequently co-occur but how this affects reinforcement learning has not been investigated. We examined the ability of young people with TS (n=18), TS+ADHD (N=17), ADHD (n=13) and typically developing controls (n=20) to learn and reverse stimulus-response (S-R) associations based on positive and negative reinforcement feedback. We used a 2 (TS-yes, TS-no)×2 (ADHD-yes, ADHD-no) factorial design to assess the effects of TS, ADHD, and their interaction on behavioural (accuracy, RT) and event-related potential (stimulus-locked P3, feedback-locked P2, feedback-related negativity, FRN) indices of learning and reversing the S-R associations. TS was associated with intact learning and reversal performance and largely typical ERP amplitudes. ADHD was associated with lower accuracy during S-R learning and impaired reversal learning (significantly reduced accuracy and a trend for smaller P3 amplitude). The results indicate that co-occurring ADHD symptoms impair reversal learning in TS+ADHD. The implications of these findings for behavioural tic therapies are discussed., (Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.)

Objective: Tic disorders such as Gilles-de-la-Tourette syndrome (TS) are associated with difficulties in withholding movements and sometimes inappropriate actions. The present study examined whether these disorders lead to a specific difficulty in withholding preprogrammed voluntary movements irrespective of decisions on whether or not to move., Method: Children with TS with or without attention-deficit hyperactivity disorder (ADHD) and controls performed a fast-paced simple reaction time task involving responses to a target in a rapid letter stream (9 letters/s, average foreperiod 332 ms) with feedback on response speed., Results: The ADHD group showed more premature responses and more variable response time than other groups, whether the timing of the target was predictable or not., Conclusion: The data indicate that in tic disorders, the presence of ADHD is associated with difficulties in waiting to initiate preprogrammed movements independently of response selection or response timing difficulties., (© The Author(s) 2013.)

Objective: To determine the impact of tic severity in children with Tourette syndrome on parenting stress and the impact of comorbid attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) symptomatology on parenting stress in both children with Tourette syndrome and typically developing children., Study Design: Children with diagnosed Tourette syndrome (n=74) and tic-free typically developing control subjects (n=48) were enrolled in a cross-sectional study., Results: Parenting stress was greater in the group with Tourette syndrome than the typically developing group. Increased levels of parenting stress were related to increased ADHD symptomatology in both children with Tourette syndrome and typically developing children. Symptomatology of OCD was correlated with parenting stress in Tourette syndrome. Parenting stress was independent of tic severity in patients with Tourette syndrome., Conclusions: For parents of children with Tourette syndrome, parenting stress appears to be related to the child's ADHD and OCD comorbidity and not to the severity of the child's tic. Subthreshold ADHD symptomatology also appears to be related to parenting stress in parents of typically developing children. These findings demonstrate that ADHD symptomatology impacts parental stress both in children with and without a chronic tic disorder., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic predisposition. Professionals need to be aware of genetic predisposition to Tourette syndrome, as children with Tourette syndrome and genetic predisposition have more severe symptoms than those children with Tourette syndrome who are without genetic predisposition., (© The Author(s) 2014.)

Tourette syndrome (TS) is a disorder that involves at least one vocal tic and two or more motor tics; however, associated symptoms of obsessive-compulsive disorder (OCD) and attention-deficit disorder or attention-deficit hyperactivity disorder (ADHD) are common. Many children with TS exhibit educational difficulties and one possible explanation may be deficits in executive functioning. The focus of this study was to look at the severity of symptoms often associated with TS (tics and OCD and ADHD symptoms) and its potential relationship with the Behavior Rating Inventory of Executive Function (BRIEF) Parent Form in 11 children diagnosed with TS aged 8 to 14 years old. The parent of the child completed the BRIEF along with symptom measures evaluating tics, OCD behaviors, and ADHD symptoms. Despite relatively low mean scores on the symptom measures and just a few children exhibiting clinically significant scores on the BRIEF indexes, at least half the children exhibited abnormal scores on the Working Memory, Inhibit, and Shift subscales of the BRIEF. Varying patterns of relationships were found on the BRIEF subscales for each symptom severity scale. Results suggest that the BRIEF may be useful in determining the specific areas of difficulty in a population with variable symptomatology.

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., (© The Author(s) 2014.)

Tourette syndrome (TS) is a chronic tic disorder often accompanied by specific obsessive-compulsive symptoms (OCS) or full-blown obsessive-compulsive disorder (OCD). Repetitive behaviours are commonly reported by patients with TS, who experience the urge to perform an action until it has been done "just right". This study investigated the clinical correlates of "not just right experiences" (NJREs) in this clinical population. A standardised battery of self-report psychometric measures was administered to 71 adult patients with TS recruited from a specialist TS clinic. NJREs were systematically screened for using the Not Just Right Experiences-Questionnaire Revised (NJRE-QR). The vast majority of patients in our clinical sample (n=57, 80%) reported at least one NJRE. Patients diagnosed with TS and co-morbid OCD/OCS (n=42, 59%) reported a significantly higher number of NJREs compared to TS patients without OCD/OCS. The strongest correlation was found between NJRE-QR scores and self-report measures of compulsivity. NJREs appear to be intrinsic to the clinical phenomenology of patients with TS and can present with higher frequency in the context of co-morbid OCD/OCS, suggesting they are more related to compulsions than tics., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Tourette syndrome (TS) is a neuropsychiatric developmental disorder characterized by the presence of multiple motor tics and one or more vocal tics. Although TS is primarily biological in origin, stress-diatheses interactions most probably play a role in the course of the illness. The precise influence of the environment on this basically biological disorder is difficult to ascertain, particularly when TS is complicated by comorbidities. Among the many questions that remain unresolved are the differential impact of positive and negative events and specific subtypes of events, and the importance of major crucial events relative to minor daily ones to tic severity., Objectives: To examine the relationships between life events, tic severity and comorbid disorders in Tourette Syndrome (TS), including OCD, ADHD, anxiety, depression and rage attacks. Life events were classified by quantity, quality (positive or negative) and classification types of events (family, friends etc.)., Subjects: Sixty patients aged 7-17 years with Tourette syndrome or a chronic tic disorder were recruited from Psychological Medicine Clinic in Schneider Children's Medical Center of Israel., Instruments: Yale Global Tic Severity Scale; Children's Yale Brown Obsessive Compulsive Scale; Life Experiences Survey; Brief Adolescent Life Events Scale; Screen for Child Anxiety Related Emotional Disorders; Child Depression Inventory/Beck Depression Inventory; ADHD Rating Scale IV; Overt Aggression Scale., Results: Regarding tics and minor life events, there was a weak but significant correlation between severity of motor tics and the quantity of negative events. No significant correlation was found between tic severity and quantity of positive events. Analysis of the BALES categories yielded a significant direct correlation between severity of vocal tics and quantity of negative events involving friends. Regarding comorbidities and minor life events, highly significant correlations were found with depression and anxiety. Regarding tics and major life events, significant correlation was found between the quantity of major life events and the severity of motor tics, but not vocal tics. Regarding comorbidities and major life events, significant correlation was found between the severity of compulsions, ADHD, and aggression and the subjects' personal evaluation of the effect of negative major life events on their lives., Conclusions: Minor life events appear to be correlated with tic severity and comorbidities in children and adolescents with Tourette syndrome. The lack of an association between major life events and tic severity further emphasizes the salient impact of minor life events that occur in temporal proximity to the assessment of tic severity. Clinically, the results match our impression from patient narratives wherein they "blamed" the exacerbations in tics on social interactions. The high correlation between negative life events and depression, anxiety and compulsions symptoms, were reported also in previous studies. In conclusion, These findings may have clinical implications for planning supportive psychotherapy or cognitive behavioral therapy for this patient population., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

There is compelling evidence for an association between structural brain deformities and psychiatric disorders. We report the case of an adolescent boy who was diagnosed with both attention-deficit/hyperactivity disorder and Tourette's syndrome. A full-blown manic episode occurred when he was 13 years old. During his admission to a psychiatric ward, closed-lip schizencephaly in the left frontal lobe and the right parietal lobe was identified through brain imaging. Effective control of his manic symptoms was achieved with quetiapine monotherapy within 3 weeks. This case report implies that the pathophysiology of psychiatric disorders, especially in young patients with multiple comorbid conditions, may be associated with abnormalities in the anatomical and functional development of the brain., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Inattentiveness, impulsivity and hyperactivity are the primary behaviors associated with attention-deficit hyperactivity disorder (ADHD). Previous studies showed that peripheral blood gene expression signatures can mirror central nervous system disease. Tourette syndrome (TS) is associated with inattention (IA) and hyperactivity/impulsivity (HI) symptoms over 50% of the time. This study determined if gene expression in blood correlated significantly with IA and/or HI rating scale scores in participants with TS., Methods: RNA was isolated from the blood of 21 participants with TS, and gene expression measured on Affymetrix human U133 Plus 2.0 arrays. To identify the genes that correlated with Conners' Parents Ratings of IA and HI ratings of symptoms, an analysis of covariance (ANCOVA) was performed, controlling for age, gender and batch., Results: There were 1201 gene probesets that correlated with IA scales, 1625 that correlated with HI scales, and 262 that correlated with both IA and HI scale scores (P<0.05, |Partial correlation (r(p))|>0.4). Immune, catecholamine and other neurotransmitter pathways were associated with IA and HI behaviors. A number of the identified genes (n=27) have previously been reported in ADHD genetic studies. Many more genes correlated with either IA or HI scales alone compared to those that correlated with both IA and HI scales., Conclusions: These findings support the concept that the pathophysiology of ADHD and/or its subtypes in TS may involve the interaction of multiple genes. These preliminary data also suggest gene expression may be useful for studying IA and HI symptoms that relate to ADHD in TS and perhaps non-TS participants. These results will need to be confirmed in future studies.

Several common developmental disorders emerge during early to middle childhood (e.g. autism, attention deficit and hyperactivity disorder) and are associated with impairments in executive function (EF). Contrary to the prevailing view, I suggest that, within populations at-risk, the association with EF is found because individuals with strong EF skills are better able to compensate for atypicalities in other brain systems early in life, and are therefore less likely to receive a diagnosis later in life. I discuss evidence consistent with this view from considerations of individual variability, neuroimaging, and genetics. To the extent that this view is correct, it offers hope for remediation of some later emerging symptoms, as evidence from typical groups indicates that training programs for EF in preschoolers may be effective in improving skills., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

Tourette's disorder (TD) in children and adolescents is frequently co-morbid with attention-deficit/hyperactivity disorder (ADHD). Dopamine-blockers are the first line treatment for TD, whereas dopamine-agonists, such as stimulants, are the gold-standard in the treatment of ADHD. These contrasting effects supported concerns about the risk that stimulants for treating ADHD may trigger or worsen co-morbid tics. Aripiprazole, a partial dopamine agonist, acts as an antagonist at dopamine D2 receptors in hyperdopaminergic conditions and displays agonist properties under hypodopaminergic conditions. The present study describes the use of aripiprazole (10.0 ± 4.8 mg/day) in a consecutive group of 28 patients with a primary diagnosis of TD and co-morbid ADHD, combined subtype. The Yale Global Tic Severity Scale (YGTSS) and the ADHD-Rating Scale (ADHD-RS-IV) were used as primary outcome measures and both significantly improved (p<0.001) after the treatment. Global measures of severity (Clinical Global Impressions-Severity) and of functional impairment (Children's Global Assessment Scale) also significantly improved during the treatment (p<0.001). At the YGTSS there was a reduction of 42.5%, in motor tics, of 47.9% in phonic tics (44.7% for the combined scores), and of 32.3% in tic impairment. Nineteen patients (67.9%) had a reduction of at least 50% of the YGTSS score (motor+phonic tics). The improvement at the ADHD-RS-IV score was 22.5%, 12 patients (42.8%) presented an improvement of 30%, but only 2 (7.1%) an improvement greater than 50%. Using a logistic regression model, a reduction of at least 30% in ADHD-RS-IV score was more likely to occur in the obsessive-compulsive disorder co-morbid group. Aripiprazole was well tolerated and none of the patients discontinued medication because of side effects. In summary, aripiprazole resulted in an effective treatment for TD, but it was only moderately effective on co-occurring ADHD symptomatology. Our preliminary data suggest that aripiprazole may represent a possible therapeutic option, among other possible monotherapies addressing both tics and ADHD.

Objective: To evaluate 410 real-life patients treated with stimulants and assessed systematically over several years., Method: Naturalistic observational study. A database was compiled on the basis of a review of the medical charts of patients attending a specialized ADHD clinic., Results: The diversity of ADHD patients was evident from the comorbidity, age at start, comedication, and treatment needs over time. Dosages corresponded to guidelines in most patients, but some needed higher dosages or got along on lower dosages for long periods. Age at start and comorbidity influenced dosage, and dosage was associated to differential outcome groups., Conclusion: The study findings underscored the diversity of ADHD patients and that individual factors should be taken into account when tailoring individual treatment schedules. Findings further showed that stimulant dosages are dynamic over time and depend on individual factors, that individual factors influence outcome, and that patients with ADHD should be individually monitored and stimulant dosages adjusted continuously.

Tourette's disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). While the relationship between TD and OCD suggests that they share etiological factors, the exact relationship between TD and ADHD is less clear. The goal of the current analyses was to understand better the familial relationship between DSM-IV ADHD and TD. Direct interview diagnostic data from a case-control study of 692 relatives of 75 comorbid TD and ADHD (TD + ADHD), 74 TD without ADHD (TD Only), 41 ADHD without TD (ADHD Only), and 49 control probands were analyzed. Hierarchical loglinear modeling was used to explore association patterns between TD, ADHD, and OCD or sub-clinical OCD (OCD/OCDsub) diagnoses among the 190 affected probands and their 538 relatives. The presence of OCD or OCDsub diagnosis in a proband was associated with a significantly increased risk of comorbid TD + ADHD in his/her relatives. The finding of an association between TD, ADHD and a proband OCD/OCDsub diagnosis was unexpected. The current results suggest that TD, ADHD, and OCD symptoms have overlapping neurobiology when occurring in families of TD and/or ADHD probands., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: Neuropsychological functioning in children with Tourette syndrome (TS) has been characterized by subtle deficits in response inhibition, visual-motor integration, and fine-motor coordination. The association of these deficits with the tics of the TS versus co-occurring attention-deficit/hyperactivity disorder (ADHD) has not been well understood because of small sample sizes and lack of adequate control conditions. We examined neuropsychological functioning in relatively large and well-characterized samples of children categorized as TS, TS-plus-ADHD, ADHD, and unaffected controls., Method: A total of 56 children with TS-only, 45 with TS-plus-ADHD, 64 with ADHD, and 71 healthy community control subjects were assessed on a battery of neuropsychological measures including the Connors' Continuous Performance Test (CPT), the Stroop Color-Word Interference Test (Stroop), the Beery Visual-Motor Integration Test (VMI), and the Purdue Pegboard Test., Results: There were no differences between children with TS-only and unaffected controls on the measures of response inhibition and visual-motor integration. Boys with TS-only but not girls with TS-only were impaired in the dominant hand Purdue performance. Children with ADHD were impaired on all study measures. Children with TS-plus-ADHD revealed no deficits on the Stroop, VMI, and Purdue tests but were impaired on the sustained attention portion of the CPT., Conclusions: These results indicate that co-occurring ADHD may be responsible for the neuropsychological deficits, or at least those assessed in the present study, in children with TS. Explanations in terms of neurobiological mechanisms of co-occurring TS and ADHD, as well as possible compensatory mechanisms in children with TS, are discussed., (Copyright © 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: This study examined the psychosocial and behavioral concomitants of anxiety in clinic-referred boys with attention-deficit/hyperactivity disorder (ADHD) with and without chronic multiple tic disorder (CMTD)., Method: ADHD boys with (n = 65) and without (n = 94) CMTD were evaluated with measures of psychiatric symptoms, mental health risk factors, and academic and social performance., Results: Boys with CMTD evidenced more severe anxiety and less social competence and were more likely to be living with only one biological parent than the ADHD Only group, but the magnitude of group differences was generally small. The severity of generalized anxiety, separation anxiety, social phobia, and obsessive-compulsive symptoms were uniquely associated with a different pattern of risk factors, and there was some evidence that these patterns differed for the two groups of boys., Conclusion: Boys with CMTD had a relatively more severe and complex pattern of anxiety that was associated with different clinical features, all of which suggests that ADHD plus CMTD might better be conceptualized as a distinct clinical entity from ADHD Only. However, findings from the extant literature are mixed, and therefore this remains a topic for further study.

Objective: Tourette syndrome (TS) and attention-deficit hyperactivity disorder (ADHD) are frequently seen in combination, though the cause of comorbidity is uncertain. Low birth weight is a known risk factor for ADHD. The objective of the study was to assess the association between pre- and perinatal morbidity and the comorbid diagnosis of ADHD in children with TS., Method: A nested case-control study of children evaluated for TS at a subspecialty clinic was performed. Cases were defined as children with TS and ADHD; controls had TS without ADHD. Exposure to pre- and perinatal morbidity was assessed using demographic information booklets completed by parents before the diagnostic interview., Results: Three hundred fifty-three children were included, 181 cases and 172 controls. Children with TS and ADHD had a greater odds of exposure to low birth weight status, prematurity, breathing problems, and maternal smoking compared with children with TS only. A multivariable logistic regression model found adjusted odds ratios for the comorbid diagnosis of TS and ADHD of 2.74 (95% CI 1.03-7.29, p = .04) in children born low birth weight, and of 2.43 (95% CI 1.23-4.82, p = .01) for children exposed to maternal smoking., Conclusion: In children with TS, there is a greater odds of comorbid ADHD in children born with low birth weight or with exposure to maternal smoking. The commonality of risk factors for ADHD only and tic-related ADHD supports a common underlying neurobiology. Women with fetuses at risk for TS should avoid smoking and preventable causes of low birth weight to minimize the risk of comorbid ADHD.

Eighty participants (62 males; 18 females; age range: 6-16 years) took part in the study, comprising four groups of 20 subjects each: TS-only, ADHD-only, TS+ADHD, controls. The age distributions, did not differ significantly among the four groups. The severity of symptoms, assessed by the TSGS, did not differ significantly between the two TS groups. Standardised measures were used throughout. The "cases" (i.e. TS-only, TS+ADHD, ADHD-only) were significantly different from controls on most measures of behavior. There were also differences amongst the various clinical subgroups, with, in general, TS-only participants being similar to controls with regards to both "total behavior" ratings and cognitive testing results. A diagnosis of ADHD, either or its own or in association with TS, was associated with greater maladaptive behavior and worse cognitive functioning. With regards to affective symptoms and anxiety, the three clinical groups did not differ from each other, but each of them was more affected than the control group. One finding in our study which differed from previous literature was that TS-only patients were rated as more "delinquent" than controls by their parents: possible reasons for this are discussed. Oppositional defiant disorder (ODD) was seen in a few (2,3,3 ODD patients in each clinical group), but as numbers were small no statistics were undertaken. Family histories were in accord with both TS and ADHD being genetic disorders, but sharing an overlap in only some cases. The "additive effect" hypothesis is discussed in detail in the light of our results and recent literature.

Objective: In children with attention deficit hyperactivity disorder (ADHD), clinical responses to the selective norepinephrine reuptake inhibitor atomoxetine (ATX) vary. We sought to determine in children with Tourette Syndrome (TS) whether clinical responses correlate with changes in short interval cortical inhibition (SICI)., Methods: Fourteen children, ages 8-16, with ADHD and TS were treated open-label with ATX for one month. ADHD rating scale scores and SICI, measured with paired-pulse transcranial magnetic stimulation (pTMS), were assessed blindly and independently at treatment onset and one month later., Results: Eleven children, mean ADHD rating scale scores 31.8 (SD 8.2) at onset, completed the study. After one month, ADHDRS changes ranged from an increase of 4 points to a decrease (improvement) of 24 points (mean change -9.6, SD 9.1). The changes in ADHDRS scores correlated with reduction in SICI (r=.74, p=.010)., Conclusions: In children with TS, one month of atomoxetine treatment appears to induce correlated improvements in ADHD and, paradoxically, further reductions in cortical inhibition., Significance: PTMS-evoked SICI in ADHD with TS may be a biomarker of both deficiency and compensatory changes within cortical interneuronal systems. Effective atomoxetine treatment may augment compensatory processes and thereby reduce SICI.

Background: Tourette syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common and debilitating neuropsychiatric illnesses that typically onset in the preschool years. Recently, both conditions have been subject to neuroimaging studies, with the aim of understanding their underlying neurobiological correlates., Objective: The relation of TS and ADHD is discussed against the background of findings from previous Magnetic Resonance Imaging (MRI) studies., Methods: We review the designs and major findings of previous studies that have examined TS with comorbid ADHD, and we briefly contrast these findings with those in ADHD without comorbid tic disorders., Results: The frequent comorbidity of TS and ADHD may reflect a common underlying neurobiological substrate, and studies confirm the hypothesized involvement of fronto-striatal circuits in both TS and ADHD. However, poor inhibitory control and volumetric reductions in fronto-striatal circuits appear to be core features of ADHD, whereas reduced volumes of the caudate nucleus, together with activation and hypertrophy of prefrontal regions that likely help to suppress tics, seem to be core features of TS., Conclusion: The etiological relationship between TS and ADHD must be clarified further with cross-sectional and, if possible, longitudinal imaging studies that examine samples of substantial size, including subgroups with pure TS and ADHD, as well as with comorbid conditions.

Noradrenergic abnormalities have been proposed in the pathophysiology of Tourette syndrome and attention-deficit hyperactivity disorder. Patients with Tourette syndrome with (n=115) and without (n=110) attention-deficit hyperactivity disorder were evaluated for association with two single nucleotide polymorphisms of the norepinephrine transporter gene (SLC6A2); a T-182C single nucleotide polymorphism located in the 5' flanking promoter region and a silent mutation (G1287A) occurring in exon 9. A polymerase chain reaction restriction enzyme assay was developed for the T-182C single nucleotide polymorphism based on a prior sequencing methodology. In this case-control study, no association was identified between either polymorphism and Tourette syndrome or attention-deficit hyperactivity disorder. In a small subset, these NET polymorphisms did not predict therapeutic response to the noradrenergic transporter inhibitor atomoxetine. Further research with additional NET polymorphisms and larger sample sizes are indicated in the pursuit of biomarkers for therapeutic responders.