Tourette's Syndrome and Tic Disorders

Histaminergic dysfunction has been recently linked to tic disorders and to aberrant striatal function. There is a particular interest in the histamine 3 receptor (H3R) due to its clinical implications for treating multiple disorders and its high expression in the brain. Striatal histamine (HA) modulates through the H3R in complex ways the release of striatal neurotransmitters into this brain region. The H3R has been classically described to be coupled to Gi , although there is evidence that revealed that striatal H3R forms heteromers with the dopamine receptors 1 and 2 in the medium spiny neurons (MSNs) than changes this signaling...

BACKGROUND: Premonitory urge ratings have advanced our understanding of urge phenomenology among individuals with tic disorders (TD). However, these ratings have been limited by their reliance on a single global dimension of urge severity. This study examined the psychometric properties of a novel scale called the Individualized Premonitory Urge for Tics Scale (I-PUTS) that assesses urge severity across multiple dimensions (number, frequency, and intensity). METHOD: Seventy-five youth with a TD and their parents participated...

OBJECTIVE: To examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders. METHODS: Data from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13...

BACKGROUND: γ-Aminobutyric acid has been implicated in the pathophysiology of Tourette's disorder. The present study primarily sought to examine in vivo γ-aminobutyric acid levels in the anterior cingulate cortex in psychotropic medication-free adolescents and young adults. Secondarily, we sought to determine associations between γ-aminobutyric acid in the anterior cingulate cortex and measures of tic severity, tic-related impairment, and anxiety and depression symptoms. METHODS: γ-Aminobutyric acid levels were measured using proton magnetic resonance spectroscopy...

In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS), deep brain stimulation (DBS) of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation...

BACKGROUND: Persons with neuropsychiatric disorders are at increased risk of suicide, but there is little data concerning Tourette's and chronic tic disorders (TD/CTD). We aimed to quantify the risk of suicidal behavior in a large nationwide cohort of patients with TD/CTD, establish the contribution of psychiatric comorbidity to this risk, and identify predictors of suicide. METHODS: Using a validated algorithm, we identified 7736 TD/CTD cases in the Swedish National Patient Register during a 44-year period (1969-2013)...

BACKGROUND: Previous studies suggest that adults with Tourette syndrome (TS) can respond unconventionally on tasks involving social cognition. We therefore hypothesized that these patients would exhibit different neural responses to healthy controls in response to emotionally salient expressions of human eyes. METHOD: Twenty-five adults with TS and 25 matched healthy controls were scanned using fMRI during the standard version of the Reading the Mind in the Eyes Task which requires mental state judgements, and a novel comparison version requiring judgements about age...

Previous studies of brain structure in Tourette syndrome (TS) have produced mixed results, and most had modest sample sizes. In the present multicenter study, we used structural magnetic resonance imaging (MRI) to compare 103 children and adolescents with TS to a well-matched group of 103 children without tics. We applied voxel-based morphometry methods to test gray matter (GM) and white matter (WM) volume differences between diagnostic groups, accounting for MRI scanner and sequence, age, sex and total GM+WM volume...

Gilles de la Tourette syndrome is a complex, idiopathic neuropsychiatric disorder whose pathophysiological mechanisms have yet to be elucidated. It is phenotypically heterogeneous and manifests more often than not with both motor and behavioral impairment, although tics are its clinical hallmark. Tics themselves present with a complex profile as they characteristically wax and wane and are often preceded by premonitory somatosensory sensations to which it is said a tic is the response. Highly comorbid with obsessive-compulsive disorder and attention deficit-hyperactivity disorder, it is purported to be an epigenetic, neurodevelopmental spectrum disorder with a complex genetic profile...

Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1- like (D1R and D5R) and D2- like receptors (D2R, D3R, and D4R)...

The article by Hashemiyoon et al. is a masterful synthesis of the clinical, genetic, and neurobiological aspects of Gilles de la Tourette's syndrome that provides unique insights into the neural state dysfunctions that underlie this enigmatic disorder. In particular, the authors make a powerful argument for the disorder arising from hyposynchronization within cortico-basal ganglia-thalamocortical systems which may result from a genetically-driven developmental insult to interneuron regulation, and suggest deep brain stimulation as a valuable tool to assess how balance may be restored to the system and reverse the pathological state...

Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with 'pure' TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively...

This study assesses the risk of fractures among children with Tourette syndrome (TS), and identifies the effects of comorbidities and antipsychotics. We randomly sampled the claims data of 1 million enrollees in the National Health Insurance program of Taiwan, and identified 1258 children with TS diagnosed between 2000 and 2010. Additionally, 12,580 children without TS who were frequency matched for sex, age, residential area, parental occupation, and index year were identified for comparison. The children's cases were followed until December 31, 2010, or censored to ascertain incident fractures cases and associations with comorbidities of attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) and treatments with antipsychotics, antidepressants, or clonidine...

OBJECTIVE: Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. METHOD: Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals...

Abnormal involuntary movements often improve in response to anti-dopaminergic drugs. In contrast to classic neuroleptics that block dopamine receptors, drugs that deplete presynaptic dopamine by blocking vesicular monoamine transporter type 2 (VMAT2) seem to be safer and have little or no risk of tardive dyskinesia. This is one reason why there has been a recent emergence of novel VMAT2 inhibitors. Areas covered: Since the approval of tetrabenazine, the classic VMAT2 inhibitor, in the treatment of chorea associated with Huntington disease (HD), other VMAT2 inhibitors (e...

Coprolalia in neuropsychiatry is typically associated with tic disorders, in particular Gilles de la Tourette syndrome. To date, there has been no report of functional coprolalia. Here, we provide the clinical characteristics of 13 adolescent and adult patients with coprolalic and other functional tic-like complex vocalizations who, on the basis of these symptoms, were misdiagnosed with a primary tic disorder, most commonly Gilles de la Tourette syndrome. We describe similarities and highlight the differences from primary tic disorders in order to provide a pragmatic list of clinical clues that will facilitate correct diagnostic labeling and thereby treatment...

Population-based assessment of Tourette syndrome (TS) and other tic disorders produces a paradox. On one hand, ideally diagnosis of tic disorders requires expert observation. In fact, diagnostic criteria for TS explicitly require expert assessment of tics for a definite diagnosis. On the other hand, large-scale population surveys with expert assessment of every subject are impracticable. True, several published studies have successfully used expert assessment to find tic prevalence in a representative population (e...

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...

Tourette's disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics...

Several lines of evidence support a "dopaminergic hypothesis" in the pathophysiology of Gilles de la Tourette syndrome (TS). The aim of this study was to investigate for the first time epigenetic changes in DNA methylation in different dopamine genes in adult patients with TS. We included 51 well characterized adult patients with TS (41 males, 10 females, mean age = 35 ± 12.6 years, range, 18-71 years) and compared results with data from a group of 51 sex- and age-matched healthy controls. Bisulfite sequencing was used to measure peripheral DNA methylation of the dopamine transporter (DAT), the dopamine D2 receptor (DRD2), and the catechol-O-methyltransferase (COMT) genes...