Tourette Research Articles

Problematic use of TikTok and mutism in an adolescent with Down syndrome: Case report and Literature Review

Problematic use of social media by adolescents, including TikTok, generates several negative consequences in the short and in the long term. This article reports the case of an adolescent who makes excessive and problematic use of social media, especially TikTok, and the development of aggressive behavior, mutism silence, and tics-like movements. During adolescence, social media is important for the development of cognitive and socio-emotional skills. However, problematic use has negative repercussions in several areas, including a higher incidence of depression, anxiety, impulsivity, psychological or sexual abuse, and recently, an increase in tics and Tourette syndrome associated with excessive use of TikTok has been described. In regards to that, it is important to raise awareness among the population on such subject, especially those who deal with adolescents, so that they can adopt strategies to limit use in order to enjoy the benefits of this technology and to minimize negative impacts on physical and mental health.

Exploring the Mechanism of Action of Spleen-Tonifying Medication in Treating Tourette Syndrome Based on Network Pharmacology and Mitochondrial Metabolism Experiment

Exploring the Mechanism of Action of Spleen-Tonifying Medication in Treating Tourette Syndrome Based on Network Pharmacology and Mitochondrial Metabolism Experiment

Reframing stigma in Tourette syndrome: an updated scoping review.

Persistent tic disorders (PTD) such as Tourette's syndrome (TS) are common childhood-onset neurodevelopmental disorders. Stigmatization of individuals with these disorders remains an ongoing problem. The purpose of this scoping review is to serve as an updated review of the research regarding stigmatization in youth with PTD since the publication of the original systematic review about this topic in 2016. The electronic databases Embase, Web of Science, PubMed, PsycINFO, and CINAHL were searched. Of the 4751 initial articles screened after removing duplications, 47 studies met the inclusion criteria. The studies were examined under the social-ecological stigmatization model, which helps categorize stigmatization into individual, interpersonal, community, and structural levels and serves as a broader definition of stigmatization than the previous systematic review. On the individual level, youth with PTD had lower self-esteem than peers, often leading to fear of future stigmatization, avoidant behaviors, and self-stigmatization. They also experienced higher rates of bullying and other forms of abuse than peers at the interpersonal level. At the community level, youth with PTD faced discriminatory environments in school and work and limited availability of community services and healthcare access. At the structural level, knowledge about PTD was limited in the general population, often about the limited portrayals of PTD in the media. We hope that the broader scope of this review serves to help inform future efforts to decrease the stigmatization faced by this group.

Functional Interdiscursivity and Linguistic Conventions in Neuronovels

This study aims to challenge, both theoretically and practically, the concept of genre in translation studies. First, starting from the conceptual delimitation and theoretical boundaries between text type, genre and register, this article presents the characteristics of these concepts and their applicability in relation to the translation process. Secondly, by exploiting the functionality of interdiscursivity and hybridisation of genres, the present analysis proposes a discussion of how the neuronovel fluidises the boundaries between literary genre and neuroscientific discourse through the “neurologisation” of vocabulary, style and narrative strategies, and of the particularities that the translation of neuronovels or literary neurotranslation reveals. The study concludes with a case study of the translation into Romanian of Jonathan Lethem’s novel Motherless Brooklyn (1999), focusing on the translation strategies of simple and complex vocal tics and on the translation difficulties imposed by the atypicality of narrative discourse told from the perspective of a character diagnosed with Tourette Syndrome.

Automated Quantification of Eye Tics Using Computer Vision and Deep Learning Techniques.

Tourette syndrome (TS) tics are typically quantified using "paper and pencil" rating scales that are susceptible to factors that adversely impact validity. Video-based methods to more objectively quantify tics have been developed but are challenged by reliance on human raters and procedures that are resource intensive. Computer vision approaches that automate detection of atypical movements may be useful to apply to tic quantification. The current proof-of-concept study applied a computer vision approach to train a supervised deep learning algorithm to detect eye tics in video, the most common tic type in patients with TS. Videos (N = 54) of 11 adolescent patients with TS were rigorously coded by trained human raters to identify 1.5-second clips depicting "eye tic events" (N = 1775) and "non-tic events" (N = 3680). Clips were encoded into three-dimensional facial landmarks. Supervised deep learning was applied to processed data using random split and disjoint split regimens to simulate model validity under different conditions. Area under receiver operating characteristic curve was 0.89 for the random split regimen, indicating high accuracy in the algorithm's ability to properly classify eye tic vs. non-eye tic movements. Area under receiver operating characteristic curve was 0.74 for the disjoint split regimen, suggesting that algorithm generalizability is more limited when trained on a small patient sample. The algorithm was successful in detecting eye tics in unseen validation sets. Automated tic detection from video is a promising approach for tic quantification that may have future utility in TS screening, diagnostics, and treatment outcome measurement. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Psychosocial experiences in youth with Tourette syndrome: a systematic review and meta-synthesis.

Suffering from Tourette syndrome (TS) disrupts the daily lives and interpersonal relationships of patients. The psychosocial experiences of young people with TS are not yet clear. The aim of the systematic review is to identify and synthesize the psychosocial experiences of young people with TS. A meta-synthesis was conducted. PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Chinese Electronic Periodical Services databases were searched for articles published from their inception to February 2023. This review followed the Joanna Briggs Institute's Guidelines for Systematic Reviews according to a previously developed protocol. We used the confidence of synthesized qualitative findings (ConQual) approach to evaluate the credibility and dependability of the synthesized findings. This review included 12 qualitative studies from Western and Asian countries published between 2005 and 2019, representing 190 young people with TS. We identified five synthesized findings: affliction by intractable TS, TS was negatively perceived in the social and cultural context, self-adjustment in response to social interaction, response to receiving various interventions, and positivity in promoting self-acceptance. The ConQual grade for each generated synthesized finding ranged from low to moderate. The psychosocial experiences of youths living with TS are unique and are influenced by their interpersonal relationships, social context, and cultural framework. The findings recommend that healthcare providers assist young people in developing personalized symptom management strategies and provide guidance and care that meets the needs of each individual.

A three-dimensional model of neural activity and phenomenal-behavioral patterns.

How phenomenal experience and behavior are related to neural activity in physiology and psychopathology represents a fundamental question in neuroscience and psychiatry. The phenomenal-behavior patterns may be deconstructed into basic dimensions, i.e., psychomotricity, affectivity, and thought, which might have distinct neural correlates. This work provides a data overview on the relationship of these phenomenal-behavioral dimensions with brain activity across physiological and pathological conditions (including major depressive disorder, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, anxiety disorders, addictive disorders, Parkinson's disease, Tourette syndrome, Alzheimer's disease, and frontotemporal dementia). Accordingly, we propose a three-dimensional model of neural activity and phenomenal-behavioral patterns. In this model, neural activity is organized into distinct units in accordance with connectivity patterns and related input/output processing, manifesting in the different phenomenal-behavioral dimensions. (1) An external neuralunit, which involves the sensorimotor circuit/brain's sensorimotor network and is connected with the external environment, processes external inputs/outputs, manifesting in the psychomotor dimension (processing of exteroception/somatomotor activity). External unit hyperactivity manifests in psychomotor excitation (hyperactivity/hyperkinesia/catatonia), while external unit hypoactivity manifests in psychomotor inhibition (retardation/hypokinesia/catatonia). (2) An internal neuralunit, which involves the interoceptive-autonomic circuit/brain's salience network and is connected with the internal/body environment, processes internal inputs/outputs, manifesting in the affective dimension (processing of interoception/autonomic activity). Internal unit hyperactivity manifests in affective excitation (anxiety/dysphoria-euphoria/panic), while internal unit hypoactivity manifests in affective inhibition (anhedonia/apathy/depersonalization). (3) An associative neuralunit, which involves the brain's associative areas/default-mode network and is connected with the external/internal units (but not with the environment), processes associative inputs/outputs, manifesting in the thought dimension (processing of ideas). Associative unit hyperactivity manifests in thought excitation (mind-wandering/repetitive thinking/psychosis), while associative unit hypoactivity manifests in thought inhibition (inattention/cognitive deficit/consciousness loss). Finally, these neural units interplay and dynamically combine into various neural states, resulting in the complex phenomenal experience and behavior across physiology and neuropsychiatric disorders.

Functional Tic-Like Behaviors: A Common Comorbidity in Patients with Tourette Syndrome.

Comorbid functional tic-like behaviors (FTB) have been described only rarely in patients with Tourette syndrome (TS). We present the first large sample of patients suffering from TS and FTB to raise awareness of this clinical presentation and to guide how to differentiate one from the other. We analyzed clinical data of 71 patients (n = 27 [38.0%] female, mean age: 21.5, range: 11-55) with TS + FTB. In the majority of patients, FTB started abruptly on average 15 years after tic onset with "treatment-resistant" complex movements and ("coprophenomena-like") vocalizations preceded by timely related psychological stressors. Psychological evaluation revealed evidence for internal conflicts (79%), emotional dysregulation (56%), and maintaining factors (70%). About one third of patients had a positive history for further medically unexplained symptoms. Compared to a large TS sample (n = 1032), patients with TS + FTB were more likely to be female, and presented significantly more common with "coprophenomena-like" symptoms, atypical influential factors, atypical descriptions of premonitory sensations, and higher rates of comorbid obsessive-compulsive disorder and "self-injurious" behavior. Based on our data it can be assumed that FTB is a common comorbidity in TS, similar to functional overlay in other movement disorders and epilepsy. Before classifying a patient as suffering from treatment-resistant TS, FTB should be ruled out.

Smart dual imprinted Origami 3D-ePAD for selective and simultaneous analysis of vanillylmandelic acid and 5-hydroxyindole-3-acetic acid carcinoid cancer biomarkers using graphene quantum dots coated with dual molecularly imprinted polymers

Measuring the levels of the biomarkers vanillylmandelic acid (VMA) and 5-Hydroxyindole-3-acetic acid (5-HIAA) is a valuable tool for clinical diagnosis not only of neuroblastoma or carcinoid syndrome, but also of essential hypertension, depression, migraine, and Tourette's syndrome. Herein, we explore using graphene quantum dots (GQDs) coated with molecularly imprinted polymer (MIP) as novel dual-imprinted sensors for selective and simultaneous determination of VMA and 5-HIAA in urine and plasma samples. The dual-MIP was successfully coated on the GQDs core via co-polymerization of (3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS), acting as functional and cross-linking monomers, respectively. In addition, we successfully created the dual imprinted VMA and 5-HIAA shell on the GQDs' core via a one-pot synthesis. We fabricated a facile and ready-to-use Origami three-dimensional electrochemical paper-based analytical device (Origami 3D-ePAD) for simultaneous determination of VMA and 5-HIAA using a GQDs@dual-MIP modified graphene electrode (GQDs@dual-MIP/SPGE). The Origami 3D-ePAD was designed to form a voltammetric cell on a three-layer foldable sheet with several advantages. For example, they were quickly assembled and enhanced the device's physical durability with the hydrophobic backup sheet. The developed dual imprinted Origami 3D-ePAD leads to substantially enhanced sensitivity and selectivity to electrochemical signal amplification generated from increasing the electrode-specific surface area, electrocatalytic activity, and the large numbers of dual imprinted sites for VMA and 5-HIAA detection. The synthetic recognition sites are highly selective for 5-HIAA and VMA molecules with an imprinting factor of 8.46 and 7.10, respectively. Quantitative analysis relying on square wave voltammetry reveals excellent linear dynamic ranges of around 0.001–25 μM, with detection limits of 0.023 nM for 5-HIAA and 0.047 nM for VMA (3Sb, n = 3). The Origami 3D-ePAD provides high accuracy and precision (i.e., recovery values of 5-HIAA ranged from 82.98 to 98.40 %, and VMA ranged from 83.28 to 104.39 %), and RSD less than 4.37 %) in urine and plasma samples without any evidence of interference. Hence, it is well suited as a facile and ready-to-use disposable device for point-of-care testing. It is straightforward, cost-effective, reproducible, and stable. Furthermore, it allows for rapid analysis (analysis time ∼20s) useful in medical diagnosis and other relevant fields.

Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD

Autism spectrum disorder (ASD), Tourette syndrome (TS), and attention-deficit/hyperactivity disorder (ADHD) display strong male sex bias, due to a combination of genetic and biological factors, as well as selective ascertainment. While the hemizygous nature of chromosome X (Chr X) in males has long been postulated as a key point of “male vulnerability”, rare genetic variation on this chromosome has not been systematically characterized in large-scale whole exome sequencing studies of “idiopathic” ASD, TS, and ADHD. Here, we take advantage of informative recombinations in simplex ASD families to pinpoint risk-enriched regions on Chr X, within which rare maternally-inherited damaging variants carry substantial risk in males with ASD. We then apply a modified transmission disequilibrium test to 13,052 ASD probands and identify a novel high confidence ASD risk gene at exome-wide significance (MAGEC3). Finally, we observe that rare damaging variants within these risk regions carry similar effect sizes in males with TS or ADHD, further clarifying genetic mechanisms underlying male vulnerability in multiple neurodevelopmental disorders that can be exploited for systematic gene discovery.

Deep brain stimulation for Tourette syndrome: modulation of the limbic-motor interface network.

Deep brain stimulation (DBS) is an effective treatment for medically refractory Tourette syndrome (TS). Several effective targets have been reported, but there is still controversy about the networks involved in the efficacy of DBS for TS. Here, the authors aimed to identify the basal ganglia-thalamo-cortical networks associated with tic and obsessive-compulsive behavior (OCB) improvement and the network link between the two main targets for TS. A retrospective analysis of 21 patients treated with pallidal and thalamic DBS was performed. Tics and OCB scores were recorded before and after DBS. The authors localized the electrodes in standard MNI (Montreal Neurological Institute) space and calculated the volume of tissue activated with the settings at the last follow-up to obtain areas of maximal improvement ("sweet spots") among all patients for the pallidal and thalamic targets. Tractography was used to show the white matter pathways associated with maximal tic and OCB improvement. Ten patients treated with pallidal DBS and 11 patients treated with thalamic DBS were included. Responder rates were 80% in the pallidal and 64% in the thalamic target groups. Sweet spots for tics and OCB clustered in several areas across the basal ganglia and thalamus delineated two main networks. Tic reduction in the pallidal target mapped to a limbic pallidothalamic network and in the thalamic target to the premotor thalamocortical network. Putting these two networks together will form the main output of the so-called limbic-motor interface network. However, OCB reduction mapped a dorsomedial prefrontal cortex/dorsal anterior cingulate (dmPFC/dACC) network. The authors demonstrated the involvement of the limbic-motor interface network during effective DBS for tics in patients with TS. OCB redution was associated with the additional involvement of dmPFC/dACC connections passing dorsal to the head of the globus pallidus pars externa on its way to the thalamus and midbrain.

Tourette syndrome: Impact of comorbid ADHD, OCD and autism spectrum

Tourette syndrome: Impact of comorbid ADHD, OCD and autism spectrum

Changes in the topological organization of the default-mode network in Tourette syndrome

Changes in the topological organization of the default-mode network in Tourette syndrome

Distinct neurexin isoforms cooperate to initiate and maintain foraging activity

Neurexins are synaptic adhesion molecules that play diverse roles in synaptic development, function, maintenance, and plasticity. Neurexin genes have been associated with changes in human behavior, where variants in NRXN1 are associated with autism, schizophrenia, and Tourette syndrome. While NRXN1, NRXN2, and NRXN3 all encode major α and β isoforms, NRXN1 uniquely encodes a γ isoform, for which mechanistic roles in behavior have yet to be defined. Here, we show that both α and γ isoforms of neurexin/nrx-1 are required for the C. elegans behavioral response to food deprivation, a sustained period of hyperactivity upon food loss. We find that the γ isoform regulates initiation and the α isoform regulates maintenance of the behavioral response to food deprivation, demonstrating cooperative function of multiple nrx-1 isoforms in regulating a sustained behavior. The γ isoform alters monoamine signaling via octopamine, relies on specific expression of NRX-1 isoforms throughout the relevant circuit, and is independent of neuroligin/nlg-1, the canonical trans-synaptic partner of nrx-1. The α isoform regulates the pre-synaptic structure of the octopamine producing RIC neuron and its maintenance role is conditional on neuroligin/nlg-1. Collectively, these results demonstrate that neurexin isoforms can have separate behavioral roles and act cooperatively across neuronal circuits to modify behavior, highlighting the need to directly analyze and consider all isoforms when defining the contribution of neurexins to behavior.

The Pathophysiology of Gilles de la Tourette Syndrome: Changes in Saccade Performance by Low-Dose L-Dopa and Dopamine Receptor Blockers.

To elucidate the pathophysiology of Gilles de la Tourette syndrome (GTS), which is associated with prior use of dopamine receptor antagonists (blockers) and treatment by L-Dopa, through saccade performance. In 226 male GTS patients (5-14 years), we followed vocal and motor tics and obsessive-compulsive disorder (OCD) after discontinuing blockers at the first visit starting with low-dose L-Dopa. We recorded visual- (VGS) and memory-guided saccades (MGS) in 110 patients and 26 normal participants. At the first visit, prior blocker users exhibited more severe vocal tics and OCD, but not motor tics, which persisted during follow-up. Patients treated with L-Dopa showed greater improvement of motor tics, but not vocal tics and OCD. Patients with and without blocker use showed similarly impaired MGS performance, while patients with blocker use showed more prominently impaired inhibitory control of saccades, associated with vocal tics and OCD. Impaired MGS performance suggested a mild hypodopaminergic state causing reduced direct pathway activity in the (oculo-)motor loops of the basal ganglia-thalamocortical circuit. Blocker use may aggravate vocal tics and OCD due to disinhibition within the associative and limbic loops. The findings provide a rationale for discouraging blocker use and using low-dose L-Dopa in GTS.

Genomic data resources of the Brain Somatic Mosaicism Network for neuropsychiatric diseases

Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and disease. To study the nature and extent of somatic mosaicism in autism spectrum disorder, bipolar disorder, focal cortical dysplasia, schizophrenia, and Tourette syndrome, a multi-institutional consortium called the Brain Somatic Mosaicism Network (BSMN) was formed through the National Institute of Mental Health (NIMH). In addition to genomic data of affected and neurotypical brains, the BSMN also developed and validated a best practices somatic single nucleotide variant calling workflow through the analysis of reference brain tissue. These resources, which include >400 terabytes of data from 1087 subjects, are now available to the research community via the NIMH Data Archive (NDA) and are described here.

Pharmacological treatment of Tourette's syndrome: from the past to the future.

Tourette's syndrome (TS) is a neuropsychiatric disease featuring tics and vocal tics, with a prevalence of approximately 1%, including 75% of the total number of male patients. TS seriously disturbs the patients' career, education, and life and brings a serious and unbearable psychological burden to the patients themselves and their families. At present, there are no specific clinical medications recommended for treating TS. Therefore, it is necessary to select the appropriate medication for symptomatic treatment based on the doctor's personal experience and the patient's symptoms, with the main goal of relieving symptoms, thus improving the patient's social skills and psychological problems. Here we conducted a comprehensive search on PubMed to review and organize the history and current status of the development of drug therapy for TS through a timeline format. We also systematically evaluated the effects of each drug for TS treatment to summarize the current problems and new research directions and to provide some ideas for clinical treatment.

Working Mechanisms of Exposure and Response Prevention in the Treatment of Tourette Syndrome and Tic Disorders Revisited: No Evidence for within-Session Habituation to Premonitory Urges.

Exposure and response prevention (ERP) has been shown to be an effective treatment for Tourette syndrome (TS) and chronic tic disorders (CTD). ERP is based on voluntary tic suppression in combination with prolonged exposure to premonitory urges preceding tics. A prevailing hypothesis of the working mechanism underlying ERP in tics is habituation to the premonitory urges as a result of prolonged exposure. However, results so far are equivocal. This study aims to further explore the relation between urges and ERP in tics, by investigating the course of premonitory urges during ERP sessions. Using a data-driven approach, within-session habituation to premonitory urge intensity was investigated. In total, 29 TS patients rated urge intensity at seven timepoints during ten 1 h ERP sessions. Latent growth modeling showed an increase in urge intensity during the first 15 min of each session followed by a plateau in the remaining 45 min of the session. This does not support the idea of within-session habituation to premonitory urges as a working mechanism of ERP. Other potential underlying working mechanisms are discussed and should be tested in future research.

Non-just-right experiences are more closely related to OCD than tics in Tourette patients

Complex tics and obsessive or compulsive behaviour can be difficult to differentiate diagnostically. The majority of adult patients with Tourette syndrome report experiencing premonitory urges before tics. Some of these experiences have been linked to non-just-right experiences (NJRE), which are frequently reported by patients with obsessive–compulsive disorder or behaviours (OCD/OCB). We aimed to assess whether NJRE are more closely related to tics and tic-associated premonitory urges or whether they are more closely associated with OCD. A total of N = 111 patients (mean age = 34.77 + /−12.93; N = 37 female) with a confirmed diagnosis of Tourette syndrome completed the premonitory urges for tic disorders scale (PUTS), the revised non-just-right experiences scale (NJRE-QR), and questionnaires regarding their tic severity, and comorbid OCD/OCB. A multi-trait-multi-methods matrix was calculated to examine associations amongst scales measuring tic-related and OCB-related phenomena. The PUTS correlated overall higher with tic questionnaires than with OCD/OCB questionnaires. The NJRE correlated higher with OCD symptoms than with tic severity. The results indicate that non-just-right experiences are more closely associated with comorbid OCB than with tics in patients with Tourette syndrome.

Prevalence, comorbidities, and profiles of neurodevelopmental disorders according to the DSM-5-TR in children aged 6 years old in a European region.

There are no studies that measure the prevalence and real comorbidities of neurodevelopmental disorders (NDDs) according to the DSM-5-TR in 6-year-old children in population and clinical samples or studies that measure them as a whole. The data on the prevalence of these disorders are usually disparate because of the estimation methods (direct/indirect), the type of sample (population/clinical/school), and the ages studied. The initial sample (289 subjects) was representative of 6-year-old children in the entire population of Menorca, obtained from pediatric primary care services (100% of the sample). The patients were divided into two groups based on the criterion of verification of clinical warning signs. One of the groups represented the clinical or experimental sample (EG) (81 subjects) at risk of NDDs; the other group was considered the control sample (CG) (210 subjects), and they were subjects without risk of suffering NDDs. A direct clinical assessment of the clinical sample was carried out, and they were administered the Wechsler Intelligence Scale for Children (WISC-V), the Clinical Evaluation of Language Fundamentals (CELF-5), the Battery for the evaluation of the processes of revised reading (Batería para la evaluación de los procesos de lectura revisada - PROLEC-R), the Test for the Diagnosis of Basic Mathematical Competences, (TEDI-MATH), and the Developmental Coordination Disorder Questionnaire (DCDQ). A total of 21.5% of the initial sample suffered from an NDD. A total of 2.4% presented autism spectrum disorder (ASD); 14% presented attention-deficit hyperactivity disorder (ADHD); 0.34% presented mild intellectual disability; 9.54% presented communication disorder (CD) (5.8% language disorder, 3.4% phonological disorder, and 0.34% stuttering); 10% presented learning disorder with reading difficulties; 5.8% presented learning disorder with difficulties in writing; 3.11% presented learning disorder with difficulties in mathematics; 1% presented transitory tic disorder; 0.34% presented chronic tic disorder; 1% presented Tourette syndrome; 2% presented motor coordination disorder (MCD); and 0.34% presented stereotypic movement disorders. Male children were more affected than female children in general, with male/female ORs of 0.14/0.92 for the presence of comorbidities, 0.11/0.88 for combined ADHD, 0.06/0.87 for language disorder, 1.02/1.27 for MCD, and 1.39/1.02 for inattentive ADHD. In disadvantaged contexts, there was a higher prevalence of NDDs and comorbidities, unless the disorder was extreme, in which case only the NDD manifestations were presented. A significant proportion of the sample had not been previously diagnosed (88.6%); therefore, early detection programs are recommended to identify warning signs and develop policies that help and support the most disadvantaged sectors of the population.