Search Results (137)

Background/Objectives: Tourette syndrome and other chronic tic disorders are neurodevelopmental conditions characterized by intermittent motor/phonic tics and frequent behavioral comorbidity. Poor sleep quality is often reported by patients with tic disorders; however, little is known about the prevalence and clinical correlates of disruption in sleep physiology. Methods: We conducted a systematic literature review of clinical studies evaluating sleep using at least one validated sleep outcome (questionnaire, polysomnography, or coded clinical diagnosis). Results: Despite high heterogeneity in age ranges, diagnostic formulations, outcome measures, and confounder handling, converging evidence across designs indicated a significantly higher prevalence of sleep disturbance in patients with Tourette syndrome and other chronic tic disorders compared to controls. Specifically, registries showed significantly greater insomnia rates (aOR 6–7); case–control studies revealed a 9-fold increase in night-waking, bedtime resistance, parasomnias, and daytime drowsiness; polysomnography studies demonstrated sleep fragmentation, with decreased efficiency, longer latency, and more awakenings. Conclusions: Sleep disorders are relatively common in patients with Tourette syndrome and other chronic tic disorders, with clinical implications for both arousal instability and sleep initiation/maintenance issues. Further research is needed to better understand the complex interplay between altered sleep patterns and tic expression, as well as the impact of behavioral comorbidities. Our findings highlight a need for personalized treatment interventions focusing on sleep problems in the context of tic disorders. Full article

The hypothesis that Group A beta-haemolytic Streptococcus (GAS) triggers an autoimmune cascade targeting basal ganglia dopaminergic circuits—producing obsessive–compulsive disorder (OCD), tic disorders, or chorea depending on the receptor subtype involved—is biologically compelling and supported by emerging molecular evidence. Yet PANDAS has remained a diagnostic conundrum since its original description in 1998, with ongoing uncertainty surrounding diagnostic criteria, the interpretation of streptococcal serology, and the distinction from primary neurodevelopmental disorders. This study aimed to review the diagnostic challenges of PANDAS, with focus on streptococcal serology interpretation, advances in dopamine receptor autoantibody biology, the genetic epidemiology of primary tic disorders, and the differential diagnosis of acute neuropsychiatric presentations in children. A structured narrative review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library for publications from 1998 to early 2025 addressing PANDAS, PANS, streptococcal antibodies, childhood movement disorders, autoimmune encephalitis, and the genetics of tic disorders. No currently available biomarker—including ASO, anti-DNase B, anti-basal-ganglia antibodies, or the Cunningham Panel—has demonstrated adequate individual-level diagnostic accuracy for PANDAS. Emerging molecular evidence identifies anti-D1R autoantibodies, acting via G protein-and beta-arrestin-mediated signalling, as candidate biomarkers for PANDAS/PANS neuropsychiatric phenotypes, and anti-D2R autoantibodies for Sydenham chorea movement phenotypes; independent replication in unselected populations is required. Primary tic disorders carry heritability estimates of 50–80% and first-degree familial risk ratios of approximately 18-fold in large population-based cohorts. Prospective blinded studies have not demonstrated a consistent population-level association between GAS infections and tic or OCD exacerbations: PANDAS and PANS remain diagnoses of exclusion. The high background prevalence of both GAS exposure and primary neurodevelopmental disorders in overlapping paediatric age ranges creates conditions for incidental temporal co-occurrence. In the absence of validated molecular biomarkers, diagnostic imprecision carries direct clinical consequences: children may be exposed to treatments with significant risk profiles—including IVIG, plasma exchange, and prolonged antibiotic prophylaxis—while evidence-based therapies are delayed. A stepwise diagnostic approach incorporating the full differential diagnosis is both an epistemological and a patient safety imperative. Full article

Background: Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) shares numerous clinical features with Tourette syndrome (TS), notably the presence of tics and frequent comorbidities such as obsessive-compulsive disorder, irritability, and ADHD-like behaviors, often indistinguishable, particularly in the early stages of the two syndromes. Also, pathogenic similarities between PANS and TS constitute a diagnostic challenge, highlighting the need for biomarkers elucidating the underpinnings of the two disorders. In this context, metabolomics has emerged as a powerful tool for identifying distinct biochemical patterns in various diseases. We previously compared PANS, autism patients, and controls, identifying specific metabolic patterns. However, no studies have directly compared the metabolomic profiles of Tourette syndrome and PANS patients. The present study aims to compare the serum metabolomic profiles of TS patients with those of PANS and healthy controls to advance the molecular understanding and clinical differentiation of these two pediatric neuropsychiatric disorders. Methods: Thirty-four PANS patients and twenty-three Tourette patients were matched with twenty-five healthy subjects (C), and their blood samples were analyzed with ¹H NMR spectroscopy. Subsequently, data were analysed with multivariate and univariate statistical approaches. Results: Supervised models indicated that the metabolomic profile of TS patients was significantly different from that of controls (p = 0.02), with altered concentrations of glutamate, glycerol, glycine, lactate, and proline. No significant differences were found in the comparison between PANS and TS patients. Conclusions: These preliminary data suggest that Tourette and Pans also seem to share the metabolic profiles, while differences were found in TS patients compared to controls. On the other hand, the PANS phenotype comprises symptoms that largely overlap with those of all other NDDs, including TS, outlining a spectrum of disorders that share common pathogenetic pathways. Larger studies are needed to confirm these findings. Full article

Background: Tourette syndrome (TS) is a chronic neurodevelopmental disorder with a significant rate of patients remaining refractory to standard treatments. Refractory TS is defined as the persistence of clinically significant tics causing functional impairment despite adequate trials of both behavioral therapy and at least two generally accepted pharmacological treatments from different classes, administered at appropriate doses and durations. This systematic review synthesizes the current evidence on alternative pharmacological and non-pharmacological interventions for treatment-resistant TS. Methods: The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Embase, and Scopus were searched for studies published from 2010 onward. Eligible publications included randomized and non-randomized clinical studies, and case reports evaluating alternative interventions in refractory TS, excluding deep brain stimulation. The primary outcome measures included validated scales assessing tic severity and functional impairment, with available data demonstrating reductions in tic severity, including clinically meaningful improvements reported in several studies. Thirteen studies met the inclusion criteria, comprising five clinical studies (including three randomized trials) and eight case reports. Heterogeneity across studies was primarily driven by differences in study design, patient populations, and variability in intervention types, protocols, and outcome assessments. Results: Investigated interventions included cannabinoids, valproic acid, deep transcranial magnetic stimulation, neurofeedback, biofeedback, electroconvulsive therapy, and ablative neurosurgical procedures. Cannabinoid-based treatments showed potential reductions in tic severity; however, results were inconsistent and often not statistically significant, with evidence largely derived from small or uncontrolled studies. Evidence for non-pharmacological approaches was limited and largely derived from individual cases, with some modalities showing potential benefit in specific subgroups, such as patients with comorbid obsessive-compulsive disorder. Conclusions: Overall, alternative interventions may offer therapeutic value for selected individuals with treatment-resistant TS, with the greatest data regarding cannabinoid use; however, the current evidence base remains heterogeneous and methodologically constrained. Deep transcranial magnetic stimulation might be beneficial in a specific patient population. Larger, well-controlled studies are required to clarify efficacy, safety, and treatment response. Full article

Background: Behavioural therapy (BT), including Comprehensive Behavioural Intervention for Tics (CBIT), is an evidence-based first-line treatment for patients with tic disorders. However, access remains limited due to a shortage of trained providers, geographical barriers, costs, and high treatment burden for patients and families. Rapid advances in digital health technologies including telemedicine, web-based treatment platforms, and mobile applications offer new opportunities to expand access to BT for individuals with tic disorders across the lifespan. Methods: For the purpose of this narrative review, we conducted a literature search in PubMed, Europe PMC, and the Cochrane Library to identify relevant studies investigating the effectiveness of digital health treatment approaches in tic disorders. Results: A total of 16 original studies were included. Although the available evidence remains limited and heterogeneous, existing studies suggest that emerging technologies for delivering behavioural interventions for tic disorders, including telehealth-based CBIT, digital therapy platforms, and app-supported habit reversal training (HRT), are feasible, cost-effective, user-friendly, flexible, and safe. These approaches also appear effective for symptom monitoring and personalized treatment support in both pediatric and adult populations. Conclusions: Recent technological advances have the potential to reduce the treatment gap in tic disorders, provided that these approaches are implemented within rigorous, evidence-based, and ethically grounded frameworks. Full article

Objectives: To access the effects of febrile seizures from coexisting neurodevelopmental conditions that are commonly associated with autism spectrum disorder. We examined whether febrile seizures are independently associated with ASD after considering neurodevelopmental comorbidities and seizure-related clinical characteristics. Methods: We conducted a nationwide population-based matched cohort study using Taiwan’s National Health Insurance Research Database. The study included 948 children with FS and 3804 age- and sex-matched controls without FS. Participants were followed longitudinally for incident ASD. Associations were evaluated using Cox proportional hazards models with additional analyses restricted to the FS cohort. Neurodevelopmental comorbidities assessed included attention-deficit/hyperactivity disorder (ADHD), epilepsy, and Tourette syndrome/tic disorder. Results: Among 4752 children followed for more than 10 years, 43 (0.9%) developed ASD. FS were not independently associated with ASD in adjusted Cox regression models. In contrast, ADHD, epilepsy, and Tourette syndrome/tic disorder were strongly and consistently associated with ASD across analytic models. Conclusions: Febrile seizures were not independently associated with autism spectrum disorder. Instead, ASD risk was largely explained by coexisting neurodevelopmental comorbidities, consistent with a shared neurodevelopmental susceptibility framework. These findings suggest that developmental surveillance should prioritize children with neurodevelopmental disorders rather than those with febrile seizures alone. Full article

Background/Objectives: Cannabinoids are increasingly recognised for their therapeutic potential beyond well-established indications such as chronic pain, multiple sclerosis, and specific epileptic syndromes. Recent advances have highlighted their possible role in less-common or orphan diseases, opening new avenues for pharmaceutical research and clinical application. Methods: This review provides a critical synthesis of the most recent evidence (2020–2025), available in PubMed and Scopus, regarding the use of cannabinoids in conditions including refractory epilepsies beyond Dravet and Lennox–Gastaut syndromes, movement disorders such as dystonia and Tourette syndrome, rare dermatological diseases like epidermolysis bullosa, and emerging data in Crohn’s disease. Results: Negative outcomes, such as those reported in Fragile X syndrome trials, are also discussed as instructive examples of methodological and pharmacological challenges. Particular attention is given to the optimisation of pharmaceutical formulations and advanced separation technologies, including oromucosal sprays, transdermal gels, and novel nanocarrier systems, which aim to overcome issues of bioavailability and variability in patient response. Finally, safety concerns, regulatory aspects, and the need for robust clinical trials are addressed. Conclusions: Overall, cannabinoids represent a promising yet underexplored therapeutic option in rare and complex disorders, warranting further investigation supported by innovative pharmaceutical approaches. Full article

Tourette Syndrome (TS) is a neurodevelopmental disorder depicted by the occurrence of tics and accompanying behavioral problems that commonly appear during childhood. Tics, both motor and vocal, may cause musculoskeletal pain. Both acute and chronic muscle pain have been recognized as a common comorbid aspect of TS-related tic disorders in childhood. The pain most reported in children includes cervical, throat, shoulder, ocular, and joint pain, with most children reporting musculoskeletal pain in more than one part of the body. The impact of muscular pain caused by motor and phonic tics can negatively affect a child’s quality of life. This review describes the association and causation of musculoskeletal pain in childhood tics and TS, which are commonly under recognized and diagnosed. An analysis of the presence of musculoskeletal pain, the severity of the pain, the location of the pain and the movement incapacity due to pain in children is reviewed. Pharmacological and non-pharmacological interventions known to improve musculoskeletal pain in children are highlighted with supportive frameworks evaluated. Further research is needed to better understand musculoskeletal pain cause(s) and prevalence along with age-appropriate assessment methods and outcomes measures. Motor- and phonic-related musculoskeletal pain should be recognized as a common comorbid characteristics of TS and tic disorders in childhood. Such recognition may lead to greater therapeutic opportunities for this problematic condition. Full article

Background: Gilles de la Tourette syndrome is a neurobehavioral disorder that typically begins in childhood, subsides during puberty, and may reappear in adolescence. Treatment is primarily conservative, involving psychological and pharmacological therapy. Patients who do not respond to conservative therapy may be treated with deep brain stimulation, although this remains an experimental treatment. Methods: In this two-case report we present the first two cases of patients with Gilles de la Tourette syndrome in Slovenia treated with deep brain stimulation of the anteromedial globus pallidus internus. Results: Over an 18-month follow-up period, we observed an improvement in both cases. In the first case, the Yale Global Tic Severity Scale score decreased from 71 (17 for motor tics, 14 for phonic tics, and 40 on the impairment scale) to 44 points (12 motor, 12 phonic, and 20 impairment). In the second case, the score decreased from 72 (16 motor, 16 phonic, and 40 impairment) to 38 points (8 motor, 10 phonic, and 20 impairment). Conclusions: Deep brain stimulation could be a promising treatment for this disorder. However, further research is needed to determine the most suitable patients and targets. Full article

Tourette syndrome (TS) is a neurodevelopmental disorder, with a male-to-female ratio of approximately 3:1, characterised by involuntary tics, frequently comorbid with conditions such as obsessive–compulsive disorder (OCD). Some patients exhibit limited responsiveness to standard medications, necessitating alternative therapeutic strategies. Clomiphene, a selective oestrogen receptor modulator (SERM), emerged as a potential candidate. However, raloxifene and bazedoxifene, which exhibit distinct chemical structures from clomiphene, present dual modulation not only as oestrogen receptor modulators but also as inverse agonists of the cannabinoid CB₂ receptor. The present study compared the efficacy of clomiphene, raloxifene, and bazedoxifene in alleviating TS/OCD-like behaviours in mice. The findings revealed dose, sex, and age differences in the effects of raloxifene, and to a lesser extent of bazedoxifene, demonstrating potential therapeutic benefit for treating TS/OCD-like behaviours. The effects of raloxifene were compared in the presence of 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced or SR141716A-induced motor-like tics, premonitory urges-induced, and OCD-like behaviours in mice. DOI-induced juvenile male and female mice responded to raloxifene, while only adolescent DOI-induced females responded to raloxifene. These results suggest that SERM drugs that are also CB₂ receptor antagonists/inverse-agonists may be a new class of drugs to reduce motor tics and OCD symptoms in patients with TS/OCD. Full article

The gut microbiome produces thousands of metabolites with potential to modulate central nervous system function through peripheral or direct neural mechanisms. Tourette syndrome, attention-deficit/hyperactivity disorder, and autism spectrum disorder exhibit shared neurotransmitter dysregulation and microbiome alterations, yet mechanistic links between microbial metabolites and receptor-mediated neuromodulation remain unclear. We screened 27,642 microbiome SMILES metabolites for blood–brain barrier permeability using rule-based SwissADME classification and a PyTorch 2.0 neural network trained on 7807 experimental compounds (test accuracy 86.2%, AUC 0.912). SwissADME identified 1696 BBB-crossing metabolites following Lipinski’s criteria, while PyTorch classified 2484 metabolites with expanded physicochemical diversity. Following 3D conformational optimization (from SMILES) and curation based on ≤32 rotatable bonds, molecular docking was performed against five neurotransmitter receptors representing ionotropic (GABRA2, GRIA2, GRIN2B) and metabotropic (DRD4, HTR1A) receptor classes. The top 50 ligands across five receptors demonstrated method-specific BBB classification (44% SwissADME-only, 44% PyTorch-only, 12% overlap), validating complementary prediction approaches. Fungal metabolites from Ascomycota dominated high-affinity top ligands (66%) and menaquinone MK-7 showed broad phylogenetic conservation (71.4% of phylum). Our results establish detailed receptor–metabolite interaction maps, with fungal metabolites dominating high-affinity ligands, challenging the prevailing bacterial focus of the microbiome and providing a foundation for precision medicine and a framework for developing microbiome-targeted therapeutics to address clinical needs in neurodevelopmental disorders. Full article

Background: Tic spectrum disorder (TSD), encompassing Tourette syndrome and chronic tic disorder, is a childhood-onset neurodevelopmental condition with complex genetic and environmental contributions. Heritable components have been implicated in TSD, but no clear genetic mechanisms have been identified. Significant aspects of TSD etiology remain unclear, with key uncertainties concerning the role of environmental influences in its development. In this study, we aimed to identify environmentally induced epigenomic and transcriptomic changes contributing to TSD pathology by investigating genetically similar monozygotic twins discordant for TSD. Methods: To investigate environmentally driven mechanisms, we analyzed peripheral blood from eleven monozygotic twin pairs, either discordant or concordant for TSD, using RNA sequencing and DNA methylation analysis. Results: Differential expression analysis identified a dozen differentially expressed genes between TSD and non-TSD individuals, most of which were long non-coding RNAs or pseudogenes. Expression of the small RNA gene RNY1 was significantly associated with tic severity, suggesting involvement of immune-related processes. DNA methylation (DNAm) analysis revealed ~30,000 probes with a nominal p < 0.05, however none of these were significant after multiple testing correction. Expression quantitative trait methylation (eQTM) analysis identified 236 methylation-associated genes. Gene set enrichment analysis demonstrated broad downregulation in TSD individuals for pathways related to translation, RNA processing, and neurobiological functions, with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including ribosome, nucleocytoplasmic transport, pluripotency signaling, and nicotine addiction. Conclusions: These results suggest that environmentally influenced gene expression may contribute to TSD pathogenesis through dysregulation of immune and neuronal pathways. Despite a small sample size, the monozygotic twin design provides strong control for genetic background and identifies significant differences that contribute to the understanding of the underlying molecular mechanisms of TSD. Full article

Tourette syndrome (TS), or Tourette’s, is a tic disorder (TD) belonging to a group of neuropsychiatric conditions marked by recurrent motor movements or vocalizations known as tics. TD, including TS, typically begins in childhood between 4 and 18 years of age and affects approximately 3% of children and adolescents. The etiology and pathogenesis of TD are multifactorial, involving genetic, immunologic, psychological, and environmental factors. Evidence suggests that neurotransmitter dysregulation, particularly within the cortical dopaminergic networks of the basal ganglia and limbic system, which support motor control and cognition, may be involved in the development of TD. Nutritional factors may modulate TD through various mechanisms, including effects on neurotransmitter synthesis and metabolism, neurodevelopment, neural architecture, and neuroimmune activity. This review integrates current evidence on the roles of vitamins D, B6, and A, as well as iron, magnesium, zinc, and copper, in TD. For each micronutrient, its physiological and neurobiological functions are discussed, along with possible mechanistic links to TD pathophysiology. Additionally, we summarize the impact of nutrient deficiencies and assess available evidence regarding their potential therapeutic potential role in TD management. Overall, this synthesis highlights how nutritional status may influence TD onset and symptom severity, suggesting that nutrient-based interventions could potentially serve as valuable adjunctive strategies in treatment. Full article

Treatment-resistant psychiatric disorders represent a major clinical challenge, with a significant proportion of patients remaining refractory to conventional pharmacological and psychotherapeutic interventions. Deep brain stimulation (DBS), a neurosurgical technique delivering targeted electrical impulses to specific brain regions, has emerged as a promising intervention across a spectrum of refractory psychiatric conditions. This comprehensive narrative review synthesizes current evidence on the efficacy, safety, and practical considerations of DBS for treatment-resistant major depressive disorder, obsessive–compulsive disorder, bipolar disorder, schizophrenia, addictions, Tourette’s syndrome, anorexia nervosa, post-traumatic stress disorder, and refractory aggression in autism spectrum disorder with severe intellectual disability. Across most conditions, DBS demonstrates clinically meaningful symptom reductions, with response and remission rates in depression and obsessive–compulsive disorder approaching 48% and 35%, respectively. For Tourette’s syndrome and refractory aggression in autism, over two-thirds of patients’ experience > 50% symptom reduction. Preliminary data in bipolar disorder, schizophrenia, addictions, and anorexia nervosa are encouraging but limited by small sample sizes and methodological heterogeneity. Safety profiles are generally acceptable, with the majority of adverse events being device- or procedure-related; psychiatric adverse effects and rare serious complications underscore the importance of careful patient selection and monitoring. However, the literature is constrained by inconsistent study designs, a paucity of randomized controlled trials, heterogeneity in DBS targets and stimulation parameters, and limited long-term and quality-of-life outcomes. Optimization of anatomical targeting, stimulation protocols, and patient selection criteria remains an ongoing challenge. Future directions require larger, rigorously controlled trials with standardized outcome measures, integration of neurobiological biomarkers, and multidisciplinary collaboration. In summary, while DBS offers transformative potential for select cases of refractory psychiatric illness, its application must be guided by scientific rigor, ethical prudence, and individualized patient-centered care. Full article

Background and Objectives: Keratoconus (KC) is a progressive corneal ectasia with multifactorial etiology, increasingly studied for potential associations with psychiatric disorders. This systematic review aimed to evaluate recent evidence linking KC with depression and other psychiatric conditions, including psychotic disorders, personality disorders, attention deficit hyperactivity disorder (ADHD), Tourette syndrome (TS), autism spectrum disorder (ASD), and obsessive–compulsive disorder (OCD). Materials and Methods: Following PRISMA guidelines, PubMed, ScienceDirect and SpringerLink were searched for English-language observational studies published since 2015 that examined psychiatric disorders in adults with keratoconus. We excluded reviews, case reports, pediatric, non-English, and inaccessible articles. Study quality was assessed using the Newcastle–Ottawa Scale and JBI Checklist. Data were narratively summarized and tabulated—without meta-analysis due to heterogeneity. Results: Twelve studies met inclusion criteria, including 41,906 KC patients and 63,267 controls. Eleven studies investigated depression and one ADHD. Findings on depression were mixed: five studies showed higher depressive symptoms among KC patients, while others found no significant association. Most were cross-sectional and of moderate-to-high quality. The single study on ADHD reported a higher prevalence of KC in males, but no evidence of casual association. Evidence on TS, ASD, and OCD was scarce and largely limited to case reports. The review was limited by heterogeneous methodologies, small sample sizes, an absence of longitudinal data, and reliance on self-report or registry data. Conclusions: Current evidence indicates increased psychological burden among some individuals with KC, particularly regarding depressive symptoms, yet casual relationships remain unproven. Male ADHD patients may have an elevated risk of KC, especially in the presence of eye rubbing. Registration: Not registered. Full article