RESUMEN
BACKGROUND: To evaluate the long-term efficacy, prognostic factors, and safety of posteroventral globus pallidus internus deep brain stimulation (DBS) in patients with refractory Tourette syndrome (RTS). METHODS: This retrospective study recruited 61 patients with RTS who underwent posteroventral globus pallidus internus (GPi) DBS from January 2010 to December 2020 at the Chinese People's Liberation Army General Hospital. The Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (YBOCS), Beck Depression Inventory (BDI), Gilles de la Tourette Syndrome Quality-of-Life Scale (GTS-QOL) were used to evaluate the preoperative and postoperative clinical condition in all patients. Prognostic factors and adverse events following surgery were analyzed. RESULTS: Patient follow up was conducted for an average of 73.33 ± 28.44 months. The final postoperative YGTSS (32.39 ± 22.34 vs 76.61 ± 17.07), YBOCS (11.26 ± 5.57 vs 18.31 ± 8.55), BDI (14.36 ± 8.16 vs 24.79 ± 11.03) and GTS-QOL (39.69 ± 18.29 vs 78.08 ± 14.52) scores at the end of the follow-up period were significantly lower than those before the surgery (p < 0.05). While age and the duration of follow-up were closely related to prognosis, the disease duration and gender were not. No serious adverse events were observed and only one patient exhibited symptomatic deterioration. CONCLUSIONS: Posteroventral-GPI DBS provides long-term effectiveness, acceptable safety and can improve the quality of life in RTS patients. Moreover, DBS is more successful among younger patients and with longer treatment duration.
Asunto(s)
Estimulación Encefálica Profunda , Síndrome de Tourette , Estimulación Encefálica Profunda/efectos adversos , Humanos , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Síndrome de Tourette/etiología , Síndrome de Tourette/terapia , Resultado del TratamientoRESUMEN
Tourette syndrome (TS) is a severe neuropsychiatric disorder characterized by recurrent, involuntary physical and verbal tics. With a prevalence as high as 1% in children, a deeper understanding of the etiology of the disorder and contributions to risk is critical. Here, we cover the current body of knowledge in scientific literature regarding the genetics of TS. We first review the history and diagnostic criteria for TS cases. We then cover the prevalence, and begin to address the etiology of the disorder. We highlight long-standing evidence for a genetic contribution to TS risk from epidemiology studies focused on twins, families, and population-scale data. Finally, we summarize current large-scale genetic studies of TS along specific classes of genetic variation, including common variation, rare copy number variation, and de novo variation that impact protein-coding sequence. Although these variants do not account for the entirety of TS genetic risk, current evidence is clear that each class of variation is a factor in the overall risk architecture across TS cases.
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Variaciones en el Número de Copia de ADN/genética , Epidemiología Molecular , Síndrome de Tourette/epidemiología , Síndrome de Tourette/genética , Humanos , Prevalencia , Síndrome de Tourette/etiologíaRESUMEN
BACKGROUND: Tourette syndrome (TS) is a complex neuropsychiatric disorder coupled with obvious genetic heterogeneity. Studies in recent years have confirmed the association of SLITRK genes with sensory and neuropsychiatric diseases. To detect whether SLITRK6 is involved in the progress of TS, a family-based association study was performed to explore the possible genetic association between SLITRK6 and TS in the Chinese Han population. METHODS: We genotyped 399 TS nuclear families trios, and then analyzed three tag SLITRK6 single nucleotide polymorphisms using the transmission disequilibrium test (TDT) haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods. RESULTS: The TDT showed no statistically significant allele transfer for the three polymorphisms. The HRR and HHRR also showed a negative association. CONCLUSIONS: Despite the results suggesting that these polymorphisms may not be associated with susceptibility to TS in the Chinese Han population, we are still unable to determine the potential role of SLITRK6 in the pathogenesis of TS. Furthermore, the results still need to be confirmed in a larger sample size and in different populations.
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Predisposición Genética a la Enfermedad , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Síndrome de Tourette/etiología , Adolescente , Alelos , Pueblo Asiatico/genética , Niño , Preescolar , China , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Proteínas de la Membrana/metabolismo , Medición de Riesgo , Síndrome de Tourette/diagnósticoRESUMEN
BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences. METHODS: A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models. RESULTS: PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys. CONCLUSIONS: Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
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Andrógenos/metabolismo , Trastorno por Déficit de Atención con Hiperactividad/etiología , Trastorno del Espectro Autista/etiología , Síndrome del Ovario Poliquístico/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Sistema de Registros/estadística & datos numéricos , Trastornos de Tic/etiología , Adolescente , Adulto , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/genética , Niño , Preescolar , Estudios de Cohortes , Familia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Síndrome del Ovario Poliquístico/epidemiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Factores Sexuales , Suecia/epidemiología , Trastornos de Tic/epidemiología , Trastornos de Tic/genética , Síndrome de Tourette/epidemiología , Síndrome de Tourette/etiologíaRESUMEN
Tourette syndrome is a heterogeneous disorder. The genetic basis is complex, and both in utero and ex utero environmental factors may modify the phenotypic expression of the disorder. Inflammation related to aberrations in immune activation appears to play a pathogenic role in some cases. Multiple neurochemical pathways are involved. Rather than being a pure movement problem, tics are now understood to also have a sensory component. This has resulted in new psychological therapeutic strategies and other potential treatments. Furthermore, comorbidities are common, particularly attention-deficit hyperactivity disorder, anxiety and obsessive-compulsive disorder, and often cause more difficulties than the tics. The approach to treatment is dependent on the degree and types of impairment. For many patients, education, acceptance and understanding are all that is needed. In more severe cases, psychological and/or pharmacological interventions may be indicated. In this article, the clinical features and pathophysiology of Tourette syndrome are reviewed, and a pragmatic management approach is discussed.
Asunto(s)
Síndrome de Tourette , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Antipsicóticos/uso terapéutico , Terapia Conductista , Niño , Comorbilidad , Humanos , Neuroimagen , Trastorno Obsesivo Compulsivo/complicaciones , Tics/fisiopatología , Síndrome de Tourette/diagnóstico por imagen , Síndrome de Tourette/etiología , Síndrome de Tourette/fisiopatología , Síndrome de Tourette/terapiaRESUMEN
Tourette syndrome (TS) is thought to involve dopaminergic disturbances, but the nature of those disturbances remains controversial. Existing hypotheses suggest that TS involves 1) supersensitive dopamine receptors, 2) overactive dopamine transporters that cause low tonic but high phasic dopamine, 3) presynaptic dysfunction in dopamine neurons, or 4) dopaminergic hyperinnervation. We review evidence that contradicts the first two hypotheses; we also note that the last two hypotheses have traditionally been considered too narrowly, explaining only small subsets of findings. We review all studies that have used positron emission tomography and single-photon emission computerized tomography to investigate the dopaminergic system in TS. The seemingly diverse findings from those studies have typically been interpreted as pointing to distinct mechanisms, as evidenced by the various hypotheses concerning the nature of dopaminergic disturbances in TS. We show, however, that the hyperinnervation hypothesis provides a simple, parsimonious explanation for all such seemingly diverse findings. Dopaminergic hyperinnervation likely causes increased tonic and phasic dopamine. We have previously shown, using a computational model of the role of dopamine in basal ganglia, that increased tonic dopamine and increased phasic dopamine likely increase the propensities to express and learn tics, respectively. There is therefore a plausible mechanistic link between dopaminergic hyperinnervation and TS via increased tonic and phasic dopamine. To further bolster this argument, we review evidence showing that all medications that are effective for TS reduce signaling by tonic dopamine, phasic dopamine, or both.
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Encéfalo/fisiopatología , Dopamina/fisiología , Neuronas Dopaminérgicas/fisiología , Síndrome de Tourette/fisiopatología , Animales , Encéfalo/diagnóstico por imagen , Humanos , Tomografía de Emisión de Positrones , Receptores Dopaminérgicos/fisiología , Tomografía Computarizada de Emisión de Fotón Único , Síndrome de Tourette/diagnóstico por imagen , Síndrome de Tourette/etiologíaRESUMEN
Tourette disorder is a developmental neuropsychiatric condition characterized by vocal and motor tics that can range in severity from mild to disabling. It represents one end of a spectrum of tic disorders and is estimated to affect 0.5-0.7% of the population. Accumulated evidence supports a substantial genetic contribution to disease risk, but the identification of genetic variants that confer risk has been challenging. Positive findings in candidate gene association studies have not replicated, and genomewide association studies have not generated signals of genomewide significance, in large part because of inadequate sample sizes. Rare mutations in several genes have been identified, but their causality is difficult to establish. As in other complex neuropsychiatric disorders, it is likely that Tourette disorder risk involves a combination of common, low-effect and rare, larger-effect variants in multiple genes acting together with environmental factors. With the ongoing collection of larger patient cohorts and the emergence of affordable high-throughput genomewide sequencing, progress is expected to accelerate in coming years.
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Trastornos de Tic/etiología , Síndrome de Tourette/etiología , Interacción Gen-Ambiente , Histidina Descarboxilasa , Humanos , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Trastornos de Tic/genética , Síndrome de Tourette/genéticaRESUMEN
Tourette syndrome (TS) is a neuropsychiatric disorder with the onset in childhood. TS is a form of tic disorders, and characterized by the motor and vocal tics, and comorbidities such as attention deficit hyperkinetic and obsessive compulsive disorders. These symptoms appear age dependently, showing a wax and wane course, and subside or abolish by the late teens. Pathophysiology of TS involves the dysfunction of both motor and non-motor basal ganglia-thalamo-cortical circuitries. The nigrostriatal dopamine (DA) system takes the exponential decrement at the striatum. In TS, this decrement is accelerated in association with DA-D2 receptor super-sensitivity, which disinhibits the descending and ascending output pathways of the basal ganglia. Disinhibited motor basal ganglia-thalamo-cortical circuitries develop the specific tics according to the target sites. Hypofunction of the 5-hydroxytriptophan (5-HT) neurons of the brainstem innervate the striatum involved in non-motor basal ganglia-thalamo-cortical circuitries and cause the obsessive compalsive disorder and other behavioral disorders. The associated DA-D2 receptor supersensitivity is assumed to be a consequence of the developmental abnormalities and not due to denervation supersensitivity. The treatments of TS aim to correct the 5-HT hypofunction by improving the environmental factors and super-sensitized DA receptors medically by a small dose of levodopa and/or aripiprazole.
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Síndrome de Tourette/fisiopatología , Edad de Inicio , Estimulación Encefálica Profunda , Neuronas Dopaminérgicas/enzimología , Humanos , Pronóstico , Síndrome de Tourette/epidemiología , Síndrome de Tourette/etiología , Síndrome de Tourette/terapiaRESUMEN
PURPOSE OF REVIEW: Describe developments in the etiological understanding of Tourette syndrome. RECENT FINDINGS: Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response. SUMMARY: At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.
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Tics , Síndrome de Tourette , Humanos , Factores de Riesgo , Tics/diagnóstico , Tics/etiología , Tics/fisiopatología , Tics/terapia , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/etiología , Síndrome de Tourette/fisiopatología , Síndrome de Tourette/terapiaRESUMEN
Gilles de la Tourette syndrome is a chronic neuropsychiatric movement disease with combined motor tics and at least one vocal tic for a minimum period of 1 year. It typically begins in the childhood (under 18 years of age).Most of the patients with Tourette syndrome have comorbidities, which often impair their quality of life more than the tics themselves.There are reported abnormalities in the cortico-striato-thalamo-cortical regions as well as in the neurotransmission of dopamine and other neurotransmission systems. Genetic and non genetic factors are discussed.In each patient psychoeducation is the basis of treatment. Specific treatment is only needed in more severe tic disorders which cause evident psychosocial impairment.Behavior therapy should be tried before drug treatment. For very severely affected adults, deep brain stimulation is a further treatment option.
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Síndrome de Tourette/psicología , Síndrome de Tourette/terapia , Adulto , Niño , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Tics/etiología , Tics/psicología , Tics/terapia , Síndrome de Tourette/complicaciones , Síndrome de Tourette/etiologíaRESUMEN
Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/fisiopatología , Síndrome de Tourette/etiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Estudios de Casos y Controles , Niño , Preescolar , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/diagnóstico , Relaciones Padres-Hijo , Embarazo , Escalas de Valoración Psiquiátrica , República de Corea , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales , Trastornos de Tic , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVE: We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD). METHOD: In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions. RESULTS: In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships. CONCLUSION: Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT.
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Trastorno Obsesivo Compulsivo/etiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Fumar/efectos adversos , Trastornos de Tic/etiología , Adolescente , Niño , Preescolar , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Masculino , Trastorno Obsesivo Compulsivo/epidemiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Fumar/epidemiología , Trastornos de Tic/epidemiología , Síndrome de Tourette/epidemiología , Síndrome de Tourette/etiologíaRESUMEN
Gilles de la Tourette's syndrome (GTS) is a disorder in which obsessive-compulsive (OC), Attention Deficit Hyperactivity Disorder (ADHD) and autism symptoms occur in up to 60% of patients, suggesting shared etiology. We explored the phenotypic structure of tic, OC, ADHD, and autism symptoms as measured by the YGTSS,Y-BOCS,CAARS and AQ, in 225 GTS patients and 371 family members. First, Confirmatory Factor Analyses (CFA) were performed on the symptom structure of each separate symptom scale. Second, the symptom dimensions derived from each scale were combined in one model, and correlations between them were calculated. Using the correlation matrix, Exploratory Factor Analyses (EFA) were performed on the symptom dimensions across the scales. EFA revealed a five factor structure: tic/aggression/symmetry; OC symptoms/compulsive tics/ numbers and patterns; ADHD symptoms; autism symptoms; and hoarding/inattention symptoms. The results are partly in line with the traditional categorical boundaries of the symptom scales used, and partly reveal a symptom structure that cuts through the diagnostic categories. This phenotypic structure might more closely reflect underlying etiologies than a structure that classically describes GTS patients according to absence or presence of comorbid OCD, ADHD and autism, and might inform both future genetic and treatment studies.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno Autístico , Tics , Síndrome de Tourette , Adolescente , Adulto , Anciano , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/etiología , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno Autístico/epidemiología , Trastorno Autístico/etiología , Trastorno Autístico/fisiopatología , Niño , Comorbilidad , Análisis Factorial , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/etiología , Trastorno Obsesivo Compulsivo/fisiopatología , Tics/epidemiología , Tics/etiología , Tics/fisiopatología , Síndrome de Tourette/epidemiología , Síndrome de Tourette/etiología , Síndrome de Tourette/fisiopatología , Adulto JovenRESUMEN
Tic disorders (TD), including chronic/persistent TD (CTD) and Tourette syndrome, have been described and studied for many years. Within the last two decades, intensified study efforts led to more specific assumptions about genesis and influences of both hereditary and environmental factors. TD in children and adolescents are very often accompanied by attention-deficit/hyperactivity disorders and obsessive-compulsive disorders (OCD) as comorbid disorders. Comorbidities are aggravating factors concerning prognosis and treatment opportunities. Therefore, etiological considerations and treatment strategies have to take associated psychiatric disorders into account. Treatment approaches are symptom targeted and include behavioral treatments and/or medication and show positive outcomes concerning tic symptomatology, global functioning, and associated psychopathology. This review presents an update of the research, definitions, and classification according to ICD-10 and DSM-5 and summarizes the diagnostic procedures and most effective clinical strategies.
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Trastornos de Tic/etiología , Trastornos de Tic/terapia , Síndrome de Tourette/etiología , Síndrome de Tourette/terapia , Adolescente , Encéfalo/fisiopatología , Niño , Epigénesis Genética , Femenino , Humanos , Masculino , Trastornos de Tic/genética , Trastornos de Tic/fisiopatología , Síndrome de Tourette/genética , Síndrome de Tourette/fisiopatologíaRESUMEN
This is the first nationwide register-based study to examine the relationship between prenatal maternal smoking and Tourette syndrome. A total of 767 children diagnosed with Tourette syndrome were identified from the Finnish Hospital Discharge Register. Each case was matched to four controls. Information on maternal smoking during pregnancy was obtained from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses. Prenatal maternal smoking was associated with Tourette syndrome when comorbid with ADHD (OR 4.0, 95 % CI 1.2-13.5, p = 0.027 for exposure during first trimester, OR 1.7, 95 % CI, 1.05-2.7, p = 0.031 for exposure for the whole pregnancy). There was no association between maternal smoking during pregnancy and Tourette syndrome without comorbid ADHD (OR 0.5, 95 % CI 0.2-1.3, p = 0.166, OR 0.9, 95 % CI 0.7-1.3, p = 0.567). Further research is needed to elucidate the mechanisms behind the association between prenatal maternal smoking and Tourette syndrome with comorbid ADHD.
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Efectos Tardíos de la Exposición Prenatal/epidemiología , Fumar/efectos adversos , Síndrome de Tourette/epidemiología , Síndrome de Tourette/etiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/etiología , Niño , Comorbilidad , Femenino , Finlandia , Edad Gestacional , Humanos , Embarazo , Primer Trimestre del Embarazo , Sistema de Registros , Estadística como AsuntoRESUMEN
After having examined the definition, clinical phenomenology, comorbidity, psychopathology, and phenotypes in the first paper of this Series, here I discuss the assessment, including neuropsychology, and the effects of Gilles de la Tourette syndrome with studies showing that the quality of life of patients with Tourette's syndrome is reduced and that there is a substantial burden on the family. In this paper, I review my local and collaborative studies investigating causal factors (including genetic vulnerability, prenatal and perinatal difficulties, and neuro-immunological factors). I also present my studies on neuro-imaging, electro-encephalograms, and other special investigations, which are helpful in their own right or to exclude other conditions. Finally, I also review our studies on treatment including medications, transcranial magnetic stimulation, biofeedback, target-specific botulinum toxin injections, biofeedback and, in severe refractory adults, psychosurgery and deep brain stimulation. This Review summarises and highlights selected main findings from my clinic (initially The National Hospital for Neurology and Neurosurgery Queen Square and University College London, UK, and, subsequently, at St George's Hospital, London, UK), and several collaborations since 1980. As in Part 1 of this Series, I address the main controversies in the fields and the research of other groups, and I make suggestions for future research.
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Síndrome de Tourette/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Terapia Cognitivo-Conductual , Costo de Enfermedad , Femenino , Humanos , Masculino , Neuroimagen , Neuropsicología , Calidad de Vida , Infecciones Estreptocócicas/complicaciones , Síndrome de Tourette/etiología , Síndrome de Tourette/patología , Síndrome de Tourette/psicologíaRESUMEN
BACKGROUND: Genetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS. METHODS: Literature was searched in multiple databases including PUBMED, COCHRANE and WEB OF SCIENCE up to July 2014. The number of the genotypes for DRD2/ANKK1 TaqIA in the TS and control subjects was extracted and statistical analysis was performed using Review Manager 5.0.16 and Stata 12.0 software. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were utilized to calculate the risk of TS with DRD2/ANKK1 TaqIA. Stratified analysis based on ethnicity was also conducted. RESULTS: 523 patients with TS, 564 controls and 87 probands plus 152 relatives from five published studies were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the DRD2/ANKK1 TaqIA A1 allele were 1.69 (95%CIs = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model. Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians (fixed-effect model: OR=1.75, 95%CI = 1.43-2.16; random-effect model: OR=1.69, 95%CI = 1.25-2.28) and in Asians (OR=1.54, 95%CI = 1.12-2.10). Meta-analysis of the A1A1 vs. A2A2 (homozygous model), A1A2 vs. A2A2 (heterozygous model) and A1A1+A1A2 vs. A2A2 (dominant model) of this polymorphism revealed a significant association with TS in overall populations and Caucasians. CONCLUSIONS: This meta-analysis suggested that the DRD2/ANKK1 TaqIA polymorphism might contribute to TS susceptibility, especially in Caucasian population. However, further investigation with a larger number of worldwide studies should be conducted to verify the association.
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Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Proteínas Serina-Treonina Quinasas/genética , Receptores de Dopamina D2/genética , Síndrome de Tourette/genética , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Genotipo , Humanos , Riesgo , Síndrome de Tourette/etiología , Población Blanca/genéticaAsunto(s)
Psiquiatría del Adolescente , Psiquiatría Infantil , Medicina de Precisión , Adolescente , Trastorno del Espectro Autista/diagnóstico , Niño , Humanos , Neuroimagen , Publicaciones Periódicas como Asunto , Trastornos Relacionados con Sustancias/terapia , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/etiologíaRESUMEN
OBJECTIVE: In a nationwide prospective cohort study, we examined the possible association between maternal autoimmune disease (AD) and later diagnosis of Tourette syndrome (TS) in offspring. METHOD: Data from national Danish health registers identified a cohort consisting of all children born in Denmark between 1990 and 2007 (n = 1,116,255), followed prospectively from birth until 2011, date of TS diagnosis, death, or emigration/disappearance, whichever came first. The incidence rate ratio (IRR) of TS, dependent on whether or not the mother had a prior diagnosis of AD, was estimated by Poisson regression with 95% CIs and adjusted for age, calendar time, place of birth, maternal and paternal age, parental psychiatric diagnoses other than TS, and parental TS. RESULTS: The cohort contributed a total of 13,000,162 person years and 2,442 participants with a diagnosis of TS (414 females and 2,028 males). Prior maternal AD was found in 110 of the 2,442 children with TS, corresponding to an increased risk of TS, with an adjusted IRR of 1.22 (95% CI = 1.01-1.48). Maternal history of a prior AD increased the risk of TS in males, with an adjusted IRR of 1.29 (95% CI = 1.05-1.58), but not in females, with an adjusted IRR of 0.89 (95% CI = 0.52-1.52). CONCLUSION: Maternal AD was associated with a 29% increased incidence rate of TS in male offspring. This finding supports the hypothesis that neuroimmunological disorders may act as a component in the etiology of a subset of TS.
Asunto(s)
Enfermedades Autoinmunes/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Síndrome de Tourette/etiología , Adolescente , Adulto , Niño , Dinamarca , Femenino , Humanos , Incidencia , Masculino , Madres , Embarazo , Estudios Prospectivos , Sistema de Registros , Análisis de Regresión , Factores Sexuales , Síndrome de Tourette/diagnóstico , Adulto JovenRESUMEN
There has been a persistent attempt to explain Mozart's talent as connected to physical and mental illness. While Mozart's musical compositions and performances were often acclaimed for their "taste," the composer's personal behavior sometimes astonished those who witnessed "blödeln" or wild horseplay, practical joking, and scatological humor. Most recently, Mozart's eccentric behavior has been attributed to Gilles de la Tourette syndrome. This chapter investigates the evidence for these retrospective diagnoses and reassesses this evidence by paying particular attention to the milieu in which Mozart lived. We argue that Mozart's putative pathological behavior was a manifestation of his resilience in face of multiple adversities and was deeply rooted in his sense of play. Our hypothesis is that play, rather than neuropsychiatric disease, was essential to the operation of his genius.