Gilles de la Tourette syndrome (GTS) is a childhood-onset neurodevelopmental disorder that is characterized by several motor and phonic tics. Tics usually develop before 10 years of age, exhibit a waxing and waning course and typically improve with increasing age. A prevalence of approximately 1% is estimated in children and adolescents. The condition can result in considerable social stigma and poor quality of life, especially when tics are severe (for example, with coprolalia (swearing tics) and self-injurious behaviours) or when GTS is accompanied by attention-deficit/hyperactivity disorder, obsessive–compulsive disorder or another neuropsychiatric disorder. The aetiology is complex and multifactorial. GTS is considered to be polygenic, involving multiple common risk variants combined with rare, inherited or de novo mutations. These as well as non-genetic factors (such as perinatal events and immunological factors) are likely to contribute to the heterogeneity of the clinical phenotype, the structural and functional brain anomalies and the neural circuitry involvement. Management usually includes psychoeducation and reassurance, behavioural methods, pharmacotherapy and, rarely, functional neurosurgery. Future research that integrates clinical and neurobiological data, including neuroimaging and genetics, is expected to reveal the pathogenesis of GTS at the neural circuit level, which may lead to targeted interventions.
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Robertson, M. M. A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. Lancet Psychiatry 2, 68–87 (2015). This two-part review gives a personal perspective of managing patients with GTS over a period of 35 years, and then compares this to updated evidence as it relates to prevalence, phenomenology, comorbidities and coexistent psychopathologies.
American Psychatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (American Psychiatric Association, 2013).
Altshuler, L. L. et al. Who seeks mental health care in China? Diagnoses of Chinese outpatients according to DSM-III criteria and the Chinese classification system. Am. J. Psychiatry 145, 872–875 (1988).
Ming-Yuan, Z. The diagnosis and phenomenology of neurasthenia a Shanghai study. Cult. Med. Psychiatry 13, 147–161 (1989).
Eapen, V. & Robertson, M. M. Are there distinct subtypes in Tourette syndrome? Pure-Tourette syndrome versus Tourette syndrome-plus, and simple versus complex tics. Neuropsychiatr. Dis. Treat. 11, 1431–1436 (2015). This paper provides crucial insights into the similarities and differences between patients presenting with only motor and vocal tics compared with those also exhibiting associated comorbidities and psychopathologies.
Eapen, V. & Črnčec, R. DSM 5 and child psychiatric disorders: what is new? What has changed? Asian J. Psychiatr. 11, 114–118 (2014).
Eapen, V., Pauls, D. L. & Robertson, M. M. Evidence for autosomal dominant transmission in Tourette's syndrome. United Kingdom cohort study. Br. J. Psychiatry 162, 593–596 (1993).
Caprini, G. & Melotti, V. Un grave sindrome ticcosa guarita con haloperidol. Riv. Sper. Freniatr. 85, 191–196 (1961).
Seignot, J. A case of tic of Gilles de la Tourette cured by R 1625. Ann. Med. Psychol. 119, 578–579 (1961).
Robertson, M. M. Tourette syndrome, associated conditions and the complexities of treatment. Brain 3, 425–462 (2000).
Roessner, V. et al. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur. Child Adolesc. Psychiatry 20, 173–196 (2011). These are the first consensus guidelines on the treatment of tic disorders and GTS, including a definition of treatment indication.
Thenganatt, M. A. & Jankovic, J. Recent advances in understanding and managing Tourette syndrome. F1000Res. 5 (F1000 Faculty Rev), 152 (2016).
Comings, D. E., Himes, J. A. & Comings, B. G. An epidemiologic study of Tourette's syndrome in a single school district. J. Clin. Psychiatry 51, 463–469 (1990).
Jankovic, J. & Kurlan, R. Tourette syndrome: evolving concepts. Mov. Disord. 26, 1149–1156 (2011).
Scahill, L., Dalsgaard, S. & Bradbury, K. in Tourette Syndrome (eds Martino, D. & Leckman, J. F. ) 121–133 (Oxford Univ. Press, 2013).
Centers for Disease Control & Prevention. Prevalence of diagnosed Tourette syndrome in persons aged 6–17 years — United States, 2007. MMWR Morb. Mortal. Wkly Rep. 58, 581–585 (2009).
Robertson, M. M. The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 1: the epidemiological and prevalence studies. J. Psychosom. Res. 65, 461–472 (2008).
Knight, T. et al. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr. Neurol. 47, 77–90 (2012). This meta-analysis has helped to clarify the variations in prevalence rates of GTS and provides directions for future epidemiological studies.
Scharf, J. M. et al. Population prevalence of Tourette syndrome: a systematic review and meta-analysis. Mov. Disord. 30, 221–228 (2015).
Steinberg, T., Tamir, I., Zimmerman-Brenner, S., Friling, M. & Apter, A. Prevalence and comorbidity of tic disorder in Israeli adolescents: results from a national mental health survey. Isr. Med. Assoc. J. 15, 94–98 (2013).
Chinese Society of Psychiatry. The Chinese Classification and Diagnostic Criteria of Mental Disorders Version 3 (CCMD-3) (Chinese Society of Psychiatry, 2001).
Jin, R. et al. Epidemiological survey of Tourette syndrome in children and adolescents in Wenzhou of PR China. Eur. J. Epidemiol. 20, 925–927 (2005).
Wang, H.-S. & Kuo, M.-F. Tourette's syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County. Brain Dev. 25, S29–S31 (2003).
Atladóttir, H. O. et al. Time trends in reported diagnoses of childhood neuropsychiatric disorders: a Danish cohort study. Arch. Pediatr. Adolesc. Med. 161, 193–198 (2007).
Leivonen, S. et al. A nationwide register study of the characteristics, incidence and validity of diagnosed Tourette syndrome and other tic disorders. Acta Paediatr. 103, 984–990 (2014).
Pauls, D. L., Fernandez, T. V., Mathews, C. A., State, M. W. & Scharf, J. M. The inheritance of Tourette disorder: a review. J. Obsessive Compuls. Relat. Disord. 3, 380–385 (2014).
Browne, H. A. et al. Familial clustering of tic disorders and obsessive–compulsive disorder. JAMA Psychiatry 72, 359–366 (2015).
Mataix-Cols, D. et al. Familial risks of Tourette syndrome and chronic tic disorders. A population-based cohort study. JAMA Psychiatry 72, 787–793 (2015).
Paschou, P. The genetic basis of Gilles de la Tourette syndrome. Neurosci. Biobehav. Rev. 37, 1026–1039 (2013).
Georgitsi, M. et al. The genetic etiology of Tourette syndrome: large-scale collaborative efforts on the precipice of discovery. Front. Neurosci. 10, 351 (2016).
Davis, L. K. et al. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet. 9, e1003864 (2013). This landmark study uses multivariate modelling to provide the first direct genetic measure of aggregated GTS genetic risk (that is, heritability) captured by genome-wide association studies and demonstrates that GTS is predominantly a polygenic disorder, with risk variants distributed widely across the genome that overlap significantly with, but are also distinct from, OCD genetic risk.
Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371–1379 (2013).
Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984–994 (2013).
Abelson, J. F. et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317–320 (2005).
Scharf, J. M. et al. Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample. Neurology 70, 1495–1496 (2008).
Miranda, D. M. et al. Association of SLITRK1 to Gilles de la Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 483–486 (2009).
O’Roak, B. J. et al. Additional support for the association of SLITRK1 var321 and Tourette syndrome. Mol. Psychiatry 15, 447–450 (2010).
Karagiannidis, I. et al. Replication of association between a SLITRK1 haplotype and Tourette syndrome in a large sample of families. Mol. Psychiatry 17, 665–668 (2012).
Ercan-Sencicek, A. G. et al. L-Histidine decarboxylase and Tourette's syndrome. N. Engl. J. Med. 362, 1901–1908 (2010).
Fernandez, T. V. et al. Rare copy number variants in Tourette syndrome disrupt genes in histaminergic pathways and overlap with autism. Biol. Psychiatry 71, 392–402 (2011).
Karagiannidis, I. et al. Support of the histaminergic hypothesis in Tourette syndrome: association of the histamine decarboxylase gene in a large sample of families. J. Med. Genet. 50, 760–764 (2013).
Scharf, J. M. et al. Genome-wide association study of Tourette's syndrome. Mol. Psychiatry 18, 721–728 (2013).
Paschou, P. et al. Genetic association signal near NTN4 in Tourette syndrome. Ann. Neurol. 76, 310–315 (2014).
Huang, A. Y. et al. Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome. Preprint at bioRxivhttp://dx.doi.org/10.1101/062471 (2016).
Sundaram, S. K., Huq, A. M., Wilson, B. J. & Chugani, H. T. Tourette syndrome is associated with recurrent exonic copy number variants. Neurology 74, 1583–1590 (2010).
Nag, A. et al. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. PLoS ONE 8, e59061 (2013).
Bertelsen, B. et al. Association of AADAC deletion and Gilles de la Tourette syndrome in a large European cohort. Biol. Psychiatry 79, 383–391 (2016).
Hirschtritt, M. E. et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry 72, 325–333 (2015).
Huisman-van Dijk, H. M., Schoot, R., Rijkeboer, M. M., Mathews, C. A. & Cath, D. C. The relationship between tics, OC, ADHD and autism symptoms: a cross-disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members. Psychiatry Res. 237, 138–146 (2016).
Mathews, C. A. & Grados, M. A. Familiality of Tourette syndrome, obsessive–compulsive disorder, and attention-deficit/hyperactivity disorder: heritability analysis in a large sib-pair sample. J. Am. Acad. Child Adolesc. Psychiatry 50, 46–54 (2011).
Karagiannidis, I. et al. The genetics of Gilles de la Tourette syndrome: a common aetiological basis with comorbid disorders? Curr. Behav. Neurosci. Rep. 3, 218–231 (2016).
McGrath, L. M. et al. Copy number variation in obsessive–compulsive disorder and tourette syndrome: a cross-disorder study. J. Am. Acad. Child Adolesc. Psychiatry 53, 910–919 (2014).
Zilhao, N. R. et al. Epigenome-wide association study of tic disorders. Twin Res. Hum. Genet. 18, 699–709 (2015).
Clarke, R., Lee, S. & Eapen, V. Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism. Transl Psychiatry 2, e158 (2012).
Yu, D. et al. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD. Am. J. Psychiatry 172, 82–93 (2015).
Anttila, V. et al. Analysis of shared heritability in common disorders of the brain. Preprint at bioRxivhttp://dx.doi.org/10.1101/048991 (2016).
Barabas, G., Matthews, W. S. & Ferrari, M. Tourette's syndrome and migraine. Arch. Neurol. 41, 871–872 (1984).
Tsetsos, F. et al. Meta-analysis of Tourette syndrome and attention deficit hyperactivity disorder provides support for a shared genetic basis. Front. Neurosci. 10, 340 (2016).
Anttila, V. et al. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat. Genet. 45, 912–917 (2013).
Bergink, V., Gibney, S. M. & Drexhage, H. A. Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biol. Psychiatry 75, 324–331 (2014).
Chao, T.-K., Hu, J. & Pringsheim, T. Prenatal risk factors for Tourette syndrome: a systematic review. BMC Pregnancy Childbirth 14, 1 (2014).
Hoekstra, P. J., Dietrich, A., Edwards, M. J., Elamin, I. & Martino, D. Environmental factors in Tourette syndrome. Neurosci. Biobehav. Rev. 37, 1040–1049 (2013).
Martino, D., Zis, P. & Buttiglione, M. The role of immune mechanisms in Tourette syndrome. Brain Res. 1617, 126–143 (2015).
Lin, H. et al. Streptococcal upper respiratory tract infections and psychosocial stress predict future tic and obsessive–compulsive symptom severity in children and adolescents with Tourette syndrome and obsessive–compulsive disorder. Biol. Psychiatry 67, 684–691 (2010).
Israelashvili, M. & Bar-Gad, I. Corticostriatal divergent function in determining the temporal and spatial properties of motor tics. J. Neurosci. 35, 16340–16351 (2015).
Dalsgaard, S., Waltoft, B. L., Leckman, J. F. & Mortensen, P. B. Maternal history of autoimmune disease and later development of Tourette syndrome in offspring. J. Am. Acad. Child Adolesc. Psychiatry 54, 495–501.e1 (2015).
Chang, Y.-T. et al. Correlation of Tourette syndrome and allergic disease: nationwide population-based case–control study J. Dev. Behav. Pediatr. 32, 98–102 (2011).
Lennington, J. B. et al. Transcriptome analysis of the human striatum in Tourette syndrome. Biol. Psychiatry 79, 372–382 (2016). This is the first analysis of the striatal transcriptome of post-mortem brains of patients with GTS, which supports a key role for GABAergic and cholinergic interneurons and microglia in the pathogenesis of GTS.
Kumar, A., Williams, M. T. & Chugani, H. T. Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and Tourette syndrome a positron emission tomographic (PET) study using C-[R]-PK11195. J. Child Neurol. 30, 749–756 (2015).
Lit, L., Enstrom, A., Sharp, F. R. & Gilbert, D. L. Age-related gene expression in Tourette syndrome. J. Psychiatr. Res. 43, 319–330 (2009).
Gunther, J. et al. Catecholamine-related gene expression in blood correlates with tic severity in Tourette syndrome. Psychiatry Res. 200, 593–601 (2012).
Tian, Y. et al. GABA- and acetylcholine-related gene expression in blood correlate with tic severity and microarray evidence for alternative splicing in Tourette syndrome: a pilot study. Brain Res. 1381, 228–236 (2011).
Wenzel, C., Wurster, U. & Müller-Vahl, K. R. Oligoclonal bands in cerebrospinal fluid in patients with Tourette's syndrome. Mov. Disord. 26, 343–346 (2011).
Delorme, C. et al. Enhanced habit formation in Gilles de la Tourette syndrome. Brain 139, 605–615 (2016).
Singer, H. S. Motor control, habits, complex motor stereotypies, and Tourette syndrome. Ann. NY Acad. Sci. 1304, 22–31 (2013).
Singer, H. S. Habitual and goal-directed behaviours and Tourette syndrome. Brain 139, 312–316 (2016).
Crittenden, J. R. & Graybiel, A. M. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments. Front. Neuroanat. 5, 59 (2011).
Singer, H. S. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 276–300 (Oxford Univ. Press, 2013).
Singer, H. S., Puts, N., Tochen, L., Edden, R. A. E. & Mahone, E. M. GABA and glutamate in children with Tourette syndrome: a 7T study. Ann. Neurol. 80, S292–S293 (2016).
Pogorelov, V., Xu, M., Smith, H. R., Buchanan, G. F. & Pittenger, C. Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition. Exp. Neurol. 265, 122–128 (2015).
Gilbert, D. L. et al. Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome. Mov. Disord. 19, 416–425 (2004).
Puts, N. A. et al. Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome. J. Neurophysiol. 114, 808–817 (2015).
Draper, A. et al. Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome. Curr. Biol. 24, 2343–2347 (2014).
Bronfeld, M., Yael, D., Belelovsky, K. & Bar-Gad, I. Motor tics evoked by striatal disinhibition in the rat. Front. Syst. Neurosci. 7, 50 (2013).
Xu, M. et al. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc. Natl Acad. Sci. USA 112, 893–898 (2015).
Nelson, A. B. et al. Striatal cholinergic interneurons drive GABA release from dopamine terminals. Neuron 82, 63–70 (2014).
Wong, D. F. et al. Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology 33, 1239–1251 (2008).
Baldan, L. C. et al. Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron 81, 77–90 (2014).
Rapanelli, M. et al. Dysregulated intracellular signaling in the striatum in a pathophysiologically grounded model of Tourette syndrome. Eur. Neuropsychopharmacol. 24, 1896–1906 (2014).
Befort, K. Interactions of the opioid and cannabinoid systems in reward: insights from knockout studies. Front. Pharmacol. 6, 6 (2015).
Massotte, D. Monitoring endogenous GPCRs: lessons for drug design. Front. Pharmacol. 6, 146 (2015).
Whiting, P. F. et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 313, 2456–2473 (2015).
Robertson, M. M. A personal 35 year perspective on Gilles de la Tourette syndrome: assessment, investigations, and management. Lancet Psychiatry 2, 88–104 (2015).
Moriarty, J. et al. HMPAO SPET does not distinguish obsessive–compulsive and tic syndromes in families multiply affected with Gilles de la Tourette's syndrome. Psychol. Med. 27, 737–740 (1997).
Muellner, J. et al. Altered structure of cortical sulci in Gilles de la Tourette syndrome: further support for abnormal brain development. Mov. Disord. 30, 655–661 (2015).
Bloch, M. H., Leckman, J. F., Zhu, H. & Peterson, B. S. Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology 65, 1253–1258 (2005).
Leckman, J. F., Bloch, M. H., Sukhodolsky, D. G., Scahill, L. & King, R. A. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 3–25 (Oxford Univ. Press, 2013).
Peterson, B. S. & Leckman, J. F. The temporal dynamics of tics in Gilles de la Tourette syndrome. Biol. Psychiatry 44, 1337–1348 (1998).
Jankovic, J. & Stone, L. Dystonic tics in patients with Tourette's syndrome. Mov. Disord. 6, 248–252 (1991).
Robertson, M. M., Trimble, M. R. & Lees, A. The psychopathology of the Gilles de la Tourette syndrome. A phenomenological analysis. Br. J. Psychiatry 152, 383–390 (1988).
Freeman, R. D. et al. An international perspective on Tourette syndrome: selected findings from 3500 individuals in 22 countries. Dev. Med. Child Neurol. 42, 436–447 (2000).
Freeman, R. D. et al. Coprophenomena in Tourette syndrome. Dev. Med. Child Neurol. 51, 218–227 (2009).
Robertson, M. M. & Gourdie, A. Familial Tourette's syndrome in a large British pedigree. Associated psychopathology, severity, and potential for linkage analysis. Br. J. Psychiatry 156, 515–521 (1990).
Eapen, V. & Robertson, M. M. Gilles de la Tourette syndrome in Malta: psychopathology in a multiply affected pedigree. Arab J. Psychiatry 6, 113–118 (1995).
Eapen, V., Robertson, M. M., Zeitlin, H. & Kurlan, R. Gilles de la Tourette's syndrome in special education schools: a United Kingdom study. J. Neurol. 244, 378–382 (1997).
Baron-Cohen, S., Scahill, V. L., Izaguirre, J., Hornsey, H. & Robertson, M. M. The prevalence of Gilles de la Tourette syndrome in children and adolescents with autism: a large scale study. Psychol. Med. 29, 1151–1159 (1999).
Baron-Cohen, S., Mortimore, C., Moriarty, J., Izaguirre, J. & Robertson, M. M. The prevalence of Gilles de la Tourette's syndrome in children and adolescents with autism. J. Child Psychol. Psychiatry 40, 213–218 (1999).
Hornsey, H., Banerjee, S., Zeitlin, H. & Robertson, M. M. The prevalence of Tourette syndrome in 13–14-year-olds in mainstream schools. J. Child Psychol. Psychiatry 42, 1035–1039 (2001).
Lin, H. et al. Psychosocial stress predicts future symptom severities in children and adolescents with Tourette syndrome and/or obsessive–compulsive disorder. J. Child Psychol. Psychiatry 48, 157–166 (2007).
Scahill, L. et al. Thermal sensitivity in Tourette syndrome: preliminary report. Percept. Mot. Skills 92, 419–432 (2001).
Cheung, M. Y. C., Shahed, J. & Jankovic, J. Malignant Tourette syndrome. Mov. Disord. 22, 1743–1750 (2007).
Robertson, M. M., Trimble, M. & Lees, A. Self-injurious behaviour and the Gilles de la Tourette syndrome: a clinical study and review of the literature. Psychol. Med. 19, 611–625 (1989).
Leckman, J. F., Walker, D. & Cohen, D. Premonitory urges in Tourette's syndrome. Am. J. Psychiatry 150, 98–102 (1993).
Woods, D. W., Piacentini, J., Himle, M. B. & Chang, S. Premonitory Urge for Tics Scale (PUTS): initial psychometric results and examination of the premonitory urge phenomenon in youths with tic disorders. J. Dev. Behav. Pediatr. 26, 397–403 (2005).
Piacentini, J. et al. Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA 303, 1929–1937 (2010). This is the first large-scale controlled evaluation of a comprehensive behavioural intervention for tics in children.
Müller-Vahl, K. R., Riemann, L. & Bokemeyer, S. Tourette patients’ misbelief of a tic rebound is due to overall difficulties in reliable tic rating. J. Psychosomat. Res. 76, 472–476 (2014).
Turtle, L. & Robertson, M. M. Tics, twitches, tales: the experiences of Gilles de la Tourette's syndrome. Am. J. Orthopsychiatry 78, 449 (2008).
Cavanna, A. E. & Nani, A. Tourette syndrome and consciousness of action. Tremor Other Hyperkinet. Mov.http://dx.doi.org/10.7916/D8PV6J33 (2013).
Patel, N., Jankovic, J. & Hallett, M. Sensory aspects of movement disorders. Lancet Neurol. 13, 100–112 (2014).
Leckman, J. F. et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J. Am. Acad. Child Adolesc. Psychiatry 28, 566–573 (1989). This is the first study to report the psychometric properties of the most widely used tic severity scale.
Martino, D. et al. Systematic review of severity scales and screening instruments for tics: critique and recommendations. Mov. Disord.http://dx.doi.org/10.1002/mds.26891 (2017).
Goetz, C. G., Pappert, E. J., Louis, E. D., Raman, R. & Leurgans, S. Advantages of a modified scoring method for the Rush Video-Based Tic Rating Scale. Mov. Disord. 14, 502–506 (1999).
Gaffney, G. R., Sieg, K. & Hellings, J. The MOVES: a self-rating scale for Tourette's syndrome. J. Child Adolesc. Psychopharmacol. 4, 269–280 (1994).
Baizabal-Carvallo, J. F. & Fekete, R. Recognizing uncommon presentations of psychogenic (functional) movement disorders. Tremor Other Hyperkinet. Mov. 5, 279–279 (2014).
Baizabal-Carvallo, J. F. & Jankovic, J. The clinical features of psychogenic movement disorders resembling tics. J. Neurol. Neurosurg. Psychiatry 85, 573–575 (2014).
Dreissen, Y., Cath, D. & Tijssen, M. Functional jerks, tics, and paroxysmal movement disorders. Handb. Clin. Neurol. 139, 247–258 (2017).
Mejia, N. I. & Jankovic, J. Secondary tics and tourettism. Rev. Bras. Psiquiatr. 27, 11–17 (2005).
Bloch, M. H. et al. Adulthood outcome of tic and obsessive–compulsive symptom severity in children with Tourette syndrome. Arch. Pediatr. Adolesc. Med. 160, 65–69 (2006). This is one of the first prospective longitudinal studies confirming that tic symptoms typically diminish in late adolescence.
Leckman, J. F. et al. Course of tic severity in Tourette syndrome: the first two decades. Pediatrics 102, 14–19 (1998).
Zinner, S. H., Conelea, C. A., Glew, G. M., Woods, D. W. & Budman, C. L. Peer victimization in youth with Tourette syndrome and other chronic tic disorders. Child Psychiatry Hum. Dev. 43, 124–136 (2012).
Pappert, E. J., Goetz, C., Louis, E., Blasucci, L. & Leurgans, S. Objective assessments of longitudinal outcome in Gilles de la Tourette's syndrome. Neurology 61, 936–940 (2003).
Jankovic, J., Gelineau-Kattner, R. & Davidson, A. Tourette's syndrome in adults. Mov. Disord. 25, 2171–2175 (2010).
Eapen, V., Robertson, M. M., Alsobrook, J. P. & Pauls, D. L. Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder. Am. J. Med. Genet. 74, 432–438 (1997).
O’Rourke, J. A. et al. The familial association of tourette's disorder and ADHD: the impact of OCD symptoms. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156, 553–560 (2011).
Clarke, R. A. & Eapen, V. Balance within the neurexin trans-synaptic connexus stabilizes behavioral control. Front. Hum. Neurosci. 8, 52 (2014).
Petek, E. et al. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome. Mol. Genet. Genomics 277, 71–81 (2007).
Delgado, M. S. et al. Screening individuals with intellectual disability, autism and Tourette's syndrome for KCNK9 mutations and aberrant DNA methylation within the 8q24 imprinted cluster. Am. J. Med. Genet. B Neuropsychiatr. Genet. 165, 472–478 (2014).
Kwak, C., Vuong, K. D. & Jankovic, J. Migraine headache in patients with Tourette syndrome. Arch. Neurol. 60, 1595–1598 (2003).
Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236–1241 (2015).
Robertson, M. M., Cavanna, A. E. & Eapen, V. Gilles de la Tourette syndrome and disruptive behavior disorders: prevalence, associations, and explanation of the relationships. J. Neuropsychiatry Clin. Neurosci. 27, 33–41 (2015).
Robertson, M. M. Mood disorders and Gilles de la Tourette's syndrome: an update on prevalence, etiology, comorbidity, clinical associations, and implications. J. Psychosomat. Res. 61, 349–358 (2006).
Pauls, D. L., Leckman, J. F. & Cohen, D. J. Evidence against a genetic relationship between Tourette's syndrome and anxiety, depression, panic and phobic disorders. Br. J. Psychiatry 164, 215–221 (1994).
Eddy, C. M. & Cavanna, A. E. On being your own worst enemy: an investigation of socially inappropriate symptoms in Tourette syndrome. J. Psychiatr. Res. 47, 1259–1263 (2013).
Kurlan, R. et al. Non-obscene complex socially inappropriate behavior in Tourette's syndrome. J. Neuropsychiatry Clin. Neurosci. 8, 311–317 (1996).
Darrow, S. M. Identification of two heritable cross-disorder endophenotypes for Tourette syndrome. Am. J. Psychiatryhttp://dx.doi.org/10.1176/appi.ajp.2016.16020240 (2016).
Hirschtritt, M. E. et al. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome. Neurology 87, 497–504 (2016).
Robertson, M. M. Movement disorders: Tourette syndrome — beyond swearing and sex? Nat. Rev. Neurol. 10, 6–8 (2014).
Khalifa, N. & Von Knorring, A.-L. Psychopathology in a Swedish population of school children with tic disorders. J. Am. Acad. Child Adolesc. Psychiatry 45, 1346–1353 (2006).
McGuire, J. F. et al. A cluster analysis of tic symptoms in children and adults with Tourette syndrome: clinical correlates and treatment outcome. Psychiatry Res. 210, 1198–1204 (2013).
Storch, E. A. et al. Suicidal thoughts and behaviors in children and adolescents with chronic tic disorders. Depress. Anxiety 32, 744–753 (2015).
Dávila, G., Berthier, M. L., Kulisevsky, J. & Chacón, S. J. Suicide and attempted suicide in Tourette's syndrome: a case series with literature review. J. Clin. Psychiatry 71, 1401–1402 (2010).
Johnco, C. et al. Suicidal ideation in youth with tic disorders. J. Affect. Disord. 200, 204–211 (2016).
Robertson, M. M., Eapen, V. & van de Wetering, B. J. Suicide in Gilles de la Tourette's syndrome: report of two cases. J. Clin. Psychiatry 56, 378 (1995).
Murphy, T. K., Lewin, A. B., Storch, E. A., Stock, S. & American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI). Practice parameter for the assessment and treatment of children and adolescents with tic disorders. J. Am. Acad. Child Adolesc. Psychiatry 52, 1341–1359 (2013).
Verdellen, C., van de Griendt, J., Hartmann, A., Murphy, T. & ESSTS Guidelines Group. European clinical guidelines for Tourette syndrome and other tic disorders. Part III: behavioural and psychosocial interventions. Eur. Child Adolesc. Psychiatry 20, 197–207 (2011).
Scahill, L. et al. Current controversies on the role of behavior therapy in Tourette syndrome. Mov. Disord. 28, 1179–1183 (2013).
Hartmann, A., Martino, D. & Murphy, T. Gilles de la Tourette syndrome — a treatable condition? Rev. Neurol. (Paris) 172, 446–454 (2016).
Azrin, N. H. & Nunn, R. G. Habit reversal: a method of eliminating nervous habits and tics. Behav. Res. Ther. 11, 619–628 (1973).
Woods, D. W. et al. Managing Tourette Syndrome: A Behavioral Intervention for Children and Adults (Therapist Guide) (Oxford Univ. Press, 2008).
Steeves, T. et al. Canadian guidelines for the evidence-based treamtent of tic disorders: behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation. Can. J. Psychiatry 57, 144–151 (2012).
Wilhelm, S. et al. Randomized trial of behavior therapy for adults with Tourette syndrome. Arch. General Psychiatry 69, 795–803 (2012).
Himle, M. B. et al. A randomized pilot trial comparing videoconference versus face-to-face delivery of behavior therapy for childhood tic disorders. Behav. Res. Ther. 50, 565–570 (2012).
Ricketts, E. J. et al. A randomized waitlist-controlled pilot trial of voice over internet protocol-delivered behavior therapy for youth with chronic tic disorders. J. Telemed. Telecare 22, 153–162 (2016).
Ricketts, E. J. et al. Pilot testing behavior therapy for chronic tic disorders in neurology and developmental pediatrics clinics. J. Child Neurol. 31, 444–450 (2016).
Deckersbach, T. et al. Neural correlates of behavior therapy for Tourette's disorder. Psychiatry Res. 224, 269–274 (2014).
Capriotti, M. R., Himle, M. B. & Woods, D. W. Behavioral treamtents for Tourette syndrome. J. Obsessive Compuls. Relat. Disord. 3, 415–420 (2014).
Verdellen, C. W. J., Keijsers, G. P. J., Cath, D. C. & Hoogduin, C. A. L. Exposure with response prevention versus habit reversal in Tourette's syndrome: a controlled study. Behav. Res. Ther. 42, 501–511 (2004).
Pringsheim, T. et al. Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy. Can. J. Psychiatry 57, 133–143 (2012).
Macerollo, A. et al. Refractoriness to pharmacological treatment for tics: a multicentre European audit. J. Neurol. Sci. 366, 136–138 (2016).
Hollis, C. et al. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis. Health Technol. Assess. 20, 1–450 (2016).
Whittington, C. et al. Practitioner review: treatments for Tourette syndrome in children and young people — a systematic review. J. Child Psychol. Psychiatry 57, 988–1004 (2016).
Roessner, V. et al. Pharmacological treatment of tic disorders and Tourette syndrome. Neuropharmacology 68, 143–149 (2013).
Weisman, H., Qureshi, I. A., Leckman, J. F., Scahill, L. & Bloch, M. H. Systematic review: pharmacological treatment of tic disorders — efficacy of antipsychotic and alpha-2 adrenergic agonist agents. Neurosci. Biobehav. Rev. 37, 1162–1171 (2013).
Almandil, N. B. et al. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Pediatr. Drugs 15, 139–150 (2013).
Robertson, M. M. Gilles de la Tourette syndrome: the complexities of phenotype and treatment. Br. J. Hosp. Med. (Lond.) 72, 100–107 (2011).
Kwak, C. H., Hanna, P. A. & Jankovic, J. Botulinum toxin in the treatment of tics. Arch. Neurol. 57, 1190–1193 (2000).
Müller-Vahl, K. R. Treatment of Tourette syndrome with cannabinoids. Behav. Neurol. 27, 119–124 (2013).
Zheng, Y. et al. A proprietary herbal medicine (5-Ling Granule) for Tourette syndrome: a randomized controlled trial. J. Child. Psychol. Psychiatry 57, 74–83 (2016). This is the largest randomized, double-blind, clinical trial ever completed for individuals 5–18 years of age with GTS (n = 603).
Kim, Y. H. et al. Herbal medicines for treating tic disorders: a systematic review of randomised controlled trials. Chinese Med. 9, 6 (2014).
Shprecher, D. R., Kious, B. M. & Himle, M. Advances in mechanistic understanding and treatment approaches to Tourette syndrome. Discov. Med. 20, 295–301 (2015).
Andrade, P. & Visser-Vandewalle, V. DBS in Tourette syndrome: where are we standing now? J. Neural Transm. (Vienna) 123, 791–796 (2016).
Hariz, M. I. & Robertson, M. M. Gilles de la Tourette syndrome and deep brain stimulation. Eur. J. Neurosci. 32, 1128–1134 (2010).
Kim, W. & Pouratian, N. Deep brain stimulation for Tourette syndrome. Neurosurg. Clin. N. Am. 25, 117–135 (2014).
Servello, D., Zekaj, E., Saleh, C., Lange, N. & Porta, M. Deep brain stimulation in Gilles de la Tourette syndrome: what does the future hold? A cohort of 48 patients. Neurosurgery 78, 91–100 (2016).
Kefalopoulou, Z. et al. Bilateral globus pallidus stimulation for severe Tourette's syndrome: a double-blind, randomised crossover trial. Lancet Neurol. 14, 595–605 (2015). This is the largest randomized, double-blind, crossover trial of globus pallidus interna DBS for severe GTS (n = 15).
Deeb, W. et al. Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: a review of emerging issues and technologies. Front. Integr. Neurosci. 10, 38 (2016).
Elstner, K., Selai, C., Trimble, M. & Robertson, M. M. Quality of life (QOL) of patients with Gilles de la Tourette's syndrome. Acta Psychiatr. Scand. 103, 52–59 (2001).
Cavanna, A. et al. The Gilles de la Tourette syndrome-Quality of Life Scale for children and adolescents (C&A-GTS-QOL): development and validation of the Italian version. Behav. Neurol. 27, 95–103 (2013).
Cavanna, A. et al. The Gilles de la Tourette syndrome–Quality of Life Scale (GTS-QOL) development and validation. Neurology 71, 1410–1416 (2008).
Cavanna, A. et al. Health-related quality of life in Gilles de la Tourette syndrome: a decade of research. Behav. Neurol. 27, 83–93 (2013).
Eapen, V., Snedden, C., Črnčec, R., Pick, A. & Sachdev, P. Tourette syndrome, co-morbidities and quality of life. Aust. N. Z. J. Psychiatry 50, 82–93 (2016).
Evans, J., Seri, S. & Cavanna, A. E. The effects of Gilles de la Tourette syndrome and other chronic tic disorders on quality of life across the lifespan: a systematic review. Eur. Child Adolesc. Psychiatry 25, 939–948 (2016).
O’Hare, D., Helmes, E., Reece, J., Eapen, V. & McBain, K. The differential impact of Tourette's syndrome and comorbid diagnosis on the quality of life and functioning of diagnosed children and adolescents. J. Child Adolesc. Psychiatr. Nurs. 29, 30–36 (2016).
Eapen, V., Cavanna, A. E. & Robertson, M. M. Comorbidities, social impact, and quality of life in Tourette syndrome. Front. Psychiatry 7, 97 (2016). This comprehensive review summarizes the literature on the impact of GTS and related comorbidities from social and QOL perspectives.
Muller-Vahl, K. et al. Health-related quality of life in patients with Gilles de la Tourette's syndrome. Mov. Disord. 25, 309–314 (2010).
Eddy, C. et al. Quality of life in young people with Tourette syndrome: a controlled study. J. Neurol. 258, 291–301 (2011).
Swain, J. E., Scahill, L., Lombroso, P. J., King, R. A. & Leckman, J. F. Tourette syndrome and tic disorders: a decade of progress. J. Am. Acad. Child Adolesc. Psychiatry 46, 947–968 (2007).
Bawden, H. N., Stokes, A., Camfield, C. S., Camfield, P. R. & Salisbury, S. Peer relationship problems in children with Tourette's disorder or diabetes mellitus. J. Child Psychol. Psychiatry 39, 663–668 (1998).
O’Hare, D. et al. Factors impacting the quality of peer relationships of youth with Tourette's syndrome. BMC Psychol. 3, 34 (2015).
Conelea, C. et al. The impact of Tourette syndrome in adults: results from the Tourette syndrome impact survey. Community Ment. Health J. 49, 110–120 (2013).
Parisi, J. Engagement in adulthood: perceptions and participation in daily activities. Act. Adapt. Aging 34, 1–16 (2010).
Haddad, A., Umoh, G., Bhatia, V. & Robertson, M. M. Adults with Tourette's syndrome with and without attention deficit hyperactivity disorder. Acta Psychiatr. Scand. 120, 299–307 (2009).
O’Hare, D. et al. Youth with Tourette syndrome: parental perceptions and experiences in the Australian context. Aust. J. Psychol.http://dx.doi.org/10.1111/ajpy.12111 (2016).
Cooper, C., Robertson, M. M. & Livingston, G. Parental stress and burden in parents of children with Gilles de la Tourette syndrome compared with parents of children with asthma. J. Am. Acad. Child Adolesc. Psychiatry 42, 1370–1375 (2003).
Levinson, D. F. et al. Genetic studies of major depressive disorder: why are there no GWAS findings, and what can we do about it? Biol. Psychiatry 76, 510–512 (2014).
Schizophrenia Psychiatric Genome-Wide Association Study Consortium. Genome-wide association study identifies five new schizophrenia loci. Nat. Genet. 43, 969–976 (2011).
Sanders, S. J. et al. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87, 1215–1233 (2015).
Roden, D. M. et al. Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin. Pharmacol. Ther. 84, 362–369 (2008).
Robinson, E. B. et al. Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population. Nat. Genet. 48, 552–555 (2016).
Darrow, S. M. et al. Web-based phenotyping for Tourette syndrome: reliability of common co-morbid diagnoses. Psychiatry Res. 228, 816–825 (2015).
National Institute of Mental Health. Strategic research priorities. NIMHhttps://www.nimh.nih.gov/about/strategic-planning-reports/strategic-research-priorities/srp-objective-1/priorities-for-strategy-12.shtml (2016).
Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–330 (2015).
Miller, J. A. et al. Transcriptional landscape of the prenatal human brain. Nature 508, 199–206 (2014).
Gamazon, E. R. et al. A gene-based association method for mapping traits using reference transcriptome data. Nat. Genet. 47, 1091–1098 (2015).
Willsey, A. J. et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell 155, 997–1007 (2013).
Hibar, D. P. et al. Common genetic variants influence human subcortical brain structures. Nature 520, 224–229 (2015).
Singer, H. S. et al. Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET. Am. J. Psychiatry 159, 1329–1336 (2002). In this study, greater putamen dopamine release was seen in adults with GTS than in control subjects.
Baldermann, J. C. et al. Deep brain stimulation for Tourette-syndrome: a systematic review and meta-analysis. Brain Stimul. 9, 296–304 (2016).
Deeb, W. et al. The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette syndrome: how does it work? Front. Neurosci. 10, 170 (2016).
Termine, C., Selvini, C., Rossi, G. & Balottin, U. Emerging treatment strategies in Tourette syndrome: what's in the pipeline. Int. Rev. Neurobiol. 112, 445–480 (2013).
Shapiro, A. K., Shapiro, E. S., Bruun, R. D. & Sweet, R. D. Gilles de la Tourette Syndrome (Raven Press Books, 1978).
Cavanna, A. E. & Piedad, J. C. P. in Tourette Syndrome (eds Martino, D. & Leckman, J. F. ) 411–438 (Oxford Univ. Press, 2013).
King, R. & Landeros-Weisenberger, A. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 402–410 (Oxford Univ. Press, 2013).
Rosario, M. C. et al. Validation of the University of São Paulo sensory phenomena scale: initial psychometric properties. CNS Spectr. 14, 315–323 (2009).
Leckman, J. F., Walker, D. E., Goodman, W. K., Pauls, D. L. & Cohen, D. J. “Just right” perceptions associated with compulsive behavior in Tourette's syndrome. Am. J. Psychiatry 151, 675–680 (1994).
The authors acknowledge all their patients and their families for their time, patience and teaching us all more about Gilles de la Tourette syndrome.
J.M.S. has received consulting fees from Nuvelution Pharma. D.W.W. receives royalties from Guilford Press and Oxford University Press and has received funding from the US National Institute of Mental Health (NIMH) through a subcontract with PsycTech. M.H. has received honoraria and travel grants from Medtronic as a speaker. J.F.L. serves on the scientific advisory boards of the Brain and Behavior Research Foundation, the European Multicentre Tics in Children Studies, the National Organization for Rare Diseases, Fondazione Child, and How I Decide. He has also received royalties from John Wiley and Sons, McGraw-Hill and Oxford University Press. M.M.R., V.E., H.S.S., D.M., P.P., V.R., C.A.M. and R.Č. declare no competing interests.
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