Robertson, M. M. A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. Lancet Psychiatry2, 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. Google Scholar
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. Psychiatry145, 872–875 (1988). Google Scholar
Ming-Yuan, Z. The diagnosis and phenomenology of neurasthenia a Shanghai study. Cult. Med. Psychiatry13, 147–161 (1989). Google Scholar
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. Google Scholar
Eapen, V. & Črnčec, R. DSM 5 and child psychiatric disorders: what is new? What has changed? Asian J. Psychiatr.11, 114–118 (2014). Google Scholar
Eapen, V., Pauls, D. L. & Robertson, M. M. Evidence for autosomal dominant transmission in Tourette's syndrome. United Kingdom cohort study. Br. J. Psychiatry162, 593–596 (1993). Google Scholar
Caprini, G. & Melotti, V. Un grave sindrome ticcosa guarita con haloperidol. Riv. Sper. Freniatr.85, 191–196 (1961). Google Scholar
Seignot, J. A case of tic of Gilles de la Tourette cured by R 1625. Ann. Med. Psychol.119, 578–579 (1961). Google Scholar
Robertson, M. M. Tourette syndrome, associated conditions and the complexities of treatment. Brain3, 425–462 (2000). Google Scholar
Roessner, V. et al. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur. Child Adolesc. Psychiatry20, 173–196 (2011). These are the first consensus guidelines on the treatment of tic disorders and GTS, including a definition of treatment indication. Google Scholar
Thenganatt, M. A. & Jankovic, J. Recent advances in understanding and managing Tourette syndrome. F1000Res.5 (F1000 Faculty Rev), 152 (2016). Google Scholar
Comings, D. E., Himes, J. A. & Comings, B. G. An epidemiologic study of Tourette's syndrome in a single school district. J. Clin. Psychiatry51, 463–469 (1990). Google Scholar
Jankovic, J. & Kurlan, R. Tourette syndrome: evolving concepts. Mov. Disord.26, 1149–1156 (2011). Google Scholar
Scahill, L., Dalsgaard, S. & Bradbury, K. in Tourette Syndrome (eds Martino, D. & Leckman, J. F. ) 121–133 (Oxford Univ. Press, 2013). Google Scholar
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). Google Scholar
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. Google Scholar
Scharf, J. M. et al. Population prevalence of Tourette syndrome: a systematic review and meta-analysis. Mov. Disord.30, 221–228 (2015). Google Scholar
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). Google Scholar
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). Google Scholar
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). Google Scholar
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). Google Scholar
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). Google Scholar
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). Google Scholar
Browne, H. A. et al. Familial clustering of tic disorders and obsessive–compulsive disorder. JAMA Psychiatry72, 359–366 (2015). Google Scholar
Mataix-Cols, D. et al. Familial risks of Tourette syndrome and chronic tic disorders. A population-based cohort study. JAMA Psychiatry72, 787–793 (2015). Google Scholar
Paschou, P. The genetic basis of Gilles de la Tourette syndrome. Neurosci. Biobehav. Rev.37, 1026–1039 (2013). Google Scholar
Georgitsi, M. et al. The genetic etiology of Tourette syndrome: large-scale collaborative efforts on the precipice of discovery. Front. Neurosci.10, 351 (2016). Google Scholar
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. Google Scholar
Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet381, 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. Science310, 317–320 (2005). Google Scholar
Scharf, J. M. et al. Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample. Neurology70, 1495–1496 (2008). Google Scholar
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). Google Scholar
O’Roak, B. J. et al. Additional support for the association of SLITRK1 var321 and Tourette syndrome. Mol. Psychiatry15, 447–450 (2010). Google Scholar
Karagiannidis, I. et al. Replication of association between a SLITRK1 haplotype and Tourette syndrome in a large sample of families. Mol. Psychiatry17, 665–668 (2012). Google Scholar
Ercan-Sencicek, A. G. et al. L-Histidine decarboxylase and Tourette's syndrome. N. Engl. J. Med.362, 1901–1908 (2010). Google Scholar
Fernandez, T. V. et al. Rare copy number variants in Tourette syndrome disrupt genes in histaminergic pathways and overlap with autism. Biol. Psychiatry71, 392–402 (2011). Google Scholar
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). Google Scholar
Scharf, J. M. et al. Genome-wide association study of Tourette's syndrome. Mol. Psychiatry18, 721–728 (2013). Google Scholar
Paschou, P. et al. Genetic association signal near NTN4 in Tourette syndrome. Ann. Neurol.76, 310–315 (2014). Google Scholar
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. Neurology74, 1583–1590 (2010). Google Scholar
Nag, A. et al. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. PLoS ONE8, e59061 (2013). Google Scholar
Bertelsen, B. et al. Association of AADAC deletion and Gilles de la Tourette syndrome in a large European cohort. Biol. Psychiatry79, 383–391 (2016). Google Scholar
Hirschtritt, M. E. et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry72, 325–333 (2015). Google Scholar
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). Google Scholar
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. Psychiatry50, 46–54 (2011). Google Scholar
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). Google Scholar
McGrath, L. M. et al. Copy number variation in obsessive–compulsive disorder and tourette syndrome: a cross-disorder study. J. Am. Acad. Child Adolesc. Psychiatry53, 910–919 (2014). Google Scholar
Zilhao, N. R. et al. Epigenome-wide association study of tic disorders. Twin Res. Hum. Genet.18, 699–709 (2015). Google Scholar
Clarke, R., Lee, S. & Eapen, V. Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism. Transl Psychiatry2, e158 (2012).
Yu, D. et al. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD. Am. J. Psychiatry172, 82–93 (2015). Google Scholar
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). Google Scholar
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). Google Scholar
Anttila, V. et al. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat. Genet.45, 912–917 (2013). Google Scholar
Bergink, V., Gibney, S. M. & Drexhage, H. A. Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biol. Psychiatry75, 324–331 (2014). Google Scholar
Chao, T.-K., Hu, J. & Pringsheim, T. Prenatal risk factors for Tourette syndrome: a systematic review. BMC Pregnancy Childbirth14, 1 (2014). Google Scholar
Hoekstra, P. J., Dietrich, A., Edwards, M. J., Elamin, I. & Martino, D. Environmental factors in Tourette syndrome. Neurosci. Biobehav. Rev.37, 1040–1049 (2013). Google Scholar
Martino, D., Zis, P. & Buttiglione, M. The role of immune mechanisms in Tourette syndrome. Brain Res.1617, 126–143 (2015). Google Scholar
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. Psychiatry67, 684–691 (2010). Google Scholar
Israelashvili, M. & Bar-Gad, I. Corticostriatal divergent function in determining the temporal and spatial properties of motor tics. J. Neurosci.35, 16340–16351 (2015). Google Scholar
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. Psychiatry54, 495–501.e1 (2015). Google Scholar
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). Google Scholar
Lennington, J. B. et al. Transcriptome analysis of the human striatum in Tourette syndrome. Biol. Psychiatry79, 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. Google Scholar
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). Google Scholar
Lit, L., Enstrom, A., Sharp, F. R. & Gilbert, D. L. Age-related gene expression in Tourette syndrome. J. Psychiatr. Res.43, 319–330 (2009). Google Scholar
Gunther, J. et al. Catecholamine-related gene expression in blood correlates with tic severity in Tourette syndrome. Psychiatry Res.200, 593–601 (2012). Google Scholar
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). Google Scholar
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). Google Scholar
Delorme, C. et al. Enhanced habit formation in Gilles de la Tourette syndrome. Brain139, 605–615 (2016). Google Scholar
Singer, H. S. Motor control, habits, complex motor stereotypies, and Tourette syndrome. Ann. NY Acad. Sci.1304, 22–31 (2013). Google Scholar
Singer, H. S. Habitual and goal-directed behaviours and Tourette syndrome. Brain139, 312–316 (2016). Google Scholar
Crittenden, J. R. & Graybiel, A. M. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments. Front. Neuroanat.5, 59 (2011). Google Scholar
Singer, H. S. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 276–300 (Oxford Univ. Press, 2013). Google Scholar
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). Google Scholar
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). Google Scholar
Gilbert, D. L. et al. Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome. Mov. Disord.19, 416–425 (2004). Google Scholar
Puts, N. A. et al. Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome. J. Neurophysiol.114, 808–817 (2015). Google Scholar
Draper, A. et al. Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome. Curr. Biol.24, 2343–2347 (2014). Google Scholar
Bronfeld, M., Yael, D., Belelovsky, K. & Bar-Gad, I. Motor tics evoked by striatal disinhibition in the rat. Front. Syst. Neurosci.7, 50 (2013). Google Scholar
Xu, M. et al. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc. Natl Acad. Sci. USA112, 893–898 (2015). Google Scholar
Nelson, A. B. et al. Striatal cholinergic interneurons drive GABA release from dopamine terminals. Neuron82, 63–70 (2014). Google Scholar
Wong, D. F. et al. Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology33, 1239–1251 (2008). Google Scholar
Baldan, L. C. et al. Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron81, 77–90 (2014). Google Scholar
Rapanelli, M. et al. Dysregulated intracellular signaling in the striatum in a pathophysiologically grounded model of Tourette syndrome. Eur. Neuropsychopharmacol.24, 1896–1906 (2014). Google Scholar
Befort, K. Interactions of the opioid and cannabinoid systems in reward: insights from knockout studies. Front. Pharmacol.6, 6 (2015). Google Scholar
Massotte, D. Monitoring endogenous GPCRs: lessons for drug design. Front. Pharmacol.6, 146 (2015). Google Scholar
Whiting, P. F. et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA313, 2456–2473 (2015). Google Scholar
Robertson, M. M. A personal 35 year perspective on Gilles de la Tourette syndrome: assessment, investigations, and management. Lancet Psychiatry2, 88–104 (2015). Google Scholar
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). Google Scholar
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). Google Scholar
Bloch, M. H., Leckman, J. F., Zhu, H. & Peterson, B. S. Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology65, 1253–1258 (2005). Google Scholar
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). Google Scholar
Peterson, B. S. & Leckman, J. F. The temporal dynamics of tics in Gilles de la Tourette syndrome. Biol. Psychiatry44, 1337–1348 (1998). Google Scholar
Jankovic, J. & Stone, L. Dystonic tics in patients with Tourette's syndrome. Mov. Disord.6, 248–252 (1991). Google Scholar
Robertson, M. M., Trimble, M. R. & Lees, A. The psychopathology of the Gilles de la Tourette syndrome. A phenomenological analysis. Br. J. Psychiatry152, 383–390 (1988). Google Scholar
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). Google Scholar
Freeman, R. D. et al. Coprophenomena in Tourette syndrome. Dev. Med. Child Neurol.51, 218–227 (2009). Google Scholar
Robertson, M. M. & Gourdie, A. Familial Tourette's syndrome in a large British pedigree. Associated psychopathology, severity, and potential for linkage analysis. Br. J. Psychiatry156, 515–521 (1990). Google Scholar
Eapen, V. & Robertson, M. M. Gilles de la Tourette syndrome in Malta: psychopathology in a multiply affected pedigree. Arab J. Psychiatry6, 113–118 (1995). Google Scholar
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). Google Scholar
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). Google Scholar
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. Psychiatry40, 213–218 (1999). Google Scholar
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. Psychiatry42, 1035–1039 (2001). Google Scholar
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. Psychiatry48, 157–166 (2007). Google Scholar
Scahill, L. et al. Thermal sensitivity in Tourette syndrome: preliminary report. Percept. Mot. Skills92, 419–432 (2001). Google Scholar
Cheung, M. Y. C., Shahed, J. & Jankovic, J. Malignant Tourette syndrome. Mov. Disord.22, 1743–1750 (2007). Google Scholar
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). Google Scholar
Leckman, J. F., Walker, D. & Cohen, D. Premonitory urges in Tourette's syndrome. Am. J. Psychiatry150, 98–102 (1993). Google Scholar
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). Google Scholar
Piacentini, J. et al. Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA303, 1929–1937 (2010). This is the first large-scale controlled evaluation of a comprehensive behavioural intervention for tics in children. Google Scholar
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). Google Scholar
Turtle, L. & Robertson, M. M. Tics, twitches, tales: the experiences of Gilles de la Tourette's syndrome. Am. J. Orthopsychiatry78, 449 (2008). Google Scholar
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). Google Scholar
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. Psychiatry28, 566–573 (1989). This is the first study to report the psychometric properties of the most widely used tic severity scale. Google Scholar
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). Google Scholar
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). Google Scholar
Baizabal-Carvallo, J. F. & Fekete, R. Recognizing uncommon presentations of psychogenic (functional) movement disorders. Tremor Other Hyperkinet. Mov.5, 279–279 (2014). Google Scholar
Baizabal-Carvallo, J. F. & Jankovic, J. The clinical features of psychogenic movement disorders resembling tics. J. Neurol. Neurosurg. Psychiatry85, 573–575 (2014). Google Scholar
Dreissen, Y., Cath, D. & Tijssen, M. Functional jerks, tics, and paroxysmal movement disorders. Handb. Clin. Neurol.139, 247–258 (2017). Google Scholar
Mejia, N. I. & Jankovic, J. Secondary tics and tourettism. Rev. Bras. Psiquiatr.27, 11–17 (2005). Google Scholar
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. Google Scholar
Leckman, J. F. et al. Course of tic severity in Tourette syndrome: the first two decades. Pediatrics102, 14–19 (1998). Google Scholar
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). Google Scholar
Pappert, E. J., Goetz, C., Louis, E., Blasucci, L. & Leurgans, S. Objective assessments of longitudinal outcome in Gilles de la Tourette's syndrome. Neurology61, 936–940 (2003). Google Scholar
Jankovic, J., Gelineau-Kattner, R. & Davidson, A. Tourette's syndrome in adults. Mov. Disord.25, 2171–2175 (2010). Google Scholar
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). Google Scholar
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). Google Scholar
Clarke, R. A. & Eapen, V. Balance within the neurexin trans-synaptic connexus stabilizes behavioral control. Front. Hum. Neurosci.8, 52 (2014). Google Scholar
Petek, E. et al. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome. Mol. Genet. Genomics277, 71–81 (2007). Google Scholar
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). Google Scholar
Kwak, C., Vuong, K. D. & Jankovic, J. Migraine headache in patients with Tourette syndrome. Arch. Neurol.60, 1595–1598 (2003). Google Scholar
Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet.47, 1236–1241 (2015). Google Scholar
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). Google Scholar
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). Google Scholar
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. Psychiatry164, 215–221 (1994). Google Scholar
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). Google Scholar
Kurlan, R. et al. Non-obscene complex socially inappropriate behavior in Tourette's syndrome. J. Neuropsychiatry Clin. Neurosci.8, 311–317 (1996). Google Scholar
Hirschtritt, M. E. et al. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome. Neurology87, 497–504 (2016). Google Scholar
Robertson, M. M. Movement disorders: Tourette syndrome — beyond swearing and sex? Nat. Rev. Neurol.10, 6–8 (2014). Google Scholar
Khalifa, N. & Von Knorring, A.-L. Psychopathology in a Swedish population of school children with tic disorders. J. Am. Acad. Child Adolesc. Psychiatry45, 1346–1353 (2006). Google Scholar
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). Google Scholar
Storch, E. A. et al. Suicidal thoughts and behaviors in children and adolescents with chronic tic disorders. Depress. Anxiety32, 744–753 (2015). Google Scholar
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. Psychiatry71, 1401–1402 (2010). Google Scholar
Johnco, C. et al. Suicidal ideation in youth with tic disorders. J. Affect. Disord.200, 204–211 (2016). Google Scholar
Robertson, M. M., Eapen, V. & van de Wetering, B. J. Suicide in Gilles de la Tourette's syndrome: report of two cases. J. Clin. Psychiatry56, 378 (1995). Google Scholar
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. Psychiatry52, 1341–1359 (2013). Google Scholar
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. Psychiatry20, 197–207 (2011). Google Scholar
Scahill, L. et al. Current controversies on the role of behavior therapy in Tourette syndrome. Mov. Disord.28, 1179–1183 (2013). Google Scholar
Hartmann, A., Martino, D. & Murphy, T. Gilles de la Tourette syndrome — a treatable condition? Rev. Neurol. (Paris)172, 446–454 (2016). Google Scholar
Azrin, N. H. & Nunn, R. G. Habit reversal: a method of eliminating nervous habits and tics. Behav. Res. Ther.11, 619–628 (1973). Google Scholar
Woods, D. W. et al. Managing Tourette Syndrome: A Behavioral Intervention for Children and Adults (Therapist Guide) (Oxford Univ. Press, 2008). Google Scholar
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. Psychiatry57, 144–151 (2012). Google Scholar
Wilhelm, S. et al. Randomized trial of behavior therapy for adults with Tourette syndrome. Arch. General Psychiatry69, 795–803 (2012). Google Scholar
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). Google Scholar
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. Telecare22, 153–162 (2016). Google Scholar
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). Google Scholar
Deckersbach, T. et al. Neural correlates of behavior therapy for Tourette's disorder. Psychiatry Res.224, 269–274 (2014). Google Scholar
Capriotti, M. R., Himle, M. B. & Woods, D. W. Behavioral treamtents for Tourette syndrome. J. Obsessive Compuls. Relat. Disord.3, 415–420 (2014). Google Scholar
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). Google Scholar
Pringsheim, T. et al. Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy. Can. J. Psychiatry57, 133–143 (2012). Google Scholar
Macerollo, A. et al. Refractoriness to pharmacological treatment for tics: a multicentre European audit. J. Neurol. Sci.366, 136–138 (2016). Google Scholar
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). Google Scholar
Whittington, C. et al. Practitioner review: treatments for Tourette syndrome in children and young people — a systematic review. J. Child Psychol.Psychiatry57, 988–1004 (2016). Google Scholar
Roessner, V. et al. Pharmacological treatment of tic disorders and Tourette syndrome. Neuropharmacology68, 143–149 (2013). Google Scholar
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). Google Scholar
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. Drugs15, 139–150 (2013). Google Scholar
Robertson, M. M. Gilles de la Tourette syndrome: the complexities of phenotype and treatment. Br. J. Hosp. Med. (Lond.)72, 100–107 (2011). Google Scholar
Kwak, C. H., Hanna, P. A. & Jankovic, J. Botulinum toxin in the treatment of tics. Arch. Neurol.57, 1190–1193 (2000). Google Scholar
Müller-Vahl, K. R. Treatment of Tourette syndrome with cannabinoids. Behav. Neurol.27, 119–124 (2013). Google Scholar
Zheng, Y. et al. A proprietary herbal medicine (5-Ling Granule) for Tourette syndrome: a randomized controlled trial. J. Child. Psychol. Psychiatry57, 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). Google Scholar
Kim, Y. H. et al. Herbal medicines for treating tic disorders: a systematic review of randomised controlled trials. Chinese Med.9, 6 (2014). Google Scholar
Shprecher, D. R., Kious, B. M. & Himle, M. Advances in mechanistic understanding and treatment approaches to Tourette syndrome. Discov. Med.20, 295–301 (2015). Google Scholar
Andrade, P. & Visser-Vandewalle, V. DBS in Tourette syndrome: where are we standing now? J. Neural Transm. (Vienna)123, 791–796 (2016). Google Scholar
Hariz, M. I. & Robertson, M. M. Gilles de la Tourette syndrome and deep brain stimulation. Eur. J. Neurosci.32, 1128–1134 (2010). Google Scholar
Kim, W. & Pouratian, N. Deep brain stimulation for Tourette syndrome. Neurosurg. Clin. N. Am.25, 117–135 (2014). Google Scholar
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. Neurosurgery78, 91–100 (2016). Google Scholar
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). Google Scholar
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). Google Scholar
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). Google Scholar
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). Google Scholar
Cavanna, A. et al. The Gilles de la Tourette syndrome–Quality of Life Scale (GTS-QOL) development and validation. Neurology71, 1410–1416 (2008). Google Scholar
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). Google Scholar
Eapen, V., Snedden, C., Črnčec, R., Pick, A. & Sachdev, P. Tourette syndrome, co-morbidities and quality of life. Aust. N. Z. J. Psychiatry50, 82–93 (2016). Google Scholar
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.Psychiatry25, 939–948 (2016). Google Scholar
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). Google Scholar
Eapen, V., Cavanna, A. E. & Robertson, M. M. Comorbidities, social impact, and quality of life in Tourette syndrome. Front. Psychiatry7, 97 (2016). This comprehensive review summarizes the literature on the impact of GTS and related comorbidities from social and QOL perspectives. Google Scholar
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). Google Scholar
Eddy, C. et al. Quality of life in young people with Tourette syndrome: a controlled study. J. Neurol.258, 291–301 (2011). Google Scholar
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. Psychiatry46, 947–968 (2007). Google Scholar
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. Psychiatry39, 663–668 (1998). Google Scholar
O’Hare, D. et al. Factors impacting the quality of peer relationships of youth with Tourette's syndrome. BMC Psychol.3, 34 (2015). Google Scholar
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). Google Scholar
Parisi, J. Engagement in adulthood: perceptions and participation in daily activities. Act. Adapt. Aging34, 1–16 (2010). Google Scholar
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). Google Scholar
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. Psychiatry42, 1370–1375 (2003). Google Scholar
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. Psychiatry76, 510–512 (2014). Google Scholar
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. Neuron87, 1215–1233 (2015). Google Scholar
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). Google Scholar
Robinson, E. B. et al. Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population. Nat. Genet.48, 552–555 (2016). Google Scholar
Darrow, S. M. et al. Web-based phenotyping for Tourette syndrome: reliability of common co-morbid diagnoses. Psychiatry Res.228, 816–825 (2015). Google Scholar
Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature518, 317–330 (2015). Google Scholar
Miller, J. A. et al. Transcriptional landscape of the prenatal human brain. Nature508, 199–206 (2014). Google Scholar
Gamazon, E. R. et al. A gene-based association method for mapping traits using reference transcriptome data. Nat. Genet.47, 1091–1098 (2015). Google Scholar
Willsey, A. J. et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell155, 997–1007 (2013). Google Scholar
Hibar, D. P. et al. Common genetic variants influence human subcortical brain structures. Nature520, 224–229 (2015). Google Scholar
Singer, H. S. et al. Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET. Am. J. Psychiatry159, 1329–1336 (2002). In this study, greater putamen dopamine release was seen in adults with GTS than in control subjects. Google Scholar
Baldermann, J. C. et al. Deep brain stimulation for Tourette-syndrome: a systematic review and meta-analysis. Brain Stimul.9, 296–304 (2016). Google Scholar
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). Google Scholar
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). Google Scholar
Shapiro, A. K., Shapiro, E. S., Bruun, R. D. & Sweet, R. D. Gilles de la Tourette Syndrome (Raven Press Books, 1978). Google Scholar
Cavanna, A. E. & Piedad, J. C. P. in Tourette Syndrome (eds Martino, D. & Leckman, J. F. ) 411–438 (Oxford Univ. Press, 2013). Google Scholar
King, R. & Landeros-Weisenberger, A. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 402–410 (Oxford Univ. Press, 2013). Google Scholar
Rosario, M. C. et al. Validation of the University of São Paulo sensory phenomena scale: initial psychometric properties. CNS Spectr.14, 315–323 (2009). Google Scholar
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. Psychiatry151, 675–680 (1994). Google Scholar