Causes and origins of Tourette syndrome 5086328 223632699 2008-07-05T00:07:59Z SandyGeorgia 878749 [[WP:GTL]] '''Causes and origins of Tourette syndrome''' have not been fully elucidated. [[Tourette syndrome]] (also called "Tourette's syndrome", "Tourette's disorder", "Gilles de la Tourette syndrome", "GTS" or "TS") is an [[inherited]] [[neurological]] disorder with onset in childhood, characterized by the presence of multiple motor [[tic]]s and at least one phonic tic, which characteristically wax and wane. Tourette's syndrome occurs along a spectrum of [[tic disorder]]s, which includes transient tics and chronic tics.<ref name=emed>Black, KJ. [http://www.emedicine.com/neuro/topic664.htm Tourette Syndrome and Other Tic Disorders.] ''eMedicine'' ([[March 22]] [[2006]]). Retrieved on [[27 June]] [[2006]].</ref><ref>Evidente, GH. [http://www.postgradmed.com/issues/2000/10_00/evidente_tic.htm "Is it a tic or Tourette's? Clues for differentiating simple from more complex tic disorders."] ''PostGraduate Medicine Online.'' October 2000 108:5. Retrieved on [[28 October]] [[2006]].</ref> The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved.<ref name=AN2intro>Walkup JT, Mink JW, Hollenback PJ, (eds). ''Advances in Neurology, Vol. 99, Tourette Syndrome.'' [[Lippincott Williams & Wilkins]], Philadelphia, PA, 2006, p. xv. ISBN 0-7817-9970-8</ref> Genetic studies have proved that the overwhelming majority of cases of Tourette's are inherited, although the exact mode of inheritance is not yet known,<ref>Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. ''Brain''. 2000;123 Pt 3:425–62. p. 425. PMID 10686169</ref> and no gene has been identified.<ref name=Zinner/> Tics are believed to result from dysfunction in the [[thalamus]], [[basal ganglia]], and [[frontal lobe|frontal cortex]] of the brain,<ref name=AN2intro>Walkup JT, Mink JW, Hollenback PJ, (eds). ''Advances in Neurology, Vol. 99, Tourette Syndrome.'' Lippincott, Williams & Wilkins, Philadelphia, PA, 2006, p. xv.</ref> involving abnormal activity of the brain chemical, or [[neurotransmitter]], [[dopamine]]. Non-genetic factors—while not causing Tourette's—can influence the severity of the disorder. Some forms of Tourette's may be genetically linked to [[obsessive-compulsive disorder]] (OCD), while the relationship between Tourette's and [[attention-deficit hyperactivity disorder]] (ADHD) is not yet fully understood. == Genetic factors== Genetic studies, including [[twin studies]],<ref>Pauls DL. The genetics of Tourette syndrome. ''Curr Psychiatry Rep.'' 2001 Apr;3(2):152-7. PMID 11276411</ref> have proven that the overwhelming majority of cases of Tourette syndrome are inherited, although the exact mode of inheritance is not yet known.<ref>Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. ''Brain''. 2000;123 Pt 3:425–462. p. 425. PMID 10686169</ref> Tic disorders have long been thought to be inherited as an [[autosomal]] [[dominant gene]], but recent research challenges the autosomal dominant hypothesis, and suggests an additive model involving multiple genes.<ref name=Zinner>Zinner SH. Tourette disorder. ''Pediatr Rev''. 2000;21(11):372. PMID 11077021</ref><ref name=Bagheri>Bagheri MM, Kerbeshian J, Burd L. Recognition and management of Tourette's syndrome and tic disorders. ''Am Fam Physician''. 1999; 59:2263–2274. PMID 10221310[http://web.archive.org/web/20050331083858/http://www.aafp.org/afp/990415ap/2263.html Full text.]</ref> According to Roger Freeman, MD, "Genes that cause tics have not yet been identified; it's very unlikely there's just one. Tics are very familial, but not in a Mendelian pattern (dominant, recessive, etc.). You can't 'inherit' the committee decision to define a problem in a specific way, so TS can't itself be inherited. It's a tic disorder that is inherited."<ref name=FreemanBlog>Freeman, RD. [http://www.tourette-confusion.blogspot.com/ Tourette's Syndrome: minimizing confusion]. Retrieved on [[8 February]] [[2006]].</ref> In some cases, tics may not be inherited; these cases are identified as "sporadic" Tourette syndrome (also known as [[tourettism]]) because a genetic link is missing.<ref name=Mejia>Mejia NI, Jankovic J. Secondary tics and tourettism. ''Rev Bras Psiquiatr''. 2005;27(1):11-7. PMID 15867978 [http://web.archive.org/web/20070628191850/http://www.scielo.br/pdf/rbp/v27n1/23707.pdf Full-text PDF]</ref> A person with Tourette syndrome has about a 50% chance of passing the gene(s) to one of his/her children. [[Gender]] appears to have a role in the expression of the genetic vulnerability, with males more likely to express tics than females.<ref name=Zinner/> Tourette syndrome is a condition of [[incomplete penetrance]], meaning not everyone who inherits the genetic vulnerability will show symptoms. Tourette's also shows [[Expressivity|variable expression]]—even family members with the same [[Genetics|genetic]] makeup may show different levels of symptom severity. The gene(s) may express as Tourette syndrome, as a milder tic disorder (transient or chronic tics), or as obsessive compulsive symptoms with no tics at all.<ref>van de Wetering BJ, Heutink P. The genetics of the Gilles de la Tourette syndrome: a review. ''J Lab Clin Med.'' 1993 May;121(5):638–45. PMID 8478592</ref> Only a minority of the children who inherit the gene(s) will have symptoms severe enough to require medical attention.<ref name=TSAFAQ> Tourette Syndrome Association. [http://web.archive.org/web/20050208082423/http://www.tsa-usa.org/what_is/Faqs.html Tourette Syndrome: Frequently Asked Questions.] Retrieved on [[8 February]] [[2005]].</ref> There is currently no way to predict the symptoms a child may display, even if the gene(s) are inherited. Recent research suggests that a small number of Tourette syndrome cases may be caused by a defect on [[chromosome 13 (human)|chromosome 13]] of gene [[SLITRK1]]. Some cases of [[tourettism]] (tics due to reasons other than inherited Tourette's syndrome) can be caused by [[mutation]].<ref name=Mejia>Mejia NI, Jankovic J. Secondary tics and tourettism. ''Rev Bras Psiquiatr''. 2005;27(1):11-7. PMID 15867978 [http://www.scielo.br/pdf/rbp/v27n1/23707.pdf Full-text PDF]</ref> The finding of a chromosomal abnormality appears to apply to a very small minority of cases (1–2%). Studies to locate all of the genes implicated in Tourette's syndrome are ongoing.<ref>Schmidt, William (19 Oct 2005). [http://www.yaledailynews.com/article.asp?AID=30408 Genetic mutation is linked to Tourette's.] ''Yale Daily News.'' </ref> ==Pathophysiology== [[Image:Brain structure.gif|thumb|right|320px|Brain structures implicated in Tourette's syndrome]] The exact mechanism affecting the inherited vulnerability has not been established, and the precise [[etiology]] of Tourette syndrome is not known. Tics are believed to result from dysfunction in the [[central nervous system]],<ref name=Bagheri/> in the cortical and subcortical regions, the [[thalamus]], [[basal ganglia]], and [[frontal lobe|frontal cortex]] of the brain.<ref name=AN2intro>Walkup JT, Mink JW, Hollenback PJ, (eds). ''Advances in Neurology, Vol. 99, Tourette Syndrome.'' Lippincott, Williams & Wilkins, Philadelphia, PA, 2006, p. xv.</ref> [[Neuroanatomy|Neuroanatomic]] models implicate failures in circuits connecting the brain's [[Cortex (anatomy)|cortex]] and subcortex,<ref name=Zinner/> and imaging techniques implicate the [[basal ganglia]] and [[frontal lobe|frontal cortex.]]<ref>Haber SN, Wolfer D. Basal ganglia peptidergic staining in Tourette syndrome. A follow-up study. ''Adv Neurol''. 1992;58:145-50. PMID 1414617 </ref><ref>Peterson B, Riddle MA, ''et al.'' Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images. ''Neurology''. 1993;43:941-9. PMID 8492950</ref> <ref>Moriarty J, Varma AR, ''et al.'' A volumetric MRI study of Gilles de la Tourette's syndrome. ''Neurology''. 1997;49:410-5. PMID 9270569</ref> Research presents considerable evidence that abnormal activity of the brain chemical, or [[neurotransmitter]], [[dopamine]], is involved.<ref>Singer HS, Walkup JT. Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and treatment. ''Medicine''. 1991;70:15–32. PMID 1988764</ref> Dopamine excess or supersensitivity of the [[Chemical synapse|postsynaptic]] [[dopamine receptor]]s may be an underlying mechanism of Tourette syndrome.<ref>Singer HS, Butler IJ, ''et al.'' Dopaminergic dysfunction in Tourette syndrome. ''Ann Neurol''. 1982;12:361-6. PMID 6184010 </ref><ref>[[Harold L. Klawans|Klawans HL]], Falk DK, Nausieda PA, Weiner WJ. Gilles de la Tourette syndrome after long-term chlorpromazine therapy. ''Neurology''. 1978;28:1064–6. PMID 284201 </ref><ref>Butler IJ, Koslow SH, ''et al.'' Biogenic amine metabolism in Tourette syndrome. ''Ann Neurol''. 1979;6:37-9. PMID 292354</ref><ref>Singer HS. Neurobiology of Tourette syndrome. ''Neurol Clin''. 1997;15:357-79. PMID 9115467</ref> Other neurotransmitters may also be involved.<ref name=TSAFAQ/> ==Non-genetic influences== Studies suggest that non-genetic, [[Natural environment|environmental]], [[infectious]], or [[psychosocial]] factors—while not causing Tourette's—can influence the severity of the disorder.<ref name=Zinner/> [[Twin studies]] have shown that the twin with lower birth weight is more likely to have more noticeable symptoms.<ref>Hyde TM, Aaronson BA, Randolph C, ''et al.'' Relationship of birth weight to the phenotypic expression of Gilles de la Tourette's syndrome in monozygotic twins. ''Neurology''. 1992 Mar;42 (3 Pt 1):652-8. PMID 1549232</ref> Other [[perinatal]] events, such as maternal stress,<ref>Leckman JF, Dolnansky ES, Hardin MT, ''et al.'' Perinatal factors in the expression of Tourette's syndrome: an exploratory study. ''J Am Acad Child Adolesc Psychiatry''. 1990 Mar;29(2):220-6. PMID 1969861</ref> maternal smoking,<ref>Mathews CA, Bimson B, Lowe TL, ''et al.'' Association between maternal smoking and increased symptom severity in Tourette's syndrome. ''Am J Psychiatry.'' 2006 Jun;163(6):1066–73. PMID 16741208</ref> and [[obstetric]] complications,<ref>Santangelo SL, Pauls DL, Goldstein JM, ''et al.'' Tourette's syndrome: what are the influences of gender and comorbid obsessive-compulsive disorder? ''J Am Acad Child Adolesc Psychiatry''. 1994 Jul-Aug;33(6):795–804. PMID 8083136</ref> while not causing tics, may be risk factors for increased severity of tics. [[Autoimmune]] processes may affect tic severity in some cases: the unproven and contentious hypothesis that Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, [[PANDAS]], plays a role in the onset of tic disorders and OCD is a current focus of research.<ref name=Swerdlow>Swerdlow, NR. Tourette Syndrome: Current Controversies and the Battlefield Landscape. ''Curr Neurol Neurosci Rep''. 2005, 5:329–331. PMID 16131414</ref><ref>Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. ''Pediatrics.'' 2004 Apr;113(4):883-6. PMID 15060240</ref> ==Relation with OCD and ADHD== Some forms of [[obsessive-compulsive disorder]] (OCD) may be [[gene|genetically]] linked to Tourette's, or an alternate expression of the condition;<ref>Pauls DL, Towbin KE, Leckman JF, ''et al.'' Gilles de la Tourette's syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship. ''Arch Gen Psychiatry''. 1986 Dec;43(12):1180–2. PMID 3465280</ref> genetic studies show an increased rate of tics and obsessive-compulsive behaviors or OCD in relatives of patients with Tourette's, and "reinforce the idea that at least some forms of OCD are [[etiologic|etiologically]] related to TS, and may, therefore, be a variant expression of the same etiologic factors that are important for the expression of tics."<ref name=Cohenetal> Cohen, DJ, Jankovic J, Goetz CG, (eds). [http://www.amazon.com/dp/0781724058 ''Advances in Neurology, Vol. 85, Tourette Syndrome''.] Lippincott, Williams & Wilkins, Philadelphia, PA, 2001.</ref> Further evidence supporting that OCD and Tourette's are alternative expressions of a common genetic vulnerability is that males inheriting the genetic vulnerability are more likely to display tics, while females are more likely to display obsessive-compulsive traits.<ref name=Bagheri/> The genetic relationship of [[attention-deficit hyperactivity disorder]] (ADHD) to Tourette's syndrome is less clear, with some evidence to suggest no genetic linkage, and some evidence to suggest that some forms of Tourette's syndrome may be genetically related to ADHD.<ref name=LCBook>Leckman JF, Cohen DJ. [http://web.archive.org/web/20050303223505/http://info.med.yale.edu/chldstdy/tsocd/tsbook.htm ''Tourette's Syndrome—Tics, Obsessions, Compulsions: Developmental Psychopathology and Clinical Care.''] John Wiley & Sons, Inc., New York, 1999.</ref> Not all persons with Tourette's syndrome will have ADHD or OCD, although in specialty clinics where the most impaired patients present, a high percentage of patients presenting for care do have ADHD.<ref name=Bagheri/> The high co-occurrence of ADHD observed in specialty clinics may be due to clinical [[ascertainment bias]]. Further study is needed to understand the genetic relationship between ADHD and Tourette's.<ref name=LCBook/> == Notes== {{reflist|2}} == External links == *[http://media.mindinstitute.org/video/dls/2007/wmv/pauls_dls_01_hi.wmv The Genetics of Gilles de la Tourette Syndrome] — 53-minute video where David Pauls discusses the results of a genetic linkage study for Tourette syndrome {{Topics related to Tourette syndrome}} <!--Category: please alphabeticize--> [[Category:Tourette syndrome]]