BRAIN and NERVE－神経研究の進歩70巻11号

2018年11月発行

増大特集 脳科学で解き明かす精神神経症候

トゥレット症候群

著者： 濱本優¹ 金生由紀子²³

所属機関： ¹東京都立小児総合医療センター児童・思春期精神科 ²東京大学医学部附属病院こころの発達診療部 ³東京大学大学院医学系研究科こころの発達医学分野

ページ範囲：P.1237 - P.1245

文献概要

トゥレット症候群は，神経発達症群に含まれる。かつては心因性と考えられたが，その後，神経学的な基盤を有して，遺伝的要因に加えて環境因も複合的に関与することがわかってきた。具体的には，ドパミンをはじめとする神経伝達物質の関与，皮質-線条体-視床-皮質回路の異常などが示唆されている。薬物療法に加えて脳深部刺激療法など，トゥレット症候群の本態を明らかにしつつその改善を目指す治療が進められている。

参考文献

1)ジャン・イタール（著）, 古武彌正（訳）: アヴェロンの野生児. 福村出版, 東京, 1975

2)Lajonchere C, Nortz M, Finger S: Gilles de la Tourette and the discovery of Tourette syndrome. Includes a translation of his 1884 article. Arch Neurol 53: 567-574, 1996

3)日本精神神経学会（日本語版用語監修）, 髙橋三郎, 大野　裕（監訳）: DSM-5®精神疾患の診断・統計マニュアル. 医学書院, 東京. 2014

4)Robertson MM: A personal 35 year perspective on Gilles de la Tourette syndrome: assessment, investigations, and management. Lancet Psychiatry 2: 88-104, 2015

5)McNaught KS, Mink JW: Advances in understanding and treatment of Tourette syndrome. Nat Rev Neurol 7: 667-676, 2011

6)Felling RJ, Singer HS: Neurobiology of tourette syndrome: current status and need for further investigation. J Neurosci 31: 12387-12395, 2011

7)Leckman JF, Bloch MH, Smith ME, Larabi D, Hampson M: Neurobiological substrates of Tourette's disorder. J Child Adolesc Psychopharmacol 20: 237-247, 2010

8)Pauls DL, Raymond CL, Stevenson JM, Leckman JF: A family study of Gilles de la Tourette syndrome. Am J Hum Genet 48: 154-163, 1991

9)Price RA, Kidd KK, Cohen DJ, Pauls DL, Leckman JF: A twin study of Tourette syndrome. Arch Gen Psychiatry 42: 815-820, 1985

10)Baron M, Shapiro E, Shapiro A, Rainer JD: Genetic analysis of Tourette syndrome suggesting major gene effect. Am J Hum Genet 33: 767-775, 1981

11)Kidd KK, Pauls DL: Genetic hypotheses for Tourette syndrome. Friedhoff AJ, Chase TN (eds): Gilles de La Tourette Syndrome. Raven Press, New York, 1982, pp. 243-249

12)Pauls DL, Towbin KE, Leckman JF, Zahner GE, Cohen DJ: Gilles de la Tourette's syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship. Arch Gen Psychiatry 43: 1180-1182, 1986

13)Curtis D, Robertson MM, Gurling HM: Autosomal dominant gene transmission in a large kindred with Gilles de la Tourette syndrome. Br J Psychiatry 160: 845-849, 1992

14)Scharf JM, Yu D, Mathews CA, Neale BM, Stewart SE, et al: Genome-wide association study of Tourette's syndrome. Mol Psychiatry 18: 721-728, 2013

15)Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, et al: Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310: 317-320, 2005

16)de Leeuw C, Goudriaan A, Smit AB, Yu D, Mathews CA, et al: Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis. Eur J Hum Genet 23: 1519-1522, 2015

17)Murphy TK, Kurlan R, Leckman J: The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol 20: 317-331, 2010

18)Selling L: The role of infection in the etiology of tics. Arch Neurol Psychiatry 22: 1163-1171, 1929

19)Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, et al: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 155: 264-271, 1998

20)National Institute of Mental Health: Information about PANS/PANDAS．https://www.nimh.nih.gov/labs-at-nimh/research-areas/clinics-and-labs/sbp/information-about-pans-pandas.shtml（最終閲覧日：2018年8月30日）

21)Moretti G, Pasquini M, Mandarelli G, Tarsitani L, Biondi M: What every psychiatrist should know about PANDAS: a review. Clin Pract Epidemiol Ment Health 4: 13, 2008［doi: 10.1186/1745-0179-4-13］

22)Lowe TL, Cohen DJ, Detlor J, Kremenitzer MW, Shaywitz BA: Stimulant medications precipitate Tourette's syndrome. JAMA 247: 1729-1731, 1982

23)Borcherding BG, Keysor CS, Rapoport JL, Elia J, Amass J: Motor/vocal tics and compulsive behaviors on stimulant drugs: is there a common vulnerability? Psychiatry Res 33: 83-94, 1990

24)Wong DF, Brasić JR, Singer HS, Schretlen DJ, Kuwabara H, 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

25)Steeves TD, Ko JH, Kideckel DM, Rusjan P, Houle S, et al: Extrastriatal dopaminergic dysfunction in tourette syndrome. Ann Neurol 67: 170-181, 2010

26)Denys D, de Vries F, Cath D, Figee M, Vulink N, et al: Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder. Eur Neuropsychopharmacol 23: 1423-1431, 2013

27)Liu H, Dong F, Meng Z, Zhang B, Tan J, et al: Evaluation of Tourette's syndrome by (99m) Tc-TRODAT-1 SPECT/CT imaging. Ann Nucl Med 24: 515-521, 2010

28)Müller-Vahl KR, Loeber G, Kotsiari A, Müller-Engling L, Frieling H: Gilles de la Tourette syndrome is associated with hypermethylation of the dopamine D2 receptor gene. J Psychiatr Res 86: 1-8, 2017

29)Maia TV, Conceição VA: The Roles of Phasic and Tonic Dopamine in Tic Learning and Expression. Biol Psychiatry 82: 401-412, 2017

30)Haugbøl S, Pinborg LH, Regeur L, Hansen ES, Bolwig TG, et al: Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome. Int J Neuropsychopharmacol 10: 245-252, 2007

31)Behen M, Chugani HT, Juhász C, Helder E, Ho A, et al: Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome. Mov Disord 22: 2256-2262, 2007

32)Xu M, Kobets A, Du JC, Lennington J, Li L, et al: Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc Natl Acad Sci U S A 112: 893-898, 2015

33)Lerner A, Bagic A, Simmons JM, Mari Z, Bonne O, et al: Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome. Brain 135: 1926-1936, 2012

34)Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, et al: Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 49: 681-689, 1992

35)Schwartz JM: Neuroanatomical aspects of cognitive-behavioural therapy response in obsessive-compulsive disorder. An evolving perspective on brain and behaviour. Br J Psychiatry Suppl 35: 38-44, 1998

36)Mink JW: Neurobiology of basal ganglia and Tourette syndrome: basal ganglia circuits and thalamocortical outputs. Adv Neurol 99: 89-98, 2006

37)Wichmann T, Delong MR: Deep brain stimulation for neurologic and neuropsychiatric disorders. Neuron 52: 197-204, 2006

38)Rodriguez-Oroz MC, Jahanshahi M, Krack P, Litvan I, Macias R, et al: Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms. Lancet Neurol 8: 1128-1139, 2009

39)深谷　親, 山本隆充: Neuromodulation—皮質-線条体-視床-皮質ループ機能障害とその治療. 脳外誌25: 137-142, 2016

40)Vandewalle V, van der Linden C, Groenewegen HJ, Caemaert J: Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus. Lancet 353: 724, 1999

41)Schrock LE, Mink JW, Woods DW, Porta M, Servello D, et al: Tourette syndrome deep brain stimulation: a review and updated recommendations. Mov Disord 30: 448-471, 2015

42)Frey KA, Albin RL: Neuroimaging of Tourette syndrome. J Child Neurol 21: 672-677, 2006

43)Peterson BS, Thomas P, Kane MJ, Scahill L, Zhang H, et al: Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry 60: 415-424, 2003

44)Bloch MH, Leckman JF, Zhu H, Peterson BS: Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome Neurology 65: 1253-1258, 2005

45)Hyde TM, Stacey ME, Coppola R, Handel SF, Rickler KC, et al: Cerebral morphometric abnormalities in Tourette's syndrome: a quantitative MRI study of monozygotic twins. Neurology 45: 1176-1182, 1995

46)Roessner V, Overlack S, Schmidt-Samoa C, Baudewig J, Dechent P, et al: Increased putamen and callosal motor subregion in treatment-naïve boys with Tourette syndrome indicates changes in the bihemispheric motor network. J Child Psychol Psychiatry 52: 306-314, 2011

47)Zimmerman AM, Abrams MT, Giuliano JD, Denckla MB, Singer HS: Subcortical volumes in girls with tourette syndrome: support for a gender effect. Neurology 54: 2224-2229, 2000

48)Baumgardner TL, Singer HS, Denckla MB, Rubin MA, Abrams MT, et al: Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder. Neurology 47: 477-482, 1996

49)Peterson BS, Staib L, Scahill L, Zhang H, Anderson C, et al: Regional brain and ventricular volumes in Tourette syndrome. Arch Gen Psychiatry 58: 427-440, 2001

50)Ganos C, Kühn S, Kahl U, Schunke O, Brandt V, et al: Prefrontal cortex volume reductions and tic inhibition are unrelated in uncomplicated GTS adults. J Psychosom Res 76: 84-87, 2014

51)Kassubek J, Juengling FD, Ludolph AG: Heterogeneity of voxel-based morphometry findings in Tourette's syndrome: an effect of age? Ann Neurol 59: 872-873, 2006

52)Müller-Vahl KR, Grosskreutz J, Prell T, Kaufmann J, Bodammer N, et al: Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms. BMC Neurosci 15: 6, 2014［doi: 10.1186/1471-2202-15-6］

53)Makki MI, Behen M, Bhatt A, Wilson B, Chugani HT: Microstructural abnormalities of striatum and thalamus in children with Tourette syndrome. Mov Disord 23: 2349-2356, 2008

54)Neuner I, Kupriyanova Y, Stöcker T, Huang R, Posnansky O, et al: Microstructure assessment of grey matter nuclei in adult tourette patients by diffusion tensor imaging. Neurosci Lett 487: 22-26, 2011

55)Jeppesen SS, Debes NM, Simonsen HJ, Rostrup E, Larsson HB, et al: Study of medication-free children with Tourette syndrome do not show imaging abnormalities. Mov Disord 29: 1212-1216, 2014

56)Worbe Y, Marrakchi-Kacem L, Lecomte S, Valabregue R, Poupon F, et al: Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome. Brain 138: 472-482, 2015

57)Cheng B, Braass H, Ganos C, Treszl A, Biermann-Ruben K, et al: Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome. Neuroimage Clin 4: 174-181, 2013

58)Ziemann U, Paulus W, Rothenberger A: Decreased motor inhibition in Tourette's disorder: evidence from transcranial magnetic stimulation. Am J Psychiatry 154: 1277-1284, 1997

59)Moll GH, Wischer S, Heinrich H, Tergau F, Paulus W, et al: Deficient motor control in children with tic disorder: evidence from transcranial magnetic stimulation. Neurosci Lett 272: 37-40, 1999

60)Wilke S, Groenveld D, Grittner U, List J, Flöel A: cSPider - Evaluation of a Free and Open-Source Automated Tool to Analyze Corticomotor Silent Period. PLOS ONE 11: e0156066, 2016［doi: 10.1371/journal.pone.0156066］

61)Stern E, Silbersweig DA, Chee KY, Holmes A, Robertson MM, et al: A functional neuroanatomy of tics in Tourette syndrome. Arch Gen Psychiatry 57: 741-748, 2000

62)Eidelberg D, Moeller JR, Antonini A, Kazumata K, Dhawan V, et al: The metabolic anatomy of Tourette's syndrome. Neurology 48: 927-934, 1997

63)Peterson BS, Skudlarski P, Anderson AW, Zhang H, Gatenby JC, et al: A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psychiatry 55: 326-333, 1998

64)Church JA, Fair DA, Dosenbach NU, Cohen AL, Miezin FM, et al: Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity. Brain 132: 225-238, 2009

65)Marsh R, Zhu H, Wang Z, Skudlarski P, Peterson BS: A developmental fMRI study of self-regulatory control in Tourette's syndrome. Am J Psychiatry 164: 955-966, 2007

66)Wang Z, Maia TV, Marsh R, Colibazzi T, Gerber A, et al: The neural circuits that generate tics in Tourette's syndrome. Am J Psychiatry 168: 1326-1337, 2011

67)Yamamuro K, Ota T, Iida J, Nakanishi Y, Uratani M, et al: Prefrontal dysfunction in pediatric Tourette's disorder as measured by near-infrared spectroscopy. BMC Psychiatry 15: 102, 2015［doi: 10.1186/s12888-015-0472-3］

68)Whittington C, Pennant M, Kendall T, Glazebrook C, Trayner P, et al: Practitioner Review: Treatments for Tourette syndrome in children and young people - a systematic review. J Child Psychol Psychiatry 57: 988-1004, 2016

69)Cavanna AE, Black KJ, Hallett M, Voon V: Neurobiology of the Premonitory Urge in Tourette's Syndrome: Pathophysiology and Treatment Implications. J Neuropsychiatry Clin Neurosci 29: 95-104, 2017

70)Conceição VA, Dias Â, Farinha AC, Maia TV: Premonitory urges and tics in Tourette syndrome: computational mechanisms and neural correlates. Curr Opin Neurobiol 46: 187-199, 2017

71)Draper A, Jackson GM, Morgan PS, Jackson SR: Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome. J Neuropsychol 10: 143-153, 2016