The Korean Journal of Nuclear Medicine (대한핵의학회지)

The Korean Society of Nuclear Medicine (대한핵의학회)
권호 표지

Dopamine Transporter Density Assessed with $[^{123}I]IPT$ SPECT Before and After Risperidone Treatment in Children with Tourette's Disorder

뚜렛 장애 아동에서 Risperidone 치료 전후 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 도파민 운반체 밀도

  • Kim, Tae-Hoon (Division of Nuclear medicine, Dept. of Diagnostic Radiology, College of Medicine, Yonsei University) ;
  • Ryu, Won-Gee (Division of Nuclear medicine, Dept. of Diagnostic Radiology, College of Medicine, Yonsei University) ;
  • Park, Se-Young (Division of Nuclear medicine, Dept. of Diagnostic Radiology, College of Medicine, Yonsei University) ;
  • Chi, Dae-Yoon (Department of Chemistry, Inha University) ;
  • Choi, Tae-Hyun (Dept. of Nuclear Medicine, Korea Cancer Center Hospital) ;
  • Lee, Kyung-Yul (Department of Neurology, College of Medicine, Yonsei University) ;
  • Cheon, Keun-Ah (Department of Psychiatry, College of Medicine, Yonsei University) ;
  • Yun, Mi-Jin (Division of Nuclear medicine, Dept. of Diagnostic Radiology, College of Medicine, Yonsei University) ;
  • Kim, Jai-Keun (Department of Diagnostic Radiology, College of Medicine, Ajou University) ;
  • Lee, Jong-Doo (Division of Nuclear medicine, Dept. of Diagnostic Radiology, College of Medicine, Yonsei University) ;
  • Ryu, Young-Hoon (Division of Nuclear medicine, Dept. of Diagnostic Radiology, College of Medicine, Yonsei University)
  • 김태훈 (연세대학교 의과대학 진단방사선과학교실 핵의학과) ;
  • 류원기 (연세대학교 의과대학 진단방사선과학교실 핵의학과) ;
  • 박세영 (연세대학교 의과대학 진단방사선과학교실 핵의학과) ;
  • 지대윤 (인하대학교 화학과) ;
  • 최태현 (원자력병원 핵의학과) ;
  • 이경열 (연세대학교 의과대학 신경과학교실) ;
  • 천근아 (연세대학교 의과대학 정신과학교실) ;
  • 윤미진 (연세대학교 의과대학 진단방사선과학교실 핵의학과) ;
  • 김재근 (아주대학교 의과대학 진단방사선과학교실) ;
  • 이종두 (연세대학교 의과대학 진단방사선과학교실 핵의학과) ;
  • 유영훈 (연세대학교 의과대학 진단방사선과학교실 핵의학과)
  • Published : 2004.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

PURPOSE: Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled $N-(3-iodopropen-2-yl)-2{\beta}-carbomethoxy-3beta-(4-chlorophenyl)tropane$ ($[^{123}I]IPT$) single photon omission computed tomography (SPECT). MATERIALS and METHODS: $[^{123}I]IPT$ SPECT Imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of $[^{123}I]IPT$. RESULTS: Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. CONCLUSION: These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.

목적 : 본 연구는 약물에 노출되지 않은 뚜렛 장애 아동들에게 치료 목적으로 일정기간 일정한 용량의 risperidone을 투여한 후 치료 전과 후의 틱증상 척도의 변화 정도와 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 DAT밀도에 변화가 있는 지 여부를 알아보고자 하였다. 대상 및 방법 :만 $6{\sim}12$세 사이의 아동으로 약물 비노출뚜렛 장애 아동 9명과 11명의 정상 대조군을 대상으로 risperidone 치료 전과 후에서 각각 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 DAT 밀도에 변화를 정량적 계측하고 치료전 약물 비노출군과 정상대조군의 기저 신경절 DAT 밀도에 차이를 통계적 분석하였으며, 약물 비노출군아동의 치료전과 치료후의 기저 신경절 DAT 밀도에 차이를 통계분석하였다. 결과: 9명의 약물 비노출뚜렛 장애 아동군과 정상 대조군 사이의 좌,우측 기저 신경절 DAT특이결합/비특이결합 비율의 비교한 결과 좌,우측 기저 신경절 모두 DAT특이결합/비특이결합 비율이 정상 대조군에 비해서 증가되어 있었다. (좌측: z=1.576, p=0.043, 우측: z=1.787, p=0.025). 9명의 뚜렛 장애 아동에서 risperidone치료 전과 후 상태에서 기저 신경절 DAT 특이결합/비특이 결합 비율 비교한 결과, risperidone 전후 사이에 유의한 차이가 관찰되지 않았다. (우측: t=-0.974, p=0.362 ; 좌측: t=-0.513, p=0.634). 결론: Risperidone 투여가 뚜렛 장애의 증상을 호전시키는 시점에서 기저 신경절 DAT 밀도는 변화시키지 앓을 수 있음을 제시한다.

Keywords

References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington DC: American Psychiatric Press; 1994
  2. Cohen DJ, Leckman JF. Developmental Psychopathology and Neurobiology of Tourette's syndrome. J Am Acad Child Adolesc Psychiatry 1994;33:2-15 https://doi.org/10.1097/00004583-199401000-00002
  3. Leckman JF, de Lotbiniere AJ, Marek K, Gracco C, Scahill L, Cohen DS. Severe disturbance in speech, swallowing, and gait following stereotatic infrathalamic lesions in Gilles de la Tourette syndrome. Neurology 1993;43: 890-4 https://doi.org/10.1212/WNL.43.5.890
  4. Peterson BS, Riddle MA, Cohen DJ, Katz LD, Smith JC, Hardin MT. Reduced basal ganglia volumes in Tourette's syndrome using 3-dimensional reconstruction techniques from magnetic resonance images. Neurology 1993;43: 941-9 https://doi.org/10.1212/WNL.43.5.941
  5. Singer HS, Reiss AL, Brown J, Aylward EH, Shih B, Chee E, et al. Volumetric MRI changes in basal ganglia of children with Tourette's syndrome. Neurology 1993;43:950-6 https://doi.org/10.1212/WNL.43.5.950
  6. Moriaty J, Costa DC. Schmitz B. Trimble MR. Ell PJ. Robertson MM. Brain perfusion abnormalities in Gilles de la Tourette's syndrome. Br J Psychiatry. 1995;167:249-54
  7. Klieger PS, Fett KA, Dimitsopulos T, Karlan R. Asymmetry of basal ganglia perfusion in Tourette's syndrome shown by Technetium-99m-HMPAO SPECT. J Nucl Med 1997;38:188-91
  8. Robertson MM. Annotation: Gilles de la Tourette Syndrome-An update. J Child Psychol Psychiatry 1994;35:597-611 https://doi.org/10.1111/j.1469-7610.1994.tb01209.x
  9. Shapiro E, Shapiro AK, Fulop G, Hubard M, Mandeli J, Nordlie J, et al. Controlled Study of haloperidol, pimozide, and placebo for the treatment of Gilles de la Tourette's syndrome. Arch Gen Psychiatry 1989;46:722-30 https://doi.org/10.1001/archpsyc.1989.01810080052006
  10. Shapiro E, Shapiro AK. Controlled Study of pimozide vs. placebo in Tourette's syndrome. J Am Acad Child Adolesc Psychiatry 1984;23:161-73
  11. Turjansky N, Sawle GV, Playford ED, Weeks R, Lammersstma AA, Lees AJ, et al. PET studies of the presynaptic and postsynaptic dopaminergic system in Tourette's syndrome. J Neurol Neurosurg Psychiatry 1994;57:688-92 https://doi.org/10.1136/jnnp.57.6.688
  12. Brooks DJ, Turjansky N, Sawle GV, Playford ED, Lees AJ. PET studies on the integrity of the pre-and postsynaptic dopaminergic system in Tourette's syndrome. Adv Neurol 1992;58:227-31
  13. George M, Trimble MR, Costa DC, Robertson MM, Ring HA, Ell PJ. Elevated frontal cerbral blood flow in Gilles de la Tourette syndrome: $a ^{99m}$Tc-HMPAO SPECT study. Psychiatry Research 1993;45:143-51 https://doi.org/10.1016/0925-4927(92)90022-V
  14. Gainetdinov RR, Jones SR, Fabio Fumagalli, Wightman RM, Marc GC. Re-evaluation of the role of the DAT in dopamine system homeostasis. Brain Research Review 1998;26:148-53 https://doi.org/10.1016/S0165-0173(97)00063-5
  15. Booij J, Tissingh G, Winogrodzka A, Van Royen EA. Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism. Eur J Nucl Med 1999;26:171-182 https://doi.org/10.1007/s002590050374
  16. Singer HS, Hahn IH, Moran TH. Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome. Ann Neurol 1991;30:558-62 https://doi.org/10.1002/ana.410300408
  17. Malison RT, McDougle CJ, van Dyck CH, Scahill L, Baldwin RM, Seibyl JP, et al. $[^{123}I]{\beta}$-CIT SPECT imaging of striatal DAT binding in Tourette's disorder. Am J Psychiatry 1995;152: 1359-61 https://doi.org/10.1176/ajp.152.9.1359
  18. Heinz A, Knable MB, Wolf SS, Jones DW, Gorey JG, Hyde TM, et al. Tourette's syndrome: $[^{123}I]{\beta}$-CIT SPECT correlates of vocal tic severity. Neurology 1998;51:1069-74 https://doi.org/10.1212/WNL.51.4.1069
  19. Stamenkovic M, Schindlera SD, Asenbaumb S, Neumeistera A, Willeita M, Willingerc U, et al. No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette's disorder patients: a $[^{123}I]{\beta}$-CIT SPECT-study. Eur Neuropsychopharm 2001;11:69-74 https://doi.org/10.1016/S0924-977X(00)00134-6
  20. Cheon K, Ryu YH, Namkoong K, Kim C, Kim J, Lee JD. Dopamine transporter density of the basal ganglia assessed with $[^{123}I]IPT$ SPECT in drug-naive children with Tourette's disorder. Psychiatry Res Neuroimaging 2004;in press
  21. Bruggeman R, van der Linden C, Buitelaar JK, Gericke GS, Hawkridge SM, Temlett JA. Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study. J Clin Psychiatry 2001;62:50-6 https://doi.org/10.4088/JCP.v62n0111
  22. Bruun RD, Budman CL. Risperidone as a treatment for Tourette's syndrome. J Clin Psychiatry 1996;57:29-31
  23. Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS. A placebo-controlled trial of risperidone in Tourette syndrome. Neurology 2003;60:1130-5 https://doi.org/10.1001/archneur.60.8.1130
  24. Jeong SJ, Ryu TY, Lee JS, Koo YJ, Jeon SI, Kim BS, Hong KE. The Reliability and Validity of Korean Yale Global Tic Severity Scale. Korean Academy of Child and Adolescent Psychiatry. October, 1997. pp70
  25. Guy W, Bonato RR. CGI, Clinical Global Impressions. In: Manual of the ECDEU Assessment Battery. Rev. Ed. Chase C. 1970
  26. Chang LT. A method for attenuation correction in ratio nuclide computed tomography. IEEE Trans Nucl Sci 1978;25:638-43 https://doi.org/10.1109/TNS.1978.4329385
  27. Wong DF, Singer HS, Branddt J. D2-like dopamine receptor density in Tourette syndrome measured by PET. J Nucl Med 1997;38:1243-47
  28. Braun AR, Stoetter B, Randolph C, Hsiao JK, Vladar K, Gernert J, et al. The functional neuroanatomy of Tourette's syndrome : An FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls. Neuropsychophamacology 1993;9:277-91 https://doi.org/10.1038/npp.1993.64
  29. Moriarty J, Costa DC, Schmitz B, Trimble MR, Ell PJ, Robertson MM. Brain perfusion abnormalities in Gilles de la Tourette's Syndrome. Br J psychiatry 1995;167:249-54 https://doi.org/10.1192/bjp.167.2.249
  30. Peterson BS. Neuroimaging studies of Tourette Syndrome: A Decade of Progress. Tourette Syndrome. Advances in Neurology vol.85 edited by Donald J.Cohen. Lippincott Williams & Wilkins. 2001. pp. 179-96
  31. Muler-Vahl KR, Berding G, Brke T, Kolbe H, Meyer GJ, Hundeshagen H, et al. DAT binding in Gilles de la Tourette syndrome. J Neurol 2000;247:514-20 https://doi.org/10.1007/PL00007806
  32. Bannon MJ, Granneman JG, Kapatos G. The DAT. Potential involvement in neuropsychiatric disorder, in: F.E. Bloom, Kupfer DJ(Eds.) Psychopharmacology: The Fourth Generation Progress, Raven, New York 1995. pp.179-88
  33. Lavalaye J, Linszen DH, Booij J, Dingemans PM, Reneman L, Habraken JB, et al. Dopamine transporter density in young patients with schizophrenia assessed with $[^{123}I]FP-CIT$ SPECT. Schizophr Res 2001;47:59-67 https://doi.org/10.1016/S0920-9964(00)00023-2
  34. Bressan RA, Erlandsson K, Jones HM, Mulligan RS, Ell PJ, Pilowsky LS. Optimizing limbic selective D2/D3 receptor occupancy by risperidone: a $[^{123}I]$epidepride SPET study. J Clin Psychopharmacol 2003;23:5-14 https://doi.org/10.1097/00004714-200302000-00002