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Development of three-dimensional atlas of neural transmission and its application for new psychotropic medication

Research Project

Project/Area Number 11557070
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Psychiatric science
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OKUBO Yoshiro  Graduate School of Allied Health Sciences, Tokyo Medical and Dental University Professor, 大学院・保健衛生学研究科, 教授 (20213663)

Co-Investigator(Kenkyū-buntansha) MATSUSHIMA Eisuke  Graduate School of Tokyo Medical and Dental University Associate Professor, 大学院・医歯学総合研究科, 助教授 (50242186)
武者 利光  東京医科歯科大学, 脳機能研究所, 所長 (70016319)
太田 克也  東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (20251514)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2000: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000)
Keywordspsychotropic drug / Schizophrenia / PET / MRI / Dopamine / 神経伝達物質 / 受容体
Research Abstract

The advent of positron emission tomography(PET) neuroreceptor imaging has facilitated an important strategy for elucidating the pathophysiology of neuropsychiatric disorders. PET studies first focused on the striatal dopamine D2 receptor in schizophrenia because of its clinical significance, leading to a revisal of the dopamine hypothesis. Furthermore, empirical data from occupancy measurements have made it possible to directly evaluate the activity of antipsychotic drugs in humans. Recent developments of new radioligands have given rise to new perspectives for understanding actions of psychotroic dugs. Using PET, we aimed to make a three-dimensional atlas of neural transmission and aimed to develop new strategy of psychtropic medication. The follwing results were obtained.
1) The use of Computerized Brain Atlas sis of [11C]FLB 457 binding made it possible to build a normal database for the extrastriatal D2 receptors in the living human brain.
2) Using [11C]FLB 457, we found reduced D2R binding in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation between D2R binding and the positive symptom score on BPRS. These findings suggest that alterations in D2R function in the extrastriatal region may underlie the positive symptoms of schizophrenia.
3) D2 receptor occupancy with risperidone in the limbic-cortical regions was similar to that of previous reports regarding the striatum, and it would be comparable to that of typical antipsychotics.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Okubo Y, Olsson H, Lofti M, Suhara T, Halldin C, Farde L: "PET mapping of extrastriatal D2-like dopamine receptors in the human brain using an anatomic standardization technique and [11C]FLB 457"Neuroimage. 10. 666-674 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, et al.: "Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography"Life Sciences. 66. 2455-2464 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuno F, Suhara T, Okubo Y, Sudo Y, Inoue M, et al.: "Dose relationship of limbic-cortical D2 -dopamine receptor occupancy with risperidone"Psychopharmacology. 154. 112-114 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito H, Sudo Y, Suhara T, Okubo Y, Halldin C, Farde L: "Error analysis for quantification of [11c]FLB 457 binding to extrastriatal D2 dopamine receptors in the human brain"Neuroimage. 13. 531-539 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suhara T, Yasuno F, Sudo Y, Inoue M, Okubo Y, et al.: "Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking"Neuroimage. 13. 891-895 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suhara T, Okubo Y, Yasuno F, Sudo Y, Inoue M: "Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia"Arch Gen Psychiatry. 59. 25-30 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 大久保善朗: "精神科臨床における画像診断"中山書店. 395-409 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okubo Y, Olsson H, Ito H, Lofti M, Suhara T, Halldin C, Farde L: "PET mapping of extrastriatal D2-like dopamine receptors in the human brain using an anatomic standardization technique and [11C]FLB 457"Neuroimage. 10. 666-74 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M, Tateno Y, Toru M: "Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography"Life Sciences. 66. 2455-2464 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuno F, Suhara T, Okubo Y, Sudo Y, Inoue M, Ichimiya T, Tanada S: "Dose relationship of limbic-cortical D 2 -dopamine receptor occupancy with risperidone"Psychopharmacology. 154. 112-114 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito H, Sudo Y, Suhara T, Okubo Y, Halldin C, Farde L: "Error analysis for quantification of [11C]FLB 457 binding to extrastriatal D2 dopamine receptors in the human brain"Neuroimage. 13. 531-539 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suhara T, Yasuno F, Sudo Y, Yamamotom M, Inoue M, Okubo Y, Suzuki K: "Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking"Neuroimage. 13. 891-895 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suhara T, Okubo Y, Yasuno F, Sudo Y, Inoue M, Ichimiya T, Nakashima Y, Nakayama K, Tanada S, Suzuki K, Halldin C, Farde L: "Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia"Arch Gen Psychiatry. 59. 25-30 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okubo,Y.: "Neuroimaging in Psychiatry"Nakayama -Shoten Co., Ltd. 395-409 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suhara, T., Okubo Y., Yasuno F. et al.: "Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia."Arch Gen Psychiatry. 59. 25-30 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ichimiya, T., Okubo Y., Suhara T., Sudo Y.: "Reduced Volume of the Cerebellar Vermis in Neuroleptic-Naive Schizophrenia."Biological Psychiatry. 49. 20-27 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sajo T., Abe T., Someya Y., Sassa T., Okubo Y. et al.: "Ten year progressive ventricular enlargement in schizophrenia : An MRI morphometrical study."Psychiatry and Clinical Neuroscience. 55. 41-47 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okubo Y., Saijo T., Oda K.: "A review of MRI studies of progressive brain changes in schizophreni"Journal of Medical and Dental Sciences. 48. 61-67 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suhara T., Yasuno F., Sudo Y., Yamamoto M., Okubo Y. et al.: "Dopamine D2 receptor in the insular cortex and the personality trait of novelty seeking"Neuroimage. 13. 891-895 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大久保善朗, 須原哲也: "受容体占有と抗精神病作用-PET/SPECTを用いた抗精神病薬の薬効評価-"精神神経学雑誌. 103. 329-340 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suhara,T.,Okubo Y.,Yasuno F. et al.: "Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia."Arch Gen Psychiatry. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ichimiya,T.,Okubo Y.,Suhara T.,Sudo Y.: "Reduced Volume of the Cerebellar Vermis inNeuroleptic -Naive Schizophrenia."Biological Psychiatry. 49. 20-27 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saijo,T.,Abe T.,Someya Y.,Sassa T.,Okubo Y. et al.: "Ten year progressive ventricular enlargement in schizophrenia : An MRI morphometrical study."Psychiatry and Clinical Neuroscience. 55. 41-47 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasuno,F.,Suhara T.,Okubo Y.,Sudo Y.,Inoue M., et al.: "Dose relationship of limbic-cortical D2-dopamine receptor occupancy with risperidone."Psychopharmacology. 154. 112-114 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasuno,Y.,Suhara T.,Sudo Y.,Yamamoto M.,Inoue M.,Okubo Y.,: "Relation among dopamine D2 receptor binding, obesity and personality in normal human subjects."Neuroscience Letters. 300. 59-61 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okubo,Y.,Suhara T.,Suzuki K. et al.: "Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography."Life Sciences. 66. 2455-2464 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurumaji,A.,Okubo,Y.: "Neurotrsnamitter receptors in actions of antipsychotic medications."CRC Press. 65-78 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suhara,T.,Okubo Y.,Sudo Y.,Tanada S: "PET research in pathophysiology and treatment of psychiatric illness."Positron Emission Tomography in the Millennium. 33-40 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Helfenbein J, Sandell J, Halldin C, Chalon S, Emond P, Okubo Y, Chou Y, Frangin Y, Douziech L, Gareau L, Swahn C, Besnard J, Frade L, Guilloteau D: "PET examination of three potent cocaine derivatives as specific radioligands for the sertonin transporter."Nuclear Medicine & Biology.. 26. 491-499 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirai N, Uchida S, Maehara T, Okubo Y, Shimizu H: "Enhanced gamma (30-150 Hz) frequency in the human medial temporal lobe."Neuroscience.. 90. 1149-1155 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito H, Okubo Y, Halldin C, Farde L: "Mapping of central D2 dopamine receptors in man using [11C]raclopride: PET with anatomic standardization technique."NeuroImage.. 9. 235-242 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sudo Y, Suhara T, Suzuki K, Okubo Y, Yoshikawa K, Uchide S, Sassa T, Okauchi T, Sasaki Y, Matsushita M: "Muscarinic receptor occupancy by biperiden in living human brain."Life Sciences.. 64. 104 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suhara T, Sudo Y, Okauchi T, Maeda J, Kawabe K, Suzuki K, Okubo Y, Y. N, Ito H, Tanada S, Halldin C, Farde L: "Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET."International Journal of Neuropsychopharmacology. 2. 73-82 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirai N, Uchida S, Maehara T, Okubo Y, Shimizu H: "Beta-1(10-20 Hz) cortical oscillations observed in the human medial temporal lobe."Neuro Report.. 10. 3055-3059 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okubo Y, Olsson H, Ito H, Lofti M, Suhara T, Halldin C, Farde L: "PET mapping of extrastriatal D2-like dopamine receptors in the human brain using an anatomic standardization technique and and [11C]FLB457."NeuroImage.. 10. 666-674 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Bergstrom KA, Halldin C, Savonen A, Okubo Y, Hiltunen J, Nobuhara K, Swahn CG, Karlsson P, McPherson D, Knapp FF, Larsson S, Schnell PO, Farde L,: "Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M-1 and M-2 muscarinic acetylcholine receptors in Alzheimer's disease."European Journal of Nuclear Medicine.. 26(11). 1482-1485 (199)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大久保善朗: "精神分裂病の画像診断"Current Approaches to Psychoses.. 4. 57-59 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 山本正浩,須原哲也,大久保善朗: "人格と脳機能画像"脳の科学. 21. 1069-1074 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 一宮哲哉,大久保善朗: "精神分裂病と小脳"脳の科学. 21. 1265-1269 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大久保善朗: "脳機能のイメージングの最前線ー精神分裂病の神経伝達機能イメージングー.第14回ブレイン・ファッンクション・イメージング・カンファレンス記録集"東京.メジフィジックス. 97-102 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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