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PET receptor studies on scgizophrenia and extrapyramidal side effects.

Research Project

Project/Area Number 07671053
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionTokyo Medical and Dental University, School of Medicine

Principal Investigator

OKUBO Yoshiro  Tokyo Medical and Dental University, School of Medicine, M.D., Ph.D., 医学部, 講師 (20213663)

Co-Investigator(Kenkyū-buntansha) OHTA Katsuya  Tokyo Medical and Dental University, M.D., 医学部, 助手 (20251514)
MATSUSHIMA Eisuke  Tokyo Medical and Dental University, M.D., Ph.D., 医学部, 助手 (50242186)
SUHARA Tesuya  Tokyo Medical and Dental University, M.D., Ph.D., 主任研究官
TORU Michio  Tokyo Medical and Dental University, School of Medicine, M.D., Ph.D., 医学部, 教授 (20013972)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsPET / Schizophrenia / Dopamine
Research Abstract

Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of dopamine D2 receptor (D2R) antagonists. D2R is expressed most highly in the striatum, but recent studies using positron emission topography (PET) have failed to show any change in D2R densities in the striatum of schizophrenics. This raises the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex, has been implicated in control of working memory, and working memory dysfunction is a prominent feature of schizophrenia. We therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, D1R binding was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of negative symptoms (for instance emotional withdrawal), and to poor performance in the Wisconsin Card Sort Test (WCST). We propose that dysfunction of D1R signaling in the PFC may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (57 results)

All Other

All Publications (57 results)

  • [Publications] Arinani,T.,Takekoshi,K.,Itokawa,M.,Hamaguchi,H.,Toru,M.: "Failure to find association of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia." Psychiatric Genetics.6.13-15 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagase, Y., Okubo, Y., Toru, M.: "Electroencephalography in schizophrenic patients : comparison between neuroleptic-naive state and after treatment." Biological Psychiatry.40.452-456 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okubo,Y.,Suhara,T.,Kobayashi,K.,Terasaki,O.,Inoue,O.,Suzuki,K.,Tateno,Y.,Toru,M.: "PET studies of D1 and D2 receptors in schizophrenic patients." Eur Neuropsychopharmacol.6(suppl3).73 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru,A.K..: "Postnatal development of peripheral-type benzodiazepine receptors in rat brain and peripheral tissues." Developmental Brain Research.22GD04:97.148-151 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okubo,Y.,Suhara,T.,Suzuki,K.,Kobayashi,K.,Inoue,O.,Terasaki,O.,Someya,Y.,Sassa,T.,Sudo,Y.et al.: "Decreased prefrontal dopdmine D1 receptors in schizophrenia revealed by PET." Nature.385. 634-636 (1997.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kurumaji,A.,Kaneko,K.,Toru,M.20GB06:Effects of chronic treatment with haloperidol on 〔3H〕 PK 11195 binding in the rat brain and peripheral.: Neurophramacology.35.1075-1079 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 須原哲也,大久保善朗,須藤泰彦: "PET/SPECTによる精神分裂病の神経伝達物質受容体研究21GC07:精神科診断学" 7. 183-205 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 染谷康宏,大久保善朗,阿部哲夫,浅井邦彦,融道男: "MRIを用いた精神分裂病患者の脳の研究-体積計測による検討-" 精神医学. 38. 55-61 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 大久保善朗: "陰性症状の画像解析-MRI、PETを用いた研究-" 臨床精神医学. 25. 169-180 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 大久保善朗: "画像解析からみた精神分裂病の異種性" 最新精神医学. 2. 71-78 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 大久保善朗: "PETによる精神分裂病におけるドーパミンD1およびD2受容体の研究" 精神科治療学. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 融道男(編): "精神医学レビュー「精神疾患のイメージング」" ライフ・サイエンス, (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 大久保善朗: "持続性広汎性異常脳波.(中井利昭編,症候・異常値診断マニュアル)" 東京、中外医学社, 428-429 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 大久保善朗: "生物学的精神医学からみた疾患概念や分類の研究動向(松下正明編.臨床精神医学講座1巻)" 東京中山書店(印刷中), (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Arinami, T., Ling Li, Mitushio, H., Itokawa, M., Hamaguchi, H., Toru, M.: "An Insersion/Deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders." Biological Psychiatry. 40. 1122-1127 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Arinami, T., Takekoshi, K., Itokawa, M., Hamaguchi, H., Toru, M.: "Failure to find association of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia." Psychiatric Genetics. 6. 13-15 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itokawa, M., Toru, M., Ito, K., Tsuga, H., Kameyama, K., Haga, T., Arinami, T., Hamaguchi, H: "Sequestration of the short and longisoforms of dopamine D2 receptors expressed in Chinese hamster ovary cells." Molecular Pharmacology. 49. 560-6 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itokawa, M., Toru, M., Ito, K., Tsuga, H., Kameyama, K., Haga, T., Arinami, T., Hamaguchi, H.: "Sequestration of the D2S and D2L dopamine receptor isoforms expressed in Chinese Hamster Ovary cells." Molecular Pharmacology. 49. 560-566 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kurumaji, A., Kaneko, K., Toru, M.: "Effects of chronic treatment with haloperidol on [3H]PK 11195 binding in the rat brain and peripheral." Neuropharmacology. 35. 1075-1079 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kurumaji, A., Watanabe, A., Kumashiro, S., Semba, J., Toru, M.: "A postomortem study of glycine and its potential precursors in chronic schizophrenics." Neurochemistry International. 29. 239-245 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagase, Y., Okubo, Y., Toru, M.: "Electroencephalography in schizophrenic patients : comparison between neuroleptic-naive state and after treatment." Biological Psychiatry. 40. 452-456 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okubo, Y., Suhara, T., Kobayashi, K., Terasaki, O., Inoue, O., suzuki, K., Tateno, Y., Toru, M.: "PET studies of D1 and D2 receptors in schizophrenic patients." Eur Neuropsychopharmacol. 6 (suppl 3). 73 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suhara, T., Sudo, Y., Fukuda, H., Okubo, Y., Inoue, O.Suzuki, K.: "Imaging of brain serotonin system." Eur Neuropsychopharmacol. 6 (Suppl 3). 165 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru, A.K.: "Postnatal development of peripheral-type benzodiazepine receptors in rat brain and peripheral tissues." Developmental Brain Research. 97. 148-151 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru, M.: "Pharmacotherapy of schizophrenia." Asian Med J. 274-8 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsunoda, A., Komatsuzaki, A., Yamada M,Terasaki O.: "Three-dimensional computed imaging using a personal computer for nasal surgery" Laryngoscope. 106. 584-588 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okubo, Y., Suhara, T., Suzuki, K., Kobayashi, K., Inoue, O., Terasaki, O., Someya, Y., Sassa, T., Sudo, Y.et al.: "Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET." Nature. 385. 634-636 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yana,K.,Kawachi,K.,Iida,K.,Okubo,Y.,Toru,M.,Okuyama,F.: "Pseudo Bayesian Screening of Psychiatric Patients" IEICE Trans.on Information and Systems. E-78D. 508-510 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Arinami,T.,Takekoshi,K.,Itokawa,M.,Hamaguchi,H.,Toru,M.: "Failure to find association of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 genewith schizophrenia" Psychiatric Genetics. 6. 13-15 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagase,Y.,Okubo,Y.,Toru,M.: "Electroencephalography in schizophrenic patients : comparison between neuroleptic-naive state and after treatment" Biological Psychiatry. 40. 452-456 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okubo,Y.,Suhara,T.,Kobayashi,K.,Terasaki,O.,Inoue,O.,Suzuki,K.,Tateno,Y.,Toru,M.: "PET studies of D1 and D2 receptors in schizophrenic patients." Eur Neuropsychopharmacol. 6(suppl3). 73 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Toru,A.K.: "Postnatal development of peripheral-type benzodiazepine receptors in rat brain and peripheral tissues" Developmental Brain Research. 97. 148-151 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okubo,Y.,Suhara,T.,Suzuki,K.,Kobayashi,K.,Inoue,O.,Terasaki,O.,Someya,Y.,Sassa,T.,Sudo,Y.,et al.: "Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET" Nature. 385. 634-636 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kurumaji,A.,Kaneko,K.,Toru,M.: "Effects of chronic treatment with haloperidol on [3H]PK 11195 binding in the rat brain and peripheral" Neurophramacology. 35. 1075-1079 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗: "PET/SPECTによる精神分裂病のドーパミン受容体の研究" 心の臨床. 14. 127-131 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗,融道男: "精神分裂病の生物学的研究-画像解析による解明-" 作業療法ジャーナル. 29. 282-286 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 融 道男: "精神分裂病の生物学的研究-グルタミン酸とドーパミンの異常を中心に-" 児童精神医学とその近接領域. 36. 152-157 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 融 道男: "講座 精神分裂病の生物学的研究-1 分裂病治療薬(抗精神病薬)の進歩" 作業療法ジャーナル. 29. 29-33 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 融 道男: "ドーパミンD2レセプターと精神分裂病" Molecular Medicine. 32. 168-173 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 須原哲也,大久保善朗,須藤康彦: "PET/SPECTによる精神分裂病の神経伝達物質受容体研究" 精神科診断学. 7. 183-205 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 染谷康宏,大久保善朗,阿部哲夫,浅井邦彦,融道男: "MRIを用いた精神分裂病患者の脳の形態研究-体積計測による検討-" 精神医学. 38. 55-61 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗: "陰性症状の画像解析-MRI、PETを用いた研究-" 臨床精神医学. 25. 169-180 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗: "画像解析からみた精神分裂病の異種性" 最新精神医学. 2. 71-78 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗: "PETによる精神分裂病におけるドーパミンD1およびD2受容体の研究" 精神科治療学. 印刷中. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 融道男(編): "精神医学レビュー「精神疾患の脳イメージング」" ライフ・サイエンス, (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗: "持続性広汎性異常脳波.(中井利昭編.症候・異常値診断マニュアル)" 東京、中外医学社, 428-429 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗: "生物学的精神医学からみた疾患概念や分類の研究動向.(松下正明編.臨床精神医学講座1巻)" 東京中山書店(印刷中), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大久保善朗,須原哲也,小林薫,et al.: "PETによる精神分裂病患者のドーパミンD1およびD2受容体の研究" 日本神経精神薬理学会雑誌. 15. 498 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 大久保善朗,融道男: "講座 精神分裂病の生物が学的研究-1「画像解析による解明」" 作業療法ジヤ-ナル. (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 大久保善朗: "PET/SPECTによる精神分裂病のドーパミン受容体の研究" 心の臨床. 127-131. (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 大久保善朗,寺崎太洋,融道男,武者利光: "双極子追跡法とMRI3次元計測法を併用したてんかんの研究" てんかん治療研究振興財団研究年報. 7. 149-155 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 大久保善朗: "陰性症状の画像診断" 臨床精神医学. 25. 169-180 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 染谷康宏,大久保善朗,阿部哲夫,浅井邦彦,融道男: "MRIを用いた精神分裂病患者の脳の形態研究" 精神医学. 38. 55-61 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yana K,Kawachi K,lida K,Okubo Y,Toru M,Okuyama F: "Pseudo Bayesian Screening of Psychiatric Patients." IEICE Trans.on lnformation and Systems.E-78D. 508-510 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Arinami T.,ltokawa M.,Aoki J.,et al.: "Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorder." Am.J.Med.Genet.(in press). (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Itokawa M.,Toru M.,Ito K.,et al.: "Sequestration of the D2S and D2L dopamine receptor isoforms expressed in Chinese Hamster Ovary cells." Mol.Pharmacol.(in press). (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kurumaji A.,Watanabe A.,Kumashiro S.,Semba J.,Toru M: "A postmortem study of glycine and its potential precursors in chronic schizophrenics." Neurochemistry lnternational.(in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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