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1997 Fiscal Year Final Research Report Summary

Studies on the brain neurotransmitter-related gene polymorphisms involved in the onset and course of schizophrenia and affective disorders.

Research Project

Project/Area Number 07457207
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

TORU Michio  Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, Professor, 医学部, 教授 (20013972)

Co-Investigator(Kenkyū-buntansha) ARINAMI Tadao  Univ. of Tsukuba, Institute of Basic Medical Sciences, Associate Professor,, 基礎医学系, 助教授 (10212648)
WATANABE Akiko  Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, Te, 医学部, 技官 (40210992)
KURUMAJI Akeo  Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, Le, 医学部, 助手 (00251504)
SHIBUYA Haruo  Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, As, 医学部, 助教授 (10158959)
Project Period (FY) 1995 – 1997
Keywordsschizophrenia / affective disorder / alcohol dependence / dopamine D2 receptor gene / MTHFR gene variant
Research Abstract

Since the potency of antipsychotic drugs correlates with their affinity for the dopamine D2 receptor, this receptor gene might be a most possible caudidate gene for the pathoetiology of schizophrenics. Case-control studies in 419 schizophrenics, 78 patients with affective disorders, 393 patients with alcohol dependence and 579 control subjects on an association of several molecular variants mainly found in the dopamine D2 receptor. The frequency of schizophrenic patients with Cys311 variant was significantly higher particularly in whom without negatic symptoms (17%) when compared with the control (4%) (p<0.00001). This variant was found more frequently in patients with affective disorders with mood-incongruent psychotic features. (33%) (p<0.00001). We found Ins/Del polymorphism at -141C in the 5'region of DRD2 gene. The Del allele frequency was significantly lower in patients with schizophrenia than control subjects (OR : 0.6, p<0.001). Ala677Val polymorphism, which is responsible for the thermolabile methylenetetrahydrofolate reductase deficiency, was significantly more frequently observed in schizophrenic patients (OR : 1.9, p<0.0006).
We examined DRD2 gene polymorphism in patients with alcohol dependence. The patients carried Cys311 variant siguificantly more frequently than control (p<0.04). Alcoholic patients had -141 Ins Alle more frequently than controls (p<0.0005). We found that there were more frequent presence of Taq Ia1 allele in DRD2 gene in patients with alcohol dependence (p<0.006).

  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Nankai, M., Yamada, S., Muneoka, K., Toru, M.: "Increased 5-HT2-mediated behavior eleven days after shock in learned helpless rats." European Journalof Pharmacology.281. 123-130 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Semba, J., Kito, S., Toru, M.: "Characterization of extracellular amino acids in striatum of freely moving rats by in vivo microdialysis." J.Neural Transm.100. 39-52 (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Semba, J., Watanabe, A., Kito, S., Toru, M.: "Behavioral and neurochemical effects of OPC-14597,a novel antipsychotics drug on dopaminergic mechanism in rat brain." Neuropharmacology.34. 785-791 (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Yamada, S., Watanabe, A., Nankai, M., Toru, M.: "Acute immobilization stress reduces(±)DOI-induced 5-HT2A receptor-mediated head shakes in rats." Psychopharmacology. 119. 9-14. (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] 融 道男(監修): "臨床ハンドブック神経伝達物質受容体" 大阪:最新医学社. (1995.)

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      「研究成果報告書概要(和文)」より
  • [Publications] Arinami, T., Itokawa, M., Aoki, J., Shibuya, H., Ookubo, Y., Iwawaki, A., Ota, K., Shimizu, H., Hamaguchi, H., Toru, M.: "Further association study on dopamine D2 receptor variant S311C in schizophrenia andaffective disorders." American Journal of Medical Genetics.67(2). 133-8 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurumaji, A., Watanabe, A., Kumashiro, S., Semba, J., Toru, M.: "A postmortem study of glycine and its potential precursors in chronic schizophrenics." Neurochemical International.29(3). 239-245. (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] Uchiyama, M., Tanaka, K., Isse, K., Toru, M.:"Efficacy of mianserin on symptoms of delirium in the aged:an open trial study." Prog.Neuro-Psychopharmacol.& Biol.Psychiat.20. 651-6. (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] Toru, M.: "Pharmacotherapy of schizophrenia." Asian Med J.39. 274-278. (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] Arinami, T., Yamada, N., Yamakawa-Kobayashi, K., Hamaguchi, H., Toru, M.: "Methyleneterahydrofolate Reductase Variant and Schizophrenia" Depression.American Journal of MedicalGenetics(Neuropsychiatric Genetics).74. 526-528 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arinami, T., Gao, M., Hamaguchi, H., Toru, M.: "A functional polymorphism in the promoter region of the dopamine D2 receptor gene isassociated with schizophrenia" Human Molecular Genetics.6(4). 577-582. (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishiguro, H., Arinami, T., Yamada, K., Otuka, Y., Toru, M., Shibuya, H.: "An association study between a transcriptional polymerphsm in the serotonin transporter gene and panic disorder in a Japanese population." Psychiatry and Clinical Neuroscinces.51(5). 333-335 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [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." Biol.Psychiatry.40. 1122-1127. (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [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(和文)」より
  • [Publications] Itokawa, M., Toru, M., Ito, K., Tsuga, H., Kameyama, K., Haga, T., Arinami, T., Hamaguchi, H.: "Sequestration of the short and long isoforms of dopamine D2 receptors expressed in Chinese hamster ovary cells." Molecular Pharmacology.49(3). 560-6. (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kaneko, K., Kurumaji, A., Shibuya, H., Nabeshima, T., Toru, M.: "The effects of single ans repeated phencyclidine administration on 125I-iomazenil binding in the rat brain." Neurochem.Int.29. 279-287 (1996)

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      「研究成果報告書概要(和文)」より
  • [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(3). 1075-1079 (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kurumaji, A., Toru, M.: "Postnatal development of periphernal-type benzochiazepine recepters in rat brain andperiphernal tissues." Developmental Brain Research.97. 148-151 (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kurumaji, A., Wakai, T., Toru, M.: "Decreases in perpheral-type benzodiazepine receptors in postmortem brains of chronicschizophrenics." J Neural Transm.104. 1361-1370 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] Okubo, Y., Suhara, T., Suzuki, K., Kobayashi, K., Inoue, O., Terasaki, O., Someya, Y., Sassa, T., Sudo, Y., Matsushima, E., Iyo, M., Teteno, Y., Toru, M.: "Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET." Nature.385(6617). 634-636 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] Ishimaru, M., Toru, M.: "The glutamate hypothesis of schizophrenia:therapeutic implications." CNS Drugs.7(1). 47-67 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] Okubo, Y., Suhara, T., Sudo, Y., Toru, M.: "An example of comparison of PET imagesof dopamine D1 receptors between a schizophrenic patient and a control subject." Molecular Psychiatry.2. 292-293 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] Okubo, Y., Suhara, T., Sudo, Y., Toru, M.: "Possible role of dopamine D1 receptorsin schizophrenia." Molecular Psychiatry.2. 291-292 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] 融 道男, 道明 智徳: "精神分裂病の神経伝達物質." ブレイン・サイエンス.8. 29-38 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] 融 道男 編: "精神医学レビューNo.21精神疾患の脳イメージング" ライフ・サイエンス, (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] 融 道男, 澁谷 治男 監訳:スティーブン・E・ハイマン, エリック・J・ネスラ-著: "精神医学の分子生物学" 東京:金剛出版, (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] 融 道男, 岩脇 淳, 伊澤 良介, 高橋 康弘, 土屋 賢治 訳:カプラン, H.I., サドック, B.J.著: "臨床精神医学ハンドブック" 東京:医学書院, (1997.)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arinami, T., Itokawa, M., Aoki, J., Shibuya, H., Ookubo, Y., Iwawaki, A., Ota, K., Shimizu, H., Hamagami, H., Toru, M.: "Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders." American Journal of Medical Genetics.67(2). 133-8 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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." Biol.Psychiatry.40. 1122-1127 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Publications] Itokawa, M., Toru, M., Ito, K., Tsuga, H., Kameyama, K., Haga, T., Arinami, T., Hamaguchi, H.: "Sequestration of the short and long isoforms 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
  • [Publications] Arinami, T., Yamada, N., Yamakawa-Kobayashi, K., Hamaguchi, H., Toru, M.: "Methyleneterahydrofolate Reductase Variant and Schizophrenia / Depression." American Journal of Medical Genetics (Neuropsychiatric Genetics).74. 526-528 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arinami, T., Gao, M., Hamaguchi, H., Toru, M.: "A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia." Human Molecular Genetics.6. 577-582 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishiguro, H., Arinami, T., Yamada, K., Otuka, Y., Toru, M., Shibuya, H.: "An association study between a transcriptional polymerphsm in the serotonin transporter gene and panic disorder in a Japanese population." Psychiatry and Clinical Neuroscinces.51(5). 333-335 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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