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Studies on the brain neurotransmitters involved in the onset and course of schizophrenia.

Research Project

Project/Area Number 05454310
Research Category

Grant-in-Aid for General Scientific Research (B)

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

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) WATANABE Akiko  Technician, ditto, 医学部, 技官 (40210992)
KURUMAJI Akeo  Lecturer, ditto, 医学部, 助手 (00251504)
SHIBUYA Haruo  Associate Professor, ditto, 医学部, 助教授 (10158959)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1994: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsSchizophrenia / Dopamine D2 receptor / Dopamine D2 receptor gene / S311C variant / Negative symptoms / アミノ酸ミスセンス変異
Research Abstract

This study attempted to examine the heterogeneity of schizophrenia by using a missense variant (S311C) found in the dopamine D2 receptor gene (DRD2). Case-control studies in 156 schizophrenics and 300 controls on an association of a molecular variant of S311C was significantly in schizophrenics (9%) compared with controls (3.7%). Schizophrenics with S311C variant showed less severe negative symptoms than those wihtout. The second association study was dose in expanded numbers of schizophrenics (292) and controls (579). In schizophrenics, significantly higher frequency of those with S311C (8.9%) was again found compared with controls (4.1%). The frequency of S331C in the schizophrenics without negative symptoms (17.1%) was remarkably higher than the controls (p<0.00001). Schizophrenics with S311C were mainly subtyped into paranoid type and a very few into disorganized type. Examination of the courses of the patients by using Bleuler's clssification of the course of schizophrenia revealed that there were significantly fewer cases who showed simple course to deterioration in those with S311C than those without.
Thus, these data suggest that the missense variant, S311C,found in DRD2 might not be a risk factor but might be one of the genetic factors which modulate the course of the disease by affecting the response of the patients to antipsychotic drug treatment.
The pharmacological properties of receptor proteins with S311C transfected in the cultured cells are now under investigation comparing with those of wild type.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (62 results)

All Other

All Publications (62 results)

  • [Publications] Yoshikawa,T. et al.: "Involvement of the fimbria fornix in the initiation but not expression of methamphetamine-induced sensitization." Pharmacol.Biochem.Behav.45. 691-695 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arinami,T. et al.: "Association between severity of alcoholism and the Al allele of the dopamine D2 receptor gane Taq I A RELP in Japanese." Biol.Psychiatry. 33. 108-114 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okubo,Y. et al.: "A follow-up study of healthy children with epileptiform EEG discharge." J.Epilepsy. 6. 250-256 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Terasaki,O. et al.: "A quantitative study on the stationarity of EEG of schizophrenics by a locally stationary autregressive model." Neurol.Psychiat.Brain Res.1. 181-185 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Senzaki,A. et al.: "Quantitative magnetic resonance imaging in patients with temporal lobe epilepsy." J.Epilepsy. 6. 243-249 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ikawa,K. et al.: "Modulation of [^3H]mazindol binding sites in rat striatum by dopaminergic agents." Eur.J.Pharmacol.250. 261-266 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Itokawa,M. et al.: "A structural polymorphism of human dopamine D2 receptor,D2(Ser^<311>→Cys)." Biochem.Biophys.Res.Comm.196. 1369-1375 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arinami,T. et al.: "Association of dopamine D2 receptor molecular variant with schizophrenia." Lancet. 343. 703-704 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ishimaru,M. et al.: "Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics:evidence for glutamate hypothesis." Biol.Psychiatry. 35. 84-95 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nankai,M. et al.: "Platelet ^3H-paroxetine binding in control subjects and depressed patients:relationship to serotonin uptake and age." Psychiatry Res.51. 147-155 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagase,Y. et al.: "Lower interhemispheric coherence in a case agenesis of the corpus callosum." Clin.Electroenceph.25. 36-39 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okubo,Y. et al.: "Epileptiform EEG discharges in healthy children:prevalence,emotional and behavioral correlates,and genetic influences." Epilepsia. 35. 832-841 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toru,M. et al.: "Minireview:Excitatory amino acids:implications for psychiatric disorders research." Life Sci.55. 1683-1699 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa,T. et al.: "Effect of a single injection of psychoactive drugs on CCK mRNA in rat brain." Peptides. 15. 471-473 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大倉 勇史 ほか: "Clonazepam 中止後、悪性症候群様の症状を呈した1症例" 精神医学. 36. 657-660 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 融 道男 ほか: "抗精神病薬の作用部位(ドーパミン受容体)の遺伝子解析" 精神神経薬理シンポジウム. 20. 87-92 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toru,M.(ed.): "Neurotransmitters in Neuronal Plasticity and Psychiatric Disorders" Excerpta Medica, 103 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 融道男・渥美義賢(編): "睡眠とその障害をめぐって" メディカルカルチュア, 227 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa, T.et al.: "Involvement of the fimbria fornix in the initiation but not expression of methamphetamine-induced sensitization." Pharmacol.Biochem.Behav.45. 691-695 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arinami, T.et al.: "Association between severity of alcoholism and the Al allele of the dopamine D2 receptor gene Taq I A RFLP in Japanese." Biol.Psychiatry. 33. 108-114 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okubo, Y.et al.: "A follow-up study of healthy children with epileptiform EEG discharge." J.Epilepsy. 6. 250-256 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Terasaki, O.et al.: "A quantitative study on the stationarity of EEG of schizophrenics by a locally stationary autoregressive model." Neurol.Psychiat.Brain Res.1. 181-185 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Senzaki, A.et al.: "Quantitative magnetic resonance imaging in patients with temporal lobe epilepsy." J.Epilepsy. 6. 243-249 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ikawa, K.et al.: "Modulation of [^3H] mazindol binding sites in rat striatum by dopaminergic agents." Eur.J.Pharmacol. 250. 261-266 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Itokawa, M.et al.: "A structural polymorphism of human dopamine D2 receptor, D2 (Ser^<311>*Cys)." Biochem.Biophys.Res.Comm.196. 1369-1375 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arinami, T.et al.: "Association of dopamine D2 receptor molecular variant with schizophrenia." Lancet. 343. 703-704 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ishimaru, M.et al.: "Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics : evidence for glutamate hypothesis." Biol.Psychiatry. 35. 84-95 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nankai, M.et al.: "Platelet ^3H-paroxetine binding in control subjects and depressed patients : relationship to serotonin uptake and age." Psychiatry Res. 51. 147-155 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagase, Y.et al.: "Lower interhemispheric coherence in a case of agenesis of the corpus callosum." Clin.Electroenceph.25. 36-39 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okubo, Y.et al.: "Epileptiform EEG discharges in healthy children : prevalence, emotional and behavioral correlates, and genetic influences." Epilepsia. 35. 832-841 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toru, M.et al.: "Minireview : Excitatory amino acids : implications for psychiatric disorders research." Life Sci.55. 1683-1699 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa, T.et al.: "Effect of a single injection of psychoactive drugs on CCK mRNA in rat brain." Peptides. 15. 471-473 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa,T.et al.: "Involvement of the fimbria fornix in the initiation but not expression of methamphetamine-induced sensitization." Pharmacol.Biochem.Behav.45. 691-695 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Arinami,T.et al.: "Association between severity of alcoholism and the Al allele of the dopamine D2 receptor gene Taq I A RFLP in Japanese." Biol.Psychiatry. 33. 108-114 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okubo,Y.et al.: "A follow-up study of healthy children with epileptiform EEG discharge." J.Epilepsy. 6. 250-256 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Terasaki,O.et al.: "A quantitative study on the stationarity of EEG of schizophrenics by a locally stationary autoregressive model." Neurol.Psychiat.Brain Res.1. 181-185 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Senzaki,A.et al.: "Quantitative magnetic resonance imaging in patients with temporal lobe epilepsy." J.Epilepsy. 6. 243-249 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ikawa,K.et al.: "Modulation of [^3H] mazindol binding sites in rat striatum by dopaminergic agents." Eur.J.Pharmacol.250. 261-266 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Itokawa,M.et al.: "A structural polymorphism of human dopamine D2 receptor,D2 (Serp^<311>→Cys)." Biochem.Biophys.Res.Comm.196. 1369-1375 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Arinami,T.et al.: "Association of dopamine D2 receptor molecular variant with schizophrania." Lancet. 343. 703-704 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ishimaru,M.et al.: "Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics : evidence for glutamate hypothesis." Biol.Psychiatry. 35. 84-95 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nankai,M.et al: "Platelet ^3H-paroxetine binding in control subjects and depressed patients : relationship to serotonin uptake and age." Psychiatry Res.51. 147-155 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagase,Y.et al.: "Lower interhemispheric coherence in a case of agenesis of the corpus callosum." Clin.Electroenceph.25. 36-39 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okubo,Y.et al.: "Epileptiform EEG discharges in healthy children : prevalence,emotional and behavioral correlates,and qenetic influences." Epilepsia. 35. 832-841 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toru,M.et al.: "Minireview : Excitatory amino acids : implications for psychiatric disorders research." Life Sci.55. 1683-1699 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshikawa,T.et al.: "Effect of a single injection of psychoactive drugs on CCK mRNA in rat brain." Peptides. 15. 471-473 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大倉 勇史 ほか: "Clonazepam 中止後、悪性症候群様の症状を呈した1症例" 精神医学. 36. 657-660 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 融 道男 ほか: "抗精神病薬の作用部位(ドーパミン受容体)の遺伝子解析" 精神神経薬理シンポジウム. 20. 87-92 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toru,M. (ed.): "Neurotransmitters in Neuronal Plasticity and Psychiatric Disorders" Excerpta Medica, 103 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 融道男・渥美義賢(編): "睡眠とその障害をめぐって" メディカルカルチュア, 227 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshikawa,T.,Watanabe,A.Shibuya,H.,and Toru,M.: "Involvement of the fimbria fornix in the initiation but not in the expression of methamphetamine-induced sensitization." Pharmacol Biochem. Behav.45. 691-695 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arinami,T.,Itokawa,M.,Komiyama,T.,Mitsushio,H.,Mori,H.,Mifune,H.,Hamaguchi,H.and Toru,M.: "Association between severity of alcoholism and the Al allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese." Biol.Psychiatry. 33. 108-114 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Okubo,Y.,Matsuura,M.,Asai,J.,Asai,K.,Kato,M.,Kojima,T.and Toru,M.: "A follow-up study of healthy children with epileptiform EEG discharges." J.Epilepsy. 6. 250-256 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Terasaki,O.,Okubo,Y.,Matsuura,M.,Toru,M.,He,Y.,Hou,Y.and Shen,Y.: "A quantitative study on the stationarity of EGGs of schizophrenics by a locally stationary autoregressive model." Neurol.Psychiat.Brain Res.1. 181-185 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Senzaki,A.,Okubo,Y.,Abe,T.,Matsuura,M.,Moriiwa,M.,Asai,K.and Toru,M.: "Quantitative magnetic resonance imaging in patients with temporal lobe epilepsy." J.Epilepsy. 6. 243-249 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ikawa,K.,Watanabe,A.,Kaneno,S.and Toru,M.: "Modulation of 【^3H】mazindol binding sites in rat striatum by dopaminergic agents." Eur.J.Pharmacol.250. 261-266 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Itokawa,M.,Arinami,T.,Futamura,N.,Hawaguchi,H.and Toru,M.: "A structural polymorphism of human dopamine D2 receptor,D2(Ser^<311>-Cys)" Biochem.Biophys.Res.Comm.196. 1369-1375 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arinami,T.,Itokawa,M.,Enguchi,H.,Tagaya,H.,Yano,S.,Shimizu,H.,Hamaguchi,H.and Toru,M.: "Association of dopamine D2 receptor molecular variant with schizophrenia Lancet" (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ishimaru,M.,Kurumaji,A.and Toru,M.: "Increases in Strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics : evidence for glutamate hypothesis." Biol.Psychiatry. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 融 道男: "20年間外来で治療中の分裂病2症例" 精神科治療学. 8. 1193-1198 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 融道男・青木淳一: "精神分裂病" 生体の科学. 44. 598-599 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 仙波純一,融道男: "抗精神病薬" 学会出版センター, 33-50 (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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