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1994 Fiscal Year Final Research Report Summary

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
KeywordsSchizophrenia / Dopamine D2 receptor / Dopamine D2 receptor gene / S311C variant / Negative symptoms
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.

  • Research Products

    (32 results)

All Other

All Publications (32 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1996-04-15  

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