Molecular mechanisms of schizophrenia and pharmacogenetics in the treatment of schizophrenia

2008 Fiscal Year Final Research Report

• Project/Area Number: 18591319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: SHINKAI Takahiro University of Occupational and Environmental Health, Japan, 医学部, 講師 (20352304)
• Co-Investigator(Kenkyū-buntansha): HORI Hiroko 産業医科大学, 医学部, 非常勤助教 (80412641) ; OHMORI Osamu 産業医科大学, 医学部, 非常勤講師 (70248558) ; MATSUMOTO Chima 産業医科大学, 医学部, 非常勤助教 (80421329) ; NAOE Yui 産業医科大学, 医学部, 専門修練医 (10421330) ; UTSUNOMIYA Kensuke 産業医科大学, 医学部, 助教 (90425314) ; FUKUNAKA Yuko 産業医科大学, 医学部, 専門修練医 (60441854) ; INOUE Yoshiaki 産業医科大学, 医学部, 助教 (10461550) ; YAMAGUCHI Wakana 産業医科大学, 医学部, 専門修練医 (20461551)
• Co-Investigator(Renkei-kenkyūsha): NAKAMUARA Jun 産業医科大学, 医学部, 教授 (40148804) ; SAKATA Shinichi 産業医科大学, 医学部, 助教 (80425313)
• Project Period (FY): 2006 – 2008
• Keywords: 統合失調症 / 遺伝子多型 / 関連研究 / 遅発性ジスキネジア / 水中毒 / オーダーメイド医療

Research Abstract

統合失調症の脆弱性(病気のかかりやすさ)、治療薬の効き目、さらに副作用の出やすさについて、遺伝的要因が関わっているという考えがあります。本研究は、それぞれ関与が予想される遺伝子の個人差を調べ、病気の診断、予防、治療に役立てようとするものです。研究した対象数がそれほど多くはなく、決定的とはいえませんが、いくつかの知見が得られました。このような研究結果が蓄積・確認されると、統合失調症のより無駄のなく合理的な診断や治療に寄与していくものと思われます。

Research Products

• [Journal Article] Association analysis between the C-1291G polymorphism in the promoter region of the adrenergic α2A receptor gene and polydipsia in schizophrenia. (2009)
  • Author(s): Yamaguchi W, Shinkai T, Inoue Y, Utsunomiya K, Sakata S, Fukunaka Y, Yamada K, Chen HI, Hwang R, Ohmori O, Nakamura J.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry (in press)
  • Peer Reviewed
• [Journal Article] No association between a functional polymorphism in the promoter region of the neuropeptide Y gene (-485C>T) and schizophrenia. (2009)
  • Author(s): Inoue Y, Shinkai T, Utsunomiya K, Sakata S, Fukunaka Y, Yamaguchi W, Yamada K, Chen HI, Hwang R, Ohmori O, Nakamura J.
  • Journal Title: Neurosci Lett. 452(1) Pages: 72-4
  • Peer Reviewed
• [Journal Article] Genetic association between the dopamine D3 gene polymorphism (Ser9Gly) and schizophrenia in Japanese populations : evidence from a case-control study and meta-analysis. (2008)
  • Author(s): Utsunomiya K, Shinkai T, De Luca V, Hwang R, Sakata S, Fukunaka Y, Chen HI, Ohmori O, Nakamura J.
  • Journal Title: Neurosci Lett. 444(2) Pages: 161-5
  • Peer Reviewed
• [Journal Article] Functional polymorphism of the human multidrug resistance gene (MDR1) and polydipsia-hyponatremia in schizophrenia (2008)
  • Author(s): Shinkai T, De Luca V, Utsunomiya K, Sakata S, Inoue Y, Fukunaka Y, Hwang R, Ohmori O, Kennedy JL, Nakamura J.
  • Journal Title: Neuromolecular Med. 10(4) Pages: 362-7
  • Peer Reviewed
• [Journal Article] The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia. (2007)
  • Author(s): Fukunaka Y, Shinkai T, Hwang R, Hori H, Utsunomiya K, Sakata S, Naoe Y, Shimizu K, Matsumoto C, Ohmori O, Nakamura J.
  • Journal Title: Neuromolecular Med. 9(4) Pages: 292-7
  • Peer Reviewed
• [Journal Article] Association analyses of the DAOA/G30 and D-amino-acid oxidase genes in schizophrenia : further evidence for a role in schizophrenia. (2007)
  • Author(s): Shinkai T, De Luca V, Hwang R, Muller DJ, Lanktree M, Zai G, Shaikh S, Wong G, Sicard T, Potapova N, Trakalo J, King N, Matsumoto C, Hori H, Wong AH, Ohmori O, Macciardi F, Nakamura J, Kennedy JL.
  • Journal Title: Neuromolecular Med. 9(2) Pages: 169-77
  • Peer Reviewed
• [Journal Article] No association between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and schizophrenia in Asian populations : Evidence from a case-control study and meta-analysis. (2007)
  • Author(s): Naoe Y, Shinkai T, Hori H, Fukunaka Y, Utsunomiya K, Sakata S, Matsumoto C, Shimizu K, Hwang R, Ohmori O, Nakamura J.
  • Journal Title: Neurosci Lett. 415(2) Pages: 108-12
  • Peer Reviewed
• [Journal Article] Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response. (2007)
  • Author(s): Hwang R, Shinkai T, De Luca V, Ni X, Potkin SG, Lieberman JA, Meltzer HY, Kennedy JL.
  • Journal Title: J Psychopharmacol. 21(7) Pages: 718-27
  • Peer Reviewed
• [Journal Article] Association study between functional polymorphisms in the cytochrome P450 1A2 and 2D6 genes and polydipsia in schizophrenia. (2006)
  • Author(s): Matsumoto C, Shinkai T, De Luca V, Hori H, Hwang R, Ohmori O, Kennedy JL, Nakamura J.
  • Journal Title: Neuromolecular Med. 8(3) Pages: 381-8
  • Peer Reviewed
• [Journal Article] No association between a functional NAD(P)H : quinone oxidoreductase gene polymorphism (Pro187Ser) and tardive dyskinesia. (2006)
  • Author(s): Hori H, Shinkai T, Matsumoto C, Ohmori O, Nakamura J.
  • Journal Title: Neuromolecular Med. 8(3) Pages: 375-80
  • Peer Reviewed
• [Journal Article] Dopamine D2 receptor gene variants and quantitative measures of positive and negative symptom response following clozapine treatment. (2006)
  • Author(s): Hwang R, Shinkai T, Deluca V, Macciardi F, Potkin S, Meltzer HY, Kennedy JL.
  • Journal Title: Eur Neuropsychopharmacol. 16(4) Pages: 248-59
  • Peer Reviewed
• [Journal Article] Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia. (2006)
  • Author(s): Shinkai T, Muller DJ, De Luca V, Shaikh S, Matsumoto C, Hwang R, King N, Trakalo J, Potapova N, Zai G, Hori H, Ohmori O, Meltzer HY, Nakamura J, Kennedy JL.
  • Journal Title: Psychiatry Res. 141(2) Pages: 123-8
  • Peer Reviewed
• [Journal Article] Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia. (2006)
  • Author(s): Shinkai T, Matsumoto C, Shaikh S, De Luca V, Muller DJ, Hwang R, King N, Trakalo J, Potapova N, Hori H, Ohmori O, Meltzer HY, Nakamura J, Kennedy JL
  • Journal Title: Psychiatry Res. 141(2) Pages: 123-8
  • Peer Reviewed
• [Presentation] Ethnic differences in pharmacogenetics of serious adverse effects of antipsychotics : tardive dyskinesia and more. (2008)
  • Author(s): Takahiro Shinkai, Hiroko Hori, Kensuke Utsunomiya, Chima Matsumoto, Shinichi Sakata, Yoshiaki Inoue, Yuko Fukunaka, Wakana Yamaguchi, Hsin-I Chen, Rudi Hwang, Vincenzo De Luca Daniel J. Muller, Osamu Ohmori, James L. Kennedy, Jun Nakamura.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka
  • Year and Date: 20081011-15
• [Presentation] Association study between the NMDA receptor subunit 2B (GRIN2B) gene and polydipsia in schizophrenia. (2008)
  • Author(s): Takahiro Shinkai, Shinichi Sakata, Hiroko Yamamoto, Kensuke Utsunomiya, Yuko Fukunaka, Yoshiaki Inoue, Wakana Yamaguchi, Kenji Yamada, Hsin-I Chen, Osamu Ohmori, Jun Nakamura.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka
  • Year and Date: 20081011-15
• [Presentation] Association between the leptin receptor gene (LEPR) polymorphism (Gln223Arg) and late-onset Alzheimer's disease. (2008)
  • Author(s): Kensuke Utsunomiya, Takahiro Shinkai, Shinichi Sakata, Yoshiaki Inoue, Yuko Fukunaka, Wakana Yamaguchi, Kenji Yamada, Osamu Ohmori, Jun Nakamura.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka
  • Year and Date: 20081011-15
• [Presentation] Association study between the DNA repair gene XRCC1 and schizophrenia. (2008)
  • Author(s): Kenji Yamada, Takahiro Shinkai, Shinichi Sakata, Kensuke Utsunomiya, Yuko Fukunaka, Osamu Ohmori, Jun Nakamura.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka
  • Year and Date: 20081011-15
• [Presentation] Genetic association analysis between the NMDA receptor subunit 2B gene and schizophrenia. (2008)
  • Author(s): Shinichi Sakata, Takahiro Shinkai, Hiroko Yamamoto, Kensuke Utsunomiya, Yoshiaki Inoue, Yuko Fukunaka, Wakana Yamaguchi, Kenji Yamada, Kazuko Shimizu, Hsin-I Chen, Osamu Ohmori, Jun Nakamura.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka
  • Year and Date: 20081011-15
• [Presentation] Genetic association analysis between the NPR-1 gene polymorphism (M341I) and polydipsia in schizophrenia. (2008)
  • Author(s): Yuko Fukunaka , Takahiro Shinkai, Hsin-I Chen , Kensuke Utsunomiya ,Shinichi Sakata, Osamu Ohmori, Jun Nakamura.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka
  • Year and Date: 20081011-15
• [Book] Tardive Dyskinesia, Molecular Mechanisms. In : Encyclopedia of Molecular Mechanisms of Disease, Florian Lang (Ed.) (2009)
  • Author(s): TAKAHIRO SHINKAI
  • Publisher: Springer(in press)