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Association of genetic polymorphisms with psychotropic-response in mental disorders

Research Project

Project/Area Number 13470198
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionFujita Health University

Principal Investigator

OZAKI Norio  Fujita Health University, School of Medicine, Professor, 医学部, 教授 (40281480)

Co-Investigator(Kenkyū-buntansha) SAWADA Makoto  Fujita Health University, Institute for Comprehensive Medical Science, Professor, 総合医科学研究所, 教授 (10187297)
NAITOU Hiroshi  Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (00247644)
IWATA Nakao  Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (60312112)
太田 龍朗  名古屋大学, 医学部, 教授 (00109323)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥8,200,000 (Direct Cost: ¥8,200,000)
KeywordsMOOD DISOREDERS / SCHIZOPHRENIA / ANXIETY DISORDERS / GENOME / PHARMACOGENETICS / ANTIPSYCHOTICS / SSRI / 遺伝子 / 精神障害 / 薬物反応性 / 多型
Research Abstract

The importance of genetic factors among inter-individual diversities of drug response has been steadily clarified. As a result, pharmacogenetics, which is defined as the science of pharmacological response and its modification by hereditary influence has been extensively carried out in order to clarify a marker of clinical response, put individualized medicine into a reality, and discover a new drug.
Thus, we carried out the following pharmacogenetic studies of psychotropics.
1.Risperidone response : D2 and 5-HT2A gene haplotype is associated with clinical efficacy of risperidone in schizophrenia.
2.SSRI response : Newly identified amino acid substitution in 5-HT transporter gene is associated with treatment resistant familiar obsessive compulsive disorder
3.Amphtamine response : VNTR polymorphism of the dopamine transporter gene is a risk factor for methamphetamine induced psychosis
We also elucidated the functional meanings of genetic polymorphism associated with mental disorders or treatment response.
1.Pro15Ser in 5-HT5A receptor gene associated with schizophrenia : The expression study using cultured cell revealed that atypical antipsychotics including zotepine, risperidone, clozpine have high affinity to 5-HT5A receptor and the Bmax of the Ser15 is about 50% of that of the Per15.
2.Cys23Ser in 5-HT2C receptor gene associated with Clozapine response : The expression study using cultured cell revealed that the Ser23 allele may be constitutively more active than Cys23l
We are going to continue pharmacogenetic studies of psychotropics to obtain a marker for the drug response and open the road to the development of a new drug.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Okada M, et al.: "Modification of Human 5-HT2C Receptor Function by Cys23Ser, an Abundant, Naturally Occurring Amino Acid Substitution"Mol.Psychiatry. 9(1). 55-64 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwata N, et al.: "No Association With the Neuregulin 1 Haplotype to Japanese Schizophrenia"Mol.Psychiatry. 9(2). 126-127 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozaki N, et al.: "Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype"Mol.Psychiatry. 8(11). 933-936 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada M, et al.: "Pepstatin A induces extracellular acidification distinct from aspartic protease inhibition in microglial cell line."Glia. 43(2). 167-174 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Noda M, et al.: "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J.Neurochem.. 84(2). 222-232 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki T, et al.: "Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia"Am.J.Med.Genet.. 131B(1). 7-13 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ujike H, Harano M, et al.: "How does prolonged caloric restriction ameliorate age-related impairment of long-term potentiation in the hippocampus?"Pharmacogenomics J. 3(4). 242-247 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamanouchi Y, et al.: "Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone."Pharmacogenomics J. 3(6). 356-361 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwase T, Ozaki N, et la.: "Mutation screening of the human Clock gene in circadian rhythm sleep disorders."Psychiatry Res. 109(2). 121-128 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirano S, Ozaki N, et al.: "Evaluating the state dependency of the Temperament and Character Inventory dimensions in patients with major depression"J Affect Disord. 69(1-3). 31-38 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwata N, N.Ozaki, T.Inada, Goldman D: "Association of a 5-HT5A receptor polymorphism, Pro15Ser, to schizophrenia."Molecular Psychiatry. 6(2). 217-219 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ebisawa T, Uchiyama M, et al.: "Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome."EMBO Rep. 2(4). 342-346 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozaki N(分担執筆): "Psychophamacogenetics, in ENCYCLOPEDIA OF THE HUMAN GENOME, vol 4"Macmillan Publishers Ltd, Nature Publishing Group. 917-922 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozaki N(分担執筆): "Recent Advances in the Research of Mood Disorder in Japan"Elsevier. 85-91 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada M, Northup J, Ozaki N, Russell J, Linnoila M, Goldman D: "Modification of Human 5-HT2C Receptor Function by Cys23Ser, an Abundant, Naturally Occurring Amino Acid Substitution."Mol Psychiatry. 9(1). 55-64 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] wata N, Suzuki T, Ikeda M, Kitajima T, Yamanouchi Y, Inada T, Ozaki N: "No Association With the Neuregulin 1 Haplotype to Japanese Schizoohrenia."Mol. Psychiatry. 9(2). 126-127 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J, Rudnick G, Murphy DL: "Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype."Mol Psychiatry. 8(11). 933-936 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada M, Irie S, Sawada M, Urae R, Urae A, Iwata N, Ozaki N, Akazawa K, Nakanishi H: "Pepstatin A induces extracellular acidification distinct from aspartic protease inhibition in microglial cell lines."Glia. 43(2). 167-174 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Noda M, Yasuda S, Okada M, Higashida H, Shimada A, Iwata N, Ozaki N, Nishikawa K, Shirasawa S, Uchida M, Aoki S, Wada K: "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways."J Neurochem. 84(2). 222-232 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki T, Iwata N, Kitamura Y, Kitajima T, Yamanouchi Y, Ikeda M, Kamatani N, Ozaki N: "Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia."Am J Med Genet. 121B(1). 7-13 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ujike H, Harano M, Inada T, Yamada M, Komiyama T, Sekine Y, Sora I, Iyo M, Katsu T, Nomura A, Nakata K, Ozaki N: "Nine-or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis."Pharmacogenomics J. 3(4). 242-247 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamanouchi Y, Iwata N, Suzuki T, Kitajima I, Ikeda M, Ozaki N: "Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone."Pharmacogenomics J. 3(6). 356-361 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwase T, Kajimura N, Uchiyama M, Ebisawa T, Yoshimura K, Kamei Y, Shibui K, Kim K, Kudo Y, Katoh M, Watanabe T, Nakajima T, Ozeki Y, Sugishita M, Hori T, Ikeda M, Toyoshima R, Inoue Y, Yamada N, Mishima K, Nomura M, Ozaki N, Okawa M, Takahashi K, Yamauchi T: "Mutation screening of the human Clock gene in circadian rhythm sleep disorders."Psychiatry Res. 109(2). 121-128 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirano S, Sato T, Narita T, Kusunoki K, Ozaki N, Kimura S, Takahashi T, Sakado K, Uehara T: "Evaluating the state dependency of the Temperament and Character Inventory dimensions in patients with major depression: a methodological contribution."J Affect Disord. 69(1-3). 31-38 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwata N, Ozaki N, Inada I, Goldman D: "Association of a 5-HT5A receptor polymorphism, Pro15Ser, to schizophrenia."Molecular Psychiatry. 6(2). 217-219 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ebisawa T, Uchiyama M, Kajimura N, Mishima K, Kamei Y, Katoh M, Watanabe T, Sekimoto M, Shibui K, Kim K, Kudo Y, Ozeki Y, Sugishita M, Toyoshima R, Inoue Y, Yamada N, Nagase T, Ozaki N, Ohara O, Ishida N, Okawa M, Takahashi K, Yamauchi I: "Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome."EMBO Rep. 2(4). 342-346 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ujike H, et al.: "Nine- or less repeat allele of VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis"Pharmacogenomics J. 3(4). 242-247 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamanouchi Y, et al.: "Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone."Pharmacogenomics J. 3(6). 356-361 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ozaki N, et al.: "Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype"Mol.Psychiatry. 8(11). 933-936 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okada M, et al.: "Modification of Human 5-HT2C Receptor Function by Cys23Ser, an Abundant, Naturally Occurring Amino Acid Substitution"Mol.Psychiatry. 9(1). 55-64 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noda M, et al.: "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J Neurochem. 84(2). 222-232 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki T, et al.: "Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia"Am J Med Genet. 121B(1). 7-13 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwata N, et al.: "No Association With the Neuregulin 1 Haplotype to Japanese Schizophrenia"Mol.Psychiatry. 9(2). 126-127 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Noda M, Ozaki N, et al.: "Recombinant human serotonin 5A receptors Stably expressed in C6 glioma cells couple to multiple signal transduction pathways"Journal of Neurochemistry. 84. 222-232 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwase T, Ozaki N, et al.: "Mutation screening of the human Clock gene in circadian rhythm sleep disorders"Psychiatry Res. 109(2). 121-128 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirano S, Ozaki N, et al.: "Evaluating the state dependency of the Temperament and Character Inventory dimensions in patients with major depression"J Affect Disord. 69(1-3). 31-38 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki, T, Ozaki, N et al.: "Association of Novel Genetic Variants in the Serotonin 5-HT4 Receptor Gene (HTR4) with Japanese Schizophrenia"Am J Med Genet. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Okada, M, Ozaki, N et al.: "Pepstatin A Induces Microglial Extracellular Acidification Distinct from Aspartic Protease Inhibition"GLIA. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamanouchi, Y, Ozaki, N et al.: "Effects of DRD2, 5-HT2A, and COMT Genes on Risperidone Treatment Response"The Pharmacogenomics Journal. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ozaki, N(分担執筆): "Recent Advances in the Research of Mood Disorder in Japan"Elsevier. 212 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwata N, N.Ozaki, T.Inada, Goldman D: "Association of a 5-HT5A receptor polymorphism, Pro15Ser, to schizophrenia"Molecular Psychiatry. 6(2). 217-219 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ebisawa T, Uchiyama M, et al.: "Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome"EMBO Rep. 2(4). 342-346 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imamura K, Sawada M, et al.: "Activation mechanism of brain microglia in patients with diffuse neurofibrillary tangles with calcification : a comparison with Alzheimer disease"Alzheimer Dis Assoc Disord. 15(1). 45-50 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hatsuda S, Sugita S, et al.: "Inhibition of K(+)-evoked release of rat striatal 5-hydroxytryptamine by an atypical antidepressant : trazodone"Neuropsychobiology. 44(2). 103-107 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 尾崎紀夫: "精神疾患の分子遺伝学的研究:ヒトゲノム計画完遂を目前にひかえて"精神神経学雑誌. 103. 532-537 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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