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Pharmacogenomic study for optimizing dosage of antipsychotic drugs based on individual genetic polymorphism

Research Project

Project/Area Number 21K07490
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionFujita Health University

Principal Investigator

Saito Takeo  藤田医科大学, 医学部, 講師 (30767611)

Co-Investigator(Kenkyū-buntansha) 池田 匡志  名古屋大学, 医学系研究科, 教授 (60424933)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords抗精神病薬 / ファーマコゲノミクス / 薬物血中濃度
Outline of Research at the Start

抗精神病薬の治療反応性には個人差が存在し、その差異には遺伝的因子が関与することは確からしい。もし、治療反応性に関連する遺伝的リスクが同定され、臨床に応用されれば薬物療法の質の向上が期待される。
そこで、本研究では薬物動態(PK)関連遺伝子に着目し、薬物代謝に関わる分子種の遺伝子多型を解析し、個々の抗精神病薬に対してどの分子種の遺伝子多型が血中濃度に影響するのかを統合的に検討、個人の抗精神病薬の投与量の適正化を目指す。

Outline of Final Research Achievements

The aim of this study was to examine the relationship between blood concentrations of antipsychotics and drug metabolizing enzyme genotypes, and to establish a basis for predicting individual optimal doses of antipsychotics. We measured the blood concentrations of clozapine and norclozapine in patients with schizophrenia and conducted association analyses between these concentrations and drug metabolizing enzyme genotypes and single nucleotide polymorphisms (SNPs). The results showed no significant associations between drug metabolizing enzyme genotypes or SNPs and clozapine blood concentrations, norclozapine blood concentrations, or the clozapine/norclozapine concentration ratio. However, it cannot be ruled out that this result may be due to low detection power caused by insufficient sample size. Therefore, further analyses with an expanded sample size are necessary.

Academic Significance and Societal Importance of the Research Achievements

本研究においてクロザピン血中濃度や代謝に有意に関連するPK関連遺伝子型、あるいはSNPは見出されなかった。しかし、この結果はサンプル数不足による検出力の低さに由来する可能性が否定できず、今後もサンプル数を拡大した解析が必要である。その結果、関連する遺伝子型が見出されれば、その遺伝子型の情報を用いることで、個人の至適用量を予測しうる可能性がある。このため、今後も本研究と同様の手法を用いた研究の継続が必要であると考える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 2021

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] GWAS-identified bipolar disorder risk allele in the FADS1/2 gene region links mood episodes and unsaturated fatty acid metabolism in mutant mice2023

    • Author(s)
      Yamamoto Hirona、Lee-Okada Hyeon-Cheol、Ikeda Masashi、Nakamura Takumi、Saito Takeo、Takata Atsushi、Yokomizo Takehiko、Iwata Nakao、Kato Tadafumi、Kasahara Takaoki
    • Journal Title

      Molecular Psychiatry

      Volume: 28 Issue: 7 Pages: 2848-2856

    • DOI

      10.1038/s41380-023-01988-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential genetic correlations across major psychiatric disorders between Eastern and Western countries2023

    • Author(s)
      Saito Takeo、Ikeda Masashi、Terao Chikashi、Ashizawa Takuma、Miyata Masami、Tanaka Satoshi、Kanazawa Tetsufumi、Kato Tadafumi、Kishi Taro、Iwata Nakao
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 77 Issue: 2 Pages: 118-119

    • DOI

      10.1111/pcn.13498

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacogenomic-guided clozapine administration based on HLA-DQB1, HLA-B and SLCO1B3-SLCO1B7 variants: an effectiveness and cost-effectiveness analysis2022

    • Author(s)
      Ninomiya Kohei、Saito Takeo、Ikeda Masashi、Iwata Nakao、Girardin Fran?ois R.
    • Journal Title

      Frontiers in Pharmacology

      Volume: 13

    • DOI

      10.3389/fphar.2022.1016669

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proportion of subjects with psychotic features in bipolar disorder correlated with treatment response by antipsychotics for acute mania2022

    • Author(s)
      Ikeda Masashi、Saito Takeo、Kanazawa Tetsufumi、Kishi Taro、Iwata Nakao
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 76 Issue: 11 Pages: 596-598

    • DOI

      10.1111/pcn.13460

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shared genetic components between metabolic syndrome and schizophrenia: Genetic correlation using multi‐population datasets2022

    • Author(s)
      Aoki Rei、Saito Takeo、Ninomiya Kohei、Shimasaki Ayu、Ashizawa Takuma、Ito Kenta、Ikeda Masashi、Iwata Nakao
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: - Issue: 8 Pages: 361-366

    • DOI

      10.1111/pcn.13372

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cost effectiveness of pharmacogenetic-guided clozapine administration based on risk of HLA variants in Japan and the UK2021

    • Author(s)
      Ninomiya Kohei、Saito Takeo、Okochi Tomo、Taniguchi Satoru、Shimasaki Ayu、Aoki Rei、Hata Takeo、Mushiroda Taisei、Kanazawa Tetsufumi、Ikeda Masashi、Iwata Nakao
    • Journal Title

      Translational Psychiatry

      Volume: 11 Issue: 1 Pages: 362-362

    • DOI

      10.1038/s41398-021-01487-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] クロザピン治療における薬理ゲノム学研究の応用と治療抵抗性統合失調症の遺伝子研究2023

    • Author(s)
      齋藤竹生
    • Organizer
      第119回日本精神神経学会学術総会,
    • Related Report
      2023 Annual Research Report
  • [Presentation] 向精神薬の薬理ゲノム学2023

    • Author(s)
      齋藤竹生
    • Organizer
      第33回日本臨床精神神経薬理学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 精神疾患のゲノム研究の現在と展望2023

    • Author(s)
      齋藤竹生
    • Organizer
      第45回日本生物学的精神医学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Differential genetic correlations across major psychiatric disorders between Eastern and Western countries2023

    • Author(s)
      齋藤竹生
    • Organizer
      Congress of Psychiatric Genetics 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 向精神薬の薬理ゲノム学2021

    • Author(s)
      齋藤竹生
    • Organizer
      第43回日本生物学的精神医学会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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