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New therapeutic strategy for major depression based on anti-inflammatory action of antidepressants and application to personalized medicine

Research Project

Project/Area Number 25460650
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionNagasaki University

Principal Investigator

TSUKAMOTO Kazuhiro  長崎大学, 医歯薬学総合研究科(薬学系), 教授 (30253305)

Co-Investigator(Renkei-kenkyūsha) KUROTAKI Naohiro  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (20423634)
Research Collaborator NISHIWAKI Kenzaburo  
KOJIMA Ryoko  
KUROKAWA Takuya  
ARAKI Chizuru  
ARATA Yuki  
SHIMOMIYAZONO Aya  
KEYA Koji  
OBATA Kyosuke  
KAWAFUCHI Yuka  
IJICHI Shunsuke  
TANIGUCHI Shunsuke  
NISHIZONO Miki  
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsうつ病 / 抗うつ薬 / 薬剤応答性遺伝子 / うつ病の病因論 / 相関解析 / 遺伝子診断 / ゲノム創薬 / 抗酸化酵素の発現調整系 / 炎症性サイトカインの産生調整系 / プロ炎症性サイトカイン / 活性酸素種 / 治療感受性遺伝子 / 炎症性サイトカイン
Outline of Final Research Achievements

Neuroinflammation and neuroplasticity contribute to the pathogenesis of major depression (MD) as well as response to antidepressant(s). In this study, in order to identify responsibility genes to antidepressant, we examined an association between polymorphisms of 161 single nucleotide polymorphisms in the 34 candidate genes and the therapeutic effect of antidepressant (SSRI or SNRI) at the period of 8-week treatment using 105 Japanese MD patients. We identified 9 SSRI-resistant responsibility genes and 2 SNRI-resistant responsibility genes.
Genetic test revealed that the best combination of polymorphisms of FRS3 and RET is useful as a biomarker for identifying non-responders to SSRI after 8-weeks treatment. Moreover, since the dual-luciferase assay showed the difference in transcriptional activity between C allele and G allele of rs1061624 in TNFRSF1B in Jurkat cells, this receptor may become a target molecule for a novel drug against SSRI-resistant MD patients.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (4 results)

All 2015 2014 2013

All Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Genetic polymorphisms in the neuroplasticity-related genes contribute to the therapeutic effect of antidepressants for major depression.2015

    • Author(s)
      Kawafuchi Y, Kurokawa T, Arata Y, Keya K, Araki T, Ijichi S, Inamine T, Kondo S, Kurataki N, Nishiwaki K, Tsukamoto K
    • Organizer
      65th American Society of Human Genetics Annual Meeting 2015
    • Place of Presentation
      Baltimore, USA
    • Year and Date
      2015-10-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] うつ病患者における抗うつ薬感受性および統合失調症併発を予測するバイオマーカーの同定2015

    • Author(s)
      毛屋幸司,荒田有貴,黒川拓也,伊地知俊介,稲嶺達夫,近藤新二,西脇健三郎,塚元和弘
    • Organizer
      第2回先導的薬剤師の未来像を考えるシンポジウム
    • Place of Presentation
      長崎(長崎大学薬学部)
    • Year and Date
      2015-02-14
    • Related Report
      2014 Research-status Report
  • [Presentation] FRS3の遺伝子多型はうつ病患者におけるSSRI/SNRIの治療効果に関与する2014

    • Author(s)
      荒田有貴,黒川拓也,毛屋幸司,稲嶺達夫,近藤新二,西脇健三郎,塚元和弘
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市( 熊本大学工学部2号館)
    • Related Report
      2013 Research-status Report
  • [Presentation] うつ病と統合失調症の合併を予測するバイオマーカーの同定2013

    • Author(s)
      荒田有貴,黒川拓也,毛屋幸司,稲嶺達夫,近藤新二,西脇健三郎,塚元和弘
    • Organizer
      第30回日本薬学会九州支部大会
    • Place of Presentation
      長崎県佐世保市( 長崎国際大学薬学部)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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