New therapeutic strategy for major depression based on anti-inflammatory action of antidepressants and application to personalized medicine
| Project/Area Number |
25460650
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| 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)
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| 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
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(4 results)
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[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
Int'l Joint Research
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