| Project/Area Number |
18K15514
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Suwa Taro 京都大学, 医学研究科, 助教 (10518153)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | NMR信号 / 治療抵抗性統合失調症 / クロザピン / NMR / clozapine / TRS / 核磁気共鳴計測 |
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| Outline of Final Research Achievements |
The aim of this study is to develop a highly accurate index to evaluate the risk of adverse drug reactions from serum samples before clozapine introduction, using a new method of NMR signal analysis that captures the structure of the entire serum, instead of focusing on individual substances or genes. Using NMR signal patterns obtained from the serum of 24 patients with treatment-resistant schizophrenia prior to clozapine induction, we were able to identify the occurrence of fever and elevated liver enzymes within one year after clozapine induction using partial least squares discriminant analysis (PLS-DA) plots. We plan to further validate the validity and usefulness of the NMR signal discrimination algorithm obtained in this study.
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| Academic Significance and Societal Importance of the Research Achievements |
いわゆる治療抵抗性統合失調症に対し、抗精神病薬クロザピンの有効性は広く知られている。しかしクロザピンの投与初期には顆粒球減少、流涎、発熱などの副作用が出現しやすく、副作用によるクロザピン治療の中断リスクの高さは臨床上の極めて大きな障害となっている。事前にこの出現リスクを評価することができればクロザピン初回導入時や中止後の再投与の安全性は大幅に向上し、治療抵抗性統合失調症患者にとっての大きな利益に繋がる。
当研究により、clozapine投与前に採取した血清のNMR信号の解析を通して、症例ごとのclozapine投与後の発熱および肝障害出現リスクの評価が行える可能性が示された。
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