Elucidating pathophysiology of schizophrenia: an AMPA PET study
| Project/Area Number |
19H03587
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Keio University |
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Principal Investigator |
UCHIDA Hiroyuki 慶應義塾大学, 医学部(信濃町), 准教授 (40327630)
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| Co-Investigator(Kenkyū-buntansha) |
中島 振一郎 慶應義塾大学, 医学部(信濃町), 講師 (60383866)
中原 理紀 慶應義塾大学, 医学部(信濃町), 准教授 (10317240)
内田 貴仁 慶應義塾大学, 医学部(信濃町), 助教 (10627061)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 統合失調症 / グルタミン酸 / AMPA受容体 / PET / グルタミン酸神経 |
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| Outline of Research at the Start |
統合失調症の原因解明は停滞しており、斬新な視点による研究が緊急課題である。グルタミン神経系のAMPA受容体は、動物研究により統合失調症の発病への関与が明らかになっているが、ヒトのデータはなかった。そこで本研究では、統合失調症患者の脳内のAMPA受容体密度を、陽電子放射断層撮影（PET)検査により測定し、AMPA受容体が統合失調症の発病にいかに関連しているか解明する。
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| Outline of Final Research Achievements |
The "dopamine hypothesis" that schizophrenia is caused by excessive dopamine release in the brain and is treated by reducing dopaminergic neural transmission has reached its limits, and a breakthrough from a completely new perspective was needed. AMPA receptors in the glutamatergic nervous system have been the focus of attention. In this study, AMPA receptors, which had been impossible to visualize in the living brain, were quantified in patients with schizophrenia for the first time in the world, and the pathophysiological basis of this disorder was clarified. The results of this study also provided important data for personalized treatment based on pathophysiology by stratifying these patients with various symptoms based on PET images. In other words, the results of this study are expected to lead to the development of novel diagnostic systems and new treatments for psychiatric disorders, including schizophrenia, based on biomarkers.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまで生体脳で可視化が不可能であったAMPA受容体を、統合失調症患者において世界で初めて定量し、本疾患の物質的基盤を明らかにした。また、本試験の結果は、多様な症状を呈する統合失調症患者をPET画像に基づいて層別化することにより、病態生理に基づいた個別化治療を行うための重要な基礎データを提供した。つまり本成果は、バイオマーカーに基づく統合失調症を含む精神疾患の新規診断体系や新規治療法開発につながることが期待される。
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Report
(4 results)
Research Products
(2 results)
