Elucidating pathophysiology of schizophrenia: an AMPA PET study

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03587
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Keio University
• Principal Investigator: UCHIDA Hiroyuki 慶應義塾大学, 医学部(信濃町), 准教授 (40327630)
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 統合失調症 / グルタミン酸 / AMPA受容体

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.

Free Research Field

精神医学

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。