2021 Fiscal Year Final Research Report
Excitatory Inhibitory Imbalance in Treatment-resistant Schizophrenia: TMS-EEG+MRS study
| Project/Area Number |
18H02755
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
三村 將 慶應義塾大学, 医学部(信濃町), 教授 (00190728)
野田 賀大 慶應義塾大学, 医学部(信濃町), 特任准教授 (20807226)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | 治療抵抗性統合失調症 / グルタミン酸 / GABA / TMS-EEG / MRS |
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| Outline of Final Research Achievements |
In schizophrenia, basal ganglia glutamate concentrations are elevated, glutamate and GABA concentrations in the middle cingulate gyrus are decreased, basal ganglia glutamate concentrations may decrease with disease progression and antipsychotic treatment, and middle cingulate gyrus GABA concentrations may increase with the onset of We found that the mid-cingulate gyrus GABA concentrations may increase with the onset of illness. Next, we reported increased glutamate concentrations in the middle cingulate gyrus in treatment-resistant schizophrenia. However, while significant differences were found between treatment-resistant schizophrenia and healthy subjects, no statistically significant differences were found between treatment-resistant schizophrenia and schizophrenia in remission, a finding that suggests heterogeneity of the condition within each group. The findings regarding elevated GABA concentrations in treatment-resistant schizophrenia are under review.
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| Free Research Field |
MRI・PET撮像・解析、TMS
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| Academic Significance and Societal Importance of the Research Achievements |
約3割の統合失調症患者に対して抗精神病薬は無効であり、その病態は従来のドパミン仮説では説明できない。新たな治療法の開発のために、興奮・抑制バランス異常仮説は治療抵抗例の病態を説明する仮説として注目を集めている。本研究でも治療抵抗例の脳内グルタミン酸神経系とGABA神経系の異常を明らかにした。この結果から、統合失調症の病態の異質性を、ドーパミン仮説と興奮・抑制不均衡仮説に基づいたディープ・フェノタイピングと多変量解析を用いたバイオタイピング、そのバイオタイプに対するバイオマーカーを用いたクローズド・ループ・ニューロモジュレーションの開発することが期待される。
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