Revisiting the treatment of treatment-resistant schizophrenia by N -methyl- D -aspartate agonists

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16640
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Chiba University
• Principal Investigator: Kimura Hiroshi 千葉大学, 大学院医学研究院, 特任講師 (10646409)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 統合失調症 / 抗精神病薬 / ドパミン過感受性 / 認知機能

Outline of Final Research Achievements

It is well known that cognitive dysfunction occurs due to decreased N-methyl-D-aspartate (NMDA) receptor functions. We previously reported that NMDA receptor function is decreased in a non-dopamine supersensitivity state (DSS) rat model that does not exhibit DSS despite chronic treatment with antipsychotic drugs. In addition, the present study revealed that DSS rats exhibit neurological deficits in the striatum and hippocampal CA3 and dentate gyrus regions, while non-DSS rats show deficits only in the dentate gyrus, suggesting that differences in the location of deficits are associated with cognitive dysfunction. Further studies are needed.

Free Research Field

統合失調症

Academic Significance and Societal Importance of the Research Achievements

これまでの治療抵抗性統合失調症研究は、抗精神病薬に対する耐性だけを基準に診断しており、実際は様々な遺伝的素因を持つグループが混在していた。今回の我々は抗精神病薬に対する反応性の違いから、治療抵抗性をドパミン過感受性グループと非ドパミン過感受性グループに分けて研究することで、よその後の評価につなげることが出来た。そのため、今後の統合失調症研究を行う上で、新しいグループ分けを提案できたと考えられ、今後より精緻な研究を進めていく足掛かりになると思われる。