2023 Fiscal Year Final Research Report
Analysis of the oxytocin and GABA pathway in refractory schizophrenia
| Project/Area Number |
21K07476
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Chiba University |
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Principal Investigator |
Kanahara Nobuhisa 千葉大学, 社会精神保健教育研究センター, 講師 (70507350)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 文晃 東北大学, 医学系研究科, 大学院非常勤講師 (10535157)
仲田 祐介 千葉大学, 医学部附属病院, 助教 (40836962)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ドパミントランスポーター / GABA / クロザピン / ドパミン過感受性 |
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| Outline of Final Research Achievements |
We performed a genetic association analysis of dopamine-related genes of patients with treatment-resistant schizophrenia (TRS). The results showed that the distribution of rs3456450 on SLC6A3 gene differed between the TRS and non-TRS/healthy control groups. An additional analysis combining rs3456450 and a functional SNP of COMT (rs4680) suggested a higher percentage of the TRS patients with the genotype combination of “low-dopamine state” compared to the non-TRS patients. In addition, we conducted a systematic review and meta-analysis of the effects of disease stage and antipsychotic medication on cortical silent period (CSP). The results showed that only clozapine significantly prolonged the CSP whereas other medications and disease stage did not seem to affect the CSP. Lastly, the multi-site retrospective study examining the efficacy of clozapine on TRS patients suggested that patients with the late-onset TRS could represent larger response to those with the early-onset TRS.
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| Free Research Field |
精神医学
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| Academic Significance and Societal Importance of the Research Achievements |
TRSに対するclozapineの反応性に関して、ドパミン系信号が関わる可能性、またclozapineがGABA信号を強化させることを示唆する。このことはclozapineの作用機序に関する理解を進めるものである。また臨床的にclozapineは後発型TRSにより効果が期待される可能性がある。後発型TRSの多くはドパミン過感受性との関連が推定されることから、ドパミン過感受性形成状態はclozapineによる反応性と関係することが示唆される。これらは臨床的にclozapineの適応や導入時期の判断に有用となる可能性があると考えられる。
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