Analysis of treatment-resistant schizophrenia focusing on dopamine supersensitivity psychosis and type of intolerance to antipsychotics

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Chiba University
• 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 統合失調症 / 治療抵抗性 / 抗精神病薬 / モノアミン / ジストニア / 遺伝子

Outline of Final Research Achievements

The present study explored the etiology of treatment-resistant schizophrenia (TRS), focusing particularly on dopamine supersensitivity psychosis (DSP) and tardive dystonia. (1) The longitudinal brain CT study for schizophrenia patients revealed that the progressive volume reduction could be related to the accumulated dosages of antipsychotics. (2) Under relapse episode due to rebound psychosis, the increase in turnover of monoamine (HVA) did not occur in patients with DSP, which differed from hyper-release of HVA in patients with first episode psychosis. (3) The exome sequencing for the three patients with severe tardive dystonia identified the novel rare variants on ZNF806 and SART3. But the subsequent association study for other 16 patients failed to confirm these genes’ involvement in dystonia. These findings suggest that patients with TRS are heterogeneous and further studies are needed to identify useful biological markers for each subtype in TRS.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

DSPを対象とした研究では、頭部画像や血液中マーカーでの検証を通じ、確たる知見まで得られてこなかった統合失調症の病態に、DSPの視点を加味することで、より明確な知見を与える可能性が示唆されることとなった。抗精神病薬治療の影響によるDSPは統合失調症患者の長期予後にも強い影響を及ぼす可能性を示すものである。遅発性ジストニア研究では原因遺伝子にまで到達は出来ていないが、本病態において遺伝的背景を有する可能性は依然としてあり、今後研究の継続が必要であると考えられる。