Development of biomarkers for predicting disease progression and treatment response for schizophrenia using large-scale patient resources and iPS technology.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18KT0022
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Hashimoto Ryota 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神疾患病態研究部, 部長 (10370983)
• Project Period (FY): 2018-07-18 – 2021-03-31
• Keywords: 精神疾患 / バイオリソース / iPS細胞 / バイオマーカー

Outline of Final Research Achievements

In iPS cell-derived differentiated neurons from patients with treatment-resistant schizophrenia and discordant responses to clozapine (10 patients in total, including monozygotic twins), the expression levels of genes encoding cell adhesion molecules, transcription factors and molecules regulating circadian rhythms are correlated with clozapine responsiveness in these patients. Importantly, we also found virtually the same results in the samples from blood cells of these patients. We also found that differences in synaptic functions, such as excitatory synaptic transmission, may be involved in the discordant responses to clozapine in these patients. Together with the results of the analysis of the clinical data of these patients, this study has provided basic data that will lead not only to the elucidation of the molecular pathogenesis of schizophrenia but also to the development of biomarkers for predicting disease progression and treatment response for schizophrenia.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

統合失調症患者からiPS細胞を樹立した報告は、現在までに数十報程度あり、患者由来神経細胞における分化・発達の異常やシナプス機能の異常等が明らかになっている。しかし、遺伝学的データや臨床データを保持する統合失調症患者について、本研究のようなiPS細胞のみならず血液サンプルも併せて用いる融合的な解析は、これまでに報告例は極めて少ない。本研究で得られた成果は、不明な点が多く残されている精神疾患の分子病態の解明に貢献するのみならず、治療反応性、病態予測等に役立つ客観的なバイオマーカーの開発のための基礎データを提供するものである。