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<p>MicroRNAs (miRNAs) are critical regulators of neurodevelopment and are implicated in the pathogenesis of schizophrenia. Schizophrenia is increasingly recognized as a neurodevelopmental disorder, with most cases emerging during late adolescence and early adulthood, which is a critical period of brain maturation. However, the study of miRNAs during this phase has been limited by the challenges of postmortem brain analysis. Neuron-derived extracellular vesicles (NEVs) have recently been proposed for investigating brain-derived molecular profiles. In this study, NEVs were enriched from plasma using the L1CAM antibody in patients with recent-onset schizophrenia (ROS) within 5 years of onsets and chronic-phase schizophrenia (CS). The miRNA profiles of these NEVs in patients with ROS and CS were compared with those of age-and sex-matched healthy controls. Differential expression analysis revealed miRNA changes specific to the recent-onset phase as well as possible pathophysiological mechanisms transitioning from the recent-onset to the chronic phases. These findings provide novel insights into the role of miRNAs in neurodevelopmental abnormalities associated with schizophrenia onset. This study highlights the utility of NEVs as a tool for accessing brain-derived miRNA profiles and diagnostic biomarkers and underscores the importance of an onset period as a critical window for understanding the molecular underpinnings of schizophrenia.</p>

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Distinct microRNA profiles in neuron-derived extracellular vesicles between recent-onset and chronic-phase schizophrenia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月28日

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  • Yasufumi Tomita,
  • Kazuya Toriumi,
  • Mitsuhiro Miyashita,
  • Kazuhiro Suzuki,
  • Hideya Kawaji,
  • Masanari Itokawa,
  • Makoto Arai

摘要

MicroRNAs (miRNAs) are critical regulators of neurodevelopment and are implicated in the pathogenesis of schizophrenia. Schizophrenia is increasingly recognized as a neurodevelopmental disorder, with most cases emerging during late adolescence and early adulthood, which is a critical period of brain maturation. However, the study of miRNAs during this phase has been limited by the challenges of postmortem brain analysis. Neuron-derived extracellular vesicles (NEVs) have recently been proposed for investigating brain-derived molecular profiles. In this study, NEVs were enriched from plasma using the L1CAM antibody in patients with recent-onset schizophrenia (ROS) within 5 years of onsets and chronic-phase schizophrenia (CS). The miRNA profiles of these NEVs in patients with ROS and CS were compared with those of age-and sex-matched healthy controls. Differential expression analysis revealed miRNA changes specific to the recent-onset phase as well as possible pathophysiological mechanisms transitioning from the recent-onset to the chronic phases. These findings provide novel insights into the role of miRNAs in neurodevelopmental abnormalities associated with schizophrenia onset. This study highlights the utility of NEVs as a tool for accessing brain-derived miRNA profiles and diagnostic biomarkers and underscores the importance of an onset period as a critical window for understanding the molecular underpinnings of schizophrenia.