Distinct microRNA Profiles in Neuron-Derived Extracellular Vesicles Between Recent-Onset and Chronic-Phase Schizophrenia

Sep 28, 2026

Uploaded by Ophelia

MicroRNAs (miRNAs) regulate neurodevelopment and are implicated in schizophrenia pathogenesis, yet miRNA dynamics during late adolescence and early adulthood remain underexplored due to limitations of postmortem brain studies. This work enriches neuron-derived extracellular vesicles (NEVs) from patient plasma using L1CAM immunoprecipitation, comparing recent-onset schizophrenia (within 5 years) and chronic-phase schizophrenia against age- and sex-matched controls. Differential expression identifies miRNA changes specific to the recent-onset phase and suggests mechanisms underlying transition to chronic stages, supporting NEVs as a source for brain-derived miRNA profiles and diagnostic biomarker discovery.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

MicroRNAs and schizophrenia onset timing

Neuron-derived extracellular vesicles as a peripheral tool

Results

Participant demographics and clinical characteristics

ARTICLE OPEN Distinct microRNA proﬁles in neuron-derived extracellular vesicles between recent-onset and chronic-phase schizophrenia Yasufumi Tomita 1,2, Kazuya Toriumi 1 ✉, Mitsuhiro Miyashita 1,3, Kazuhiro Suzuki 1,4,5, Hideya Kawaji 6, Masanari Itokawa1,2 and Makoto Arai 1 | | 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 inneurodevelopmental 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. | | | | | Schizophrenia (2025)11:158; [https://doi.org/10.1038/s41537-025-00706-x](https://doi.org/10.1038/s41537-025-00706-x) | | | | | | INTRODUCTION MicroRNAs (miRNAs) are small non-coding RNAs, composed of 20–24 nucleotides that regulate gene expression by binding tomRNAs with complementary sequences, leading to their degradation or inhibition of protein translation1. They play crucial roles in various biological processes, including neurogenesis and synaptic connectivity, making them essential for brain development from the fetal stage to adolescence2,3. Several studies have reported an association between miRNAsand schizophrenia4–7. The signs and symptoms of schizophrenia typically emerge during late adolescence and early adulthood, with approximately 60–70% of patients experiencing their ﬁrst occurrence between the ages of 14 and 25 years and additional cases, particularly in early adulthood, extending into the late twenties8. While many patients develop the disorder during late adolescence, a substantial subset, particularly women, experience onset in early adulthood or even after the age of 309. Late adolescence and early adulthood are critical periods for brain maturation10–13, and schizophrenia is increasingly understood as aneurodevelopmental disorder 14–16. Therefore, understanding brain processes during this developmental time window and onset period is essential for elucidating the pathogenesis related to the onset of schizophrenia16, 17. Despite this, few studies have focused on miRNA dynamics during this pivotal period in the context of schizophrenia18. Recently, neuron-derived extracellular vesicles (NEVs) have attracted signiﬁcant attention as a novel tool for investigating brain physiology and pathology through peripheral samples 19–22. Extracellular vesicles (EVs) are small phospholipid bilayer-enclosed vesicles that are abundant in body ﬂuids such as blood and urine23,24. They originate from various cell types and carry proteins, nucleic acids, and metabolites, reﬂecting the molecular environment of their tissues of origin25–27. Moreover, EVs possess t

FAQs

Why are microRNAs important for studying schizophrenia?

MicroRNAs regulate gene expression and are involved in neurodevelopmental processes. Changes in miRNA profiles have been associated with schizophrenia, particularly around key developmental windows.

How were neuron-derived extracellular vesicles (NEVs) obtained in this study?

NEVs were enriched from plasma using immunoprecipitation with the neuron-specific marker L1CAM. The resulting vesicles were used to analyze miRNA profiles.

What differences in miRNA profiles were observed between recent-onset and chronic-phase schizophrenia?

Differential expression analysis revealed miRNA changes specific to the recent-onset phase and suggested possible pathophysiological mechanisms that may transition from recent onset to chronic stages.

Sep 28, 2026

Uploaded by Ophelia