Dong Yeqing, Wang Shuo, Li Meijuan, Su Qiao, Bi Fuyou, Sun Xiaoxiao, Qiu Yuying, Li Jie
Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, 300222, China.
BMC Psychiatry. 2025 Aug 6;25(1):764. doi: 10.1186/s12888-025-07205-4.
Schizophrenia (SZ) is a debilitating mental illness with uncertain etiology and challenges in early diagnosis and treatment outcomes. For the first time, we applied a multiomics techniques to explore plasma exosomal markers of SZ and underlying molecular mechanisms.
Exosomes were separated and identified from ten drug-naive first-episode SZ patients and ten healthy controls. Then small RNA-seq and high-performance liquid chromatography-tandem mass spectrometry technology were used to detect the profiles of microRNAs (miRNAs) and proteomics, respectively. The integrative multiomics analysis was further performed.
A total of 167 differentially expressed miRNAs (DE miRNAs) were identified in plasma exosomes from drug-naive first-episode SZ patients. The potential target genes of DE miRNAs were predicted, and GO and KEGG enrichment analysis showed that they were associated with RNA catabolic process, proteasome-mediated ubiquitin-dependent protein catabolic process, etc. Proteomic analysis identified 274 differentially expressed proteins (DEPs), and DEPs were mainly enriched in immune response and some signaling pathways. The combination of Top 10 DE miRNAs/ DEPs both had good values to diagnose SZ. Importantly, miRNA-protein ceRNA networks were constructed by integrating multiomics, one consisting of 21 downregulated DE miRNAs and 21 upregulated DEPs and the other consisting of 64 upregulated DE miRNAs and 86 downregulated DEPs in SZ patients.
In conclusion, our study delineates the multiomics landscape of plasma exosomes in first-episode drug-naïve SZ, and constructed two ceRNA networks (21 downregulated miRNAs/21 upregulated proteins and 64 upregulated miRNAs/86 downregulated proteins), providing novel insights into the early diagnosis and treatment strategies of SZ. These findings hold promise for advancing diagnostic and therapeutic strategies in SZ management.
The online version contains supplementary material available at 10.1186/s12888-025-07205-4.
精神分裂症（SZ）是一种使人衰弱的精神疾病，其病因不明，早期诊断和治疗效果面临挑战。我们首次应用多组学技术来探索精神分裂症的血浆外泌体标志物及其潜在分子机制。
从十名未用药的首发精神分裂症患者和十名健康对照中分离并鉴定外泌体。然后分别使用小RNA测序和高效液相色谱-串联质谱技术检测微小RNA（miRNA）和蛋白质组学谱。进一步进行综合多组学分析。
在未用药的首发精神分裂症患者的血浆外泌体中鉴定出总共167个差异表达的miRNA（DE miRNA）。预测了DE miRNA的潜在靶基因，基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析表明它们与RNA分解代谢过程、蛋白酶体介导的泛素依赖性蛋白质分解代谢过程等相关。蛋白质组学分析鉴定出274个差异表达的蛋白质（DEP），DEP主要富集于免疫反应和一些信号通路。排名前十的DE miRNA/DEP组合对精神分裂症的诊断均具有良好价值。重要的是，通过整合多组学构建了miRNA-蛋白质ceRNA网络，一个由21个下调的DE miRNA和21个上调的DEP组成，另一个由64个上调的DE miRNA和86个下调的DEP组成。
总之，我们的研究描绘了未用药的首发精神分裂症患者血浆外泌体的多组学图谱，并构建了两个ceRNA网络（21个下调的miRNA/21个上调的蛋白质和64个上调的miRNA/86个下调的蛋白质），为精神分裂症的早期诊断和治疗策略提供了新见解。这些发现有望推进精神分裂症管理中的诊断和治疗策略。
在线版本包含可在10.1186/s12888-025-07205-4获取的补充材料。
