The multiomics landscape of plasma exosomes in first-episode drug-naïve of schizophrenia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-025-07205-4.