Identification of Peripheral Blood miRNA Biomarkers in First-Episode Drug-Free Schizophrenia Patients Using Bioinformatics Strategy.

Schizophrenia (SCZ) is a polygenic, complex mental disorder of which a diagnosis is often made based on psychiatric history and clinical observation with few available objectives and detectable biomarkers. To identify co-expressed miRNA modules in schizophrenia patients and verify the possibility of using peripheral blood miRNAs as novel biomarkers, high-throughput sequencing was performed on 15 first-episode schizophrenia patients (FES) and 15 healthy controls (CTL). We found 79 differential expressed miRNAs (DEMs) in FES patients and three FES-related co-expression miRNA modules by miRNA-seq data standardized difference analysis and weighted gene co-expression network analysis (WGCNA). Then, 41 hub miRNAs were screened from the intersection of key modules and DEMs, among which miR-9-5p, miR-144-3p, miR-328-3p, and miR-4467 were selected for qRT-PCR verification in a larger sample (FES = 35, CTL = 60). The level of miR-9-5p in FES patients was downregulated, and miR-4467 was upregulated with better diagnostic performance (AUC = 0.719). The target genes of miR-9-5p engage in the biological processes (BP) such as body behaviour, neuronal differentiation regulation, nervous system development, and neurotrophin signaling pathways. Their hub target genes were also located, including NEDD4, EIF4G1, FBXL16, and FBXL3. Summarily, miR-9-5p and miR-4467 hold promise in blood diagnosis for SCZ, and miR-9-5p might affect the onset and development of SCZ through target regulation of neurodevelopment-related mRNAs. Our findings revealed the complex relationship between the miRNA co-expression network and FES, providing more verifiable biomarkers for SCZ early diagnosis and clues for the etiology of schizophrenia.