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

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Abstract

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.

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Data Availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the professional help provided by the psychiatrists in the study. We are very grateful to all the participants who volunteered to participate in this study.

Funding

This work was supported by the National Natural Science Foundation of China [81673253] and the Jilin Provincial Ministry of Education S & T Project [JJKH20190091KJ].

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun, 130021, China

    Mengdi Jin, Xiaojing Zhu, Yaoyao Sun, Zhijun Li, Xinwei Li, Lizhe Ai, Yang He, Yane Liu, Ningning Jia, Guoyan Hu, Xingyao Cui, Mengtong Xie, Yuqing Yang & Qiong Yu

  2. Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Xiaojing Zhu

Authors
  1. Mengdi Jin
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  2. Xiaojing Zhu
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  14. Qiong Yu
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Contributions

QY and MDJ conceived and designed the study. XJZ and YYS did the material preparation. Data analysis and experiment were performed by MDJ and ZJL. MDJ and XWL wrote the first draft of the manuscript. NNJ and YEL collected the data. LZA, GYH, XYC, MTX, and YQY revised the graphs. All authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Qiong Yu.

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Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Ethics Committee of the School of Public Health of Jilin University.

Consent to Participate

Informed consent was obtained from all individual participants or their guardians included in the study.

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Not applicable.

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The authors declare no competing interests.

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Jin, M., Zhu, X., Sun, Y. et al. Identification of Peripheral Blood miRNA Biomarkers in First-Episode Drug-Free Schizophrenia Patients Using Bioinformatics Strategy. Mol Neurobiol 59, 4730–4746 (2022). https://doi.org/10.1007/s12035-022-02878-4

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