Plasma miRNAs as potential biomarkers for schizophrenia in a Jordanian cohort.

Background: Schizophrenia (SZ), a complex and chronic neuropsychiatric disorder affecting approximately 1 % of the general population, presents diagnostic challenges due to the absence of reliable biomarkers, and relying mainly on clinical observations. MicroRNAs (miRNAs) signatures in a wide range of diseases, including psychiatric disorders, hold immense potential for serving as biomarkers. This study aimed to analyze the expression levels of specific microRNAs (miRNAs) namely miR-29b-3p, miR-106b-5p, and miR-199a-3p and explore their diagnostic potential for SZ in Jordanian patients.

Methods: Small RNAs (miRNAs) were extracted from plasma samples of 30 SZ patients and 35 healthy controls. RNA was reverse transcribed and quantified by real-time polymerase chain reaction (qRT-PCR). The expression levels of three miRNAs (miR-29b-3p, miR-106b-5p and miR-199a-3p) were analyzed. Receiver operating characteristic (ROC) curves analysis was performed to evaluate diagnostic value of these miRNAs. Target genes prediction, functional enrichment and pathway analyses were done using miRWalk and Metascape. STRING database was used to construct protein-protein network and identify hub genes.

Results: Notably, miR-106b-5p and miR-199a-3p were significantly upregulated (p < 0.0001), while miRNA-29b-3p was downregulated (p < 0.0001) in SZ patients compared to controls. The diagnostic potential was assessed through ROC curves, revealing substantial diagnostic value for miR-199a-3p (AUC: 0.979) followed by miR-106b-5p (AUC: 0.774), with limited diagnostic efficacy for miR-29b-3p. Additionally, bioinformatic analyses for the predicted target genes of the diagnostically significant miRNAs uncovered Gene Ontology (GO) terms related to neurological development, including morphogenesis, which is involved in neuron differentiation, brain development, head development, and neuron projection morphogenesis. These findings highlight a potential connection between the identified miRNAs and SZ pathophysiology in the studied Jordanian population. Furthermore, a protein-protein interaction network from the target genes identified in association with neurological development in the Gene Ontology (GO) terms deepens our comprehension of the molecular landscape of the regulated target genes.

Conclusions: This comprehensive exploration highlights the promising role of miRNAs in unraveling intricate molecular pathways associated with SZ in the Jordanian cohort and suggests that plasma miRNAs could serve as reliable biomarkers for SZ diagnosis and disease progression. Remarkably, this study represents the first investigation into the role of circulating miRNA expression among Jordanian patients with SZ, providing valuable insights into the diagnostic landscape of this disorder.