Increased RHOA expression in peripheral blood mononuclear cells of patients with acute schizophrenia.

BACKGROUND: RhoA-a member of the Rho family of GTPases-critically regulates synaptic plasticity and immune cell function, which have emerged as key mechanisms in schizophrenia pathogenesis. METHODS: In this study, we measured RHOA mRNA expression levels in the peripheral blood mononuclear cells (PBMCs) from patients with acute schizophrenia and healthy controls. We also conducted integrative bioinformatics analyses to investigate transcription factors (TFs) and genetic variants in miRNAs predicted to regulate RHOA mRNA expression in schizophrenia. RESULTS: Quantitative real-time PCR (qPCR) revealed a significant upregulation of RHOA mRNA expression in the PBMCs from patients with acute schizophrenia compared with controls. Although sex-stratified analysis showed a significant association in males, the group × sex interaction was not significant. Moreover, multivariable robust regression adjusted for sex, educational level, age, BMI, and smoking confirmed a significant group effect, reflecting higher RHOA mRNA expression in patients than in controls. Integrative bioinformatics analyses identified five candidate miRNAs (hsa-miR-183-3p, hsa-miR-574-5p, hsa-miR-4429, hsa-miR-4686, and hsa-miR-5002-5p) that were differentially expressed in schizophrenia and predicted to target RHOA. Subsequent analysis revealed six variants within these candidate miRNAs with the highest predicted ΔG values and potential to affect mature miRNA expression. Moreover, 10 hub TFs (EP300, HDAC1, TP53, CREBBP, HDAC2, ESR1, MYC, JUN, SP1, and BRCA1) were predicted to regulate RHOA mRNA expression. CONCLUSION: These findings suggest that RHOA upregulation in PBMCs may be associated with the pathophysiology of schizophrenia. Further investigations are needed to validate these results and elucidate the mechanistic role of RHOA dysregulation in the disorder.