The Effect of miR-1273d Between Chronic Childhood Stress and Positive Symptoms in Schizophrenia: A Preliminary Mediation Analysis

Purpose: High disability and recurrence rates have driven researchers to explore the etiology and pathological processes of schizophrenia (SCZ). This study aimed to investigate the relationship between chronic childhood stress and positive symptoms in SCZ patients from the perspective of microRNA (miRNA) expression levels in peripheral blood. Patients and Methods: 80 SCZ patients and 80 sex- and age-matched healthy individuals were enrolled and assessed using Positive and Negative Syndrome Scale (PANSS) and Childhood Chronic Stress Questionnaire (CCSQ). The miRNA expression level were detected by Quantitative Real-Time PCR (qRT-PCR). Results: The area under the curve of combined receiver operating characteristic (ROC) curve for aberrantly expressed miRNAs was 0.958, with sensitivity and specificity of 0.838 and 0.963, respectively ( P < 0.001). Score of peer bullying (PB), abuse and neglect (AN), adverse life events (ALE), and CCSQ in SCZ group were higher ( P < 0.05 or 0.01). Outside miRNA-3064-5p, the ΔCT values of miRNA-1273d, miRNA-1303, miRNA-21, miRNA-3131, miRNA-3687, miRNA-4428, miRNA-4725-3p, and miRNA-5096 negatively correlated with positive symptom subscale (PSS), while PB, AN, ALE, CCSQ positively correlated with PSS and negative symptom scale (NSS) ( P < 0.05 or 0.01). Multivariate regression analysis suggested miRNA-1273d and AN significantly associated with PSS and accounted for 25.33% of its variation in SCZ patients ( P < 0.05 or 0.01). The predictive effect of AN on PSS in the SCZ group was not significant in the mediation model ( P = 0.229), while AN was significantly associated with PSS, miRNA-1273d in the direct model ( P < 0.05 or 0.001). Conclusion: Differentially expressed miRNAs as predictors of psychopathological symptoms in SCZ patients may be potential biomarkers for SCZ diagnosis. Chronic childhood stress may regulate susceptibility gene expression and pathological processes of SCZ by affecting miRNA-1273d expression. Keywords: schizophrenia, microRNA, biomarker, chronic stress, childhood