Circulating miR-1260a as a potential biomarker for First-Episode of Psychosis: a replication study in a treatment-Naïve Romanian cohort

The diagnosis of first-episode psychosis (FEP) in adolescents and young adults remains primarily clinical, often complicated by symptom overlap and the heterogeneity of psychiatric presentations. There is a critical need for non-invasive, objective biomarkers to support early diagnosis and patient stratification. This study aimed to replicate a panel of 10 candidate microRNAs (miRNAs) identified in a previous exploratory study within a larger, independent cohort of treatment-naïve Romanian adolescents and young adults. This cross-sectional study included 50 participants (22 drug-naïve FEP patients and 28 age- and sex-matched controls). Total RNA was isolated from plasma, and the levels of miRNAs were measured using qRT-PCR. Clinical symptoms were assessed using standardized psychiatric scales (PANSS, HDRS, YMRS). We successfully replicated miR-1260a as significantly modified in the plasma of treatment-naïve FEP patients compared to controls (FDR Adj. p = 0.04). ROC analysis for miR-1260a yielded an AUC of 0.741 (p = 0.004). Furthermore, exploratory correlation analyses conducted exclusively within the FEP patient group indicated a negative correlation between miR-1260a levels and the positive PANSS score (p = 0.017, rho = -0.503), which did not retain statistical significance after FDR correction (FDR Adj. p = 0.102). Our results corroborate and enhance our prior exploratory research, highlighting miR-1260a as a prominent candidate among circulating biomarkers for early psychosis. Future longitudinal studies are necessary to evaluate the diagnostic, prognostic, and clinical monitoring efficacy of this miRNA.