Circulating exosomal biomarkers in schizophrenia: Diagnostic utility and clinical implications
N. Igor, B. LarisaIntroduction
Validated blood biomarkers for schizophrenia remain unavailable. Circulating exosomes (extracellular vesicles, EVs) carrying microRNAs and proteins provide measurable signals. In first-episode psychosis, microRNA panels show high diagnostic accuracy (sensitivity 76–96%, specificity 78–96%, AUC up to 0.94). Brain-derived exosomes reveal disrupted signalling and mitochondrial dysfunction correlating with symptoms. Clinical studies suggest exosomes are promising biomarkers for early diagnosis, therapy monitoring, and pathogenetic research.
Objectives
To summarize diagnostic characteristics (sensitivity [Se], specificity [Sp], AUC) of exosomal biomarkers in schizophrenia, quantitatively assess their performance, and examine Se–Sp relationships.
Methods
Due to scarce randomized clinical trials (RCTs) and limited Se/Sp data, all peer-reviewed studies (2019–2024) were included regardless of design (case–control, cross-sectional, cohort, including three RCTs). Criteria: (1) schizophrenia patients with healthy or clinical comparators; (2) reported Se/Sp and/or AUC. Descriptive statistics (medians/ranges), linear regression (Sp on Se), and Pearson correlation (95% CI) were performed. Between-test differences were assessed with ANOVA, Levene’s test, and Shapiro–Wilk. No individual data were pooled.
Results
Across 12 studies, median Se was 85.35% (range 64.9–100), Sp 86.50% (60.2–100), and AUC 90.25% (66.1–100). Se correlated positively with Sp (r = 0.76, 95% CI 0.34–0.93, p < 0.01); regression slope β = 0.81 (p = 0.004), R² = 0.59. Between-test differences were nonsignificant (ANOVA F = 0.63, p = 0.538). An 11-miRNA exosomal signature achieved AUC 0.94 (95% CI 0.88–1.00) in training and 0.753 (0.61–0.90) in testing. Complement-enriched exosomal proteins (C3, C4, C4BPA, PROS1) discriminated schizophrenia from controls (AUC 0.895) and from bipolar disorder (0.966). Multicenter data support generalizability.
Conclusions
Exosomal biomarkers demonstrate high diagnostic performance (AUC ≈ 0.90; Se/Sp ≈ 85–87%) with consistent Se–Sp association. Panels combining miRNAs and complement proteins are especially promising. Limitations include design heterogeneity and few RCTs. Harmonized EV protocols, blinded multicenter validation, and studies of treatment-response prediction are needed.
Disclosure of Interest
None Declared