Metabolomic Identification of Exosome-Derived Biomarkers for Schizophrenia: A Large Multicenter Study

• Published in: Schizophrenia bulletin Vol. 47; no. 3; pp. 615 - 623
• Main Authors: Du, Yang, Chen, Lei, Li, Xue-Song, Li, Xiao-Lin, Xu, Xiang-Dong, Tai, Shao-Bin, Yang, Geng-Lin, Tang, Quan, Liu, Hua, Liu, Shu-Han, Zhang, Shu-Yao, Cheng, Yong
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.05.2021
• Subjects: Biomarkers; Metabolites; Regular; Schizophrenia; schizophrenia; biomarker; metabolomics; exosome
• ISSN: 0586-7614; 1745-1701; 1745-1701
• DOI: 10.1093/schbul/sbaa166

Abstract Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.