Identification of Plasma Biomarkers in Untreated Schizophrenia Patients Using Untargeted Lipid Metabolomics

Purpose: Schizophrenia (SCZ) is a profound psychosomatic illness with an unidentified cause and no definitive biomarkers. This study sought to investigate plasma biomarkers linked to schizophrenia by untargeted metabolomics. Patients and Methods: A total of 50 medication-naïve SCZ patients and 25 healthy controls were eligible and participated in this study. Psychiatric symptomatology was evaluated employing the Positive and Negative Syndrome Scale. We quantified the concentration of lipid metabolites in plasma from all participants using untargeted metabolomics and classified metabolites that were significantly different between both groups. We subsequently assessed the diagnostic potential of metabolites on the basis of receiver operating characteristic curves and examined metabolites affiliated with psychotic symptomatology in SCZ patients. Results: Fourteen metabolites exhibited compelling disparities in schizophrenia patients relative to healthy controls. Eight metabolites, including methylphosphatidylcholine, acylcarnitine, sphingomyelin, and (O-acyl)-1-hydroxy fatty acids (38:4), could significantly distinguish between schizophrenia and healthy controls, with all their areas under the curve (AUC) exceeding 0.7. The peak area under the curve (CV-AUC) for AcCa(20:4) was 0.92 ± 0.03. In schizophrenia patients, negative symptoms exhibited a negative correlation with acylcarnitines, while cognitive symptoms had a substantial positive correlation with methylphosphatidylcholine and phosphatidylcholine. Conclusion: The findings reveal lipid metabolism dysregulation as a potential pathophysiological mechanism of schizophrenia. The identified metabolites, such as AcCa and phosphatidylcholine, serve as promising biomarkers for the diagnosis and symptom evaluation, suggesting their direct involvement in the disease's pathogenesis.