Dysregulation of Serum Exosomal Lipid Metabolism in Schizophrenia: A Biomarker Perspective

Exosomes, crucial extracellular vesicles, have emerged as potential biomarkers for neurological conditions, including schizophrenia (SCZ). However, the exploration of exosomal lipids in the context of SCZ remains scarce, necessitating in-depth investigation. Leveraging ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), this study aimed to characterize the lipidomic profile of serum exosomes from SCZ patients, assessing their potential as novel biomarkers for SCZ diagnosis through absolute quantitative lipidomics. Our comprehensive lipidomic analysis unveiled 39 serum exosomal lipids that were differentially expressed between SCZ patients (n = 20) and healthy controls (HC, n = 20). These findings revealed a profound dysregulation in lipid metabolism pathways, notably in sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. Among these, seven exosomal lipids stood out for their diagnostic potential, exhibiting remarkable ability to differentiate SCZ patients from HCs with an unparalleled classification performance, evidenced by an area under the curve (AUC) of 0.94 (95% CI, 0.82-1.00). These lipids included specific ceramides and phosphoethanolamines, pointing to a distinct lipid metabolic fingerprint associated with SCZ. Furthermore, bioinformatic analyses reinforced the pivotal involvement of these lipids in SCZ-related lipid metabolic processes, suggesting their integral role in the disorder's pathophysiology. This study significantly advances our understanding of SCZ by pinpointing dysregulated exosomal lipid metabolism as a key factor in its pathology. The identified serum exosome-derived lipids emerge as compelling biomarkers for SCZ diagnosis, offering a promising avenue towards the development of objective and reliable diagnostic tools.