Plasma metabolomics of schizophrenia with cognitive impairment: A pilot study

Schizophrenia (SCZ) acts as a complex and burdensome disease, in which the functional outcome can be validly predicted by cognitive impairment, as one of the core features. However, there still lack considerable markers of cognitive deficits in SCZ. Based on metabolomics, it is expected to identify different metabolic characteristics of SCZ with cognitive impairment. In the present study, 17 SCZ patients with cognitive impairment (CI), 17 matched SCZ patients with cognitive normal (CN), and 20 healthy control subjects (HC) were recruited, whose plasma metabolites were measured using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The result of metabolic profiling indicated the identification of 46 differentially expressed metabolites between HC, CN, and CI groups, with 7 differentially expressed metabolites between CN and CI groups. Four differential metabolites (imidazolepropionic acid, Homoserine, and Aspartic acid) were repeatedly found in both screenings, by which the formed biomarker panel could discriminate SCZ with cognitive impairment from matched patients (AUC = 0.974) and health control (AUC = 0.841), respectively. Several significant metabolic pathways were highlighted in pathway analysis, involving Alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, and Citrate cycle (TCA cycle). In this study, several differentially expressed metabolites were identified in SCZ with cognitive impairment, providing novel insights into clinical treatment strategies.