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Objectives: Objective measures integrated with clinical symptoms may improve early prevention and detection of schizophrenia. Herein we aim to evaluate potential water-soluble metabolic biomarkers in schizophrenia. Methods: We recruited adults with schizophrenia (n = 113) who had not received pharmacological treatment for at least 1 month prior to enrollment and 111 age- and sex-matched healthy subjects from Weifang, Shandong province, China. All serum samples were analysed using liquid chromatography-tandem mass spectrometry coupled with a hydrophilic interaction liquid chromatography column. Results: Eleven metabolites, namely carnitines (oleoylcarnitine, l-palmitoylcarnitine, 9-decenoylcarnitine and 2-trans,4-cis-decadienoylcarnitine), polar lipids (lysophosphatidylcholine (LPC)(P-16:0), LPC (16:0), LPC (15:0) and LPC(14:0)), amino acids (taurine and l-arginine), and organic acid (2,5-dichloro-4-oxohex-2-enedioate), separated the patients and healthy controls. Compared with healthy controls, taurine, l-palmitoylcarnitine and oleoylcarnitine levels were higher, whereas the remaining eight metabolites were lower in patients with schizophrenia. A combination of four metabolites, i.e., oleoylcarnitine, 9-decenoylcarnitine, LPC (15:0) and LPC (14:0), provided the most robust between-group separation. Conclusions: This study appears to distinguish between groups of patients and controls, which should be considered as a contribution to putative potential biomarkers. The water-soluble metabolites were determined to be significantly different between the groups in the current study, and were primarily related to cellular bioenergetics, notably oxidative stress. [ABSTRACT FROM AUTHOR]