Alterations of eicosanoids and related mediators in patients with schizophrenia

Abstract

Schizophrenia (SCZ) is a multifactorial psychiatric disorder. Currently, its molecular pathogenesis remains largely unknown, and no reliable test for diagnosis and therapy monitoring is available. Polyunsaturated fatty acids (PUFAs) and their derived eicosanoid signaling abnormalities are relevant to the pathophysiology of schizophrenia. However, comprehensive analysis of eicosanoids and related mediators for schizophrenia is very rare. In this study, we applied a targeted liquid chromatography-mass spectrometry based method to monitor 158 PUFAs, eicosanoids and related mediators from enzyme-dependent or independent pathways, in the serum samples of 109 healthy controls, and 115 schizophrenia patients at baseline and after an 8-week period of antipsychotic therapy. Twenty-three metabolites were identified to be significantly altered in SCZ patients at baseline compared to healthy controls, especially arachidonic acid (AA) derived eicosanoids. These disturbances may be related to altered immunological reactions and neurotransmitter signaling. After 8-week antipsychotic treatment, there were 22 metabolites, especially AA and linoleic acid derived eicosanoids, significantly altered in posttreatment patients. Some metabolites, such as several AA derived prostaglandins, thromboxanes, and di-hydroxy-eicosatrienoic acids were reversed toward normal levels after treatment. Based on univariate analysis and orthogonal partial least-squares discriminant analysis, anandamide, oleoylethanolamine, and AA were selected as a panel of potential biomarkers for differentiating baseline SCZ patients from controls, which showed a high sensitivity (0.907), good specificity (0.843) and excellent area under the receiver operating characteristic curve (0.940). This study provided a new perspective to understand the pathophysiological mechanism and identify potential biomarkers of SCZ.

Keywords: Biomarker; Eicosanoids; Liquid chromatography-mass spectrometry; Metabolomics; Polyunsaturated fatty acids; Schizophrenia.