Serum Metabolomic Profiling Based on Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometry: Do the Dysfunctions of Metabolic Pathways Reveal a Universal Risk of Oxidative Stress in Schizophrenia?

Schizophrenia is a chronic, disabling, and complex mental illness, of which the pathogenesis remains elusive. To provide clues for the pathogenesis and etiology of schizophrenia, we performed serum metabolic profiling in 54 patients with schizophrenia and 54 matched healthy controls using Fourier transform-ion cyclotron resonance-mass spectrometry. Based on 94 differential metabolites identified, we discovered two dysregulated metabolic pathways in schizophrenia, including the upregulated arachidonic acid-related pathway and the downregulated aromatic amino acid-related pathway. Moreover, carnitine was identified as a promising diagnostic biomarker for schizophrenia with an area under the curve of 0.997. Given the antioxidant and pro-oxidant properties of these altered metabolites, these results pointed to an imbalance of the redox homeostasis in schizophrenia, which was further confirmed by a remarkable elevation of 8-hydroxydeoxyguanosine (8-OHdG), a reactive oxidative stress marker. Furthermore, correlation analyses demonstrated that 8-OHdG was negatively correlated with antioxidant biliverdin and positively related to oxidation products, 9-hydroxylinoleic acid and o-tyrosine, and that total antioxidant capacity was positively associated with antioxidant acetylcarnitine in schizophrenia. Our results lead to the hypothesis that the disturbed metabolic characteristics reveal enhanced oxidative stress, which in turn results in the damage of lipids, proteins, and DNA and ultimately promotes the development of schizophrenia.