Searching for biomarkers in schizophrenia and psychosis: Case‐control study using capillary electrophoresis and liquid chromatography time‐of‐flight mass spectrometry and systematic review for biofluid metabolites

Abstract

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Progress in The Research of Lactate Metabolism Disruption And Astrocyte‐Neuron Lactate Shuttle Impairment in Schizophrenia: A Comprehensive Review

“…A few of these scholars support the idea that lactate levels are reduced in schizophrenia, [58] whereas abnormally elevated lactate in schizophrenia is recognized by most researchers. [21,43,[55][56][57][59][60][61] Regenold WT et al first found that lactate concentrations in the cerebrospinal fluid of patients with schizophrenia and bipolar disorder were increased by 23% and 34%, respectively, compared to healthy control. [55] Higher levels of lactate were also present in the anterior cingulate cortex (ACC) of SCZ patients, which was associated with poorer cognitive and functional performance, and the abnormally high levels of lactate in this brain region are thought to be related to increased glycolysis due to mitochondrial dysfunction.…”

“…In addition to the brain, blood lactate levels are commonly elevated in patients with schizophrenia. [21,[59][60][61] One study interpreted elevated lactate levels in venous blood of SCZ patients as gastric acid retention and tissue-derived hypoxia. [21] Interestingly, serum lactate levels seem to fluctuate at different stages of schizophrenia.…”

“…Abnormalities in lactate metabolism are prevalent in the brain [43,[55][56][57][58][59] and blood [19,21,60,61] of patients with schizophrenia, as well as in the brains of animal models of SCZ. [43,[62][63][64][65][66][67][68][69][70][71] Currently, in addition to the determination of blood lactate levels in schizophrenic patients by GC × GC-TOFMS-based small-polarity metabolite analysis platforms, [60] CE-TOFMS and LC-TOFMS, [61] fully automated blood gas analyzers, [21] stoichiometrically related nuclear magnetic resonance (NMR) analyses, [19] and highperformance liquid chromatography (HPLC), [72] magnetic resonance spectroscopy (MRS) [56,58,59] and 7-Tesla MRI [57] have been increasingly used for the detection of brain lactate levels in patients with SCZ. Most studies of animal models of SCZ have examined their brain lactate, with commonly used assays including 13C and 1H MRS, [62,66] 11.7 T MRS, [67] microdialysis, [65] R fu, [70] and lactate kits.…”

“…[87] Elevated levels of glutamatergic metabolites and reduced levels of GABAergic metabolites in schizophrenia spectrum disorders indicate a disruption of the excitatory/inhibitory balance in the brain, which is relevant to the pathophysiology of schizophrenia. [108] Interestingly, abnormalities of glutamate and its related metabolites are also frequently found in schizophrenic patients with abnormal lactate metabolism [56,[59][60][61] and in animal models of SCZ. [62,66,67,70] In one study, glutamate levels in the DLPFC were higher in the short-duration SCZ group than in the long-duration SCZ group.…”

Metabolomics, Lipidomics, and Antipsychotics: A Systematic Review

“…and univariate approaches (e.g., t-tests with multiple testing corrections). Seven studies found >10 significant metabolites associated with antipsychotic use, while six studies found <10 metabolites, and one study found no associations [22] Fifty-four associations with metabolite classes were identified across all studies, with carboxylic acids being the most commonly identified in nine studies. General metabolite class identifications are detailed in Table 2, and in-depth findings are provided in Supplementary Table S2.…”