A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study

Abstract

Few biomarkers have been known that can easily measure clinical conditions in mental illnesses such as schizophrenia. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) is a new method that can measure ionized and low-molecular-weight metabolites. To explore global metabolomic alterations that characterize the onset of schizophrenia and identify biomarkers, we profiled the relative and absolute concentrations of the plasma metabolites from 30 patients with first-episode schizophrenia (FESZ, four drug-naïve samples), 38 healthy controls and 15 individuals with autism spectrum disorders using CE-TOFMS. Five metabolites had robust changes (increased creatine and decreased betaine, nonanoic acid, benzoic acid and perillic acid) in two independent sample sets. Altered levels of these metabolites are consistent with well-known hypotheses regarding abnormalities of the homocysteine metabolism, creatine kinase-emia and oxidative stress. Although it should be considered that most patients with FESZ received medication, these metabolites are candidate biomarkers to improve the determination of diagnosis, severity and clinical stages, especially for FESZ.

Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis

“…Upregulation of plasma homocysteine is associated with various physical illnesses such as arterial sclerosis, thus the eliminative role of betaine is suggested to be crucial to homeostasis [32, 33]. Increasing levels of homocysteine also induce inflammation in the brain via increasing oxidative stress and inflammatory cytokines, and a recent study revealed a lower plasma concentration of betaine in patients with first-episode schizophrenia [34]. Based on the above evidence, betaine is suggested to play important roles in expressing mental dysfunctions including depressive mood by regulating the BHMT reaction and the following systematic changes.…”

Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis

“…23 Two studies using this technique showed robust changes in four molecules (arginine, taurine, 5-oxoproline and lactic acid) in the plasma of autism spectrum disorders, 24 and significant changes in the five molecules (creatine, betaine, nonanoic acid, benzoic acid and perillic acid) in the plasma of first-episode, medicated patients with schizophrenia. 25 However, there are no reports using this technique in CSF samples from BD patients.…”

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

“…Studies applying metabolomic profiling of patient serum are also starting to be used to explore the biology of psychiatric disorders [41,42,43,44,45,46]. Such studies have suggested the possibility of identifying biomarkers for schizophrenia [47,48,49,50,51,52], major depressive disorder [53,54] and posttraumatic stress disorder [55], and have also been used to study medication-induced metabolic changes [56,57]. In bipolar disorder, metabolomic studies have been undertaken in urine samples to identify potential biomarkers [58,59,60,61].…”