Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

• Published in: PloS one Vol. 8; no. 9; p. e73814
• Main Authors: Kuwabara, Hitoshi, Yamasue, Hidenori, Koike, Shinsuke, Inoue, Hideyuki, Kawakubo, Yuki, Kuroda, Miho, Takano, Yosuke, Iwashiro, Norichika, Natsubori, Tatsunobu, Aoki, Yuta, Kano, Yukiko, Kasai, Kiyoto
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.09.2013; Public Library of Science (PLoS)
• Subjects: Acids; Adult; Amino acids; Arginine; Arginine - blood; Autism; Biomarkers; Biomarkers - blood; Capillary electrophoresis; Case-Control Studies; Child Development Disorders, Pervasive - blood; Child Development Disorders, Pervasive - diagnosis; Child Development Disorders, Pervasive - physiopathology; Children & youth; Chromatography; Consent; Diagnosis; Electrophoresis; Electrophoresis, Capillary - methods; Exploration; Humans; Lactic acid; Lactic Acid - blood; Male; Males; Mass spectrometry; Mass spectroscopy; Medical research; Medicine; Metabolites; Metabolome; Mitochondria; NMR; Nuclear magnetic resonance; Oxidative Stress; Plasma levels; Psychiatrists; Pyrrolidonecarboxylic Acid - blood; Rodents; Schizophrenia; Severity of Illness Index; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Spectroscopy; Spectrum analysis; Studies; Subjective assessment; Systematic review; Taurine; Taurine - blood; Urine; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073814

Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD.