Altered metabolites in the plasma of autism spectrum disorder: a capillary electrophoresis time-of-flight mass spectroscopy study

PLoS One. 2013 Sep 18;8(9):e73814. doi: 10.1371/journal.pone.0073814. eCollection 2013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Child Development Disorders, Pervasive / blood*
  • Child Development Disorders, Pervasive / diagnosis
  • Child Development Disorders, Pervasive / physiopathology
  • Electrophoresis, Capillary / methods
  • Humans
  • Lactic Acid / blood*
  • Male
  • Metabolome*
  • Oxidative Stress
  • Pyrrolidonecarboxylic Acid / blood
  • Severity of Illness Index
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Taurine / blood


  • Biomarkers
  • Taurine
  • Lactic Acid
  • Arginine
  • Pyrrolidonecarboxylic Acid

Grant support

A part of this study was supported by CREST, Japan Science and Technology Agency, and the “Development of biomarker candidates for social behavior” carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. to funding.