Enrichment of elevated plasma F2t-isoprostane levels in individuals with autism who are stratified by presence of gastrointestinal dysfunction

• Published in: PloS one 2013-07, Vol.8 (7), p.e68444-e68444
• Main Authors: Gorrindo, Phillip, Lane, Christianne Joy, Lee, Evon Batey, McLaughlin, Bethann, Levitt, Pat
• Format: Article
• Language: English
• Subjects: Adolescent; Autism; Bioindicators; Biomarkers; Biomarkers - blood; Brain; Brain research; Chemical compounds; Child; Child Development Disorders, Pervasive - blood; Child Development Disorders, Pervasive - complications; Children; Enrichment; Etiology; F2-Isoprostanes - blood; Female; Free radicals; Gastroenterology; Gastrointestinal diseases; Gastrointestinal Diseases - complications; Gastrointestinal system; Group dynamics; Homogeneity; Humans; Hypotheses; Isoprostanes; Lipid peroxidation; Lipids; Male; Medicine; Metabolism; Microbiota; Neurosciences; Oxidative stress; Pathogenesis; Pediatrics; Plasma; Plasma levels; Stroke; Studies; Subgroups; Triglycerides - blood
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068444

Etiology is unknown in the majority of individuals with autism spectrum disorder (ASD). One strategy to investigate pathogenesis is to stratify this heterogeneous disorder based on a prominent phenotypic feature that enriches for homogeneity within population strata. Co-occurring gastrointestinal dysfunction (GID) characterizes a subset of children with ASD. Our current objective was to investigate a potential pathophysiological measure to test the hypothesis that children with both ASD and GID have a more severe metabolic dysfunction than children with ASD-only, given that the highly metabolically active brain and gastrointestinal system may additively contribute measurable impairment. Plasma levels of F2t-Isoprostanes (F2-IsoPs), a gold standard biomarker of oxidative stress, were measured in 87 children in four groups: ASD-GID, ASD-only, GID-only and Unaffected. F2-IsoP levels were elevated in all 3 clinical groups compared to the Unaffected group, with the ASD-GID group significantly elevated above the ASD-only group (mean, SD in pg/mg: ASD-GID 53.6, 24.4; ASD-only 36.5, 13.3; p = 0.007). Adjusting for age, sex, and triglyceride levels, F2-IsoP levels remained significantly different between study groups, with a moderate effect size of η(p)(2) = 0.187 (p = 0.001). Elevation in peripheral oxidative stress is consistent with, and may contribute to, the more severe functional impairments in the ASD-GID group. With unique medical, metabolic, and behavioral features in children with ASD-GID, the present findings serve as a compelling rationale for both individualized approaches to clinical care and integrated studies of biomarker enrichment in ASD subgroups that may better address the complex etiology of ASD.