title: Enrichment of elevated plasma F2t-isoprostane levels in individuals with autism who are stratified by presence of gastrointestinal dysfunction.
abstract: 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.
authors.affiliation: Medical Scientist Training Program, Vanderbilt University, Nashville, Tennessee, United States of America. phillip.gorrindo@Vanderbilt.Edu
authors.forename: Phillip
authors.initials: P
authors.lastname: Gorrindo
authors.forename: Christianne Joy
authors.initials: CJ
authors.lastname: Lane
authors.forename: Evon Batey
authors.initials: EB
authors.lastname: Lee
authors.forename: Bethann
authors.initials: B
authors.lastname: McLaughlin
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000097:blood* / Q000150:complications*; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications*; D006801:Humans; D008297:Male; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D014280:Triglycerides