title: Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.
abstract: BACKGROUND
  A number of previous studies examined a possible association of toxic metals and autism, and over half of those studies suggest that toxic metal levels are different in individuals with Autism Spectrum Disorders (ASD). Additionally, several studies found that those levels correlate with the severity of ASD.
  
  
  METHODS
  In order to further investigate these points, this paper performs the most detailed statistical analysis to date of a data set in this field. First morning urine samples were collected from 67 children and adults with ASD and 50 neurotypical controls of similar age and gender. The samples were analyzed to determine the levels of 10 urinary toxic metals (UTM). Autism-related symptoms were assessed with eleven behavioral measures. Statistical analysis was used to distinguish participants on the ASD spectrum and neurotypical participants based upon the UTM data alone. The analysis also included examining the association of autism severity with toxic metal excretion data using linear and nonlinear analysis. "Leave-one-out" cross-validation was used to ensure statistical independence of results.
  
  
  CONCLUSIONS
  Average excretion levels of several toxic metals (lead, tin, thallium, antimony) were significantly higher in the ASD group. However, ASD classification using univariate statistics proved difficult due to large variability, but nonlinear multivariate statistical analysis significantly improved ASD classification with Type I/II errors of 15% and 18%, respectively. These results clearly indicate that the urinary toxic metal excretion profiles of participants in the ASD group were significantly different from those of the neurotypical participants. Similarly, nonlinear methods determined a significantly stronger association between the behavioral measures and toxic metal excretion. The association was strongest for the Aberrant Behavior Checklist (including subscales on Irritability, Stereotypy, Hyperactivity, and Inappropriate Speech), but significant associations were found for UTM with all eleven autism-related assessments with cross-validation R2 values ranging from 0.12-0.48.
authors.affiliation: Arizona State University, Tempe, AZ, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Adams
authors.affiliation: Rensselaer Polytechnic Institute, Troy, NY, United States of America.
authors.forename: Daniel P
authors.identifier: http://orcid.org/0000-0002-7177-1342
authors.initials: DP
authors.lastname: Howsmon
authors.affiliation: Rensselaer Polytechnic Institute, Troy, NY, United States of America.
authors.forename: Uwe
authors.initials: U
authors.lastname: Kruger
authors.affiliation: Arizona State University, Tempe, AZ, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Geis
authors.affiliation: Arizona State University, Tempe, AZ, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Gehn
authors.affiliation: Arizona State University, Tempe, AZ, United States of America.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fimbres
authors.affiliation: Arizona State University, Tempe, AZ, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Pollard
authors.affiliation: Southwest College of Naturopathic Medicine, Tempe, AZ, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: Arizona State University, Tempe, AZ, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Ingram
authors.affiliation: Arizona Allergy Associates, Phoenix, AZ, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Hellmers
authors.affiliation: Doctor's Data, St. Charles, IL, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Quig
authors.affiliation: Rensselaer Polytechnic Institute, Troy, NY, United States of America.
authors.forename: Juergen
authors.initials: J
authors.lastname: Hahn
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000209:etiology* / Q000652:urine*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D005260:Female; D000075322:Heavy Metal Poisoning; D006801:Humans; D008297:Male; D019216:Metals, Heavy / Q000652:urine*; D017711:Nonlinear Dynamics; D010641:Phenotype; D011041:Poisoning; D025341:Principal Component Analysis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019216:Metals, Heavy