Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.

INTRODUCTION: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...

Full description

Bibliographic Details
Main Authors: James Adams, Daniel P Howsmon, Uwe Kruger, Elizabeth Geis, Eva Gehn, Valeria Fimbres, Elena Pollard, Jessica Mitchell, Julie Ingram, Robert Hellmers, David Quig, Juergen Hahn
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5222512?pdf=render
_version_ 1818282310200459264
author James Adams
Daniel P Howsmon
Uwe Kruger
Elizabeth Geis
Eva Gehn
Valeria Fimbres
Elena Pollard
Jessica Mitchell
Julie Ingram
Robert Hellmers
David Quig
Juergen Hahn
author_facet James Adams
Daniel P Howsmon
Uwe Kruger
Elizabeth Geis
Eva Gehn
Valeria Fimbres
Elena Pollard
Jessica Mitchell
Julie Ingram
Robert Hellmers
David Quig
Juergen Hahn
author_sort James Adams
collection DOAJ
description INTRODUCTION: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. RESULTS AND DISCUSSION: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.
first_indexed 2024-12-13T00:18:59Z
format Article
id doaj.art-044d95a2d6e6469e968c1c0c2fa9ebdd
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-13T00:18:59Z
publishDate 2017-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-044d95a2d6e6469e968c1c0c2fa9ebdd2022-12-22T00:05:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e016952610.1371/journal.pone.0169526Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.James AdamsDaniel P HowsmonUwe KrugerElizabeth GeisEva GehnValeria FimbresElena PollardJessica MitchellJulie IngramRobert HellmersDavid QuigJuergen HahnINTRODUCTION: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. RESULTS AND DISCUSSION: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.http://europepmc.org/articles/PMC5222512?pdf=render
spellingShingle James Adams
Daniel P Howsmon
Uwe Kruger
Elizabeth Geis
Eva Gehn
Valeria Fimbres
Elena Pollard
Jessica Mitchell
Julie Ingram
Robert Hellmers
David Quig
Juergen Hahn
Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.
PLoS ONE
title Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.
title_full Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.
title_fullStr Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.
title_full_unstemmed Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.
title_short Significant Association of Urinary Toxic Metals and Autism-Related Symptoms-A Nonlinear Statistical Analysis with Cross Validation.
title_sort significant association of urinary toxic metals and autism related symptoms a nonlinear statistical analysis with cross validation
url http://europepmc.org/articles/PMC5222512?pdf=render
work_keys_str_mv AT jamesadams significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT danielphowsmon significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT uwekruger significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT elizabethgeis significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT evagehn significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT valeriafimbres significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT elenapollard significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT jessicamitchell significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT julieingram significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT roberthellmers significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT davidquig significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation
AT juergenhahn significantassociationofurinarytoxicmetalsandautismrelatedsymptomsanonlinearstatisticalanalysiswithcrossvalidation