Investigating plasma amino acids for differentiating individuals with autism spectrum disorder and typically developing peers

Troy Vargason, Uwe Kruger, Deborah L. McGuinness, James Adams, Elizabeth Geis, Eva Gehn, Devon Coleman, Juergen Hahn

Research output: Contribution to journalArticle

Abstract

Background: Plasma amino acid measurements have been extensively investigated in individuals with autism spectrum disorder (ASD). Results thus far have been inconclusive as studies generally disagree on which amino acids are different in individuals with ASD versus their typically developing (TD) peers, due in part to methodological limitations of several studies. Method: This paper investigates plasma amino acids in children and adults with ASD using data from Arizona State University's Comprehensive Nutritional and Dietary Intervention Study. Measurements from 64 individuals with ASD and 49 TD controls were analyzed using univariate and multivariate statistical techniques. Results: Univariate analysis indicated increased median levels of glutamate (+21%, p = 0.014) and serine (+8%, p = 0.043), and increased mean levels of hydroxyproline (+17%, p = 0.018) for the ASD cohort, although these differences were insignificant after correcting for multiple comparisons. A multivariate approach was used to classify study participants into ASD/TD cohorts using Fisher discriminant analysis (FDA) and its nonlinear extension, kernel Fisher discriminant analysis (KFDA). Model fitting with FDA using all available measurements produced Type I and Type II errors of 27.0% and 27.8%, respectively. KFDA was most effective when using hydroxyproline, leucine, and threonine as inputs; however, leave-one-out cross-validation with this nonlinear model only resulted in 70.3% sensitivity and 77.6% specificity. Conclusions: The finding of elevated glutamate in ASD is in agreement with several other studies. Overall, however, these results suggest that plasma amino acid measurements are of limited use for purposes of ASD classification, which may explain some of the inconsistencies in results presented in the literature.

Original languageEnglish (US)
Pages (from-to)60-72
Number of pages13
JournalResearch in Autism Spectrum Disorders
Volume50
DOIs
StatePublished - Jun 1 2018

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Amino Acids
Discriminant Analysis
Hydroxyproline
Glutamic Acid
Nonlinear Dynamics
Autism Spectrum Disorder
Threonine
Leucine
Serine
Sensitivity and Specificity

Keywords

  • Autism spectrum disorder
  • Classification
  • Cross-validation
  • Fisher discriminant analysis
  • Multivariate statistics
  • Plasma amino acids

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Investigating plasma amino acids for differentiating individuals with autism spectrum disorder and typically developing peers. / Vargason, Troy; Kruger, Uwe; McGuinness, Deborah L.; Adams, James; Geis, Elizabeth; Gehn, Eva; Coleman, Devon; Hahn, Juergen.

In: Research in Autism Spectrum Disorders, Vol. 50, 01.06.2018, p. 60-72.

Research output: Contribution to journalArticle

Vargason, Troy ; Kruger, Uwe ; McGuinness, Deborah L. ; Adams, James ; Geis, Elizabeth ; Gehn, Eva ; Coleman, Devon ; Hahn, Juergen. / Investigating plasma amino acids for differentiating individuals with autism spectrum disorder and typically developing peers. In: Research in Autism Spectrum Disorders. 2018 ; Vol. 50. pp. 60-72.
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abstract = "Background: Plasma amino acid measurements have been extensively investigated in individuals with autism spectrum disorder (ASD). Results thus far have been inconclusive as studies generally disagree on which amino acids are different in individuals with ASD versus their typically developing (TD) peers, due in part to methodological limitations of several studies. Method: This paper investigates plasma amino acids in children and adults with ASD using data from Arizona State University's Comprehensive Nutritional and Dietary Intervention Study. Measurements from 64 individuals with ASD and 49 TD controls were analyzed using univariate and multivariate statistical techniques. Results: Univariate analysis indicated increased median levels of glutamate (+21{\%}, p = 0.014) and serine (+8{\%}, p = 0.043), and increased mean levels of hydroxyproline (+17{\%}, p = 0.018) for the ASD cohort, although these differences were insignificant after correcting for multiple comparisons. A multivariate approach was used to classify study participants into ASD/TD cohorts using Fisher discriminant analysis (FDA) and its nonlinear extension, kernel Fisher discriminant analysis (KFDA). Model fitting with FDA using all available measurements produced Type I and Type II errors of 27.0{\%} and 27.8{\%}, respectively. KFDA was most effective when using hydroxyproline, leucine, and threonine as inputs; however, leave-one-out cross-validation with this nonlinear model only resulted in 70.3{\%} sensitivity and 77.6{\%} specificity. Conclusions: The finding of elevated glutamate in ASD is in agreement with several other studies. Overall, however, these results suggest that plasma amino acid measurements are of limited use for purposes of ASD classification, which may explain some of the inconsistencies in results presented in the literature.",
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