Troy Vargason1, Uwe Kruger1, Deborah L McGuinness2, James B Adams3, Elizabeth Geis3, Eva Gehn3, Devon Coleman3, Juergen Hahn1,4. 1. Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA. 2. Department of Computer Science, Rensselaer Polytechnic Institute, Troy, NY, USA. 3. Autism/Asperger's Research Program, Arizona State University, Tempe, AZ, USA. 4. Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
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.
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.
Authors: Rabindra Tirouvanziam; Tetyana V Obukhanych; Julie Laval; Pavel A Aronov; Robin Libove; Arpita Goswami Banerjee; Karen J Parker; Ruth O'Hara; Leonard A Herzenberg; Leonore A Herzenberg; Antonio Y Hardan Journal: J Autism Dev Disord Date: 2012-05