Vargason Troy, Kruger Uwe, McGuinness Deborah L, Adams James B, Geis Elizabeth, Gehn Eva, Coleman Devon, Hahn Juergen
Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
Department of Computer Science, Rensselaer Polytechnic Institute, Troy, NY, USA.
Res Autism Spectr Disord. 2018 Jun;50:60-72. doi: 10.1016/j.rasd.2018.03.004. Epub 2018 Mar 30.
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.
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.
Univariate analysis indicated increased median levels of glutamate (+21%, =0.014) and serine (+8%, =0.043), and increased mean levels of hydroxyproline (+17%, =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.
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.
血浆氨基酸测量已在自闭症谱系障碍（ASD）个体中进行了广泛研究。迄今为止，结果尚无定论，因为研究通常在哪些氨基酸在ASD个体与其发育正常（TD）的同龄人中存在差异这一问题上存在分歧，部分原因是几项研究存在方法学上的局限性。
本文利用亚利桑那州立大学综合营养与饮食干预研究的数据，对患有ASD的儿童和成人的血浆氨基酸进行了研究。使用单变量和多变量统计技术分析了64名ASD个体和49名TD对照的测量数据。
单变量分析表明，ASD队列中谷氨酸的中位数水平升高（+21%，P = 0.014）和丝氨酸的中位数水平升高（+8%，P = 0.043），羟脯氨酸的平均水平升高（+17%，P = 0.018），尽管在进行多重比较校正后这些差异不显著。使用Fisher判别分析（FDA）及其非线性扩展核Fisher判别分析（KFDA）的多变量方法将研究参与者分类为ASD/TD队列。使用所有可用测量值进行FDA模型拟合时，I型和II型错误分别为27.0%和27.8%。当使用羟脯氨酸、亮氨酸和苏氨酸作为输入时，KFDA最为有效；然而，使用此非线性模型进行留一法交叉验证时，灵敏度仅为70.3%，特异性为77.6%。
ASD中谷氨酸升高的发现与其他几项研究一致。然而，总体而言，这些结果表明血浆氨基酸测量在ASD分类中的用途有限，这可能解释了文献中呈现的一些结果不一致的情况。
