Altered metabolism of mothers of young children with Autism Spectrum Disorder: a case control study
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RESEARCH ARTICLE
Open Access
Altered metabolism of mothers of young children with Autism Spectrum Disorder: a case control study Kathryn Hollowood-Jones1, James B. Adams2*, Devon M. Coleman2, Sivapriya Ramamoorthy3, Stepan Melnyk4, S. Jill James4, Bryan K. Woodruff5, Elena L. Pollard2, Christine L. Snozek5, Uwe Kruger1, Joshua Chuah1 and Juergen Hahn1*
Abstract Background: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism. Methods: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods. Results: Univariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules. Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8–15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules. Conclusions: Mothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2–5 years after birth. Keywords: Autism, Metabolic profile, Fisher discriminant analysis, Logistic regression, Metabolomics, Mothers
* Correspondence: [email protected]; [email protected] 2 School for Engineering of Matter, Transport and Energy, Arizona State University, P.O. Box 879309, ECG 302, 501 E Tyler Mall, Tempe, AZ 85287-9309, USA 1 Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY 12180, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated
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