Metabolomic Signatures of Autism Spectrum Disorder
Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic anal...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/10/1727 |
| _version_ | 1797472153601310720 |
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| author | Danielle Brister Shannon Rose Leanna Delhey Marie Tippett Yan Jin Haiwei Gu Richard E. Frye |
| author_facet | Danielle Brister Shannon Rose Leanna Delhey Marie Tippett Yan Jin Haiwei Gu Richard E. Frye |
| author_sort | Danielle Brister |
| collection | DOAJ |
| description | Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis. |
| first_indexed | 2024-03-09T19:58:07Z |
| format | Article |
| id | doaj.art-847aea7db2304c189e9a42300ff83701 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T19:58:07Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-847aea7db2304c189e9a42300ff837012023-11-24T00:50:59ZengMDPI AGJournal of Personalized Medicine2075-44262022-10-011210172710.3390/jpm12101727Metabolomic Signatures of Autism Spectrum DisorderDanielle Brister0Shannon Rose1Leanna Delhey2Marie Tippett3Yan Jin4Haiwei Gu5Richard E. Frye6College of Liberal Arts and Sciences, School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USAArkansas Children’s Research Institute and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USAArkansas Children’s Research Institute and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USAArkansas Children’s Research Institute and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USACenter for Translational Science, Florida International University, Port St. Lucie, FL 34987, USACenter for Translational Science, Florida International University, Port St. Lucie, FL 34987, USARossignol Medical Center, Phoenix, AZ 85050, USAAutism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis.https://www.mdpi.com/2075-4426/12/10/1727amino acid metabolismautism spectrum disorderenergy metabolismmass spectrometrymetabolomicsmitochondria |
| spellingShingle | Danielle Brister Shannon Rose Leanna Delhey Marie Tippett Yan Jin Haiwei Gu Richard E. Frye Metabolomic Signatures of Autism Spectrum Disorder Journal of Personalized Medicine amino acid metabolism autism spectrum disorder energy metabolism mass spectrometry metabolomics mitochondria |
| title | Metabolomic Signatures of Autism Spectrum Disorder |
| title_full | Metabolomic Signatures of Autism Spectrum Disorder |
| title_fullStr | Metabolomic Signatures of Autism Spectrum Disorder |
| title_full_unstemmed | Metabolomic Signatures of Autism Spectrum Disorder |
| title_short | Metabolomic Signatures of Autism Spectrum Disorder |
| title_sort | metabolomic signatures of autism spectrum disorder |
| topic | amino acid metabolism autism spectrum disorder energy metabolism mass spectrometry metabolomics mitochondria |
| url | https://www.mdpi.com/2075-4426/12/10/1727 |
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