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(1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome
We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patient...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658067/ https://www.ncbi.nlm.nih.gov/pubmed/36362721 http://dx.doi.org/10.3390/jcm11216493 |
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author | Gagliano, Antonella Murgia, Federica Capodiferro, Agata Maria Tanca, Marcello Giuseppe Hendren, Aran Falqui, Stella Giulia Aresti, Michela Comini, Martina Carucci, Sara Cocco, Eleonora Lorefice, Lorena Roccella, Michele Vetri, Luigi Sotgiu, Stefano Zuddas, Alessandro Atzori, Luigi |
author_facet | Gagliano, Antonella Murgia, Federica Capodiferro, Agata Maria Tanca, Marcello Giuseppe Hendren, Aran Falqui, Stella Giulia Aresti, Michela Comini, Martina Carucci, Sara Cocco, Eleonora Lorefice, Lorena Roccella, Michele Vetri, Luigi Sotgiu, Stefano Zuddas, Alessandro Atzori, Luigi |
author_sort | Gagliano, Antonella |
collection | PubMed |
description | We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers. |
format | Online Article Text |
id | pubmed-9658067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96580672022-11-15 (1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome Gagliano, Antonella Murgia, Federica Capodiferro, Agata Maria Tanca, Marcello Giuseppe Hendren, Aran Falqui, Stella Giulia Aresti, Michela Comini, Martina Carucci, Sara Cocco, Eleonora Lorefice, Lorena Roccella, Michele Vetri, Luigi Sotgiu, Stefano Zuddas, Alessandro Atzori, Luigi J Clin Med Article We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers. MDPI 2022-11-01 /pmc/articles/PMC9658067/ /pubmed/36362721 http://dx.doi.org/10.3390/jcm11216493 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gagliano, Antonella Murgia, Federica Capodiferro, Agata Maria Tanca, Marcello Giuseppe Hendren, Aran Falqui, Stella Giulia Aresti, Michela Comini, Martina Carucci, Sara Cocco, Eleonora Lorefice, Lorena Roccella, Michele Vetri, Luigi Sotgiu, Stefano Zuddas, Alessandro Atzori, Luigi (1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
title | (1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
title_full | (1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
title_fullStr | (1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
title_full_unstemmed | (1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
title_short | (1)H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
title_sort | (1)h-nmr-based metabolomics in autism spectrum disorder and pediatric acute-onset neuropsychiatric syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658067/ https://www.ncbi.nlm.nih.gov/pubmed/36362721 http://dx.doi.org/10.3390/jcm11216493 |
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