<sup>1</sup>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...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/21/6493 |
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| author | Antonella Gagliano Federica Murgia Agata Maria Capodiferro Marcello Giuseppe Tanca Aran Hendren Stella Giulia Falqui Michela Aresti Martina Comini Sara Carucci Eleonora Cocco Lorena Lorefice Michele Roccella Luigi Vetri Stefano Sotgiu Alessandro Zuddas Luigi Atzori |
| author_facet | Antonella Gagliano Federica Murgia Agata Maria Capodiferro Marcello Giuseppe Tanca Aran Hendren Stella Giulia Falqui Michela Aresti Martina Comini Sara Carucci Eleonora Cocco Lorena Lorefice Michele Roccella Luigi Vetri Stefano Sotgiu Alessandro Zuddas Luigi Atzori |
| author_sort | Antonella Gagliano |
| collection | DOAJ |
| 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 (<i>p</i> = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (<i>p</i> = 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. |
| first_indexed | 2024-03-09T18:58:07Z |
| format | Article |
| id | doaj.art-dadb5858877b4a288745f774bd310170 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T18:58:07Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-dadb5858877b4a288745f774bd3101702023-11-24T05:18:35ZengMDPI AGJournal of Clinical Medicine2077-03832022-11-011121649310.3390/jcm11216493<sup>1</sup>H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric SyndromeAntonella Gagliano0Federica Murgia1Agata Maria Capodiferro2Marcello Giuseppe Tanca3Aran Hendren4Stella Giulia Falqui5Michela Aresti6Martina Comini7Sara Carucci8Eleonora Cocco9Lorena Lorefice10Michele Roccella11Luigi Vetri12Stefano Sotgiu13Alessandro Zuddas14Luigi Atzori15Child & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyClinical Metabolomics Unit, Department of Biomedical Sciences, University of Cagliari, 09042 Cagliari, ItalyChild & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyChild & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyFaculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UKChild & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyChild & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyChild & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyChild & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyMultiple Sclerosis Regional Center, ASSL Cagliari, Department of Medical Sciences and Public Health, University of Cagliari, 09126 Cagliari, ItalyMultiple Sclerosis Regional Center, ASSL Cagliari, 09126 Cagliari, ItalyDepartment of Psychology, Educational Science and Human Movement, University of Palermo, 90128 Palermo, ItalyOasi Research Institute-IRCCS, Via Conte Ruggero 73, 94018 Troina, ItalyChild Neuropsychiatry Unit, Department of Medicine, Surgery and Farmacy, University of Sassari, 07100 Sassari, ItalyChild & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, “A. Cao” Paediatric Hospital, University of Cagliari, 09121 Cagliari, ItalyClinical Metabolomics Unit, Department of Biomedical Sciences, University of Cagliari, 09042 Cagliari, ItalyWe 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 (<i>p</i> = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (<i>p</i> = 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.https://www.mdpi.com/2077-0383/11/21/6493autism spectrum disorderpediatric acute-onset neuropsychiatric syndromemetabolomicsbiomarkers’ evaluationpathways analysis |
| spellingShingle | Antonella Gagliano Federica Murgia Agata Maria Capodiferro Marcello Giuseppe Tanca Aran Hendren Stella Giulia Falqui Michela Aresti Martina Comini Sara Carucci Eleonora Cocco Lorena Lorefice Michele Roccella Luigi Vetri Stefano Sotgiu Alessandro Zuddas Luigi Atzori <sup>1</sup>H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome Journal of Clinical Medicine autism spectrum disorder pediatric acute-onset neuropsychiatric syndrome metabolomics biomarkers’ evaluation pathways analysis |
| title | <sup>1</sup>H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
| title_full | <sup>1</sup>H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
| title_fullStr | <sup>1</sup>H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
| title_full_unstemmed | <sup>1</sup>H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
| title_short | <sup>1</sup>H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome |
| title_sort | sup 1 sup h nmr based metabolomics in autism spectrum disorder and pediatric acute onset neuropsychiatric syndrome |
| topic | autism spectrum disorder pediatric acute-onset neuropsychiatric syndrome metabolomics biomarkers’ evaluation pathways analysis |
| url | https://www.mdpi.com/2077-0383/11/21/6493 |
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