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Neurometabolic profiles of autism spectrum disorder patients with genetic variants in specific neurotransmission and synaptic genes

2025-10-17Journal article Open access
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datacite.subject.fosCiências Médicas
dc.contributor.authorVilela, Joana
dc.contributor.authorPereira, Andreia C.
dc.contributor.authorViolante, Inês R.
dc.contributor.authorMouga, Susana
dc.contributor.authorRasga, Célia
dc.contributor.authorSantos, João Xavier
dc.contributor.authorMartiniano, Hugo
dc.contributor.authorMarques, Ana Rita
dc.contributor.authorOliveira, Guiomar
dc.contributor.authorCastelo-Branco, Miguel
dc.contributor.authorVicente, Astrid Moura
dc.date.accessioned2025-12-03T11:33:26Z
dc.date.available2025-12-03T11:33:26Z
dc.date.issued2025-10-17
dc.description.abstractAutism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impaired social interaction, and restricted and repetitive patterns of behavior. ASD presents as a clinical spectrum, with variable levels of severity and multiple co-occurring conditions. The etiology of ASD may involve hundreds of genes and there is evidence that neurotransmitter and synaptic (NS) pathways are implicated. Proton Magnetic Resonance Spectroscopy (H-MRS) has made it possible to study the concentration of brain neurometabolites and compare their levels in the brains of ASD and control individuals. We integrated genetic variants in NS genes with H-MRS analysis, and identified 12 predicted damaging variants (PDVs) in 12 NS genes in 10 ASD individuals, most mapping to genes involved in Gamma-aminobutyric acid (GABA) and glutamate pathways. Total creatine (tCr) and total N-acetyl aspartate (tNAA), markers of bioenergetics and neuronal metabolism, respectively, were lower in ASD patients with genetic alterations in NS genes compared to a control group without ASD. We conclude that PDVs in NS genes that are important for the regulation of glutamate or involved in GABAergic functions are associated with neurometabolic alterations, and that dysfunction in glutamatergic and/or GABAergic pathways may be implicated as these pathways are linked to the metabolic measures altered in cases.eng
dc.description.sponsorshipThis research was funded by Fundação para a Ciência e a Tecnologia (FCT), Portugal, Centre grants to BioISI (DOI: https://doi.org/10.54499/UIDB/04046/2020, UIDP/04046/2020, UID/04046/2025), PAC-POCI-01-0145-FEDER-016428 MEDPERSYST and the National Institute of Health Doutor Ricardo Jorge. J.V., A.R.M. and J.X.S. are recipients of a fellowship from the BioSys PhD program PD65-2012 (J.V. Ref: PD/BD/131390/2017; A.R.M. Ref: PD/BD/113773/2015; and J.X.S. Ref: PD/BD/114386/2016) from Fundação para a Ciência e a Tecnologia (FCT), (Portugal). SM was funded under Fundação para a Ciência e a Tecnologia (Portugal) CEEC Grant ref 2022.00474.CEECIND/CP1714/CT0030(https://doi.org/10.54499/2022.00474.CEECIND/CP1714/CT0030).
dc.identifier.citationSci Rep. 2025 Oct 17;15(1):36318. doi: 10.1038/s41598-025-20090-x
dc.identifier.doi10.1038/s41598-025-20090-x
dc.identifier.eissn2045-2322
dc.identifier.pmid41107264
dc.identifier.urihttp://hdl.handle.net/10400.18/10631
dc.language.isoeng
dc.peerreviewedyes
dc.publisherNature Research
dc.relationBiosystems and Integrative Sciences Institute
dc.relationBiosystems & Integrative Sciences Institute
dc.relation.hasversionhttps://www.nature.com/articles/s41598-025-20090-x
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAutism Spectrum Disorder
dc.subjectGABA
dc.subjectGlutamate
dc.subjectMagnetic Resonance Spectroscopy
dc.subjectNeurogenetics
dc.subjectSynapse
dc.subjectPerturbações do Desenvolvimento Infantil e Saúde Mental
dc.titleNeurometabolic profiles of autism spectrum disorder patients with genetic variants in specific neurotransmission and synaptic geneseng
dc.typejournal article
dcterms.referenceshttps://static-content.springer.com/esm/art%3A10.1038%2Fs41598-025-20090-x/MediaObjects/41598_2025_20090_MOESM1_ESM.xlsx
dspace.entity.typePublication
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleBiosystems & Integrative Sciences Institute
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04046%2F2019/PT
oaire.citation.issue1
oaire.citation.startPage36318
oaire.citation.titleScientific Reports
oaire.citation.volume15
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isProjectOfPublicatione8390b4d-1833-4925-a0ab-5fff0527efaa
relation.isProjectOfPublication35168786-8dfc-4a00-9759-dab3669fe1ae
relation.isProjectOfPublication.latestForDiscoverye8390b4d-1833-4925-a0ab-5fff0527efaa

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