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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 (\n                    <jats:sup>1<\/jats:sup>\n                    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\n                    <jats:sup>1<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-20090-x","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:23:52Z","timestamp":1760711032000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurometabolic profiles of autism spectrum disorder patients with genetic variants in specific neurotransmission and synaptic genes"],"prefix":"10.1038","volume":"15","author":[{"given":"Joana","family":"Vilela","sequence":"first","affiliation":[]},{"given":"Andreia C.","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"In\u00eas R.","family":"Violante","sequence":"additional","affiliation":[]},{"given":"Susana","family":"Mouga","sequence":"additional","affiliation":[]},{"given":"C\u00e9lia","family":"Rasga","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Xavier","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Hugo","family":"Martiniano","sequence":"additional","affiliation":[]},{"given":"Ana Rita","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Guiomar","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Castelo-Branco","sequence":"additional","affiliation":[]},{"given":"Astrid Moura","family":"Vicente","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"20090_CR1","unstructured":"A. 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