{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:56:04Z","timestamp":1762430164856,"version":"build-2065373602"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>\n                    Epigenetic regulation is significantly altered in individuals with alcohol use disorder (AUD), representing a promising avenue for understanding its pathomechanisms and developing new therapies. In an earlier epigenome-wide study of CD3+ T cells, we identified\n                    <jats:italic>SYNGAP1<\/jats:italic>\n                    \u2013a critical regulator of synaptic plasticity that influences neuronal communication and network remodeling\u2013as epigenetically dysregulated, with significantly lower DNA methylation (DNAm) in patients than controls. After three weeks of inpatient withdrawal,\n                    <jats:italic>SYNGAP1<\/jats:italic>\n                    DNAm increased to control levels. In the present study, we aimed to validate these differential\n                    <jats:italic>SYNGAP1<\/jats:italic>\n                    DNAm levels in an independent cohort of 64 AUD patients and 83 healthy controls in peripheral blood and saliva, to assess its potential as a biomarker. Using a linear mixed-effects model including AUD status and covariates, no significant differences were observed.\n                    <jats:italic>Post hoc<\/jats:italic>\n                    analyses revealed an unexpected pattern: In blood,\n                    <jats:italic>SYNGAP1<\/jats:italic>\n                    DNAm was higher in patients before treatment than controls, with no difference after withdrawal; in saliva, no differences or therapy effects were detected. Overall, these results did not confirm our previous findings, suggesting limited value of\n                    <jats:italic>SYNGAP1<\/jats:italic>\n                    DNAm as a biomarker for AUD. While blood methylation showed some association, the effect direction contradicted earlier results, and saliva showed no signal. Further research is needed to clarify\n                    <jats:italic>SYNGAP1<\/jats:italic>\n                    epigenetic regulation in AUD and its potential relevance for biomarkers or therapy.\n                  <\/jats:p>","DOI":"10.3389\/fpsyt.2025.1661760","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:48:02Z","timestamp":1762429682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic regulation of SYNGAP1 in alcohol use disorder in whole blood and 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