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Adverse childhood experiences (ACE) increase PTSD risk in adulthood. Epigenetic mechanisms play important roles in PTSD pathogenesis and a mutation in the <jats:italic>methyl-CpG binding protein 2<\/jats:italic> (<jats:italic>MECP2<\/jats:italic>) in mice provide susceptibility to PTSD-like alterations, with sex-dependent biological signatures. The present study examined whether the increased risk of PTSD associated with ACE exposure is accompanied by reduced <jats:italic>MECP2<\/jats:italic> blood levels in humans, with an influence of sex. <jats:italic>MECP2<\/jats:italic> mRNA levels were analyzed in the blood of 132 subjects (58 women). Participants were interviewed to assess PTSD symptomatology, and asked to retrospectively report ACE. Among trauma-exposed women, <jats:italic>MECP2<\/jats:italic> downregulation was associated with the intensification of PTSD symptoms linked to ACE exposure. <jats:italic>MECP2<\/jats:italic> expression emerges as a potential contributor to post-trauma pathophysiology fostering novel studies on the molecular mechanisms underlying its potential sex-dependent role in PTSD onset and progression.<\/jats:p>","DOI":"10.1038\/s41398-023-02529-9","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T15:02:04Z","timestamp":1688742124000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Methyl-CpG binding protein 2 expression is associated with symptom severity in patients with PTSD in a sex-dependent manner"],"prefix":"10.1038","volume":"13","author":[{"given":"Livia","family":"Cosentino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1571-1468","authenticated-orcid":false,"given":"Stephanie H.","family":"Witt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6188-807X","authenticated-orcid":false,"given":"Helene","family":"Dukal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2507-0542","authenticated-orcid":false,"given":"Francesca","family":"Zidda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Siehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4809-5398","authenticated-orcid":false,"given":"Herta","family":"Flor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6508-1206","authenticated-orcid":false,"given":"Bianca","family":"De Filippis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"2529_CR1","doi-asserted-by":"publisher","first-page":"1353383.","DOI":"10.1080\/20008198.2017.1353383","volume":"8","author":"RC Kessler","year":"2017","unstructured":"Kessler RC, Aguilar-Gaxiola S, Alonso J, Benjet C, Bromet EJ, Cardoso G, et al. 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