{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T03:25:35Z","timestamp":1785641135628,"version":"3.56.0"},"reference-count":28,"publisher":"Royal College of Psychiatrists","issue":"3","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH040695"],"award-info":[{"award-number":["MH040695"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH090964"],"award-info":[{"award-number":["MH090964"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec id=\"S0007125023000132_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125023000132_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT<jats:sub>1A<\/jats:sub>) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and <jats:italic>in vivo<\/jats:italic> 5-HT<jats:sub>1A<\/jats:sub> receptor binding potential (BP<jats:sub>F<\/jats:sub>) determined by positron emission tomography (PET) in 13 <jats:italic>a priori<\/jats:italic> brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).<\/jats:p><\/jats:sec><jats:sec id=\"S0007125023000132_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>Medication-free participants with MDD (<jats:italic>n<\/jats:italic> = 192: 110 female, 81 male, 1 other) and controls (<jats:italic>n<\/jats:italic> = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (\u22121019, \u22121007, \u2212681) of the 5-HT<jats:sub>1A<\/jats:sub> receptor gene. A subgroup (<jats:italic>n<\/jats:italic> = 119) had regional brain 5-HT<jats:sub>1A<\/jats:sub> receptor BP<jats:sub>F<\/jats:sub> quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BP<jats:sub>F<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125023000132_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Recent stress correlated positively with blood monocyte methylation at the \u2212681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT<jats:sub>1A<\/jats:sub> BP<jats:sub>F<\/jats:sub> in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the \u22121007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BP<jats:sub>F<\/jats:sub> in participants with MDD.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125023000132_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>These findings support a model in which recent stress increases 5-HT<jats:sub>1A<\/jats:sub> receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2023.13","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T09:21:54Z","timestamp":1688376114000},"page":"415-421","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":4,"title":["Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression"],"prefix":"10.1192","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7156-6106","authenticated-orcid":false,"given":"Hanga","family":"Galfalvy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Shea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"de Vegvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiro","family":"Pantazatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-yu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainsley K.","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Elizabeth","family":"Sublette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Oquendo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Zanderigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0265-6586","authenticated-orcid":false,"given":"J. John","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"S0007125023000132_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.03.023"},{"key":"S0007125023000132_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(14)70220-2"},{"key":"S0007125023000132_ref18","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200007000-00011"},{"key":"S0007125023000132_ref3","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-012-0337-4"},{"key":"S0007125023000132_ref19","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.52"},{"key":"S0007125023000132_ref21","volume-title":"R: A Language and Environment for Statistical Computing","year":"2020"},{"key":"S0007125023000132_ref22","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxi044"},{"key":"S0007125023000132_ref9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3769-04.2005"},{"key":"S0007125023000132_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2008.07.012"},{"key":"S0007125023000132_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.01.006"},{"key":"S0007125023000132_ref11","volume-title":"Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition. 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Published by Cambridge University Press on behalf of the Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}