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Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400\u2009000 sites across the genome in Romanian adoptees exposed to either extended (6\u201343 months; <jats:italic>n<\/jats:italic>=16) or limited duration (&lt;6 months; <jats:italic>n<\/jats:italic>=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (<jats:italic>n<\/jats:italic>=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (<jats:italic>CYP2E1<\/jats:italic>) on chromosome 10 (corrected <jats:italic>P<\/jats:italic>=2.98 \u00d7 10<jats:sup>\u22125<\/jats:sup>). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes.<\/jats:p>","DOI":"10.1038\/tp.2016.95","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T15:02:40Z","timestamp":1465311760000},"page":"e830-e830","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1"],"prefix":"10.1038","volume":"6","author":[{"given":"R","family":"Kumsta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S J","family":"Marzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Viana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E L","family":"Dempster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Rutter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Mill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E J S","family":"Sonuga-Barke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,6,7]]},"reference":[{"key":"BFtp201695_CR1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/nn.3093","volume":"15","author":"RJ Davidson","year":"2012","unstructured":"Davidson RJ, McEwen BS . 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He also received Speaker fees from Janssen Cilag and Consultancy from Neurotech solutions, Aarhus University, Copenhagen University and Berhanderling, Skolerne, Copenhagen, KU Leuven. He obtained Book royalties from OUP and Jessica Kingsley. He also received grants from MRC, ESRC, Wellcome Trust, Solent NHS Trust, European Union, Child Health Research Foundation New Zealand, NIHR, Nuffield Foundation, Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO) and MQ - Transforming Mental Health. The remaining authors declare no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}