Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620274
Title:
Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.
Authors:
Kumsta, R.; Marzi, S. J.; Viana, J.; Dempster, E. L.; Crawford, B.; Rutter, M. K.; Mill, Jonathan; Sonuga-Barke, E. J. S.
Abstract:
Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. 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 ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6-43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=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 (CYP2E1) on chromosome 10 (corrected P=2.98 × 10(-5)). 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.
Citation:
Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1. 2016, 6 (6):e830 Transl Psychiatry
Publisher:
Nature
Journal:
Translational psychiatry
Issue Date:
7-Jun-2016
URI:
http://hdl.handle.net/11287/620274
DOI:
10.1038/tp.2016.95
PubMed ID:
27271856
Additional Links:
http://dx.doi.org/10.1038/tp.2016.95
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
2158-3188
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorKumsta, R.en
dc.contributor.authorMarzi, S. J.en
dc.contributor.authorViana, J.en
dc.contributor.authorDempster, E. L.en
dc.contributor.authorCrawford, B.en
dc.contributor.authorRutter, M. K.en
dc.contributor.authorMill, Jonathanen
dc.contributor.authorSonuga-Barke, E. J. S.en
dc.date.accessioned2017-03-13T10:17:29Z-
dc.date.available2017-03-13T10:17:29Z-
dc.date.issued2016-06-07-
dc.identifier.citationSevere psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1. 2016, 6 (6):e830 Transl Psychiatryen
dc.identifier.issn2158-3188-
dc.identifier.pmid27271856-
dc.identifier.doi10.1038/tp.2016.95-
dc.identifier.urihttp://hdl.handle.net/11287/620274-
dc.description.abstractExposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. 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 ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6-43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=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 (CYP2E1) on chromosome 10 (corrected P=2.98 × 10(-5)). 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.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/tp.2016.95en
dc.rightsArchived with thanks to Translational psychiatryen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Psychologyen
dc.titleSevere psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.en
dc.typeJournal Articleen
dc.identifier.journalTranslational psychiatryen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

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