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Published VersionCC BY-NC-SA V3.0, Open Access
Journal article
Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder
Translational Psychiatry, Vol.4(3), pp.1-7
2014
PMCID: PMC3966043
PMID: 24594779
Abstract
Some individuals suffering from posttraumatic stress disorder (PTSD) exhibit lower basal salivary cortisol and higher glucocorticoid receptor (GR) sensitivity. Recent studies suggest that epigenetic mechanisms regulate the activity of cortisol and GR. As a means to combine and cross-validate those findings, we compared cortisol, GR expression and promoter methylation levels in peripheral T lymphocytes of healthy controls versus individuals endorsing a diagnosis of lifetime PTSD. Thirty subjects with lifetime (current or remitted) PTSD and 16 subjects never exposed to trauma were recruited. Salivary cortisol was collected at six time points over the course of a single weekday and analyzed utilizing a time-resolved fluorescence immunoassay. GR expression (GRtotal, 1B, 1C, 1F and 1H) was measured by quantitative RT-PCR. DNA methylation levels in human glucocorticoid receptor (hGR) 1B and 1C variant's promoter were quantified by epityper in T lymphocytes isolated by magnetic-assisted cell sorting. Individuals with lifetime PTSD have lower morning cortisol release, higher mRNA expression of hGRtotal, 1B, and 1C and lower overall methylation levels in hGR 1B and 1C promoters. Cortisol levels were inversely correlated with hGR 1B mRNA expression. Moreover, overall and CpG site-specific methylation levels were inversely correlated with hGRtotal and 1B mRNA expression. There was no difference between current and remitted PTSD across cortisol, GR expression mRNA and DNA methylation data. Traumatic events induce DNA methylation alterations in distinct promoters of hGR with transcriptional modifications that associate with hypoactive hypothalamus-pituitary-adrenal axis in individuals with PTSD. Our results also point toward an important role of hGR 1B variant in PTSD. [Author Abstract] KEY WORDS: cortisol; DNA methylation; epigenetics; glucocorticoid receptors; HPA axis; PTSD
Details
- Title
- Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder
- Authors
- Benoit Labonté (Author) - McGill UniversityNelson Harold Edward AzoulayVolodymyr Yerko - McGill UniversityGustavo Turecki (Corresponding Author) - McGill UniversityAlain Brunet (Corresponding Author) - McGill University
- Publication details
- Translational Psychiatry, Vol.4(3), pp.1-7
- Publisher
- Nature Publishing Group
- Date published
- 2014
- DOI
- 10.1038/tp.2014.3
- ISSN
- 2158-3188
- PMID
- 24594779; PMC3966043
- Copyright note
- This work is licensed under a Creative Commons AttributionNonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
- Grant note
- GT and AB obtained a salary award from the Fonds de Recherche du Québec en santé (FRQ-S). BL is supported by a Frederick Banting and Charles Best doctoral fellowship from the Canadian Institutes of Health Research (CIHR).
- Organisation Unit
- Thompson Institute
- Language
- English
- Record Identifier
- 991105740502621
- Output Type
- Journal article
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