Archival ReportLower Methylation of Glucocorticoid Receptor Gene Promoter 1F in Peripheral Blood of Veterans with Posttraumatic Stress Disorder
Section snippets
Participants and Clinical Assessment
This article reports on data from 122 participants (61 with PTSD, 61 without PTSD) in whom NR3C1-1F promoter methylation and gene expression was determined in PBMCs, in addition to other neuroendocrine biomarkers. Participants were recruited as part of a larger study that was designed as an initial investigation of male combat veterans, to be followed by a replication and longitudinal validation study in men and women. Combat veterans were recruited at two sites, the James J. Peters Veterans
Demographic and Clinical Information
Table 1 presents demographic and clinical characteristics of the PTSD+ and PTSD− groups. Because the sample was intentionally selected to be comparable in age, race, and ethnicity, there were no group differences for these variables. Early trauma exposure scores (on the Early Trauma Inventory) ranged from 0−21, and the groups did not differ. The PTSD+ group reported higher scores on measures of PTSD-related symptoms (Table 1). There were no differences in the lymphocyte or monocyte numbers or
Discussion
This is the first report of NR3C1-1F promoter methylation in purified PBMCs in individuals with PTSD. The primary focus was on DNA methylation, which is a comparatively stable biochemical modification (as opposed to GR transcription, which can vary dynamically in association with prevailing contextual influences). The NR3C1-1F promoter was examined because it is also highly active in brain tissue (22). The NR3C1-1F promoter lies within a CpG island located immediately upstream of the exon NR3C1
Acknowledgments and Disclosures
This work was supported by grant funding from the Department of Defense (Grant No. W911NF-09-1-0298 to RY and Grant No. W81XWH-09-2-0044 to CRM). We thank Dr. Owen Wolkowitz for scientific collaboration and for funding that permitted additional recruitment (Department of Defense Grant No. W81XWH-10-1-0021).
The authors report no biomedical financial interests or potential conflicts of interest.
References (44)
- et al.
The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research
Psychiatry Res
(1989) - et al.
Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors
J Psychiatr Res
(2009) - et al.
Relationship between dexamethasone-inhibited lysozyme activity in peripheral mononuclear leukocytes and the cortisol and glucocorticoid receptor response to dexamethasone
J Psychiatr Res
(2003) - et al.
Enhanced cortisol suppression to dexamethasone associated with Gulf War deployment
Psychoneuroendocrinology
(2006) - et al.
Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed
Psychoneuroendocrinology
(2010) - et al.
Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse
Biol Psychiatry
(2012) - et al.
Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood
J Psychiatr Res
(2013) - et al.
Genomic DNA methylation: The mark and its mediators
Trends Biochem Sci
(2006) - et al.
Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks
Biol Psychiatry
(2009) The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders
Psychoneuroendocrinology
(2009)
Glucocorticoid receptors in major depression: Relevance to pathophysiology and treatment
Biol Psychiatry
The corticosteroid receptor hypothesis of depression
Neuropsychopharmacology
A controlled pore glass bead assay for the measurement of cytoplasmic and nuclear glucocorticoid receptors
J Steroid Biochem
Normal lymphocyte responsiveness to lectins but impaired sensitivity to in vitro glucocorticoids in major depression
J Affect Disord
Relations among posttraumatic stress disorder, comorbid major depression, and HPA function: A systematic review and meta-analysis
Clin Psychol Rev
Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions
Nat Neurosci
Epigenetic programming by maternal behavior
Nat Neurosci
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
Nat Neurosci
Stress-related psychiatric disorders with low cortisol levels: A metabolic hypothesis
Endocrinology
Pre-existing high glucocorticoid receptor number predicting development of posttraumatic stress symptoms after military deployment
Am J Psychiatry
The development of a Clinician-Administered PTSD Scale
J Trauma Stress
Structured Clinical Interview for DSM-IV (SCID)
Cited by (221)
DNA methylation in regulatory elements of the FKBP5 and NR3C1 gene in mother-child binomials with depression
2023, Journal of Affective DisordersDNA methylation and other epigenetic modifications mediating the transgenerational impacts of paternal exposures on offspring phenotypes
2023, Sex, Gender, and Epigenetics: From Molecule to BedsideMethylation of genes and regulation of inflammatory processes on emotional response in young adults with alcoholic parents
2022, Brain, Behavior, and Immunity - HealthProminent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans
2024, Molecular Biology ReportsThe psychedelic future of post-traumatic stress disorder treatment
2024, Current Neuropharmacology