Glucocorticoid receptor polymorphisms and post-traumatic stress disorder

Bachmann, Anthony W., Sedgley, Teresa L., Jackson, Richard V., Gibson, John N., Young, Ross McD. and Torpy, David J. (2005) Glucocorticoid receptor polymorphisms and post-traumatic stress disorder. Psychoneuroendocrinology, 30 3: 297-306. doi:10.1016/j.psyneuen.2004.08.006


Author Bachmann, Anthony W.
Sedgley, Teresa L.
Jackson, Richard V.
Gibson, John N.
Young, Ross McD.
Torpy, David J.
Title Glucocorticoid receptor polymorphisms and post-traumatic stress disorder
Journal name Psychoneuroendocrinology   Check publisher's open access policy
ISSN 0306-4530
Publication date 2005-04-01
Sub-type Article (original research)
DOI 10.1016/j.psyneuen.2004.08.006
Open Access Status Not Open Access
Volume 30
Issue 3
Start page 297
End page 306
Total pages 10
Editor N. H. Kalin
R. Dantzer
Place of publication UK
Publisher Pergamon-Elsevier Science Ltd
Language eng
Subject C1
321004 Endocrinology
321021 Psychiatry
730211 Mental health
Abstract Post-traumatic stress disorder (PTSD) is reported in some studies to be associated with increased glucocorticoid (GC) sensitivity. Two common glucocorticoid receptor (GR) potymorphisms (N363S and 8cll) appear to contribute to the population variance in GC sensitivity. There is some evidence that there may be a genetic predisposition to PTSD. Hence we studied 118 Vietnam war veterans with PTSD for (i) GR polymorphisms, particularly the N363S and the Bcll polymorphisms which are thought to be GC sensitising, and (ii) two measures of GC sensitivity, the tow-dose 0.25 mg dexamethasone suppression test (LD-DST) and the dermal vasoconstrictor assay (DVVA). The DST and GR polymorphisms were also performed in 42 combat exposed Vietnam war veterans without PTSD. Basal plasma cortisol levels were not significantly different in PTSD (399.5 +/- 19.2 nmol/L, N=75) and controls (348.6 +/- 23.0 nmol/L, N = 33) and the LD-DST resulted in similar cortisol suppression in both groups (45.6 +/- 3.2 vs. 40.8 +/- 4.1%). The cortisol suppression in PTSD patients does not correlate with Clinician Administered PTSD Scores (CAPS), however there was a significant association between the Bcll GG genotype and low basal cortisol levels in PTSD (P=0.048). The response to the DVVA was similar to controls (945 +/- 122, N = 106 vs. 730 +/- 236, N = 28, P = 0.42). PTSD patients with the GG genotype, however, tended to be more responsive to DVVA and in this group the DVVA correlated with higher CAPS scores. The only exon 2 GR polymorphisms detected were the R23K and N363S. Heterozygosity for the N363S variant in PTSD, at 5.1% was not more prevalent than in other population studies of the N363S polymorphism in Caucasians (6.0-14.8%). The GG genotype of the Bcll polymorphism found to be associated with increased GC sensitivity in many studies showed a tendency towards increased response with DVVA and correlated with higher CAPS scores. In conclusion, the N363S and Bcll GR polymorphisms were not more frequent in PTSD patients than controls and reported population frequencies. Our PTSD group did not display GC hypersensitivity, as measured by the LD-DST and DVVA. In a subset of PTSD patients with the Bcll GG genotype, CAPS scores and basal cortisol Levels were negatively correlated. (C) 2004 Elsevier Ltd. All rights reserved.
Keyword Endocrinology & Metabolism
Neurosciences
Glucocorticoid Receptor Polymorphisms
Glucocorticoid Sensitivity
Post-traumatic Stress Disorder
Cortisol
Low-dose Dexamethasone Suppression Test
Dermal Vessel Vasoconstrictor Assay
Pituitary-adrenal Axis
Fragment-length-polymorphism
Plasma-cortisol
Dexamethasone Suppression
Psychophysiological Responses
Feedback Sensitivity
Vietnam Veterans
Gene
Association
Activation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 16:23:06 EST