Glucocorticoid receptor polymorphisms and post-traumatic stress disorder

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.

Randomised controlled trial of health assessments for older Australian veterans and war widows

Objective: To assess the effect of home-based health assessments for older Australians on health-related quality of life, hospital and nursing home admissions, and death. Design: Randomised controlled trial of the effect of health assessments over 3 years. Participants and setting: 1569 community-living veterans and war widows receiving full benefits from the Department of Veterans' Affairs and aged 70 years or over were randomly selected in 1997 from 10 regions of New South Wales and Queensland and randomly allocated to receive either usual care (n = 627) or health assessments (n = 942). Intervention: Annual or 6-monthly home-based health assessments by health professionals, with telephone follow-up, and written report to a nominated general practitioner. Main outcome measures: Differences in health-related quality of life, admission to hospital and nursing home, and death over 3 years of follow-up. Results: 3-year follow-up interviews were conducted for 1031 participants. Intervention-group participants who remained in the study reported higher quality of life than control-group participants (difference in Physical Component Summary score, 0.90; 95% CI, 0.05-1.76; difference in Mental Component Summary score, 1.36; 95% CI, 0.40-2.32). There was no significant difference in the probability of hospital admission or death between intervention and control groups over the study period. Significantly more participants in the intervention group were admitted to nursing homes compared with the control group (30 v 7; P < 0.01). Conclusions: Health assessments for older people may have small positive effects on quality of life for those who remain resident in the community, but do not prevent deaths. Assessments may increase the probability of nursing-home placement.