Search

Background Enhanced glucocorticoid receptor (GR) sensitivity is present in people with posttraumatic stress disorder (PTSD), but the molecular mechanisms of GR sensitivity are not understood. Epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained PTSD symptoms given that PTSD develops in only a subset of trauma survivors. Methods Cytosine methylation of a relevant promoter of the GR gene ( NR3C1 -1 F promoter) and three functional neuroendocrine markers of hypothalamic-pituitary-adrenal axis function were examined in a sample of 122 combat veterans. Results Lower NR3C1 -1 F promoter methylation in peripheral blood mononuclear cells (PBMCs) was observed in combat veterans with PTSD compared with combat-exposed veterans who did not develop PTSD. NR3C1 -1 F promoter methylation was also associated with three functional measures of glucocorticoid activity that have been associated with PTSD in combat veterans: PBMCs' lysozyme inhibition on the lysozyme suppression test, plasma cortisol decline on the low-dose (.50 mg) dexamethasone suppression test, and 24-hour urinary cortisol excretion. Finally, NR3C1 -1 F promoter methylation was inversely correlated with clinical markers and symptoms associated with PTSD. Conclusions Alterations in NR3C1 -1 F promoter methylation may reflect enduring changes resulting from combat exposure that lead to functional neuroendocrine alterations. Because epigenetic measures are thought to reflect enduring effects of environmental exposures, they may be useful in distinguishing combat-exposed veterans who do or do not develop PTSD.

The hypothalamic-pituitary-adrenal axis is a major stress response system hypothesized to be involved in the pathogenesis of posttraumatic stress disorder (PTSD). However, few studies have prospectively examined the relationships among pre-exposure hypothalamic-pituitary-adrenal activity, acute stress reactions and PTSD.Two hundred ninety-six police recruits were assessed during academy training before critical incident exposure and provided salivary cortisol at first awakening and after 30 minutes. A measure of cortisol awakening response (CAR) was computed as the change in cortisol level from the first to the second collection. At 12, 24, and 36 months following the start of active police service, officers were assessed for peritraumatic distress, peritraumatic dissociation, acute stress disorder (ASD) symptoms, and PTSD symptoms to their self-identified worst duty-related critical incident. Mixed models for repeated measures were used to analyze the effects of CAR on the outcome variables pooled across the three follow-up assessments.After controlling for time of awakening, first awakening cortisol levels, and cumulative critical incident stress exposure, CAR during academy training was associated with greater peritraumatic dissociation, β = .14, z = 3.49, p.0001, and greater ASD symptoms during police service assessed at 12, 24, and 36 months, β = .09, Z = 2.03, p.05, but not with peritraumatic distress, β = .03, z = .81, p = .42, or PTSD symptoms, β = -.004, z = -.09, p = .93.These findings suggest that greater cortisol response to awakening is a pre-exposure risk factor for peritraumatic dissociation and ASD symptoms during police service.

Childhood trauma is a risk factor for anxiety disorders in adulthood. One possible mechanism for this association is an increased neuroendocrine response to stress in adults with a history of childhood trauma.In a cross-sectional study, 76 police academy recruits (mean [+/-SD] age 28 +/- 5 years, 10 female) were exposed to a video depicting real-life officers exposed to highly stressful incidents. Salivary cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG, the major metabolite of norepinephrine) were collected at baseline, immediately after the video, and 20 min after the video. Childhood trauma before age 14 was assessed with an interview (Life Stressor Checklist-Revised).Exposure to the video elicited significant MHPG and cortisol responses in both groups. Recruits with childhood trauma histories (n = 16) had a significantly greater MHPG response, as evidenced by a group effect (F = 8.0, p.01), and a group x time interaction (F = 4.1, p.05). The cortisol response did not differ between groups.Police academy recruits with childhood trauma histories have an increased catecholamine response to psychological stress. This might serve as a risk factor for anxiety disorders in recruits, and these findings might generalize to other groups with a history of childhood trauma.