The cortisol and glucocorticoid receptor response to low dose dexamethasone administration in aging combat veterans and holocaust survivors with and without posttraumatic stress disorder (original) (raw)
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Journal of Psychiatric Research, 2008
Reports about alterations of hypothalamic-pituitary-adrenocortical (HPA) function in patients with chronic posttraumatic stress disorder (PTSD) are inconsistent and controversial. More refined laboratory tests and subgrouping of PTSD patients might help to decrease variance of findings. 14 subjects with chronic PTSD and 14 healthy controls were examined between 13:00 and 17:00 using a modified combined dexamethasone/CRH test (0.5 mg dexamethasone at 23:00, 100 microg CRH at 15:00). Plasma adenocorticotropic hormone (ACTH), cortisol and blood pressure were measured every 15 min from 14:45 until 17:00. No significant differences between patients and controls were found in the analyses of ACTH and cortisol levels, but a significantly elevated systolic and diastolic blood pressure in PTSD. Severity of depressive symptoms had no influence. However, explorative analyses showed that patients with a history of childhood traumatization had significantly higher post-dexamethasone-ACTH levels and a significantly lower diastolic blood pressure in comparison to patients without early trauma. In this first pilot study in a typical clinical sample of patients with chronic PTSD we found effects of severe adverse events in childhood on HPA axis regulation. Maybe, childhood traumatization could influence HPA axis findings in PTSD. Further research is needed, especially dose-response studies with different doses of dexamethasone in dexamethasone/CRH tests in PTSD.
Biological Psychiatry, 2001
Background: Decreased basal cortisol levels have been reported in individuals with posttraumatic stress disorder (PTSD). There is evidence for enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD, which could account for this, but other possible mechanisms have not been ruled out. We examined the HPA axis employing a metyrapone-cortisol infusion protocol designed to study negative feedback sensitivity. Methods: Vietnam combat trauma-exposed subjects met DSM-IV criteria for PTSD. Exclusion criteria included substance abuse and most medications. Endogenous feedback inhibition was removed by blocking cortisol synthesis with oral metyrapone and reintroduced by intravenous infusion of cortisol. In a placebo condition, subjects received oral placebo and normal saline infusion. Serial blood samples drawn over 4 hours were assayed for adrenocorticotrophic hormone (ACTH), cortisol, and 11deoxycortisol. Selected samples were assayed for cortisol binding globulin (CBG) and dehydroepiandrosterone (DHEA). Results: Basal plasma cortisol was significantly decreased in PTSD subjects (n ϭ 13) compared with control subjects (n ϭ 16). No significant difference in the ACTH response to cortisol infusion following metyrapone was observed; however 11-deoxycortisol was significantly decreased in PTSD subjects. In addition, CBG was significantly increased in PTSD subjects, and DHEA was significantly decreased in both PTSD and combat-exposed control subjects. Conclusions: These observations suggest decreased adrenocortical responsiveness may be an additional or alternative mechanism accounting for low cortisol in PTSD.
Open Access Macedonian Journal of Medical Sciences, 2014
Aim: To further examine the neurobiological mechanisms and their outcomes responsible for the PTSD sequelae induced by laboratory animal model and to explore the effects of chronic psychosocial paradigm. We tested the hypothesis that our animal model of PTSD would display abnormalities in glucocorticoid levels that are manifest in people with PTSD and that psychosocially stressed rats exhibit a significantly greater suppression of corticosterone levels than control rats following the administration of dexamethasone.Methods: Animals were divided into two groups. The experimental group was scheduled to exposure to two types of stressors: double exposure to acute immobilization stress, and combined predator-threat stress and daily social stress. There was also administration of dexamethasone in combination with stress exposure.Results: There was a statistical difference between masses of thymus in the stress group and stress group with dexamethasone appliance (p=0.024). We found statis...
Hypothalamus-pituitary-adrenal axis functioning and glucocorticoid receptor number on lymphocyte subsets were investigated in patients with posttraumatic stress disorder related to type I trauma, trauma-exposed subjects without posttraumatic stress disorder and trauma-unexposed control subjects (n=13 per group) applying a detailed endocrinological assessment. Salivary cortisol profiles were obtained, first, as diurnal baseline cortisol (unstimulated), and second, after dexamethasone administration (stimulated cortisol) to investigate the negative feedback inhibition of the hypothalamus-pituitary-adrenal axis. For further assessment of glucocorticoid receptor binding, glucocorticoid receptor counts on lymphocytes were obtained from blood samples. After stimulation with dexamethasone, the three groups differed significantly in the mean increase of salivary cortisol in the morning, with the highest increase in the trauma group and the lowest increase in the posttraumatic stress disorde...
A combined dexamethasone/corticotropin-releasing hormone test in patients with chronic PTSD
Pharmacopsychiatry, 2007
Background. Studies of hypothalamic-pituitary-adrenal (HPA) axis function in chronic fatigue syndrome (CFS) point to hypofunction, although there are negative reports. Suggested mechanisms include a reduced hypothalamic or supra-hypothalamic stimulus to the HPA axis and enhanced sensitivity to the negative feedback of glucocorticoids. The aim of the current study was to investigate HPA axis function in CFS with the dexamethasone/corticotropin-releasing factor (Dex/CRF) test, in analogy with research in affective disorders.
Low-Dose Cortisol for Symptoms of Posttraumatic Stress Disorder
American Journal of Psychiatry, 2004
Because elevated cortisol levels inhibit memory retrieval in healthy human subjects, the present study investigated whether cortisol administration might also reduce excessive retrieval of traumatic memories and related symptoms in patients with chronic posttraumatic stress disorder (PTSD). Method: During a 3-month observation period, low-dose cortisol (10 mg/day) was administered orally for 1 month to three patients with chronic PTSD in a double-blind, placebo-controlled, crossover design. Results: In each patient investigated, there was a significant treatment effect, with cortisol-related reductions of at least 38% in one of the daily rated symptoms of traumatic memories, as assessed by self-administered rating scales. In accordance, Clinician-Administered PTSD Scale ratings assessed after each month showed cortisol-related improvements for reexperiencing symptoms and, additionally, in one patient for avoidance symptoms. Conclusions: The results of this pilot study indicate that lowdose cortisol treatment reduces the cardinal symptoms of PTSD.
Neuropsychopharmacology, 2007
Though both glucocorticoid alterations and memory impairments have been noted in posttraumatic stress disorder (PTSD), it is not clear if these phenomena are causally linked. As there is emerging evidence that these domains become further altered in PTSD with increasing age, it is of interest to examine these relationships in an older cohort. Aging (mean age, 62.778.9; range, 52-81) combat veterans with (n ¼ 13) and without (n ¼ 17) PTSD received an intravenous bolus of 17.5 mg hydrocortisone (cortisol), a naturally occurring glucocorticoid, or placebo in a randomized, double-blind manner, on two mornings approximately 1-2 weeks apart. Neuropsychological testing to evaluate episodic and working memory performance was performed 75 min later. Cortisol enhanced episodic memory performance in both groups of subjects, but enhanced elements of working memory performance only in the PTSD + group. The preferential effect of cortisol administration on working memory in PTSD may be related to the superimposition of PTSD and age, as cortisol had impairing effects on this task in a previously studied, younger cohort. The findings suggest that there may be opportunities for developing therapeutic strategies using glucocorticoids in the treatment of aging combat veterans.
Journal of Traumatic Stress, 2010
. It is unclear whether trauma exposure during adulthood in the absence of psychopathology is also associated with HPA-axis dysregulation. Thirty-six trauma-exposed peacekeepers, 23 nonexposed peacekeepers, and 25 nonexposed civilians, all without lifetime psychopathology were studied. Basal HPA-axis functioning was assessed with salivary cortisol samples obtained over 2 days. HPA-axis reactivity was assessed with the dexamethasone/corticotropin-releasing hormone test. Lower afternoon salivary cortisol levels were found in both veteran groups versus controls after adjustment for confounders. The authors concluded that this study does not support the idea that HPA-axis functioning is durably altered by trauma exposure during adulthood in men. The hypothalamic-pituitary-adrenal (HPA) axis is involved in stress-related disorders, with cortisol being the predominant corticosteroid secreted from the adrenal cortex. Since Mason, Giller, Kosten, Ostroff, and Podd (1986) first reported on low urinary free-cortisol levels in patients with posttraumatic stress disorder (PTSD), many studies on cortisol under basal and challenged conditions in patients with this disorder have been published. Thus far, most studies have focused on individuals with current or remitted stress-related disorders, making it impossible to discriminate between the possible effects of psychiatric morbidity and trauma exposure on HPA-axis functioning. In a review, reported increased salivary cortisol levels in response to a cognitive challenge, as well as more plasma cortisol suppression after administration of 0.5 mg of dexamethasone in PTSD patients versus controls without PTSD or trauma exposure. However, it was concluded that interpretation of the results The authors kindly thank the Dutch Veterans Institute, Doorn, the Netherlands for providing the opportunity to recruit the Veterans.