Urinary Free-Cortisol Levels in Posttraumatic Stress Disorder Patients

Mason, John W.; Giller, Earl L.; Kosten, Thomas R.; Ostroff, Robert; Podd, Linda

doi:10.1097/00005053-198603000-00003

Cited by 413 publications

(181 citation statements)

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“…However, there seems to be controversy about alterations in CORT levels. Both increased levels (Lemieux and Coe, 1995;Maes et al, 1998) and decreased levels (Mason et al, 1986;Pitman and Orr, 1990;Yehuda et al, 1990Yehuda et al, , 1995Boscarino, 1996) of CORT have been found in PTSD patients compared with individuals without PTSD. The disagreement of these results suggests that a simple change in CORT levels in itself cannot explain the symptoms of the disorder.…”

Section: Animal Model Translation To Ptsdmentioning

confidence: 99%

Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress

Perusini

Meyer

Long

et al. 2015

Neuropsychopharmacol

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Fear promotes adaptive responses to threats. However, when the level of fear is not proportional to the level of threat, maladaptive fear-related behaviors characteristic of anxiety disorders result. Post-traumatic stress disorder develops in response to a traumatic event, and patients often show sensitized reactions to mild stressors associated with the trauma. Stress-enhanced fear learning (SEFL) is a rodent model of this sensitized responding, in which exposure to a 15-shock stressor nonassociatively enhances subsequent fear conditioning training with only a single trial. We examined the role of corticosterone (CORT) in SEFL. Administration of the CORT synthesis blocker metyrapone prior to the stressor, but not at time points after, attenuated SEFL. Moreover, CORT co-administered with metyrapone rescued SEFL. However, CORT alone without the stressor was not sufficient to produce SEFL. In these same animals, we then looked for correlates of SEFL in terms of changes in excitatory receptor expression. Western blot analysis of the basolateral amygdala (BLA) revealed an increase in the GluA1 AMPA receptor subunit that correlated with SEFL. Thus, CORT is permissive to trauma-induced changes in BLA function.

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Section: Animal Model Translation To Ptsdmentioning

confidence: 99%

Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress

Perusini

Meyer

Long

et al. 2015

Neuropsychopharmacol

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“…Increased hypothalamic CRF has also been inferred from a number of studies that have found elevated cortisol levels in PTSD (De Bellis et al, 1999;Lemieux and Coe, 1995;Liberzon et al, 1999;Maes et al, 1998;Pitman and Orr, 1990). Despite possible elevated hypothalamic CRF activity, PTSD subjects in a large number of studies have been found to have either normal (Baker et al, 1999) or decreased 24-h urinary cortisol (Mason et al, 1986;Yehuda et al, 1995;Yehuda et al, 1990), normal (Kellner et al, 2002) or decreased plasma cortisol (Jensen et al, 1997;Yehuda et al, 1996b), increased lymphocyte glucocorticoid receptors (Yehuda et al, 1991), normal (Kosten et al, 1990) or increased suppression of cortisol in response to dexamethasone (Goenjian et al, 1996;Grossman et al, 1996;Stein et al, 1997;Yehuda et al, 1993), and a buffered ultradian pattern of cortisol release (Yehuda et al, 1996b). Most of these findings are consistent with the hypothesis that PTSD is associated with enhanced negative feedback of the HPA axis, or reduced adrenal output, or a combination of these two mechanisms (for a review, see Yehuda, 2002).…”

Section: Introductionmentioning

confidence: 94%

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Neylan

Lenoci

Maglione

et al. 2003

Neuropsychopharmacol

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Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combatrelated PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD.

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“…It is perhaps more accurate to conclude that such alterations have not always been detected; perhaps reflecting that cortisol levels are dynamic and subject to a large degree of measurement error and individual variation. The initial observation by Mason et al demonstrated that cortisol levels were significantly lower in combat veterans with PTSD than other psychiatric patients even though they showed sustained elevations in urinary catecholamine levels [1]. These observations were later confirmed by carefully controlled studies of plasma cortisol release over the diurnal cycle [2,3].…”

mentioning

confidence: 96%

“…That glucocorticoids decrease the retrieval of fear memories was the explanation initially posited for the observation that patients who received high doses of glucocorticoids for the treatment of septic shock were significantly less likely to suffer from traumatic recollections of the event or to develop PTSD [12,13]. Subsequent small randomized trials provide preliminary evidence that the effects of glucocorticoids in the prevention of PTSD resulted from decreasing the traumatizing effects of the memory [1,14]. A pilot crossover study of low-dose glucocorticoid treatment demonstrated a significant reduction in PTSD symptoms, which the authors attributed to the effects of cortisol in impairing retrieval of traumatic memories [15].…”

mentioning

confidence: 99%