Neuroendocrine and Psychophysiologic Responses in PTSD: A Symptom Provocation Study

Liberzon, Israel; Abelson, James L.; Flagel, Shelly B.; Raz, Jonathan; Young, Elizabeth A.

doi:10.1016/s0893-133x(98)00128-6

Cited by 252 publications

(151 citation statements)

References 41 publications

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“…That finding is in agreement with our results and suggests that cortisol levels are low in comorbid MDE and PTSD as has been shown in PTSD alone. However, not all studies find low cortisol with PTSD alone (Liberzon et al, 1999;Pitman and Orr, 1990;Lemieux and Coe, 1995;Maes et al, 1999;Smith et al, 1989;Baker et al, 1999), perhaps because of subject selection, diagnostic criteria utilized, or other methodological issues. Although hypersuppression in response to dexamethasone has been reported in sexual abuse victims, most of whom had PTSD, compared to normal controls (Stein et al, 1997), normal suppression (Dinan et al, 1990;Halbreich et al, 1989) has also been reported.…”

Section: Hpa Axis Hypoactivity In Ptsd+mdementioning

confidence: 99%

Lower Cortisol Levels in Depressed Patients with Comorbid Post-Traumatic Stress Disorder

Oquendo

Echavarría

Galfalvy

et al. 2002

Neuropsychopharmacol

104

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Post-traumatic stress disorder (PTSD) is often comorbid with major depressive episodes (MDEs) and both conditions carry a higher rate of suicidal behavior. Hypothalamic-pituitary-adrenal (HPA) axis and serotonin abnormalities are associated with both conditions and suicidal behavior, but their inter-relation is not known. We determined cortisol response to placebo or fenfluramine in MDE, MDE and PTSD (MDE+PTSD), and healthy volunteers (HVs) and examined the relation of cortisol responses to suicidal behavior. A total of 58 medication-free patients with MDE (13 had MDE+PTSD) and 24 HVs were studied. They received placebo on the first day and fenfluramine on the second day. Cortisol levels were drawn before challenge and for 5 h thereafter. The MDE+PTSD group had the lowest plasma cortisol, the MDE group had the highest, and HVs had intermediate levels. There were no group differences in cortisol response to fenfluramine. Suicidal behavior, sex, and childhood history of abuse were not predictors of baseline or postchallenge plasma cortisol. Cortisol levels increased with age. This study finds elevated cortisol levels in MDE and is the first report of lower cortisol levels in MDE+PTSD. The findings underscore the impact of comorbidity of PTSD with MDE and highlight the importance of considering comorbidity in psychobiology.

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Section: Hpa Axis Hypoactivity In Ptsd+mdementioning

confidence: 99%

Lower Cortisol Levels in Depressed Patients with Comorbid Post-Traumatic Stress Disorder

Oquendo

Echavarría

Galfalvy

et al. 2002

Neuropsychopharmacol

104

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“…Increased hypothalamic CRF in PTSD is thought to explain, in part, the blunted ACTH response to CRF in PTSD found in some (Heim et al, 2001;Smith et al, 1989) but not all studies (Kellner et al, 2002;Rasmusson et al, 2001). 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).…”

Section: Introductionmentioning

confidence: 99%

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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“…[8][9][10][11] Over the last decade many studies have reported on the activity of the HPA axis in PTSD, but these studies did not always report consistent findings. [12][13][14][15][16][17][18][19][20][21] Preclinical research has shown that the central nervous system, the endocrine system and the immune system closely interact. 22 Traumatic or chronic stress may therefore have an effect on the regulation of both HPA axis 8,11 and immune system 23,24 separately, as well as on their interaction.…”

Section: Introductionmentioning

confidence: 99%

Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder

et al. 2007

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Post-traumatic stress disorder (PTSD) is associated with a dysregulation of the hypothalamus-pituitary-adrenal axis (HPA axis). In addition, there is evidence for altered glucocorticoid receptor (GR) expression and function in peripheral blood mononuclear cells. The aim of the present study was to differentiate between the effect of trauma exposure and PTSD on leukocyte GR expression and glucocorticoid immune regulation. Leukocyte GR binding characteristics and glucocorticoid sensitivity of immune activity, determined as the effect of dexamethasone (DEX) on in vitro cytokine release and T-cell proliferation, were compared between veterans with PTSD, traumatized veterans without PTSD and healthy controls. Leukocyte GR density was significantly lower in veterans with and without PTSD compared to healthy controls. DEX-induced inhibition of T-cell proliferation was significantly lower in PTSD compared to trauma and healthy controls. DEX-induced increase in lipopolysaccharidestimulated interleukin-10 was less pronounced in traumatized veterans with and without PTSD compared to healthy controls. No group differences were observed in the effect of DEX on other cytokines or in baseline immune activity, except for lower tumor necrosis factor-a production in PTSD patients compared to healthy controls. The results suggest that trauma exposure is sufficient to induce changes in GR binding characteristics, whereas resistance of T-cell proliferation to DEX only occurs in PTSD. DEX resistance of in vitro immune activity was not a general phenomenon, but was restricted to specific immune functions.

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Neuroendocrine and Psychophysiologic Responses in PTSD: A Symptom Provocation Study

Abstract: Biological research on post-traumatic stress disorder (PTSD) has focused on autonomic, sympatho-adrenal, and hypothalamo-pituitary-adrenal (HPA)

Cited by 252 publications

References 41 publications

Lower Cortisol Levels in Depressed Patients with Comorbid Post-Traumatic Stress Disorder

Lower Cortisol Levels in Depressed Patients with Comorbid Post-Traumatic Stress Disorder

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder

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