Neuroendocrine Regulation of Sleep Disturbances in PTSD (original) (raw)
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Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder
Neuropsychopharmacology, 2003
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 11deoxycortisol 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.
Psychoneuroendocrinology, 2017
Disturbed sleep is a core feature of posttraumatic stress disorder (PTSD), characterized in part by decreased delta power sleep that may result from stress-related alterations in corticotropin releasing factor (CRF), hypothalamic pituitary adrenal axis (HPA) regulation and glucocorticoid signaling. Overnight HPA axis response mediating sleep disturbances in men and women with PTSD was examined using a metyrapone challenge. Metyrapone blocks cortisol synthesis, removing negative feedback, and increases the release of hypothalamic CRF and pituitary adrenocorticotropic hormone (ACTH). Laboratory-based polysomnography was used to monitor the sleep of 66 medically healthy, medication-free men and pre-menopausal follicular phase women including 33 with chronic PTSD (16 women and 17 men) and 33 age- and sex-matched controls (14 women and 19 men) over 3 consecutive nights. Participants completed an overnight metyrapone challenge after an adaptation and baseline night of sleep and ACTH was o...
Hypothalamic–Pituitary–Adrenal Axis Activity and Sleep in Posttraumatic Stress Disorder
Neuropsychopharmacology, 2005
Alterations of the hypothalamic–pituitary–adrenal (HPA) axis and sleep disturbances have been described separately in post-traumatic stress disorder (PTSD). It is not known if HPA alterations and sleep disturbances are associated in PTSD. This study examined sleep and HPA activity in 20 male medication-free subjects with PTSD and 16 matched healthy controls. Two nights of polysomnography were obtained and 24-h urinary
Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD
Biological Psychiatry, 1995
In association with sleep recording, subjects saved their urine for 24 hours in three 8-hour collections in order to obtain "daytime" (8:00 AM to 4-00 PM, 4-00 P M tO MN) and "nocturnal" (MN to 8:00 AM) catecholamine measures. PTSD patients had decreased sleep efficiency relative to controls and increased REM density; 24-hour norepinephrine and MHPG (the more centrally derived metabolite ) did not differ between patients and controls. "Nocturnal" excretion of MHPG minus the average of the two "daytime" values was negative in the controls, slightly' positive in the patients, and differed significantly between the two groups. "Nocturnal minus daytime" MHPG also correlated negatively with total sleep time in the PTSD patients (R = -.45, p < .05). Our data support a relationship of nondiminished central noradrenergic activity at night, and sleep disturbance, in chronic', combat-related PTSD.
A Multidimensional Approach to Post-Traumatic Stress Disorder - from Theory to Practice, 2016
Stress-induced alterations in sleep have been linked to the development of posttraumatic stress disorder (PTSD) and sleep complaints and disturbances in arousal are continuing symptoms in patients. PTSD-related changes in sleep have not been fully characterized but involve persistent disturbances in both rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). PTSD is considered a disorder of the fear circuitry, which includes the amygdala, dorsal anterior cingulate, hippocampus, and ventromedial prefrontal cortex. Currently, several animal models are used to examine the underlying neurobiology of PTSD; however, sleep has been characterized in only a limited number of models. Intense conditioned fear training, which may best model PTSD in rodents, can produce reductions in REMS as well as alterations in NREMS that may vary with mouse and rat strains. The amygdala, a central region in current concepts of PTSD, plays significant roles in regulating the stress response and changes in stress-induced alterations in arousal and sleep. This chapter reviews sleeprelated findings in patients with PTSD and in animal experimental paradigms currently utilized to model the disorder, as well as the neurobiology that has been linked to disturbed sleep in PTSD. It will also discuss the impact of PTSD treatments on sleep disturbances.
Background: Nightmares and insomnia in PTSD are hallmark symptoms, yet poorly understood in comparison to the advances toward a biological framework for the disorder. According to polysomnography (PSG), only minor changes in sleep architecture were described. This warrants alternative methods for assessing sleep regulation in PTSD. Methods: After screening for obstructive sleep apnea and period limb movement disorder, veterans with PTSD (n = 13), trauma controls (TCs, n = 17) and healthy controls (HCs, n = 15) slept in our sleep laboratory on two consecutive nights with an IV catheter out of which blood was sampled every 20 min from 22:00 h to 08:00 h. Nocturnal levels of plasma adrenocorticotropic hormone (ACTH), cortisol, melatonin were assessed in conjunction with PSG registration, as well as subjective sleep parameters. Results: PTSD patients showed a significant increase in awakenings during sleep in comparison to both control groups. These awakenings were correlated with ACTH levels during the night, and with the subjective perception of sleep depth. Also, heart rate (HR) was significantly increased in PTSD patients as compared with both control groups. The diurnal regulation of ACTH, cortisol and melatonin appeared undisturbed. PTSD patients exhibited lower cortisol levels at borderline
Neurobiology of Sleep and Sleep Treatments in PTSD (NOS-STIP)
2010
Approved for public release; distribution unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation.
Sleep Medicine Reviews, 2008
Posttraumatic stress disorder (PTSD) is a prevalent disorder that is associated with poor clinical and health outcomes, and considerable health care utilization and costs. Recent estimates suggest that 5% to 20% of military personnel who serve in current conflicts in Iraq and Afghanistan meet diagnostic criteria for PTSD. Clinically, sleep disturbances are core features of PTSD that are often resistant to first-line treatments, independently contribute to poor daytime functioning, and often require sleep-focused treatments. Physiologically, these observations suggest that PTSD is partially mediated by sleep disruption and its neurobiological correlates that are not adequately addressed by first-line treatments. However, polysomnographic studies have provide limited insights into the neurobiological underpinnings of PTSD during sleep. There is an urgent need to apply state-of-thescience sleep measurement methods to bridge the apparent gap between the clinical significance of sleep disturbances in PTSD and the limited understanding of their neurobiological underpinnings. Here, we propose an integrative review of findings derived from neurobiological models of fear conditioning and fear extinction, PTSD, and sleep-wake regulation suggest that the amygdala and medial prefrontal cortex can directly contribute to sleep disturbances in PTSD. Testable hypotheses regarding the neurobiological underpinnings of PTSD across the sleep-wake cycle are offered.