Editors' ChoicePosttraumatic Stress Disorder

Stress signal ACTs to hinder sleep in PTSD

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Science Translational Medicine  20 Dec 2017:
Vol. 9, Issue 421, eaar4439
DOI: 10.1126/scitranslmed.aar4439

Abstract

Adrenocorticotropic hormone (ACTH) modulation is associated with sleep disturbances in individuals with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder that occurs after a psychological traumatic event and increases individual vulnerability to adverse health outcomes in both military and civilian populations. PTSD is heterogeneous, often presenting with re-experiencing, avoidance, numbing, and hyperarousal symptoms, as well as sleep disturbances. While alterations in stress axis function in those with PTSD have been implicated in the pathophysiology of dysregulated fear responses central to the disorder, it remains unclear how the stress axis influences sleep in PTSD. To address this gap in knowledge, Inslicht and colleagues designed a pharmacological challenge study to characterize the effects of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) on delta power electroencephalographic (EEG) activity during sleep, previously shown to be perturbed in PTSD.

Polysomnography and serial blood sampling were used to monitor the effects of metyrapone (a cortisol synthesis blocker that increases endogenous CRF and ACTH release) on sleep and circulating concentrations of cortisol and ACTH in 33 medication-free men and women with PTSD and 33 matched controls. Data showed that metyrapone administration resulted in significantly greater increases in ACTH and greater attenuations in cortisol and delta power EEG activity during sleep in individuals with PTSD compared with controls. Furthermore, greater increases in ACTH upon metyrapone administration predicted greater decreases in delta power only in individuals with PTSD. Overall, these results suggest that alterations in stress axis function in PTSD contribute to sleep disturbances associated with the disorder. The mechanisms underlying the differences between healthy and PTSD subjects remain unknown, as alterations in CRF, ACTH, and/or cortisol signaling and receptor sensitivity could all be responsible for the described effects. Future studies are necessary to determine whether drugs that target the stress axis, such as CRF and glucocorticoid antagonists, are beneficial for sleep disturbances in those with PTSD, and to identify other biological signals that may influence the stress axis to impact sleep.

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