Sleep and hypothalamic pituitary adrenal axis responses to metyrapone in posttraumatic stress disorder.
Sleep and hypothalamic pituitary adrenal axis responses to metyrapone in posttraumatic stress disorder.
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创伤后应激障碍患者对甲吡酮的睡眠和下丘脑垂体肾上腺轴反应。
DOI：
10.1016/j.psyneuen.2017.12.002
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发表时间：
2018-03
影响因子：
3.7
通讯作者：
Neylan TC
中科院分区：
文献类型：
--
作者：
Inslicht SS;Rao MN;Richards A;O'Donovan A;Gibson CJ;Baum T;Metzler TJ;Neylan TC
睡眠障碍是创伤后应激障碍（PTSD）的一个核心特征，其部分特征是由于促肾上腺皮质激素释放因子（CRF）、下丘脑-垂体-肾上腺轴（HPA）调节和糖皮质激素信号的压力相关改变而导致的delta功率睡眠减少。夜间HPA轴反应介导的睡眠障碍的男性和女性创伤后应激障碍的研究使用美吡酮挑战。美曲酮阻断皮质醇合成，消除负反馈，增加下丘脑CRF和垂体促肾上腺皮质激素（ACTH）的释放。采用实验室多导睡眠图对66名医学上健康、无药物治疗的男性和绝经前卵泡期女性进行连续3个晚上的睡眠监测，其中包括33名慢性PTSD患者（16名女性和17名男性）和33名年龄和性别匹配的对照组（14名女性和19名男性）。参与者在适应和基线睡眠后完成了一夜的美替拉酮挑战，并通过重复血液采样获得ACTH。与对照组相比，Metyrapone导致PTSD受试者ACTH增加更大，皮质醇和δ谱功率睡眠减少更大，女性ACTH增加比男性更大。甲屈拉酮对脉冲功率睡眠的影响无性别差异，甲屈拉酮与ACTH或脉冲功率睡眠的性别相互作用对PTSD的影响均不显著。回归分析表明，创伤后应激障碍受试者ACTH反应的增加与δ功率睡眠反应的减少有关，但在对照组中没有发现这种关系。PTSD组的差异在男性和女性中是相似的。这些结果表明，PTSD患者中与压力相关的下丘脑轴改变可能导致睡眠困难。以下丘脑轴为靶点的治疗方法有望在未来治疗创伤后应激障碍和相关睡眠困难。
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 obtained by repeated blood sampling. Metyrapone resulted in a greater increase in ACTH and greater decreases in cortisol and delta spectral power sleep in PTSD subjects compared to controls, and a greater increase in ACTH in women compared to men. There was no sex difference in metyrapone effects on delta power sleep, and no significant metyrapone by PTSD by sex interactions with either ACTH or delta power sleep. Regression analyses indicated that a greater increase in ACTH response was associated with a greater decrease in delta power sleep response in PTSD subjects, but no such relationship was found in controls. The PTSD group difference was similar in men and women. These results suggest that stress-related alterations of the HPA axis in PTSD may contribute to sleep difficulties. Therapeutics that target the HPA axis may offer promise as a potential future treatment for PTSD and related sleep difficulties.
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影响因子：
--
作者：
BORN, J;DEKLOET, ER;FEHM, HL
通讯作者：
FEHM, HL
影响因子：
4.4
作者：
Richards A;Metzler TJ;Ruoff LM;Inslicht SS;Rao M;Talbot LS;Neylan TC
通讯作者：
Neylan TC
影响因子：
3.2
作者：
FIAD, TM;KIRBY, JM;MCKENNA, TJ
通讯作者：
MCKENNA, TJ
DOI：
10.1016/j.ecl.2013.05.004
发表时间：
2013-09-01
影响因子：
4.5
作者：
Daskalakis, Nikolaos P.;Lehrner, Amy;Yehuda, Rachel
通讯作者：
Yehuda, Rachel
影响因子：
4.7
作者：
Landolt, HP;Borbély, AA
通讯作者：
Borbély, AA