Vgontzas Alexandros N, Fernandez-Mendoza Julio, Lenker Kristina Puzino, Basta Maria, Bixler Edward O, Chrousos George P
Sleep Research & Treatment Center, Penn State Health Milton S. Hershey Medical Center, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania, USA.
Department of Psychiatry, University of Crete, University Hospital of Heraklion, Heraklion, Greece.
J Sleep Res. 2022 Jun;31(3):e13526. doi: 10.1111/jsr.13526. Epub 2021 Nov 25.
Although insomnia is by far the most common sleep disorder, our understanding of its neurobiology is limited. Insomnia, particularly when associated with objective sleep disturbance, has been associated with activation of the hypothalamic-pituitary-adrenal axis. The objective of this experimental study was to compare the response of the hypothalamic-pituitary-adrenal axis to ovine corticotropin-releasing hormone, a stress test, in men with insomnia versus controls. Circulating adrenocorticotropic hormone and cortisol levels were assayed before (-30 min, -15 min), at (0 min) and after (+5 min, +15 min, +30 min, +60 min, +90 min, +120 min) exogenous ovine corticotropin-releasing hormone administration in 23 men (11 insomnia, 12 controls), who underwent four consecutive nights of in-lab polysomnography. Men with insomnia compared with controls demonstrated markedly and significantly shorter total sleep time (368.4 ± 8.99 min versus 411.61 ± 8.61 min; p < 0.01) and lower sleep efficiency (76.77 ± 1.80% versus 86.04 ± 1.72%; p < 0.01) on polysomnography, and showed decreased adrenocorticotropic hormone and cortisol levels after ovine corticotropin-releasing hormone administration. Adrenocorticotropic hormone levels at 15 min and 30 min were significantly lower in men with insomnia than in controls (p < 0.05). Similarly, the peak levels of cortisol at +60 min, and the total and net area under the curve levels of this hormone were significantly lower in men with insomnia than controls (all p < 0.01). Adrenocorticotropic hormone and cortisol response to ovine corticotropin-releasing hormone administration was attenuated in men with insomnia associated with objective sleep disturbance, suggesting that objectively defined insomnia subtypes have a disrupted hypothalamic-pituitary-adrenal axis function and highlight the need to develop treatments targeting the underlying hypothalamic-pituitary-adrenal axis dysregulation.
尽管失眠是目前最常见的睡眠障碍，但我们对其神经生物学的了解仍然有限。失眠，尤其是与客观睡眠障碍相关的失眠，与下丘脑 - 垂体 - 肾上腺轴的激活有关。这项实验研究的目的是比较失眠男性与对照组在下丘脑 - 垂体 - 肾上腺轴对羊促肾上腺皮质激素释放激素（一种应激测试）的反应。在23名男性（11名失眠患者，12名对照者）中，在静脉注射外源性羊促肾上腺皮质激素释放激素之前（-30分钟、-15分钟）、注射时（0分钟）以及注射后（+5分钟、+15分钟、+30分钟、+60分钟、+90分钟、+120分钟）测定促肾上腺皮质激素和皮质醇的循环水平，这些男性连续四个晚上在实验室进行多导睡眠监测。与对照组相比，失眠男性在多导睡眠监测中表现出明显且显著缩短的总睡眠时间（368.4 ± 8.99分钟对411.61 ± 8.61分钟；p < 0.01）和更低的睡眠效率（76.77 ± 1.80%对86.04 ± 1.72%；p < 0.01），并且在注射羊促肾上腺皮质激素释放激素后促肾上腺皮质激素和皮质醇水平降低。失眠男性在15分钟和30分钟时的促肾上腺皮质激素水平显著低于对照组（p < 0.05）。同样，失眠男性在+60分钟时皮质醇的峰值水平以及该激素曲线下的总面积和净面积均显著低于对照组（所有p < 0.01）。与客观睡眠障碍相关的失眠男性对羊促肾上腺皮质激素释放激素注射的促肾上腺皮质激素和皮质醇反应减弱，这表明客观定义的失眠亚型存在下丘脑 - 垂体 - 肾上腺轴功能紊乱，并突出了开发针对潜在下丘脑 - 垂体 - 肾上腺轴失调的治疗方法的必要性。
