BIOLOGICAL MECHANISMS OF THE ANTIDEPRESSANT EFFECTS OF SLEEP DEPRIVATION

完全睡眠剥夺一晚导致60例患者暂时缓解 %的重度抑郁症患者;它也可以诱发躁狂症， 躁郁症患者 此外，一小时的睡眠也会引发 抑郁症患者在睡眠剥夺后有所改善。 因此，在本发明中， 睡眠似乎有一种兴奋的效果，而清醒则是一种情绪提升 效果 这些观察对管理层有实际意义 情感性疾病 例如，一些患者的抑郁症可能是 睡眠剥夺治疗，睡眠中断有时是一种 可识别和可预防躁狂症的原因。 这个项目的目的 试图找出抗抑郁药的生物学机制， 睡眠剥夺的影响。 生物学机制的识别 将增加对抑郁症和躁狂症发病机制的了解 并有望导致新的、快速激活的药物治疗 治疗抑郁和躁狂 目前的项目旨在测试一个假设，即体温调节 睡眠改变情绪的机制 剥夺 这个假设是基于我们的观察， 对睡眠的生理反应类似于对热暴露的反应。 像 热暴露，睡眠开始刺激分泌汗液，催乳素（PRL） 和生长激素（GH），它抑制代谢产热， 促甲状腺激素（TSH）和三碘甲状腺原氨酸（T3）的分泌。 喜欢冷 睡眠剥夺会产生相反的效果。 我们正在测试 睡眠的类热性质和类冷性质 睡眠剥夺是导致他们的临床和神经内分泌 对抑郁症患者的影响 根据这一假设， 与凉爽的环境相比， 睡眠剥夺的抗抑郁和神经内分泌作用。 患者 有一次在33度的环境温度下睡眠不足 在另一个场合，在18摄氏度的环境温度下。 已经对12名患者进行了研究，结果与 假说. 在凉爽条件下睡眠剥夺后， 温暖条件下的抗抑郁作用更强（P<0.03）， 促甲状腺激素分泌的增加更大（p<0.05）， 对PRL的抑制作用更强（p <0.03）。 结果 表明睡眠的神经和神经内分泌效应可以 通过热暴露来模仿。 在我们实验室进行的动物研究可以解释为 提供了进一步的证据，证明冷却具有抗抑郁作用（ZO 1 MH 02294-06 CP）。 在仓鼠中，用三类抗抑郁药长期治疗 药物（5-羟色胺再摄取抑制剂、单胺氧化酶抑制剂，和 锂）在睡眠时降低大脑温度0.5摄氏度。 与此相反， 抗躁狂剂氟哌啶醇在睡眠时会提高大脑温度。 最后，在冬季抑郁症患者中， 睡眠时的温度为0.5 ℃。

Total sleep deprivation for one night induces temporary remissions in sixty percent of patients with major depression; it can also induce mania in bipolar patients. Furthermore, as little as one hour sleep can trigger depression in patients who have improved after sleep deprivation. Thus, sleep appears to have a depressant effect and wakefulness a mood-elevating effect. These observations have practical implications for the management of affective illness. For example, some patients' depression can be treated with sleep deprivation, and sleep disruption is sometimes an identifiable and preventable cause of mania. The purpose of this project is to attempt to identify biological mechanisms of the antidepressent effects of sleep deprivation. Identification of biological mechanisms would increase understanding of the pathogenesis of depression and mania and could be expected to lead to new, rapidly activating drug treatments for depression and mania. The current project is designed to test a hypothesis that thermoregulatory mechanisms underlie the mood-altering effects of sleep and sleep deprivation. The hypothesis is based on our observation that many of the physiological responses to sleep resemble responses to heat exposure. Like heat exposure, sleep onset stimulates secretion of sweat, prolactin (PRL) and growth hormone (GH), and it inhibits metabolic heat production and secretion of thyrotropin (TSH) and triiodothyronine (T3). Like cold exposure, sleep deprivation has opposite effects. We are testing the hypothesis that the heat-like property of sleep and the cold-like property of sleep deprivation are responsible for their clinical and neuroendocrine effects in depressed patients. According to this hypothesis, a warm environment, compared with a cool environment, should blunt the antidepressant and neuroendocrine effects of sleep deprivation. Patients are sleep-deprived on one occasion in an ambient temperature of 33 degrees C, and on another occasion in an ambient temperature of 18 degrees C. Twelve patients have been studied, and the results are consistent with the hypothesis. After sleep deprivation in the cool condition compared with the warm condition antidepressant effects were greater (p<0.03), augmentation of TSH secretion was greater (p<0.05), augmentation of T3 was greater (p<0.01), and suppression of PRL was greater (p<0.03). The results show that the depressant and neuroendocrine effects of sleep can be mimicked by heat exposure. Animal studies being carried out in our laboratory could be interpreted as providing further evidence that cooling is antidepressant (ZO1 MH 02294-06 CP). In hamsters, chronic treatment with three classes of antidepressant drugs (a serotonin reuptake inhibitor, a monoamine oxidase inhibitor, and lithium) lower brain temperature 0.5 degrees C during sleep. In contrast, the antimanic agent, haloperidol, raises brain temperature during sleep. Finally, in patients with winter depression, phototherapy lowers rectal temperature 0.5 degrees C during sleep.