THERAPEUTIC AND MECHANISTIC EFFECTS OF SLEEP DEPRIVATION IN DEPRESSION

睡眠剥夺对抑郁症的治疗作用和机制作用

• 批准号: 2578744
• 负责人: R M POST
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2578744
• 关键词: antidepressants; bipolar depression depressed phase; brain metabolism; circadian rhythms; clinical depression; clinical research; emotions; hormone regulation /control mechanism; human subject; human therapy evaluation; hypothalamic pituitary axis; limbic system; neuroendocrine system; pituitary thyroid axis; psychotherapy; sleep deprivation; thyrotropin releasing hormone; thyroxine; triiodothyronine

One night's total sleep deprivation can induce profound antidepressant effects in depressed patients. Following the absence of sleep for one night, 40-60% of depressed patients typically show the transient onset of mood improvement, which is then lost following a nap or the next night's recovery sleep. Thus, the sleep deprivation paradigm becomes a non-pharmacological means of acutely inducing altered mood states in a fashion that may yield important information about underlying mechanisms. While the mood changes are usually transient they may provide insights into neural systems involved in mood dysregulation and its acute reversal. Some patients show stable degrees of improvement, while others show either tolerance or progressive improvement following repeat sleep deprivation. In rapid-cycling bipolar patients there is a relative refractoriness to sleep deprivation-induced mood improvement early in a depressive episode, but as the episode progresses transient improvement is noted, and toward the end of an episode more dramatic improvement or long-lasting switches out of depression occur. These data suggest that there are differential neurobiological substrates as a function of the temporal phase of bipolar episodes. Sleep deprivation is associated with significant increases in TSH, T3, T4, and free T4. Increases in TSH secretion have been reported correlated with the degree of clinical re- sponse to sleep deprivation in some studies. Our findings do not show consistent statistical significance in most measures, but delta TSH is correlated with degree of self-rated (delta Beck Depression Scores) improvement. As sleep deprivation may remove inhibit-ory control over TSH secretion (possibly at the level of increased TRH) these data are consistent with other suggested alterations in the limbic-hypothalamic- pituitary-thyroid (L-HPT) axis in affective illness. Since Ketter et al have found that relative hypothyroidism (higher TSH) is associated with frontal hypometabolism on PET, and sleep deprivation responders have relative limbic hyperactivity at baseline, it is possible that sleep deprivation removes this inhibitor tone, increasing TSH and helping to correct the frontal defect in metabolism. TRH infusions may also affect the frontal hypometabolism more directly. However, initial analyses suggest that positive response to sleep deprivation is not directly associated with positive response to TRH or to drugs such as carbamazepine, which increases TRH in CSF of our patients.

一晚的完全睡眠剥夺会引起深刻的抗抑郁药 在抑郁症患者中的影响。在没有睡眠之后 晚上，40-60％的抑郁症患者通常显示瞬态发作 情绪改善，然后在午睡或下一次午睡后丢失 夜晚的睡眠。 因此，睡眠剥夺范式变成了 急性诱导情绪状态的非药理学手段 可能产生有关潜在机制的重要信息的时尚。 尽管情绪变化通常是短暂的，但它们可能会提供见解 进入涉及情绪失调及其急性的神经系统 逆转。 一些患者表现出稳定的改善程度，而另一些患者 重复睡眠后显示耐受性或逐步改善 剥夺。在快速循环双极患者中，有一个相对 耐睡眠剥夺引起的情绪改善的早期 抑郁发作，但随着情节的发展，短暂的改进 注意到一集的结尾，更具戏剧性的改进或 发生持久的转换从抑郁症发生。这些数据表明 有差异神经生物学底物作为 双极发作的时间阶段。睡眠剥夺与 TSH，T3，T4和游离T4的显着增加。 TSH的增加 据报道，分泌与临床重新的程度相关 在某些研究中对睡眠剥夺的响应。我们的发现没有显示 在大多数措施中，一致的统计显着性一致，但delta tsh是 与自我评估程度相关（Delta Beck抑郁得分） 改进。因为睡眠剥夺可能会消除对TSH的抑制作用控制 分泌（可能在TRH增加的水平上）这些数据是 与边缘 - 高层丘脑的其他建议改变一致 情感疾病中的垂体 - 甲状腺（L-HPT）轴。因为Ketter等人 已经发现相对甲状腺功能减退症（较高的TSH）与 对宠物和睡眠剥夺者的额额不代谢有反应者 基线时相对边缘多动症，可能睡眠 剥夺消除了这种抑制剂的语调，增加了TSH并帮助 纠正代谢中的额叶缺陷。 TRH输注也可能影响 额叶短缺代谢更直接。但是，初步分析 表明对睡眠剥夺的积极反应不是直接的 与对TRH或对药物的积极反应相关 卡马西平，它增加了我们患者CSF的TRH。