EFFECTS OF NOCTURNAL TRH ADMINISTRATION ON TSH, MOOD, AND MOTOR ACTIVITY

夜间服用 TRH 对 TSH、情绪和运动活动的影响

• 批准号: 2783136
• 金额: $ 2.45万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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/2783136
• 关键词: bipolar depression; body physical activity; circadian rhythms; clinical research; clinical trials; emotions; hormone therapy; human subject; human therapy evaluation; hypothalamic pituitary axis; mental disorder chemotherapy; outcomes research; pituitary thyroid axis; sleep; thyrotropin; thyrotropin releasing hormone

One night of sleep deprivation during the early morning hours (PSD: patient awake 0200-2100 hours) produces an acute, but transient antidepressant response in over 60% of bipolar subjects. Until recently, PSD has shown little clinical utility because its effects wane within 48 hours. However, four studies have now documented that concurrent lithium treatment maintains the acute antidepressents effects of sleep deprivation indefinitely, void of heterocyclic-induced mania risk. While effective, sleep deprivation is cumbersome; patients are often skeptical and persuading them to undergo it, or continue with it once begun, is difficult. If, however we understood the mediating factors, we might be able to bypass sleep deprivation and administer the mediator instead. The hypothalmic-thyroid axis (HPT) may be such a mediator. Nocturnal TSH secretion is reduced in bipolar depression and normalizes with successful treatment. PSD increases TSH and increases in TSH levels during sleep deprivation correlate with antidepressant effect. TSH produces an acute, but transient, antidepressant effect in patients with depression. The similarities between the descriptions of the acute, but transient, antidepressant effects of PSD and TRH are striking. We postulate that the antideressant effects of sleep deprivation are due to HPT stimulation at the level of the hypothalalmus or pituitary. We will administer TRH or placebo during the early morning hours to bipolar depressed subjects to determine effects on TSH, mood, and motor activity. We predict that TRH will increase nocturnal TSH levels and produce same- day, but short-term, increases in mood and locomotion. We hope to use the data derived from this study as initial data for developing a prospective study of the HPT axis, antidepressant, and locomotor effects of lithium/PSD and lithium/TRH in bipolar illness.

一晚清晨睡眠不足（PSD： 患者清醒0200-2100小时）产生急性但短暂的 超过 60% 的双相情感障碍受试者有抗抑郁反应。 直到最近， PSD 几乎没有表现出临床实用性，因为其效果在 48 年内减弱 小时。 然而，四项研究现已证明，同时锂 治疗可维持睡眠剥夺的急性抗抑郁作用 无限期地，消除杂环引起的躁狂风险。 虽然有效，但睡眠剥夺却很麻烦。患者常常 持怀疑态度并说服他们接受或继续一次 开始，是困难的。 然而，如果我们了解中介因素，我们也许能够 绕过睡眠剥夺并改为管理中介。 这 下丘脑-甲状腺轴（HPT）可能是这样的介质。夜间促甲状腺激素 双相抑郁症患者的分泌减少并正常化 治疗成功。 PSD 会增加 TSH 并增加 TSH 水平 睡眠不足与抗抑郁作用相关。 促甲状腺激素 对患有以下疾病的患者产生急性但短暂的抗抑郁作用 沮丧。 急性的描述之间的相似之处，但是 PSD 和 TRH 的短暂抗抑郁作用是惊人的。 我们 假设睡眠剥夺的抗抑郁作用是由于 HPT 刺激下丘脑或垂体水平。 我们将 在清晨给予双相情感障碍患者 TRH 或安慰剂 抑郁受试者以确定对 TSH、情绪和运动活动的影响。 我们预测 TRH 会增加夜间 TSH 水平并产生相同的- 白天，但短期内，情绪和运动会增加。 我们希望使用本研究得出的数据作为初始数据 开展 HPT 轴、抗抑郁药和抗抑郁药物的前瞻性研究 锂/PSD 和锂/TRH 在双相情感障碍中的运动效应。