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: 5216074
• 负责人: MARTIN P SZUBA
• 金额: --
• 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/5216074
• 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; 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 antidepressants 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 hypothalamic-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. TRH 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 antidepressant effects of sleep deprivation are due to HPT stimulation at the level of the hypothalamus 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.

一晚清晨睡眠剥夺（PSD： 患者清醒0200-2100小时）产生急性但短暂的 超过60%的双相情感障碍患者有抗抑郁反应。直到最近， PSD几乎没有临床效用，因为其效果在48 小时然而，四项研究已经证明， 治疗维持了睡眠的急性抗抑郁作用 无限期剥夺，没有杂环诱导躁狂风险。 虽然有效，但睡眠剥夺是麻烦的;患者经常 怀疑并说服他们接受它，或者继续一次 开始，很难。 但是，如果我们了解了这些中介因素， 我们也许可以绕过睡眠剥夺， 而不是.下丘脑-甲状腺轴（HPT）可能是这种介质。 双相抑郁症患者夜间TSH分泌减少并恢复正常 成功的治疗。PSD增加TSH和TSH水平升高 与抗抑郁作用有关。TRH 对患有以下疾病的患者产生急性但短暂的抗抑郁作用： 萧条急性期的描述之间的相似性，但 PSD和TRH的短暂抗抑郁作用是显著的。我们 假设睡眠剥夺的抗抑郁作用是由于 在下丘脑或垂体水平的HPT刺激。我们将 在清晨给予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， 同一天，但短期，情绪和运动增加。 我们希望将这项研究得出的数据作为初步数据， 开展一项关于HPT轴、抗抑郁药和 锂/PSD和锂/TRH在双相情感障碍中的运动效应