VARIABILITY OF THE HUMAN MELATONIN PHASE-RESPONSE CURVE
人类褪黑素相位反应曲线的可变性
基本信息
- 批准号:3378186
- 负责人:
- 金额:$ 16.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1984
- 资助国家:美国
- 起止时间:1984-12-01 至 1996-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We have recently discovered that appropriately-timed administration of
a physiological dose of exogenous melatonin (M) can cause circadian phase
shifts in sighted humans. In fact, our pilot data describe a phase
response curve (PRC) that is about 12 hours out of phase with the human
PRCs for light. The thirty time points on this curve come from nine
individuals who average only three - four points per person. We now
propose to test 12 time points per person to precisely delineate the
shape of the human M PRC. We will do this in 15 individuals, in order
to determine the variability in PRC shape. This study is essential
before undertaking the next step in our on-going work , the examination
and treatment of biological mechanisms of winter depression and other
chronobiologic disorders, including jet lag, maladaptation to shift work
and certain types of sleep disorders.
Data obtained from further study of the M PRC will also eventually make
possible the use of M administration in order to test the leading -- but
controversial -- phase-shift hypothesis for winter depression. According
to this hypothesis, most winter depressives become depressed in the
winter because of a circadian phase delay cued to the later dawn at this
time of the year. Also according to this hypothesis, morning light
should be most antidepressant because it provides a corrective phase
advance. In many -- but not all -- studies, morning light has been shown
to be superior to light exposure scheduled at other times. Some critics
have argued, however, that the superior antidepressant effect of morning
light may be unrelated to its phase-advancing effect. The present
proposal will enable us to subject the phase-shift hypothesis to a
critical test: if we cannot show that melatonin administered at a time
to cause a phase advance is more antidepressant than melatonin
administered at a time to cause a phase delay, then the phase-shift
hypothesis fails. This future study will be particularly important,
because it will provide a very good control for the placebo response that
has plagued light treatment studies from the outset.
Even if melatonin proves unsuccessful in the treatment of winter
depression, we need to delineate the M PRC which will be extremely
important in developing melatonin as a treatment for other circadian
phase disorders. Treatment with M should have the distinct advantage of
avoiding problems commonly associated with currently used medications.
Sedative/hypnotics have many serious side effects, including confusion
(in the geriatric population), potentiation of alcohol intoxication,
tolerance, habituation, addiction and memory impairment; antidepressants
can have anticholinergic and cardiotoxic side effects, among many other
problems. In contrast, the only known side effect of low doses of M is
mild drowsiness and this is rarely seen at the very low (0.5) mg dose
that we use. Finally, towards our goal of developing techniques for
assessing and treating circadian phase disorders, we propose to continue
validating M as a circadian phase marker and to continue establishing a
M RlA and a salivary M assay, so that M will become more useful in the
clinical setting.
我们最近发现,适当的时间管理
生理剂量的外源性褪黑激素(M)可引起昼夜节律阶段
有视力的人类发生变化。 事实上,我们的试点数据描述了一个阶段
响应曲线 (PRC) 与人类相差约 12 小时
用于光的 PRC。 这条曲线上的三十个时间点来自九个
平均每人只有三到四分的人。 我们现在
建议每人测试 12 个时间点,以精确描绘
人类 M PRC 的形状。 我们将在 15 个人中进行此操作,以便
以确定 PRC 形状的变异性。 这项研究很有必要
在我们正在进行的下一步工作之前,检查
以及冬季抑郁症等的生物学机制的治疗
时间生物学疾病,包括时差、不适应轮班工作
和某些类型的睡眠障碍。
从对 M PRC 的进一步研究中获得的数据也将最终使
可能使用 M 管理来测试领先——但是
有争议的——冬季抑郁症的相移假说。 根据
根据这一假设,大多数冬季抑郁症患者在
冬天是因为昼夜节律相位延迟导致黎明较晚
一年中的某个时间。 同样根据这个假设,晨光
应该是最有效的抗抑郁药,因为它提供了一个纠正阶段
进步。 在许多(但不是全部)研究中,晨光已被证明
优于其他时间安排的曝光。 一些批评家
然而,有人认为早晨的抗抑郁效果更好
光可能与其相位超前效应无关。 现在的
该提案将使我们能够将相移假设置于
关键测试:如果我们不能证明褪黑激素在某一时间施用
导致相位提前比褪黑激素更能抗抑郁
一次施加以引起相位延迟,然后相移
假设失败。 未来的这项研究将尤为重要,
因为它可以很好地控制安慰剂的反应
从一开始就困扰着光治疗研究。
即使褪黑激素在治疗冬季方面被证明不成功
抑郁症,我们需要划定 M PRC,这将是极其严重的
对于开发褪黑激素作为其他昼夜节律的治疗方法很重要
相位障碍。 M 治疗应具有以下明显优势:
避免与当前使用的药物相关的常见问题。
镇静/催眠药有许多严重的副作用,包括混乱
(在老年人群中),酒精中毒加剧,
耐受性、习惯性、成瘾性和记忆障碍;抗抑郁药
可能具有抗胆碱能和心脏毒性副作用等
问题。 相比之下,低剂量 M 唯一已知的副作用是
轻度嗜睡,这种情况在极低 (0.5) 毫克剂量下很少见
我们使用的。 最后,为了实现我们开发技术的目标
评估和治疗昼夜节律紊乱,我们建议继续
验证 M 作为昼夜节律阶段标记并继续建立
M RlA 和唾液 M 测定,以便 M 将在
临床环境。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('ALFRED J LEWY', 18)}}的其他基金
PHASE-SHIFTING EFFECTS OF MELATONIN IN WINTER DEPRESSION
褪黑激素对冬季抑郁症的相移作用
- 批准号:
7206553 - 财政年份:2005
- 资助金额:
$ 16.66万 - 项目类别:
MELATONIN ENTRAINMENT OF ELDERLY BLIND FREE-RUNNERS
老年盲人自由跑步者的褪黑激素摄入
- 批准号:
7206598 - 财政年份:2005
- 资助金额:
$ 16.66万 - 项目类别:
MELATONIN FOR CIRCADIAN SLEEP DISORDERS IN THE BLIND
褪黑素治疗盲人昼夜节律睡眠障碍
- 批准号:
7206580 - 财政年份:2005
- 资助金额:
$ 16.66万 - 项目类别:
Melatonin Entrainment of Elderly Blind Free-runners
老年盲人自由跑步者褪黑激素的诱导作用
- 批准号:
6981131 - 财政年份:2003
- 资助金额:
$ 16.66万 - 项目类别:
Melatonin for Circadian Sleep Disorders in the Blind
褪黑激素治疗盲人昼夜节律睡眠障碍
- 批准号:
6981110 - 财政年份:2003
- 资助金额:
$ 16.66万 - 项目类别:
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