Melatonin Studies of Totaly Blind Children

全盲儿童褪黑激素研究

• 批准号: 7590966
• 负责人: ALFRED J LEWY
• 金额: $ 38.5万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7590966
• 关键词: Adolescent; Adult; Affect; Age; Animal Experiments; Applications Grants; Child; Circadian Rhythms; Cues; Devices; Disease; Female; Future; Hormonal; Hour; Lead; Light; Melatonin; Modality; Mood Disorders; Perception; Production; Puberty; Relative (related person); Running; Safety; Salivary; Sampling; Sleep; Social Interaction; Study Subject; Surveys; Time; Vision; Visually Impaired Persons; Wrist; actigraphy; blind; cohort; light effects; male; response; sight for the blind

Totally blind people with no light perception cannot synchronize (entrain) their circadian rhythms to the light/dark cycle. Nevertheless, about half of these people are entrained to the 24- hour day. The time cues for entrainment are not known and may include social interactions. Those who are not naturally entrained free-run, usually with a circadian period slightly longer than 24 hours, resulting in their endogenous rhythms drifting a little later each day. We have found that all free-running blind people shift their circadian rhythms in response to these time cues in the same way: they drift later ( delay) at a faster rate when the onset of endogenous melatonin production is drifting across the day than when it is drifting across the night, which in animal experiments is termed relative coordination. Because the confounding effect of light has been naturally removed in totally blind people, we have also been able to precisely quantify their amplitude (amount) of relative coordination, the greater the amplitude, the greater the sensitivity. Remarkably, free-running adult females have a greater amplitude than adult males. Consistent with this finding is that more adult females appear to be naturally entrained to these time cues than males, a difference that appears to occur after puberty; in fact, it may be reversed before puberty, in that in the small number of subjects studied thus far, there may be a higher proportion of pre-pubertal males than pre- or post-pubertal females. We think these findings may be preliminary evidence for greater sensitivity to these time cues in females compared to post-pubertal males, whereas pre-pubertal males may possibly be more sensitive than pre- and post-pubertal females. We now propose to physiologically survey blind children and older adolescents (ages 5-8 and 17-20) across the nation to assess the proportion of naturally entrained males and females using actigraphy devices worn continuously on the wrist (as well as collecting salivary melatonin samples in some highly motivated subjects), which will lead to studies to identify these as of yet unknown non-photic time cues, as well as hormonal and other factors that affect sensitivity to them, thus leading to new treatment modalities for circadian disorders of both blind and sighted people. In a future grant application, we will assess feasibility of a large-scale, multi-center study of melatonin safety and efficacy, which may also be of benefit sighted people with circadian rhythm sleep and mood disorders

没有光感的完全失明的人无法同步（引导）他们的昼夜节律 光暗周期的节奏然而，这些人中约有一半被带到24- 小时一天。夹带的时间线索是未知的，可能包括社会互动。 那些不自然夹带自由运行，通常与昼夜周期稍长 超过24小时，导致他们的内源性节奏每天晚一点漂移。我们有 发现所有自由奔跑的盲人都会根据这些时间改变他们的昼夜节律 线索以同样的方式：他们漂移后（延迟）在一个更快的速度时，发病的内源性 褪黑激素的产生在白天比在晚上漂移， 动物实验称为相对协调。因为光的干扰效应 在完全失明的人身上，我们也能够精确地量化他们的 相对协调的幅度（量），幅度越大， 灵敏度值得注意的是，自由奔跑的成年雌性比成年雄性有更大的振幅。 与这一发现相一致的是，更多的成年女性似乎是自然夹带到这些 时间线索比男性多，这种差异似乎发生在青春期后;事实上，它可能会逆转 在青春期之前，在迄今为止研究的少数受试者中，可能有更高的 青春期前男性的比例高于青春期前或后女性。我们认为这些发现 可能是女性对这些时间线索更敏感的初步证据， 青春期后男性，而青春期前男性可能比青春期前和青春期前更敏感 青春期后的女性我们现在建议对盲童和老年人进行生理调查， 青少年（5-8岁和17-20岁）在全国各地评估的比例自然 使用连续佩戴在手腕上的活动记录装置（以及 收集唾液褪黑激素样本在一些高度积极的主题），这将导致 研究，以确定这些未知的非光的时间线索，以及激素和其他 影响对它们敏感性的因素，从而导致昼夜节律的新治疗方式 盲人和有视力的人的疾病。在未来的拨款申请中，我们将评估 褪黑激素安全性和有效性的大规模、多中心研究的可行性， 有益于有昼夜节律睡眠和情绪障碍的视力正常者