Melatonin Studies of Totaly Blind Children

完全失明、没有光感的人不能同步(携带)他们的生物钟 光/暗循环的节奏。然而，这些人中约有一半被带到了24- 一天一小时。夹带的时间线索是未知的，可能包括社会互动。 那些不是天生就有自由奔跑的人，通常会有稍微长一点的昼夜节律 超过24小时，导致它们的内源节律每天漂移得稍晚一些。我们有 研究发现，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 同样的方式：当内源性刺激开始时，它们以更快的速度漂移(延迟) 褪黑激素的生产在白天漂移，而不是在夜间漂移，这在 动物实验被称为相对协调。因为光的混杂效应 在完全失明的人身上自然移除，我们也能够准确地量化他们的 相对坐标的幅度(量)，幅度越大，越大 敏感度。值得注意的是，自由奔跑的成年雌性比成年雄性的幅度更大。 与这一发现一致的是，更多的成年女性似乎自然地受到这些 这种差异似乎发生在青春期之后；事实上，这种差异可能会颠倒过来 在青春期之前，在迄今研究的少数受试者中，可能有更高的 青春期前男性比青春期前或青春期后女性的比例。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 青春期后的雌性。我们现在建议对失明儿童和老年人进行生理调查。 全国青少年(5-8岁和17-20岁)评估自然死亡的比例 使用连续佩戴在手腕上的动作记录设备(以及 收集一些高积极性受试者的唾液褪黑素样本)，这将导致 研究以确定这些未知的非光时间线索，以及荷尔蒙和其他 影响对它们的敏感性的因素，从而导致新的昼夜节律治疗方式 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 对褪黑素的安全性和有效性进行大规模、多中心研究的可行性，这也可能 对有昼夜节律睡眠和情绪障碍的视力正常的人有好处

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