CLOCK RESETTING WITH EXTRAOCULAR LIGHT--DOSE RESPONSE

描述(改编自申请者的摘要)：昼夜节律睡眠障碍影响着广泛年龄段的大量人群。定时强光暴露是治疗这种被认为涉及生物钟的睡眠障碍的一种有前途的方法。然而，目前实施的光疗法有明显的缺点：大多数光疗法的耗时和乏味的性质使得许多人很难持续地使用它们。此外，内源性生物钟对光的反应的性质决定了在人们通常睡着的时候获得最大的影响。我们已经证明，生物钟对眼外光线的反应方式与光线进入眼睛时的反应方式相同。这一发现为目前使强光治疗用途复杂化的问题提供了潜在的令人兴奋的解决方案。通过消除通过视网膜接收光线的需要，光传输系统可以更容易地携带，从而减少对用户行为的干扰。同样重要的是，通过消除通过眼睛接受光线的需要，可以想象，治疗可以在患者睡着的时候进行，从而利用最佳的光照时间。然而，在利用眼外部位成功开发治疗方法之前，需要更好地了解眼外光线暴露的基本特性。这个项目将研究在这方面最重要的问题之一，即诱导时钟重置所需的光强度。在一项基于实验室的平衡研究中，我们将在12名健康的年轻人中检测两种光强度水平的相移能力。这项研究解决了一个对使用眼外暴露成功实施光线治疗至关重要的问题，因为降低强度水平的功效展示可以大大促进便携式和负担得起的设备的开发。拟议的商业应用：如果拟议的设备在治疗SAD方面有效，那么数百万患有这种疾病的人将可以从商业上获得一种简单、廉价、方便的设备。这种装置还可以用于治疗其他季节性精神障碍、昼夜节律紊乱，如睡眠综合征，在某些情况下还可以治疗非季节性抑郁症。

DESCRIPTION (Adapted from applicant's abstract): Circadian rhythm sleep disorders affect a large number of people across a wide age range. Timed bright light exposure is a promising treatment for such sleep disorders that are thought to involve the biological clock. Yet, light treatment as currently practiced has significant drawbacks: The time- consuming and tedious nature of most light treatment regimens make them difficult for many people to use on a consistent and continuing basis. Moreover, the nature of the endogenous clock's response to light dictates that maximum effects are obtained at times when people are typically asleep. We have shown that the circadian clock responds to extraocular light in the same manner as when light is presented to the eyes. This finding offers potentially exciting solutions to problems currently complicating the therapeutic use of bright light. By eliminating the need to receive light via the retina, light delivery systems can be made more easily portable, and thus, less intrusive on users' behavior. As importantly, by eliminating the need to receive light through the eyes, treatments conceivably may occur while patients are asleep, thus taking advantage of the most optimal times of light exposure. Yet, before treatments can be successfully developed using extraocular sites, a better understanding of the basic properties of extraocular light exposure is required. This project will examine one of the most important issues in this regard the intensity of light required to induce clock resetting. In a counter-balanced, laboratory-based study, we will examine the phase shifting capacity of two light intensity levels in 12 healthy young adults. The study addresses an issue crucial to the successful implementation of light treatments using extraocular exposure, since demonstration of efficacy with reduced intensity levels could substantially enhance development of portable and affordable devices. PROPOSED COMMERCIAL APPLICATION: If the proposed device is effective in treating SAD, a simple, inexpensive, convenient unit would be commercially available for millions of individuals who suffer from this disorder. Such a unit could also be useful in treatment of other seasonal psychiatric disorders, circadian rhythm disorders such as sleep syndromes, and in some instances non-seasonal depression.