EXTRAOCULAR CIRCADIAN PHOTOTRANSDUCTION IN HUMANS

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DESCRIPTION (applicant's abstract): Circadian rhythm sleep disorders and seasonal affective disorder affect a large number of individuals across a wide age range. Timed exposure to bright light shows promise as an effective treatment for alleviation of such sleep and mood disorders which are thought to involve the biological timing system. Yet, light treatment as currently practiced has significant drawbacks in terms of user compliance and efficacious timing of administration. 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 human circadian clock responds to extraocular light exposure in a manner similar to that when light is presented to the eyes. This finding of extraocular circadian clock resetting in humans offers potentially exciting solutions to the problems currently complicating the therapeutic use of bright light. By eliminating the need to receive light via the retinae, light delivery systems can be made more easily portable, and therefore, less intrusive on users' behavior. Perhaps more importantly, by eliminating the need to receive light through the eyes, treatment regimens conceivably may be implemented even while patients are asleep, thus enhancing ease of use and taking advantage of the most optimal times of light administration. Yet, before treatment approaches and regimens can be successfully developed and implemented using extraocular sites, it is important to confirm and expand our original findings. This project will take two important steps in this regard: First, we propose to replicate our original study using a larger study sample and more suitable controls. Secondly, it is proposed to characterize the phase response of the circadian clock to extraocular light presented during sleep. In two laboratory-based studies, both using a counter-balanced design, we will examine relevant circadian parameters in a total of 72 healthy young adults during baseline, active and control conditions. These studies address issues crucial to the successful development and implementation of light treatments using extraocular exposure, and they form the basis for a more complete understanding of the role of light in human circadian physiology.