Sensitization of Human Circadian Responses to Light

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DESCRIPTION (provided by applicant): Sleep disorders affect 35-40% of adults, resulting in diminished quality of life, and increased morbidity, mortality, and risk of automobile and occupational accidents. Circadian rhythm sleep disorders form a distinct class of sleep disorders characterized by misalignment between the timing of sleep and the circadian pacemaker. While light therapy can be an effective treatment of circadian rhythm sleep disorders, there are numerous practical limitations. Light is the most powerful signal from the environment that influences and regulates daily biological rhythms. It is well-established that the irradiance, duration, and timing of light exposure all affect the response of the circadian system. While it was once thought that these responses were mediated through the visual system, it is now known that there is a network of intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate circadian responses to light. Other new studies have demonstrated that recent light exposure history affects the circadian response to light in humans. These recent findings have important implications for the use of light to treat circadian rhythm disorders, including delayed and advanced sleep phase disorders, shift work sleep disorder, and jet lag, and they may also have relevance for the use of light to treat seasonal affective disorder. Up to now, little attention has been paid to the duration or intensity of light exposure prior to such light treatments. We now have evidence that the human circadian system can become desensitized to light during long exposures and evidence that it can be sensitized to light by prior exposure to dim light. These recent findings suggest that light treatment protocols that sensitize the circadian system prior to the light treatment will be more effective than those currently in use. The studies we propose will examine the effect on the human circadian system of four different durations of dim-light sensitization prior to a standardized light treatment. These results will be compared within subjects in a randomized cross-over design study in which each healthy subject will receive a control treatment and a light treatment with prior dim-light sensitization. We will also include one group of delayed sleep phase disorder patients to test these mechanisms in the target patient population. Our findings will provide an important step in understanding how new knowledge about the circadian photoreceptive system can be used to refine and provide better treatment options for circadian rhythm disorders. PUBLIC HEALTH RELEVANCE: Circadian rhythm disorders are a class of sleep disorders characterized by misalignment between the timing of sleep and the circadian pacemaker. Light therapy can effectively treat these disorders, but the intensity and duration of light exposure required to do so has limited its practical use. Here we will test how pre exposure to dim light can enhance the response of the circadian system to light therapy, resulting in shorter treatments that have greater practical application.