LIGHT-INDUCED SUPPRESSION OF MELATONIN IN ADVANCED AND DELAYED SLEEP

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Over the past few years, great progress has been made in uncovering the molecular basis for the generation of circadian rhythms in mammals. These molecular studies in rodents and flies have stimulated a search for genetic differences that could underlie altered circadian rhythms and/or sleep disorders in humans. Two of the most common sleep disorders in humans that are thought to be due to alterations in circadian timing are classified as the Delayed Sleep Phase Syndrome (DSPS) and Advanced Sleep Phase Syndrome (ASPS). DSPS is characterized by a persistent inability to initiate sleep before 2 to 6 AM and difficulty waking up until 10 AM to 1 PM, whereas, ASPS is characterized by habitual and involuntary sleep and wake times that are at least several hours earlier than societal means. The most common complaints are sleepiness in the late afternoon or evening, and early morning awakening of 2-5 AM. Based on studies of extended families, there are now two recent reports indicating that both ASPS and DSPS can have a genetic basis, and may be due to allelic differences in at least two of the newly discovered circadian clock genes. In addition, a recent study of sporadic DSPS indicates that allelic differences in a second clock gene may underlie this condition. While studies on the genetic basis of DSPS and ASPS represent a new and exciting avenue to elucidate how the sleep-wake and circadian clock systems are integrated with each other, and how alterations in specific circadian clock genes can lead to alterations in the timing of sleep and wake, our understanding of the physiological mechanisms responsible for these circadian sleep disorders is actually quite limited. One of the objectives of the parent NIH funded grant is to test various hypotheses that could explain how an alteration in the circadian clock system could lead to changes in the phase of the sleep-wake cycle relative to the light-dark cycle. The objective of this project is to test the hypothesis that the altered circadian phase in ASPS or DSPS is due to an alteration in the way that the circadian clock responds to light.