Abstract
Many aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance patterns, and many daily hormone profiles. These rhythms are spontaneously generated by an internal "pacemaker" in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external environment. Sighted individuals take this daily synchronization process for granted, although they experience some of the consequences of circadian desynchrony when "jetlagged" or working night shifts. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the hypothalamic circadian clock, resulting in cyclical episodes of poor sleep and daytime dysfunction. Daily melatonin administration, which provides a replacement synchronizing daily "time cue, " is a promising therapeutic strategy, although optimal treatment dose and timing remain to be determined.