Abstract: BACKGROUND: Complete blindness generally results in the loss of synchronization of circadian rhythms to the 24-hour day and in recurrent insomnia. However, some blind patients maintain circadian entrainment. We undertook this study to determine whether some blind patients' eyes convey sufficient photic information to entrain the hypothalamic circadian pacemaker and suppress melatonin secretion, despite an apparently complete loss of visual function. METHODS: We evaluated the input of light to the circadian pacemaker by testing the ability of bright light to decrease plasma melatonin concentrations in 11 blind patients with no conscious perception of light and in 6 normal subjects. We also evaluated circadian entrainment over time in the blind patients. RESULTS: Plasma melatonin concentrations decreased during exposure to bright light in three sightless patients by an average (+/- SD) of 69 +/- 21 percent and in the normal subjects by an average of 66 +/- 15 percent. When two of these blind patients were tested with their eyes covered during exposure to light, plasma melatonin did not decrease. The three blind patients reported no difficulty sleeping and maintained apparent circadian entrainment to the 24-hour day. Plasma melatonin concentrations did not decrease during exposure to bright light in seven of the remaining blind patients; in the eighth, plasma melatonin was undetectable. These eight patients reported a history of insomnia, and in four the circadian temperature rhythm was not entrained to the 24-hour day. CONCLUSIONS: The visual subsystem that mediates light-induced suppression of melatonin secretion remains functionally intact in some sightless patients. The absence of photic input to the circadian system thus constitutes a distinct form of blindness, associated with periodic insomnia, that afflicts most but not all patients with no conscious perception of light.

Abstract: In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.

Abstract: The bedtime of preschoolers/pupils/students in Japan has become progressively later with the result sleep duration has become progressively shorter. With these changes, more than half of the preschoolers/pupils/students in Japan recently have complained of daytime sleepiness, while approximately one quarter of junior and senior high school students in Japan reportedly suffer from insomnia. These preschoolers/pupils/students may be suffering from behaviorally induced insufficient sleep syndrome due to inadequate sleep hygiene. If this diagnosis is correct, they should be free from these complaints after obtaining sufficient sleep by avoiding inadequate sleep hygiene. However, such a therapeutic approach often fails. Although social factors are often involved in these sleep disturbances, a novel clinical notion--asynchronization--can further a deeper understanding of the pathophysiology of these disturbances. The essence of asynchronization is a disturbance in various aspects (e.g., cycle, amplitude, phase and interrelationship) of the biological rhythms that normally exhibit circadian oscillation, presumably involving decreased activity of the serotonergic system. The major trigger of asynchronization is hypothesized to be a combination of light exposure during the night and a lack of light exposure in the morning. In addition to basic principles of morning light and an avoidance of nocturnal light exposure, presumable potential therapeutic approaches for asynchronization involve both conventional ones (light therapy, medications (hypnotics, antidepressants, melatonin, vitamin B12), physical activation, chronotherapy) and alternative ones (kampo, pulse therapy, direct contact, control of the autonomic nervous system, respiration (qigong, tanden breathing), chewing, crawling). A morning-type behavioral preference is described in several of the traditional textbooks for good health. The author recommends a morning-type behavioral lifestyle as a way to reduce behavioral/emotional problems, and to lessen the likelihood of falling into asynchronization.