• Lewy, Alfred (PI)

Project: Research project

Project Details


We have concentrated all of our research efforts on the study of the role of biological rhythms in sleep and mood disorders. We have found that human nighttime melatonin production is suppressed by bright light. This discovery led to the use of bright light in the morning in order to cause a phase advance and in the evening to cause a phase delay. These findings have been applied in the treatment of circadian phase disorders, which include advanced and delayed sleep phase syndrome, jet lag and maladaptation to shift work. One of the most responsive disorders to bright light treatment is winter depression. However, it is not known whether or not this disorder has a significant biological rhythm component. We have proposed a biological rhythm hypothesis in order to further our knowledge of why these patients become depressed in the winter and how bright light exposure is antidepressant. The phase shift hypothesis states that winter depressives become phase delayed in response to the short natural photoperiod (the later dawn) at this time of year. It further states that bright light exposure should be most antidepressant when scheduled in the morning at which time it will cause a corrective circadian phase advance. Although the phase shift hypothesis is probably the most actively tested of the winter depression hypotheses, it is controversial: some studies show morning light to be more antidepressant than evening light, other studies show no difference. We have recently completed the largest single comparison of morning versus. evening light in this patient population, the results of which support the phase shift hypothesis. However, although morning light is more antidepressant than evening light, evening light depression ratings are lower than baseline ratings. Therefore, it is still possible that the antidepressant response to light is not dependent upon a phase advance. The present study proposes to determine whether or not a phase advance is a significant component of morning light's antidepressant effect. It is based on our recent discovery of a phase response curve for exogenous administration of melatonin in humans: administration of melatonin in the afternoon causes a phase advance similar to that caused by morning light exposure; administration of melatonin in the morning causes a phase delay similar to that caused by evening light. By causing circadian phase shifts through an entirely different phase-resetting agent, we can conduct an important test of the phase shift hypothesis. The proposed study should further our understanding of light melatonin and biological rhythms in winter depression.
Effective start/end date9/1/974/30/04


  • National Institutes of Health: $154,874.00
  • National Institutes of Health: $145,981.00
  • National Institutes of Health: $159,521.00


  • Medicine(all)


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