• Sack, Robert (PI)

Project: Research project

Project Details


There is increasing evidence that circadian rhythm abnormalities
are important in the pathophysiology of some affective and sleep
disorders. The mechanism of aciton of antidepressant drugs may
involve correction of circadian rhythm abnormalities. However,
assessing the chronobiologic effects of drugs in humans has been
impeded by problems with imprecise markers for circadian
rhythms and by the confounding influence of time cues which
entrain circadian rhythms to a 24-hour day. In blind people, the entraining effects of the light-dark cycle are
eliminated, often resulting in autonomous (free-running) rhythms
which reflect the intrinsic period of the endogenous biological
clock (usually about 25 hours). Measuring melatonin onsets at
biweekly intervals provides a convenient and efficient way to
monitor the free-running rhythms. Our pilot studies have shown
that the period (tau) of the free-running melatonin rhythm is
remarkably consistent making it possible to efficiently detect
drug-induced changes in the rhythm. Thus we were able to show
that bedtime administration of both melatonin and triazolam
phase advanced the rhythm (shifted it to an earier time). In this project we will identify blind people with free-running
rhythms and will measure the effects of acute and prolonged
administration of triazolam, melatonin and lithium on the
melatonin rhythm. We anticipate that these chronobiologic
effects of drugs in humans. This may lead to treatments for blind
people who suffer bouts of insomnia and daytime sleepiness as a
result of free-running rhythms. This information will also lead to
new insight into the mechanism of action of psychotropic drugs
which will potentially benefit sighted people who suffer circadian
rhythm disturbances associated with sleep and mood disorders,
shift work and jet lag.
Effective start/end date8/1/877/31/90


  • National Institutes of Health


  • Medicine(all)


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