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Sent: Thursday, February 22, 2007 10:21 PM
Subject: [blindambitionsgroups] circadian-rhythm sleep disorder


(By Lynne Lamberg. Reprinted from Psychiatric News, copyright Sept. 1, 2006)
Totally blind people, who cannot perceive light, often report difficulty 
falling
asleep and staying
asleep, as well as fatigue, poor concentration and irritability while awake. 
More
than half of
these people, an estimated 50,000 to 100,000 people in the United States 
alone, may
have a
potentially correctable circadian-rhythm sleep disorder, sleep specialists 
say.
Exogenous melatonin is the treatment of choice for blind people with 
non-24-hour
sleep-wake disorder, said Robert Sack, M.D., a professor of psychiatry at 
Oregon
Health and
Science University (OHSU) in Portland. Sack chaired a symposium on using 
melatonin
with
blind patients at the annual meeting of the Associated Professional Sleep 
Societies
in Salt Lake
City, UT, in June 2006. He and other speakers recently discussed their 
research
with Psychiatric
News.
The high prevalence of sleep problems among blind people underscores the 
importance
of
light in regulating circadian rhythms in the sighted, Sack said. In sighted 
people,
sunlight signals
travel from the eyes to the body's master biological clock in the 
hypothalamus over
a pathway
distinct from that for vision. Shifting levels of light across the day 
entrain,
or synchronize, the
sleep-wake cycle, endogenous melatonin release, and other biological rhythms 
with
the Earth's
day/night cycle.
Most people, sighted and blind, have innate daily cycles of 24-25 hours, 
noted Alfred
Lewy, M.D., professor and senior vice chair of psychiatry at OHSU. In 
sighted people,
daily
exposure to sunlight automatically reseats cycle length to the world's 24- 
hour day.
More than
half of totally blind people have a 24.5- hour circadian cycle, Lewy said. 
They
commonly drift
later and later around the real-time clock, a phenomenon known as free 
running.
Even if they try to sleep at regular times, they typically sleep well only a 
few
days a
month, when their internal clocks fall in sync with preferred schedules. At 
other
times, they
sleep poorly and feel drowsy while awake. Some experience depressive 
symptoms.
Daily oral
doses of melatonin can entrain these blind free-runners, researchers at the 
University
of Surrey in
the United Kingdom reported in January 2000 in the Journal of Endocrinology.
Lewy's group suggests that doses of about .02-.3 mg/day, approximating 
physiological
secretion, usually taken in the late afternoon or early evening, may be most 
effective.
They
published a dose-response curve for use of exogenous melatonin in the 
physiological
range in
totally blind people in Chronobiology International in December 2005.
Jonathan Emens, M.D., an assistant professor of psychiatry at OHSU, working 
with
Lewy
and others, reported at the APSS meeting that his group had shown for the 
first time
that
exogenous melatonin also can entrain blind free-runners with periods less 
than 24
hours. The
researchers helped a blind 41- year-old woman and a blind 9-year-old girl 
stop drifting
earlier
around the clock. (The long-term safety of giving melatonin to prepubertal 
children
has not been
established.)
Melatonin also may help blind people with 24-hour rhythms that persistently 
run early
or
late, disrupting work and social life, Emens said. Melatonin shifts 
biological rhythms
earlier or
later, depending on when it is taken.
Findings from research on blindness, he suggested, may be applicable to 
shift work,
jet
travel and other circadian sleep disorders.
Determining the optimal dose and timing of melatonin administration for the 
individual
user is a key focus of ongoing research, said Debra Skene, Ph.D., a 
professor of
neuroendocrinology at the School of Biomedical and Molecular Sciences, 
University
of Surrey in
Guildford, Surrey, UK. An individual's response to melatonin depends on both 
clock
time and
circadian time, she said, and on how long the person takes it.
Individual circadian cycle length also may affect treatment outcome, Skene 
said.
People
with an innate period longer than 24.5 hours seem to have more trouble 
entraining
than those
with shorter cycles. Different formulations of melatonin, including 
fast-release,
sustained-release, and controlled-release, may have different effects.
Before treatment starts, every patient needs a correct diagnosis, said 
Steven Lockley,
Ph.D., an assistant professor of medicine at Harvard Medical School.
I know of blind people with non-24-hour sleep-wake disorder who have been 
given
hypnotics to use at night and stimulants to use in the day because their 
physicians
did not
recognize the cyclic nature of their disorder, he said.
An estimated one in four totally blind people can entrain to 24-hour rhythms 
using
nonphotic time cues in their environment, Lockley noted. These cues include 
regular
times for
sleep, meals, exercise, work, social relationships, caffeine and 
medications. Some
blind people
with no conscious light perception still may have light-sensitive cells in 
the retina
that enable
entrainment.
Blind people able to perceive any light are unlikely to have a 
circadian-rhythm sleep
disorder, he said. However, visually impaired people overall have higher 
rates of
sleep disorders
than people with normal vision.
Asking a patient to keep a sleep diary or wear a wrist activity monitor for 
at least
two
months probably will reveal a cyclic sleep-wake disorder if one exists, he 
said.
Collection of
urine samples every four to eight hours for 48 hours every two weeks for two 
months
to assess
melatonin or cortisol rhythms can help make a definitive diagnosis and aid a 
decision
about
appropriate treatment timing. These noninvasive, relatively inexpensive 
measures,
he said, are
practical in primary care practice.
Melatonin may improve sleep regardless of circadian entrainment, he added, 
but
correcting an underlying circadian disorder, if one is present, can improve 
daytime
performance,
alertness and overall quality of life. 



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