Scientific American Mind-June/July 2007

( None of us should ignore our internal clock; our health )
is more dependent on it than we think.
ning, in addition to receiving light by day. When
stimulated by the SCN, the pineal gland releases
melatonin, primarily at night, signaling back to
the SCN the start of the sleep phase [see box on
opposite page]. Many experts trace insomnia in
the elderly to decreasing melatonin production.
“With the onset of dementia, melatonin synthesis
decreases even more. This further weakens
another important input to the SCN,” van Someren
adds.
The scientists observed 189 Alzheimer’s patients
for up to three and a half years. As predicted,
melatonin and light therapy reset some
patients’ circadian rhythms. The longer these
subjects received treatment, the better they slept.
In addition, moods improved, particularly in
those prone to depression. But another fi nding
surprised the scientists: the mere installation of
full-spectrum lamps slowed mental deterioration
at least as well as cholinesterase inhibitors—the
most prevalent type of drug used to treat Alzheimer’s—have
been reported to do. Light combined
with melatonin worked even better.
“If the issue is putting the brakes on cognitive
deterioration,” van Someren asserts, “our method
is superior to cholinesterase inhibitors.” Light
therapy and melatonin have not consistently
helped Alzheimer’s patients in other studies.
Harper notes that treatment needs to be tailored
to individual time zones; not all circadian delays
are shifted to the same degree. Still, the Dutch
studies are promising. A circadian rhythm that
has been knocked out of phase is not merely a
consequence of neurodegenerative disease but
itself contributes causally to the most important
symptom—mental deterioration.
Schizophrenic Time
Like Alzheimer’s patients, people who have
schizophrenia frequently become active at night
and sleep by day. Many psychologists believe that
because of the disease’s symptoms—hearing
voices, optical hallucinations, loss of a sense of
reality—schizophrenic patients cannot find
work. Consequently, they need not get up in the
morning, and so they do not. Foster sees things
differently. He believes that the circadian rhythms
of schizophrenic patients are shifted such that
they must sleep into the afternoon.
To test this hypothesis, Foster and his team
outfi tted 14 schizophrenic patients with wristwatchlike
devices to record physical activity. In
addition, they regularly measured the subjects’
blood melatonin levels. They quickly determined
that melatonin production—and with it, sleep—
came late, rarely before 2 or 3 a.m. In some subjects,
both melatonin production and sleep lagged
so far behind that the rhythm actually collapsed.
“We’d never seen anything like it,” Foster relates.
“Their internal clocks were apparently completely
decoupled from their surroundings and simply
fl uctuated uncontrollably over time.”
Such decoupling occurs in certain forms of
blindness. If people cannot perceive light, they
lack the winding key that sets their body clock.
But how sighted people could have such an uncoupled
biological clock remains a mystery. Foster
hypothesizes that there may be genetic defects
at work. More to the point, Foster wonders whether
the circadian system might offer an entirely
new therapeutic approach to alleviating schizophrenic
symptoms, including depression, cognitive
problems, memory loss and psychotic episodes.
“A disturbed sleep-waking rhythm can
trigger precisely the same problems,” he explains.
“It may be that the symptoms are not actually a
symptom of schizophrenia but a secondary consequence
of abnormal sleep.”
Foster and his colleagues are attempting to
readjust the internal clocks of people suffering
from schizophrenia using the same methods as
van Someren—more bright light during the day
and melatonin at night. The fi rst lamps have been
installed, and the study will begin soon. Already
Foster is sure of one thing: “None of us should
ignore our internal clock but rather accept that
our well-being and health are more dependent on
it than most of us think.” M
(Further Reading)
◆ Differential Circadian Rhythm Disturbances in Men with Alzheimer Disease
and Frontotemporal Degeneration. David G. Harper, Edward G. Stopa,
Ann C. McKee, Andrew Satlin, Patricia C. Harlan, Rachel Goldstein and
Ladislav Volicer in Archives of General Psychiatry, Vol. 58, No. 4, pages
353–360; April 2001.
◆ Rhythms of Life. Russell Foster and Leon Kreitzman. Profi le Books, 2005.
◆ The Suitability of Actigraphy, Diary Data, and Urinary Melatonin Profi les
for Quantitative Assessment of Sleep Disturbances in Schizophrenia:
A Case Report. K. Wulff, E. Joyce, B. Middleton, D. J. Dijk and R. G. Foster
in Chronobiology International, Vol. 23, Nos. 1–2, pages 485–495;
May 2006.
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