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Exercises
Mind
over Time
by Mark Yolen
Suppose
you could reset the inner clocks that run your life—programming
yourself, for example, to wake up fresh and alert at 5:30
AM if you had to make a crucial breakfast meeting, or shutting
off the hunger that drives you to swallow a bag of
chips every afternoon. If the prospect of controlling your
body's timers seems a pleasing luxury, consider the case of
Jason K., a New Jersey attorney. Jason suffers from a weakening
malfunction of his biological clock called seasonal affective
disorder, or SAD. It may seem a remote or even a fanciful
ailment, especially during the summer, when its effects ebb,
but it can throw the entire year, not to mention a whole life,
into terrible turmoil.
"It
came up on me gradually, over time," Jason says.
As the days got darker and darker going into fall and then
winter, "My mood got darker. By winter I'd feel an overall
sluggishness that made the work difficult; it took dramatically
more effort to get anything done. Sleep wasn't restful; I
found myself waking up 15 minutes every night just to see
what time it was. And I developed an excessive craving for
sweets."
Jason's experience is not uncommon. In a recent
New York City survey, more than one-third of responding adults
reported at least mild winter ;
6 out of 100 reported severe depression. Michael Terman, a
clinical psychologist at New York State Psychiatric Institute
in New York City, and a leading SAD researcher, notes that
the degree of suffering goes well beyond typical holiday blues.
"When it hits," Terman says,
"it's not just
a matter of mood. It can be truly disabling for five months
of the year, and it can cause an active social withdrawal—mothers who can't mother, a loss of interest in work, a
total loss of libido." Although the pall usually lifts during
the spring, he says, SAD can throw life permanently off course:
"It's no small thing if you can't maintain a nine-to-five
work schedule in winter." Some
SAD sufferers, he says, simply gravitate toward a lifestyle
that accommodates the disease. "They tend to drift
into work subcultures. They become freelancers, theater people,
perennial graduate students—and many end up feeling their
early goals in life are unachievable."
Yet the
is only one among a constellation of sleep disorders and related
ills caused by the malfunctioning biological clocks. Indeed,
inner clocks can sometimes cause trouble even when they're
ticking away smoothly. The
bleary-eyed miseries of jet lag are a familiar example of
what can happen when you're hurled across time zones and your
personal clock bumps out of sync with the pace of the rest
of the world. These are only the obvious disorders.
Susceptibility to pain, for example, tends to crest in the
morning and ebb as the day wears on. Heart attacks are most
likely to strike in midmorning. And biological rhythms can
stretch across months as well as days and weeks: many animal
species migrate and mate only according to strict seasonal
timetables.
Folklore and common sense have been telling
us for centuries that we depend on inner clocks, but what
and where they are and how they work had long remained a mystery.
Now, thanks to a series of recent laboratory coups, the once-baffling
components of our biological clocks have become clearer. For
the first time, scientists have a diagram, remarkable in both
elegance and simplicity, that shows where in our brains the
timer is, how it uses the machinery in our cells as clockwork,
and how ─ like the clacking and jangling Baby
Bens that once regulated the pace of American days—it can be slowed down, speeded up, or reset. Most recently
researchers have divined how the brain's clock can switch
on and turn off pieces of biological machinery, suggesting
that we may ultimately be able to regulate these processes
at our pleasure, instead of submitting unreliably to their
regulating us.
In the brain, a recently discovered cluster
of nerve cells called the , or SCN, appears to be at the heart of
timekeeping. In mammals, the organ is remarkably reliable:
even if it's removed from an experimental animal and placed
in a dish, it can continue to keep time on its own for at
least a day. The SCN is actually a pair of structures, like
most parts of the brain. One half sits in the left hemisphere
and one in the right, just behind and a bit below the eyes. "Each is made up of about 10 000 densely packed
neurons,"
explains Steven Reppert, the Harvard whose laboratory has been a key player in recent
discoveries. "The SCNs are located just above where your optic
nerves come together at the base of the brain." This is no
accident: the SCN depends on light for what -clock
experts call entertainment — synchronizing the inner clock
with the cycles of light and darkness in the world outside.
Some of the latest research, on mice, suggests that mammals
have a set of special
in their eyes, which pick up light signals and carry them
directly to the SCN.These
photoreceptors are different from the rods and cons used to
perceive light hitting the .
A flood of light striking the right photoreceptors
at the right time does just what the knobs on the back of
that vintage Baby Ben do: reset the hands of the clock. A
burst of light in the morning sets the clock ahead; a burst
in the evening puts it backward. If, like Jason, you're a
northerner, your inner clock may run slow in winter, falling
behind without early-morning light that would normally nudge
it forward. "When I talk with patients here in New York,"
Terman explains, "I tell them that, biologically speaking,
they're living in Chicago." When the bedside alarm goes off,
New York wakes up, slipping into high gear. But their inner
timers lag an hour or more behind, at Chicago or even California
time, insisting that their brain and bodies should still be
sound asleep.
Not
everyone has the problem. Most people aren't as vulnerable
to a lack of morning light, which helps keep the inner clock
in tune with the external environment. Every morning, the
light of dawn makes its way to the SCN and advances the inner
clock, allowing it to catch up with local time, rousing and
easing us into daytime activity in blissful synchrony with
local time. And because the nerve pathway from the eyes into
the SCN bypasses those parts of the brain that register conscious
sight, the inner clock can react to ambient light even when
we're sound asleep. The light of dawn penetrates the eyelids,
registers on the retina, and relays a silent signal into the
SCN. If the internal clock has a tendency to run slow, morning
light automatically shifts it ahead, putting it back in step
with the world outside. It's beautifully simple—unless you
live far enough above the equator so that in winter you're
up, breakfasted, and at work before dawn. In fact, SAD seems
to be more common in northern latitudes. When natural light
is scarce, the best way to reset the inner clock is with a
burst of artificial light.
The vital importance of the SCN as a biological
time setter is a recent discovery, though not a new one. While
its roots go back to the early 1900s it wasn't characterized
until the early 1970s. What's really new is an understanding
of the SCN's internal mechanism. Neuroscientists have begun
to pry off the clock's cover to get a look at the workings.
Research at a number of laboratories has revealed the workhorse
of the biological clock to be an ingenious and ingeniously
simple device in the individual cells that make up the SCN
(and perhaps other time-sensitive organs as well). Such cells
seem to run the whole system from the bottom up. "We're now
pretty certain," Reppert says, "that the SCN is made up of
numerous autonomous clocks in individual cells—and all the
molecular machinery you need seems to reside in a single
neuron."
Underneath
it all is one clock, the clock in the cell.
The clocks are self-starting and remarkably
reliable. Even when cut off from eternal light and temporary
cues that reveal the time of the day, they slip out of alignment
only gradually. Ambient light doesn't control the clocks;
it simply helps adjust them.
Although we're still uncertain how a malfunctioning
biological clock affects behavior, or how it can lead to weakening
cycles of gloom and anguish, Reppert's team has just published
a paper suggesting an answer. They established a connection
between the individual nerve cells whose microscopic inner
machinery drives the SCN mechanism, and the manufacture of
the hormones. The same proteins that built up and break down
over a 24-hour cycle to run the circadian clock directly cause
the release of a hormone that can regulate how animals act. "Basically, we had a framework for the molecule gears of the
circadian clock in mammals," Reppert says, "What we wanted
to get was a link to actual behavior."
Reppert found that clock proteins switch on
and off the gene that produces vasopressin. Outside the brain,
vasopressin is important in controlling the salt and water
balance in the body. In the brain, however, it's practically
a different hormone, implicated in cycles of rest and activity
in mammals. While vasopressin doesn't seem to influence the
kinds of behavior involved in seasonal affective disorder,
it does supply an exciting model for a-to-z operation of biological
clocks and for how a malfunction can cause abnormalities in
mood or behavior. Now scientists can see a continuum from
the cycling of light and dark in the atmosphere around us,
the world clock, inward to the SCN personal clock, then still
further inward to the microscopic nerve-cell clocks, and finally,
to the production of a hormone.
That is only a beginning. Vasopressin is just
one of a vast range of substances that regulate behavior.
Cellular clocks haven't yet been directly linked to the cycling
of familiar behavior- and mood-modulating substances like
serotonin and melatonin. "It's going to take another decade
to work out a connection between Reppert's work and ,"
Terman predicts. But it isn't hard to foresee how visionary
circadian-clock therapies might work. As a matter of fact,
a couple is already in place. Jet lag, for example, might
respond favorably to melatonin, at least for some people.
And there's also an effective treatment for SAD. In 1980,
Alfred Lewy, at the Oregon Health Sciences University's Sleep
and Mood Disorders Laboratory, successfully relieved a man
who suffered from recurrent winter depression simply by exposing
him to bright light over several days, from six to nine every
morning and four to seven every evening. In
later treatments Lewy worked the dosage down to two hours
of exposure a day at an intensity of 2 500 lux, which approximates
the strength of natural light just after the sun has fully
risen. Today, standard therapy for SAD patients
involves exposure to artificial light for 30 minutes each
morning at an intensity of 1 000 lux (which approximates the
strength of natural light about 40 minutes after sunset.)
Terman's group has been working on refining
the treatment: a computerized light system for the bedroom,
imitating the gradual, naturally intensifying light of dawn.
Jason tried it, and it worked beautifully. "Over a couple
of hours it simulates the sun coming up," he says. "Somehow
you're aware of it even when you're asleep: the light coming
through your eyelids is a luxurious feeling." Within
days, Jason's depression dissipated, his sleep habits returned
to normal, and the sweet tooth cravings became somewhat less
pronounced.
The possibilities raised by the discoveries
on the workings of the biological clock go beyond moodiness
and depression. If heart attacks happen at the prompting of
a time signal, for example, is there a way to turn that signal
off? Is there a way to control weight by spacing out the timing
of hunger pangs? Is it possible to predict, even control,
not just the day, but the hour, a baby is born? For the first
time, science knows where and how to look for the answers
to these questions.
(2 057 words)
(From Discover, July 1999 )
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