Mind Over Time

By Mark Caldwell, Discover magazine

Suppose you could reset the inner clocks that run your life -- programming yourself to wake up fresh and alert at 5:30 a.m. if you had to make a crucial breakfast meeting, or shutting off the hunger that drives you to scarf a bag of tortilla chips every afternoon.

If the prospect of controlling your body's chronometers seems a pleasing luxury, consider the case of Jason K., a New Jersey attorney. Jason suffers from a debilitating 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 a person's life into terrible turmoil.

``It came up on me gradually,'' Jason says. As the days got darker going into fall and then winter, ``My mood got darker. By winter it took dramatically more effort to get anything done. And I developed an excessive craving for sweets.''

``When it hits, it's not just a matter of mood,'' says Michael Terman, a clinical psychologist at Columbia Presbyterian Medical Center's New York State Psychiatric Institute in New York City, and a leading SAD researcher. ``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.''

Yet the syndrome is only one among a constellation of sleep disorders and related ills caused by biological clocks run amok. 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 jolts out of sync with the pace of the rest of the world.

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 has 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 that shows where in our brains the chronometer is, how it uses the machinery in our cells as clockwork, and how it can be slowed down, speeded up or reset.

In the brain, a recently discovered cluster of nerve cells called the suprachiasmatic nucleus, or SCN, appears to be at the heart of timekeeping.

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 neurobiologist 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 circadian-clock mavens call entrainment -- 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 photoreceptors in their eyes, which pick up light signals and carry them directly to the SCN.

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.

Not everyone has the problem. Most people aren't 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.

Although we're still uncertain how a malfunctioning biological clock affects behavior, or how it can lead to debilitating 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 hormones.

The same proteins that operate over a 24-hour cycle to run the circadian clock directly cause an oscillation in the release of a hormone -- vasopressin -- that can regulate how animals act.

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 therapeutics,'' Terman predicts. But it isn't hard to foresee how visionary circadian-clock therapies might work.

As a matter of fact, a couple are 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.

Today, standard therapy for SAD patients involves exposure to artificial light for 30 minutes each morning at an intensity of 10,000 lux (which approximates the strength of natural light about 40 minutes after sunrise).

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. For example, is there a way to control weight by spacing out the timing of hunger pangs? For the first time, science knows where and how to look for the answer to such a question.