Act more like a zebra and it won't kill you.

By Robert Burton
Published March 20, 2000 5:00PM (EST)

I have a column deadline. The weather is fab. I'd rather check the latest Nasdaq stats or go to the beach. Instead I cull through the med journals, stop at the proposal that the human genome project may allow us to live to 150. I put down the journal, mull over the notion of fate, and wonder why I was born too soon to take
advantage of the future. I phone the hospital, am put on hold and hear this recording: "If you have an emergency, please dial another number."

I contemplate the Eastern practice of sitting, envision monks in the lotus position, eyes closed, mind clear. Maybe meditation works for others, but my mind is stubborn, resistant, a steel bar that will not bend to my will. I realize that my racing mind may be ruining my

Since information is my latest pacifier, I punch up Medline to see how bad stress really is. There are so many articles that I go into speed-reading mode. I scan a hundred, remember none and wonder about early dementia.

Take a deep breath, my inner voice warns, annoying me. I know that. You don't have to tell me, I tell myself before I become engrossed in the sociobiology of stress.

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You turn a corner and are accosted by a mugger. Your body responds with a "fight or flight" outpouring of adrenaline and cortisol (the naturally occurring cortisone secreted by the adrenal gland). You make it safely to your car, outrunning the
overweight, out-of-shape mugger. If you were a zebra that had just outrun a lion, you would relax and return to daily zebra business, with no accompanying implications. And, if you were a zebra, your stress hormone levels would quickly return to normal.

But we are human. Most of us don't or can't let such a terrifying event go. We imagine a host of what ifs. We ruminate, develop opinions, carry grudges, consider carrying a gun for self-defense, join support groups, become political activists. The event grows in importance, acute becomes chronic, our stress hormones remain sky-high. It is this chronic stress hormone elevation that does us in.

There is no uniformity of opinion as to the physiology of stress, but let's look at some recent provocative studies.

Scientists at Bristol University, England, injected newborn rats with an extract of bacteria sufficient to create a brief, mild fever. The rats recovered and resumed normal development. But as adults, when exposed to stressful laboratory conditions, they produced markedly elevated levels of stress hormones compared to a control group.

In a second study, newborn rats were briefly removed from their mothers' care, then returned to the mother. Again, the animals developed abnormal stress responses that persisted into adulthood. In both studies, chemical analysis revealed higher brain
levels of corticotrophin-releasing hormone (the brain-generated hormone that stimulates the adrenal gland to release cortisol).

The sad conclusion: a brief toxic event in early life (either physical or psychological) condemned the animals to a lifelong excessive stress response. At present the main mechanism seems to be the generation of increased amounts of brain cortisol. (Note the similarity to neuroscientist Joseph LeDoux's observation
in "The Emotional Brain" that a single childhood trauma can produce a chronic lifelong tendency toward anxiety.)

Recent research at the University of Leiden has demonstrated that the brain has separate receptors for detecting low and high levels of cortisol. These receptors are located in regions of the cerebral cortex where mood, emotion and cognitive processes
are regulated. Homeostasis (the internal balance of an organism) is
dependent upon the proper, finely tuned interaction between the two systems.

Now consider a separate line of evidence, that depression is a well-recognized common side effect of taking cortisone as an anti-inflammatory medication. The proposed mechanism -- cortisol -- increases the metabolism of serotonin, effectively lowering brain serotonin levels. Serotonin depletion is thought to be the major neurochemical basis for depression; antidepressants such as Prozac work primarily by restoring proper serotonin

The equation undoubtedly isn't as simple as I've described it, but the above scenario seems very convincing as a general argument relating stress, increased stress hormones and mood disorders. To appreciate the very physical symptoms of altered cortisol metabolism, think back to your worst case of jet lag. Cortisol,
like all hormones, has its own daily rhythm, rising to a maximum about an hour or so before we wake up in the morning, then slowly falling throughout the day so that it reaches very
low levels between midnight and 2 a.m. When we move to a different time zone, our cortisol rhythm takes up to a week to readjust. Until then, we have jet lag.

We can understand jet lag as a physiological shift in circadian rhythms. But what exactly is stress?

Neuroendocrinologists have developed a learned helplessness laboratory animal model of depression. Rats are submitted to a situation from which they can either escape, or that they can accept. Some escape. Others give up and simply lie down. The
latter animals have all the typical biochemical markers of depression.

Chital deer are from India, where their natural predator is the tiger. When attacked, the animal has the choice to either stay and fight or run. Naturally the deer choose to run. But transport the Chital deer into a captive situation like a fenced-in farmyard, and because they can't flee from what they see as a danger, they stand still in a group in a corner of the yard. They appear calm, yet if the threat remains for 15 minutes, one or two of the deer in the group will simply lie down and die. Autopsy shows diffuse internal bleeding. Blood tests show that their muscles have released enormous amounts of enzymes normally used to facilitate running away. The disease is called capture myopathy (myopathy means muscle disease).

After 20 years of studying baboons in the wild, Robert Sapolsky, a Stanford neuroscientist, has found that in a stable social circumstance, those lowest on the social hierarchy totem pole, whether in getting food or sex, had the highest levels of
stress hormones and the highest rates of stress-related disease such as hypertension.

In a separate monkey study, the situation was reversed. Animals were fed diets that predisposed them to atherosclerosis. Then they were put in unstable social circumstances (the animals were regularly switched between groups so that they had to continuously reestablish their dominance and interpersonal relationships). Under these circumstances, the most dominant males had the highest incidence of coronary artery

In both monkey groups stress was clearly related to social position. What reversed the stress effect was whether or not the social circumstances remained static.

A few cardiac observations in humans: In a recent study from Yale University, cardiac patients performing mental arithmetic or recalling former episodes of anger had a greatly increased
rate and duration of potentially fatal ventricular arrhythmias. (During the major Los Angeles earthquake of 1994, the number of sudden cardiac deaths rose from a daily average of
4.6 to 24 on the day of the earthquake.) The rate of ischemic changes on 24-hour EKG monitoring of coronary patients rises directly in relationship to the patients describing themselves as being happy, tense, frustrated or sad. One of the highest
coronary artery death rates is in the recently bereaved.

But, on a more hopeful note, 16 years ago, at the Stress Research Unit at York University, England, psychologists began looking for the aspects of personality that might moderate the impact of stress. The most powerful predictor turned out to be the tendency
to ruminate about emotional upset. This led them to redefine stress as precisely that: rumination about negative emotion.

According to Derek Roger, head psychologist at the
Stress Unit, the stimulus for arousal (running into the mugger) is not the same as chronic stress, and calling epinephrine and cortisol 'stress hormones' is a misnomer -- they're merely hormones, and potentially damaging only if their elevation is
prolonged. The simplest way to prolong them is to go on ruminating, which produces physiological adaptation in the absence of the event.

"Conventional stress management is about symptoms, life events and relaxation, but the first offers no insight into causes and the second is misleading in making stress an inescapable property of events. I would argue that there is no such thing as a
'stressful event,' only a stressful way of responding to an event. And relaxation techniques are only palliative."

What has become clear from the research evidence is that stress is
primarily a cognitive process, and is not inherent in so-called life events. Indeed, the life-events approach is extremely pessimistic -- how many of the events and people that have to be dealt with on a day-to-day basis could actually be avoided? If these things are inherently stressful, then stress is inevitable. An alternative view is that stress is determined by the way we respond to events, and while you may not be able to change events, you can certainly change your mind.

We cannot change our pasts. We cannot undo whatever negative childhood insults (physical and/or psychological) have shaped our lifelong response to stress. If we are high-stress responders, so be it. We may not be able to change our chemistry, but we can modify how we think about life events that are beyond our
control. It is up to us to decide what is stressful. Chronic stress is a
perceptual disorder. In other words, maybe my racing mind isn't so bad except when I worry about it racing.

Robert Burton

Robert Burton M.D. is the former chief of neurology at Mount Zion-UCSF Hospital and the author of "On Being Certain: Believing You Are Right Even When You're Not" and "A Skeptic's Guide to the Mind." A former columnist for Salon, he has also been published in the New York Times, Aeon and Nautilus, and currently writes a column at the Cambridge Quarterly for Healthcare Ethics.

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