Why Zebras Don't Get Ulcers: The Acclaimed Guide to Stress, Stress-Related Diseases, and Coping

by Robert M. Sapolsky

A large body of evidence suggests that stress-related disease emerges, predominantly, out of the fact that we so often activate a physiological system that has evolved for responding to acute physical emergencies, but we turn it on for months on end, worrying about mortgages, relationships, and promotions.

All these different variables are maintained in homeostatic balance, the state in which all sorts of physiological measures are being kept at the optimal level.

The brain, it has been noted, has evolved to seek homeostasis.

A stressor is anything in the outside world that knocks you out of homeostatic balance, and the stress-response is what your body does to reestablish homeostasis.

A stressor can also be the anticipation of that happening. Sometimes we are smart enough to see things coming and, based only on anticipation, can turn on a stress-response as robust as if the event had actually occurred.

It is not so much that the stress-response runs out, but rather, with sufficient activation, that the stress-response can become more damaging than the stressor itself, especially when the stress is purely psychological. This

The first is that if you plan to get stressed like a normal mammal, dealing with an acute physical challenge, and you cannot appropriately turn on the stress-response, you’re in big trouble.

If you repeatedly turn on the stress-response, or if you cannot turn off the stress-response at the end of a stressful event, the stress-response can eventually become damaging. A large percentage of what we think of when we talk about stress-related diseases are disorders of excessive stress-responses.

The sympathetic nervous system kicks into action during emergencies, or what you think are emergencies. It helps mediate vigilance, arousal, activation, mobilization.

sympathetic nervous system mediating the four F’s of behavior—flight, fight, fright, and sex.

parasympathetic component mediates calm, vegetative activities—everything but the four F’s. If you are a growing kid and you have gone to sleep, your parasympathetic system is activated. It promotes growth, energy storage, and other optimistic processes. Have a huge meal, sit there bloated and happily drowsy, and the parasympathetic is going like gangbusters.

sympathetic and parasympathetic projections from the brain course their way out to a particular organ where, when activated, they bring about opposite results. The sympathetic system speeds up the heart; the parasympathetic system slows it down. The sympathetic system diverts blood flow to your muscles; the parasympathetic does the opposite.

Sympathetic arousal is a relative marker of anxiety and vigilance, while heavy secretion of glucocorticoids is more a marker of depression.

Whenever you inhale, you turn on the sympathetic nervous system slightly, minutely speeding up your heart. And when you exhale, the parasympathetic half turns on, activating your vagus nerve in order to slow things down (this is why many forms of meditation are built around extended exhalations).

The official numbers are that stress makes about two-thirds of people hyperphagic (eating more) and the rest hypophagic.* Weirdly, when you stress lab rats, you get the same confusing picture, where some become hyperphagic, others hypophagic.

endorphins play a role in blocking pain perception and are secreted in response to exercise (helping to account for the famed “runner’s high” or “endorphin high” that hits many hardy joggers around the 30-minute mark).

However, the same pattern has been reported for other cancers as well. The cancer-prone personality, we’re told, is one of repression—emotions held inside, particularly those of anger. This is a picture of an introverted, respectful individual with a strong desire to please—conforming and compliant. Hold those emotions inside and it increases the likelihood that out will come cancer, according to this view.

Pain is useful to the extent that it motivates us to modify our behaviors in order to reduce whatever insult is causing the pain, because invariably that insult is damaging our tissues. Pain is useless and debilitating, however, when it is telling us that there is something dreadfully wrong that we can do nothing about. We must praise the fact that we have evolved a physiological system that lets us know when our stomachs are empty.

Neurochemists went wild at this point looking for endogenous morphine. Soon they found exactly what they were looking for: endogenous compounds with chemical structures reminiscent of the opiate drugs. They turned out to come in three different classes—enkephalins, dynorphins, and the most famous of them all, endorphins (a contraction for “endogenous morphines”).

Predictably, it comes at the most unpredictable times. I’ll be lecturing, bored, telling the same story about neurons I did last year, daydreaming, looking at the ocean of irritatingly young undergraduates, and then it hits, producing almost a sense of wonderment. “How can you just sit there? Am I the only one who realizes that we’re all going to die someday?”

the wave of bitterness will sweep over me. “All of you damned medical experts, and not one of you can make me live forever.”

Place two people in adjoining rooms, and expose both to intermittent noxious, loud noises; the person who has a button and believes that pressing it decreases the likelihood of more noise is less hypertensive. In one variant on this experiment, subjects with the button who did not bother to press it did just as well as those who actually pressed the button. Thus, the exercise of control is not critical; rather, it is the belief that you have it.

An everyday example: airplanes are safer than cars, yet more of us are phobic about flying. Why? Because your average driver believes that he is a better-than-average driver, thus more in control. In an airplane, we have no control at all. My wife and I tease each other on plane

Think about what our lives are about. None of us will live forever, and on occasion we actually believe it; our days are filled with disappointments, failures, unrequited loves. Despite this, almost inconceivably, we not only cope but even feel vast pleasures.

Your style, your temperament, your personality have much to do with whether you regularly perceive opportunities for control or safety signals when they are there, whether you consistently interpret ambiguous circumstances as implying good news or bad, whether you typically seek out and take advantage of social support.

What is anxiety? A sense of disquiet, of disease, of the sands constantly shifting menacingly beneath your feet—where constant vigilance is the only hope of effectively protecting yourself. Anxiety disorders come in a number of flavors. To name just a few: generalized anxiety disorder is just that—generalized—whereas phobias focus on specific things. In people with panic attacks, the anxiety boils over with a paralyzing, hyperventilating sense of crisis that causes massive activation of the sympathetic nervous system. In obsessive-compulsive disorder, the anxiety buries and busies itself in endless patterns of calming, distracting ritual. In post-traumatic stress disorder, the anxiety can be traced to a specific trauma.

Anxiety is about dread and foreboding and your imagination running away with you. Much as with depression, anxiety is rooted in a cognitive distortion. In this case, people prone toward anxiety overestimate risks and the likelihood of a bad outcome. Unlike depressives, the anxiety-prone person is still attempting to mobilize coping responses. But the discrepancy is the distorted belief that stressors are everywhere and perpetual, and that the only hope for safety is constant mobilization of coping responses.

You can show this with a lab rat. Rats, being nocturnal creatures, don’t like bright lights, are made anxious by them. Put a rat in a cage whose edges are dark, just the place a rat likes to hunker down. But the rat is really hungry and there’s some wonderful food in the middle of the cage, under a bright light. Massive anxiety—the rat starts toward the food, pulls back, again and again, frantically tries to figure ways to the food that avoid the light. This is anxiety, a disorganized attempt to cope, and this phase is dominated by catecholamines. If it goes on for too long, the animal gives up, just lies there, in the shaded perimeter. And that is depression, and it is dominated by glucocorticoids.

Two cardiologists, Meyer Friedman and Ray Rosenman, coined the term Type A in the early 1960s to describe a collection of traits that they found in some individuals. They didn’t describe these traits in terms related to stress (for example, defining Type-A people as those who responded to neutral or ambiguous situations as if they were stressful), although I will attempt to do that reframing below. Instead, they characterized Type-A people as immensely competitive, overachieving, time-pressured, impatient, and hostile. People with that profile, they reported, had an increased risk of cardiovascular disease.

Peter Sterling, of allostasis fame, has written brilliantly about how our sources of pleasure have become so narrowed and artificially strong. His thinking centers around the fact that our anticipatory pleasure pathway is stimulated by many different things. For this to work, the pathway must rapidly habituate, must desensitize to any given source that has stimulated it, so that it is prepared to respond to the next stimulant. But unnaturally strong explosions of synthetic experience and sensation and pleasure evoke unnaturally strong degrees of habituation. This has two consequences. As the first, soon we hardly notice anymore the fleeting whispers of pleasure caused by leaves in autumn, or by the lingering glance of the right person, or by the promise of reward that will come after a long, difficult, and worthy task. The other consequence is that, after awhile, we even habituate to those artificial deluges of intensity and moment-ness. If we were nothing but machines of local homeostatic regulation, as we consume more, we would desire less. But instead, our tragedy is that we just become hungrier. More and faster and stronger. “Now” isn’t as good as it used to be, and won’t suffice tomorrow.

If we can’t consider disease outside the context of the person who is ill, we also can’t consider it outside the context of the society in which that person has gotten ill, and that person’s place in that society.

showed how the “executive stress syndrome” is mostly a myth—people at the top give ulcers, rather than get them. Most studies have shown that it is middle management that succumbs to the stress-related diseases. This is thought to reflect the killer combination that these folks are often burdened with, namely, high work demands but little autonomy—responsibility without control.

you’re eighty-five, and you get to influence your nation’s laws for a century to come, or spend your days aerobically exercising by waving your baton about and determining whether a whole orchestra full of adults gets a potty break before or after another run through Wagner’s Ring Cycle.*

All of these examples show that the workings of the stress-response can change over time. We grow, learn, adapt, get bored, develop an interest, drift apart, mature, harden, forget.

God grant me the serenity to accept the things I cannot change, courage to change the things I can, and wisdom to know the difference.

In the face of strong winds, let me be a blade of grass. In the face of strong walls, let me be a gale of wind.

It is here that we must turn from the physicians and their ability to clean up the mess afterward and recognize our own capacity to prevent some of these problems beforehand in the small steps with which we live our everyday lives.