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

by Robert M. Sapolsky

A central feature of an outlet being effective is if it distracts from the stressor. But, obviously, more important is that it also be something positive for you—a reminder that there is more to life than whatever is making you crazed and stressed at the time. The frustration-reducing effects of exercise provide an additional layer of benefit, one harking back to my dichotomy, repeated ad nauseam, between the zebra running for its life and the psychologically stressed human. The stress-response is about preparing your body for an explosive burst of energy consumption right now; psychological stress is about doing all the same things to your body for no physical reason whatsoever. Exercise finally provides your body for the outlet that it was preparing for.

A variant of Weiss’s experiment uncovers a special feature of the outlet-for-frustration reaction. This time, when the rat gets the identical series of electric shocks and is upset, it can run across the cage, sit next to another rat and…bite the hell out of it. Stress-induced displacement of aggression: the practice works wonders at minimizing the stressfulness of a stressor. It’s a real primate specialty as well. A male baboon loses a fight. Frustrated, he spins around and attacks a subordinate male who was minding his own business.

Humans are pretty good at it, too, and we have a technical way of describing the phenomenon in the context of stress-related disease: “He’s one of those guys who doesn’t get ulcers, he gives them.” Taking it out on someone else—how well it works at minimizing the impact of a stressor.

Thus, some powerful psychological factors can trigger a stress-response on their own or make another stressor seem more stressful: loss of control or predictability, loss of outlets for frustration or sources of support, a perception that things are getting worse. There are obviously some overlaps in the meaning of these different factors. As we saw, control and predictability are closely aligned; combine them with a perception of things worsening, and you have the situation of bad things happening, out of your control, and utterly unpredictable. The primatologist Joan Silk of UCLA has emphasized how, among primates, a great way to maintain dominance is for the alpha individual to mete out aggression in a randomly brutal way. This is our primate essence of terrorism.

Depression is a term that we all use in an everyday sense. Something mildly or fairly upsetting happens to us, and we get “the blues” for a while, followed by recovery. This is not what occurs in a major depression. One issue is chronicity—for a major depression to be occurring, the symptoms have to have persisted for at least two weeks. The other is severity—this is a vastly crippling disorder that leads people to attempt suicide; its victims may lose their jobs, family, and all social contact because they cannot force themselves to get out of bed, or refuse to go to a psychiatrist because they feel they don’t deserve to get better. It is a horrific disease, and throughout this chapter I will be referring to this major, devastating form of depression, rather than the transient blues that we may casually signify with the term “feeling depressed.”

The defining feature of a major depression is loss of pleasure. If I had to define a major depression in a single sentence, I would describe it as a “genetic/neurochemical disorder requiring a strong environmental trigger whose characteristic manifestation is an inability to appreciate sunsets.”

An additional vegetative symptom is extremely relevant to this chapter, namely that major depressives often experience elevated levels of glucocorticoids. This is critical for a number of reasons that will be returned to, and helps to clarify what the disease is actually about. When looking at a depressive sitting on the edge of the bed, barely able to move, it is easy to think of the person as energy-less, enervated. A more accurate picture is of the depressive as a tightly coiled spool of wire, tense, straining, active—but all inside. As we will see, a psychodynamic view of depression shows the person fighting an enormous, aggressive mental battle—no wonder they have elevated levels of stress hormones.

In another subset of depression the rhythm is annual, where sufferers get depressed during the winter. These are called seasonal affective disorders (SADs; “affective” is the psychiatric term for emotional responses), and are thought to be related to patterns of exposure to light; recent work has uncovered a class of retinal cells that respond to light intensity and, surprisingly, send their information directly into the limbic system, the emotional part of the brain. Again, the rhythmicity appears independent of external life events; a biological clock is ticking away in there that has something to do with mood, and something is seriously wrong with its ticking.

This theory also explains the tendency of major depressives in such circumstances to, oddly, begin to take on some of the traits of the lost loved/hated one—and not just any traits, but invariably the ones that the survivor found most irritating. Psychodynamically, this is wonderfully logical. By taking on a trait, you are being loyal to your lost, beloved opponent. By picking an irritating trait, you are still trying to convince the world you were right to be irritated—you see how you hate it when I do it; can you imagine what it was like to have to put up with that for years? And by picking a trait that, most of all, you find irritating, you are not only still trying to score points in your argument with the departed, but you are punishing yourself for arguing as well.

In some models of learned helplessness, animals mutilate themselves, biting at themselves.

If a teacher at a critical point of our education, or a loved one at a critical point of our emotional development, frequently exposes us to his or her own specialized uncontrollable stressors, we may grow up with distorted beliefs about what we cannot learn or ways in which we are unlikely to be loved.

We have now seen some important links between stress and depression: extremes of psychological stress can cause something in a laboratory animal that looks pretty close to a depression. Moreover, stress is a predisposing factor in human depression as well, and brings about some of the typical endocrine changes of depression. In addition, genes that predispose to depression only do so in a stressful environment. Tightening the link further, glucocorticoids, as a central hormone of the stress-response, can bring about depression-like states in an animal, and can cause depression in humans. And finally, both stress and glucocorticoids can bring about neurochemical changes that have been implicated in depression.

With these findings in hand, the pieces begin to fit together. Stress, particularly in the form of extremes of lack of control and outlets, causes an array of deleterious changes in a person. Cognitively, this involves a distortive belief that there is no control or outlets in any circumstance-learned helplessness. On the affective level, there is anhedonia; behaviorally, there is psychomotor retardation. On the neurochemical level, there are likely disruptions of serotonin, norepinephrine, and dopamine signaling—as will be shown in chapter 16, prolonged stress can deplete dopamine in the pleasure pathways. Physiologically, there are alterations in, among other things, appetite, sleep patterns, and sensitivity of the glucocorticoid system to feedback regulation. We call this array of changes, collectively, a major depression.

But the most basic question remains, why do only some of us get depressed? An obvious answer is because some of us are exposed to a lot more stressors than others. And, when factoring in development, that can be stated in a way that also includes history—not only are some of us exposed to more stressors than others, but if we are exposed to some awful stressors early in life, forever after we will be more vulnerable to whatever subsequent stressors are thrown at us. This is the essence of allostatic load, of wear and tear, where exposure to severe stress produces rents of vulnerability.

Thus, after factoring out rank, lower basal glucocorticoid levels are found in males who are best at telling the difference between threatening and neutral interactions; who take the initiative if the situation clearly is threatening; who are best at telling whether they won or lost; and, in the latter case, who are most likely to make someone else pay for the defeat. This echoes some of the themes from the chapter on psychological stress. The males who were coping best (at least by this endocrine measure) had high degrees of social control (initiating the fights), predictability (they can accurately assess whether a situation is threatening, whether an outcome is good news), and outlets for frustration (a tendency to give rather than get ulcers). Remarkably, this style is stable over the years of these individuals’ lives, and carries a big payoff—males with this cluster of low-glucocorticoid traits remain high ranking significantly longer than average.

Thus, among some male baboons, there are at least two routes for winding up with elevated basal glucocorticoid levels, independent of social rank—an inability to keep competition in perspective and social isolation. Stephen Suomi at the National Institutes of Health has studied rhesus monkeys and identified another personality style that should seem familiar, which carries some physiological correlates. About 20 percent of rhesus are what he calls “high-reactors.” Just like the baboons who find a rival napping to be an arousing threat, these individual monkeys see challenges everywhere. But in their case, the response to the perceived threat is a shrinking timidity. Put them into a novel environment that other rhesus monkeys would find to be a stimulating place to explore, and they react with fear, pouring out glucocorticoids. Place them with new peers, and they freeze with anxiety—shy and withdrawn, and again releasing vast amounts of glucocorticoids. Separate them from a loved one, and they are atypically likely to collapse into a depression, complete with excessive glucocorticoids, overactivation of the sympathetic nervous system, and immunosuppression. These appear to be lifelong styles of dealing with the world, beginning early in infancy.

It would seem relatively straightforward to pull together some sound psychotherapeutic advice for these unhappy beasts. But in reality, it’s hopeless. Baboons and macaques get distracted during therapy sessions, habitually pulling books off the shelves, for example; they don’t know the days of the week and thus constantly miss appointments; they eat the plants in the waiting room, and so on. Thus, it might be more useful to apply those same insights to making sense of some humans who are prone toward an overactive stress-response and increased risk of stress-related disease.

Some researchers have identified one subgroup of women with repeated “psychogenic” abortions (accounting for about half the cases) as being “retarded in their psychological development.” They are characterized as emotionally immature women, highly dependent on their husbands, who on some unconscious level view the impending arrival of the child as a threat to their own childlike relationship with their spouse.

Many experts are skeptical about the studies behind these characterizations, however. The first reason harks back to a caveat I aired early in the book: a diagnosis of “psychogenic” anything (impotency, amenorrhea, abortion, and so on) is usually a diagnosis by exclusion. In other words, the physician can’t find any disease or organic cause, and until one is discovered, the disorder gets tossed into the psychogenic bucket. This may mean that, legitimately, it is heavily explained by psychological variables, or it may simply mean that the relevant hormone, neurotransmitter, or genetic abnormality has not yet been discovered. Once it is discovered, the psychogenic disease is magically transformed into an organic problem—“Oh, it wasn’t your personality after all.” The area of repeated aborting seems to be one that is rife with recent biological insights—in other words, if so many of last decade’s psychogenic aborters now have an organic explanation for their malady, that trend is likely to continue. So be skeptical of any current “psychogenic” label.

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 none of these cases is the anxiety about fear. Fear is the vigilance and the need to escape from something real. 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. Life consists of the concrete, agitated present of solving a problem that someone else might not even consider to exist.*

former

latter

When it comes to psychiatric disorders, it seems that increases in the catecholamines have something to do with still trying to cope and the effort that involves, where overabundance of glucocorticoids seems more of a signal of having given up on attempting to cope.

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.

By the late 1980s, the Type-A concept underwent some major modifications. One was the recognition that personality factors are more predictive of heart disease when considering people who get their first heart attack at an early age—by later years, the occurrence of a first heart attack is more about fats and smoking. Moreover, work by Redford Williams of Duke University convinced most in the field that the key factor in the list of Type A-ish symptoms is the hostility. For example, when scientists reanalyzed some of the original Type-A studies and broke the constellation of traits into individual ones, hostility popped out as the only significant predictor of heart disease.

Friedman and colleagues stuck with an alternative view. They suggested that at the core of the hostility is a sense of “time-pressuredness”—“Can you believe that teller, how slowly he’s working. I’m going to be here all day. I can’t waste my life on some bank line. How did that kid know I was in a rush? I could kill him”—and that the core of being time-pressured is rampant insecurity. There’s no time to savor anything you’ve accomplished, let alone enjoy anything that anyone else has done, because you must rush off to prove yourself all over again, and try to hide from the world for another day what a fraud you are. Their work suggested that a persistent sense of insecurity is, in fact, a better predictor of cardiovascular profiles than is hostility, although theirs appears to be a minority view in the field.

By contrast, in the reanalysis of the original Type-A data a particularly powerful predictor of heart disease was not only high degrees of hostility, but also the tendency not to express it when angry. This latter view is supported by some fascinating work by James Gross of Stanford University. Show volunteers a film clip that evokes some strong emotion. Disgust, for example (thanks to a gory view of someone’s leg being amputated). They writhe in discomfort and distaste and, no surprise, show the physiological markers of having turned on their sympathetic nervous systems. Now, show some other volunteers the same film clip but, beforehand, instruct them to try not to express their emotions (“so that if someone were watching, they’d have no idea what you were feeling”). Run them through the blood and guts, and, with them gripping the arms of their chairs and trying to remain stoic, and still, the sympathetic activation becomes even greater. Repressing the expression of strong emotions appears to exaggerate the intensity of the physiology that goes along with them.

For anxious people, life is full of menacing stressors that demand vigilant coping responses. For the Type A, life is full of menacing stressors that demand vigilant coping responses of a particularly hostile nature.

“If you want to know if the elephant at the zoo has a stomachache, don’t ask the veterinarian, ask the cage cleaner.”

Some personality tests, pioneered by Richard Davidson, identify repressive individuals. For starters, as noted, the personality tests show that these people aren’t depressed or anxious. Instead, the tests reveal their need for social conformity, their dread of social disapproval, and their discomfort with ambiguity, as shown by the extremely high rates at which they agree with statements framed as absolutes, statements filled with “never” and “always.” No gray tones here.

Intertwined with those characteristics is a peculiar lack of emotional expression. The tests reveal how repressive people “inhibit negative affect”—no expressing of those messy, complicated emotions for them, and little recognition of those complications in others. For example, ask repressors and non-repressors to recall an experience associated with a specific strong emotion. Both groups report that particular emotion with equal intensity. However, when asked what else they were feeling, non-repressors typically report an array of additional, nondominant feelings: “Well, it mostly made me angry, but also a little sad, and a little disgusted too….” Repressors steadfastly report no secondary emotions. Black-and-white feelings, with little tolerance for subtle blends.

there’s really no such thing as an ex-addict—it is simply an addict who is not in the context that triggers use.

Alcohol, for example, has been reported in some cases to decrease the extent of sympathetic nervous system arousal and to dampen CRH-mediated anxiety.

mean? Basically, if you’re in such a mess of an altered state that you can barely remember what species you are, you may not pick up on the subtle fact that something stressful has occurred.

acute stress increases the reinforcing potential of a drug.

Stress increases the likelihood of self-administering a drug to an addictive extent, but this time we’re talking about stress during childhood. Or even as a fetus. Stress a pregnant rat and her offspring will have an increased propensity for drug self-administration as adults. Give a rat an experimentally induced birth complication by briefly depriving it of oxygen at birth, and you produce the same. Ditto if stressing a rat in its infancy. The same works in nonhuman primates—separate a monkey from its mother during development, and that animal is more likely to self-administer drugs as an adult. The same has been shown in humans.

addiction can broadly serve two dissociable functions. One involves positive affect—drugs can generate pleasure (albeit with an ultimate cost that offsets the transient rewards). The other function concerns negative affect—drugs can be used to try to self-medicate away pain, depression, fear, anxiety, and stress. This dual purpose transitions us to the next chapter with its theme that society does not evenly distribute healthy opportunities for pleasure, or sources of fear and anxiety. It is hard to “just say no” when life demands a constant vigilance and when there are few other things to which to say “yes.”

(Such third-party “displacement aggression” accounts for a huge percentage of baboon violence. A middle-ranking male gets trounced in a fight, turns and chases a subadult male, who lunges at an adult female, who bites a juvenile, who slaps an infant.)

Stress can wreak havoc with your metabolism, raise your blood pressure, burst your white blood cells, make you flatulent, ruin your sex life, and if that’s not enough, possibly damage your brain.*

The same pattern occurs in many other realms in which life tests us. Ten men are released from years spent as political hostages. Nine come out troubled, estranged from friends and family, with nightmares, difficulties readapting to everyday life; some of those nine will never function well again. Yet invariably there is one guy who comes out saying, “Yeah, the beatings were awful, the times they put a gun to my head and cocked the trigger were the worst in my life, of course I would never want to do it again, but it wasn’t until I was in captivity that I realized what is really important, that I decided to devote the rest of my life to X. I’m almost grateful.” How did he do it? What explains the extraordinarily rare Holocaust survivor who came out nearly as mentally healthy as when she went in?

frankl again

When it comes to humans who wish to cope with stress and achieve successful aging, you should be sure to pick the right parents’ genes, and the right parents’ socioeconomic status as well.

called John Henryism. The name refers to the American folk hero who, hammering a six-foot-long steel drill, tried to outrace a steam drill tunneling through a mountain. John Henry beat the machine, only to fall dead from the superhuman effort. As James defines it, John Henryism involves the belief that any and all demands can be vanquished, so long as you work hard enough. On questionnaires, John Henry individuals strongly agree with statements such as “When things don’t go the way I want them, it just makes me work even harder,” or “Once I make up my mind to do something, I stay with it until the job is completely done.” This is the epitome of individuals with an internal locus of control—they believe that, with enough effort and determination, they can regulate all outcomes.

I think it would be helpful to put my cards on the table before tackling this subject. I had a highly orthodox religious upbringing and believed devoutly. Except that now I am an atheist, have no room in my life for spirituality of any kind, and believe that religion is phenomenally damaging. Except that I wish I could be religious. Except that it makes no sense to me and I’m baffled by people who believe. Except that I’m also moved by them. So I’m confused. On to the science.

If your special stress reduction trick is to stand on a busy street corner in a toga reciting Teletubbies monologues, you’re going to benefit from that, simply because you’ve decided that making a change is enough of a priority that you’re willing to say no to all the things that can’t be said no to, in order to do that Tinkie-Winkie soliloquy. Don’t save your stress management for the weekend, or for when you’re on hold on the phone for thirty seconds. Take the time out to do it almost daily. And if you manage that, change has become important enough to you that you’re already a lot of the way there—maybe not really 80 percent, but at least a great start.

In the face of terrible news beyond control, beyond prevention, beyond healing, those who are able to find the means to deny tend to cope best. Such denial is not only permitted, it may be the only means of sanity; truth and mental health often go hand in hand, but not necessarily in situations like these. In the face of lesser problems, one should hope, but protectively and rationally. Find ways to view even the most stressful of situations as holding the promise of improvement but do not deny the possibility that things will not improve. Balance these two opposing trends carefully. Hope for the best and let that dominate most of your emotions, but at the same time let one small piece of you prepare for the worst.

Those who cope with stress successfully tend to seek control in the face of present stressors but do not try to control things that have already come to pass. They do not try to control future events that are uncontrollable and do not try to fix things that are not broken or that are broken beyond repair. When faced with the large wall of a stressor, it is great if there emerges one singular solution that makes the wall crumble. But often, a solution instead will be a series of footholds of control, each one small but still capable of giving support, that will allow you to scale the wall.

Pearl suggested that it may have evolved for male reproduction—the acidity of urine isn’t very healthy for sperm (in ancient times, women would use half a lemon as a diaphragm),

I once received a letter from the chief medical examiner of Vermont describing his investigation of what he concluded to be a case of stress-induced cardiac arrest: an eighty-eight-year-old man with a history of heart disease, lying dead of a heart attack next to his beloved tractor, while just outside the house, at an angle where she could have seen him prone in the barn, was his eighty-seven-year-old wife, more recently dead of a heart attack (but with no history of heart disease and nothing obviously wrong found at autopsy). At her side was the bell she had used to summon him to lunch for who knows how many years.

The jury remains out as to whether the folks who become hyperphagic after stress also develop a specific craving for carbohydrates. Clinical lore supports this picture, as do some laboratory studies. However, there’s a problem here, which is that high-carb foods are typically easier to eat than low-carb foods, since the former tend to be snacks. So it’s not clear if people really get a craving for carbohydrates, or if they get a craving for easy, mindless eating.