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

by Robert M. Sapolsky

element of surprise. Under those conditions, there is even greater release of dopamine. Right after the task is completed, dopamine release starts to rise far higher than usual, peaking right around the time that the reward, if it’s going to happen, should be arriving. Introduce, “This is going to be great…maybe…probably…” and your neurons spritz dopamine all over the place in anticipation.

So dopamine plays an important role in the anticipation of pleasure and in energizing you in order to respond to incentives.

What makes for the benign sort of environment in which uncertainty is pleasurable, rather than stressful? One key element is how long the experience goes on. Pleasurable lack of control is all about transience—it’s not for nothing that roller-coaster rides are three minutes rather than three weeks long. Another thing that biases toward uncertainty being pleasurable is if it comes bound within a larger package of control and predictability. No matter how real and viscerally gripping the scary movie may be, you still know that Anthony Perkins is stalking Janet Leigh, not you.

And what is the pattern of glucocorticoid exposure that maximized dopamine release? You can probably guess already. A moderate rise that doesn’t go on for too long. As we’ve seen, experience severe and prolonged stress, and learning, synaptic plasticity, and immune defenses are impaired. As we saw, experience moderate and transient stress, and memory, synaptic plasticity, and immunity are enhanced. Same thing here. Experience severe and prolonged glucocorticoid exposure, and we’ve returned to chapter 14—dopamine depletion, dysphoria, and depression.

with moderate and transient glucocorticoid elevation you release dopamine. And transient activation of the amygdala releases dopamine as well. Couple the glucocorticoid rise with the accompanying activation of the sympathetic nervous system, and you’re also enhancing glucose and oxygen delivery to the brain. You feel focused, alert, alive, motivated, anticipatory. You feel great. We have a name for such transient stress. We call it “stimulation.”

Food for a hungry rat, sex for a horny one, and dopamine levels rise 50 to 100 percent in this pathway. But give the rat some cocaine and there is a THOUSAND-FOLD increase in dopamine release.

It’s been months, years, even decades since he’s gone near the drug. But uncontrollable circumstances put him back where he always used the drug back when—back on that same street corner, in that same music studio, back in the same overstuffed armchair near the bar in the country club—and the craving comes roaring back like it was yesterday. The capacity to induce that craving doesn’t necessarily decline with time; as many drug abusers in that situation will say, it is as if they had never stopped using.

This is the phenomenon of context-dependent relapse—the itch is stronger in some places than others, specifically in places that you associate with prior drug use. You can show the identical phenomenon in a lab rat.

This process of associating drug use with a particular setting is a type of learning, and a lot of current addiction research explores the neurobiology of such learning. This work focuses not so much on those dopamine neurons, but on the neurons that project to them. Many of them come from cortical and hippocampal regions that carry information about setting. If you repeatedly use a drug in the same setting, those projections onto those dopamine neurons are repeatedly activated and eventually become potentiated, strengthened, in the same ways as the hippocampal synapses

When those projections get strong enough, if you return to that setting, the dopamine anticipation of the drug gets triggered merely by the context.

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

We begin by considering what taking any of various psychostimulant drugs does to the stress-response. And everyone knows the answer to that one—“I’m not feeling any pain.” Drugs of abuse make you feel less stressed.

How does this work? Many drugs, including alcohol, raise glucocorticoid levels when they are first taken. But with more sustained use, various drugs can blunt the nuts and bolts of the stress-response. Alcohol, for example, has been reported in some cases to decrease the extent of sympathetic nervous system arousal and to dampen CRH-mediated anxiety.

As the blood levels of the drug drop, as the effects wear off, the cognition and reality sneak back in and, if anything, the drugs become just the opposite, become anxiety-generating. The dynamics of many of these drugs in the body is such that the amount of time that blood levels are rising, with their stress-reducing effects, is shorter than the amount of time that they are dropping.

What does stress have to do with the likelihood of taking (and abusing) drugs? The clear punch line is that stress pushes you toward more drug use and a greater chance of relapse, although it’s not completely clear how stress does this.

Thus, 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.

What about once the addiction has occurred—what does ongoing stress do to the extent of abuse? No surprise, it increases it.

Moreover, glucocorticoid secretion is consistently elevated during withdrawal, into the range where it depletes dopamine. And what happens if you add additional stress on top of that? All that the extra glucocorticoids can do in this scenario is make the dopamine depletion even worse. Thus increasing the craving for that drug-induced boost of dopamine.

What about that rare individual who manages to stop abusing whatever drug she’s addicted to and successfully goes on the wagon? Stress increases the odds of her relapsing into drug use.

So stress can increase the odds of abusing a drug to the point of addiction in the first place, make withdrawal harder, and make relapse more likely.

At one extreme, you have the mainstream medical crowd that is concerned with reductive biology. For them, poor health revolves around issues of bacteria, viruses, genetic mutations, and so on. At the other extreme are the folks anchored in mind-body issues, for whom poor health is about psychological stress, lack of control and efficacy, and so on. A lot of this book has, as one of its goals, tried to develop further links between those two viewpoints. This has come in the form of showing how sensitive reductive biology can be to some of those psychological factors, and exploring the mechanisms that account for this.

among subordinate male baboons, resting levels of glucocorticoids are significantly higher than among dominant individuals—for a subordinate, everyday basal circumstances are stressful. And that’s just the start of subordinates’ problems with glucocorticoids. When a real stressor comes along, their glucocorticoid response is smaller and slower than in dominant individuals. And when it’s all passed, their recovery appears to be delayed.

More problems for subordinate individuals: elevated resting blood pressure; sluggish cardiovascular response to real stressors; a sluggish recovery; suppressed levels of the good HDL cholesterol; among male subordinates, testosterone levels that are more easily suppressed by stress than in dominant males; fewer circulating white blood cells; and lower circulating levels of something called insulin-like growth factor-I, which helps heal wounds. As should be clear umpteen pages into this book, all these are indices of bodies that are chronically stressed.

There are lots of species in which social subordination is not associated with an overactive stress-response.

To the experts on each primate species, we posed the same questions: in the species that you study, what are the rewards of being dominant? How much of a role does aggression play in maintaining dominance? How much grief does a subordinate individual have to take? What sources of coping and support (including the presence of relatives) do subordinates of that species have available to them? What covert alternatives to competition are available? If subordinates cheat at the rules, how likely are they to get caught and how bad is the punishment? How often does the hierarchy change?

So rank means different things in different species. It turns out that rank can also mean different things in different social groups within the same species.

Another critical variable is an animal’s personal experience of both its rank and society.

As a final variable, it is not just rank that is an important predictor of the stress-response, not just the society in which the rank occurs, or how a member of the society experiences both; it’s also personality—the topic of chapter 15. As we saw, some primates see glasses as half empty and life as full of provocations, and they can’t take advantage of outlets or social support—those are the individuals with overactive stress-responses. For them, their rank, their society, their personal experiences might all be wonderfully salutary, but if their personality keeps them from perceiving those advantages, their hormone levels and arteries and immune systems are going to pay a price.

“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.

being poor is associated with more stress-related diseases.

During periods of remission, parents who denied that relapse and death were likely and instead focused on the seemingly healthy moment had lower glucocorticoid levels (as we will see shortly, this facet of the study had a very different postscript).

The researchers found that if you can look at your child having cancer and decide that God is choosing you for this special task, you are likely to have less of a stress-response (the larger issue of religious belief and health will be considered shortly).

Parents somehow shouldering the burden of their child’s fatal illness, a low-ranking baboon who has a network of friends, a dog resisting learned helplessness—these are striking examples of individuals who, faced with a less than ideal situation, nevertheless excel at coping.

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.

we can change the way we cope, both physiologically and psychologically. As the most obvious example, physical conditioning brought about by regular exercise will lower blood pressure and resting heart rate and increase lung capacity, just to mention a few of its effects.

Among Type-A people, psychotherapy can change not only behaviors but also cholesterol profiles, risk of heart attack, and risk of dying, independent of changes in diet or other physiological regulators of cholesterol.

pain and stressfulness of childbirth can be modulated by relaxation tech...

Sheer repetition of certain activities can change the connection between your behavior and activa...

What are the buttons we can use to manipulate the system in a way that will benefit us? The issues raised in the chapter on the psychology of stress are obviously critical: control, predictability, social support, outlets for frustration.

Back to the parents of children with cancer who were in remission. Eventually, all the children came out of remission and died. When that occurred, how did the parents fare? There were those who all along had accepted the possibility, even probability, of a relapse, and there were those who staunchly denied the possibility. As noted, during the period of remission the latter parents tended to be the low glucocorticoid secretors. But when their illusions were shattered and the disease returned, they had the largest increases in glucocorticoid concentrations.

Exercise enhances mood and blunts the stress-response only for a few hours to a day after the exercise session. Exercise is stress reducing so long as it is something you actually want to do. Let rats voluntarily run in a running wheel and their health improves in all sorts of ways. Force them to, even while playing great dance music, and their health worsens. The studies are quite clear that aerobic exercise is better than anaerobic exercise for health (aerobic exercise is the sustained type that, while you’re doing it, doesn’t leave you so out of breath that you can’t talk). Exercise needs to occur on a regular basis and for a sustained period. While whole careers are consumed figuring out exactly what schedule of aerobic exercise works best (how often, for how long), it’s pretty clear that you need to exercise a minimum of twenty or thirty minutes at a time, a few times a week, to really get the health benefits. Don’t overdo it. Remember the lessons of chapter 7—too much can be at least as bad as too little.

When done on a regular, sustained basis (that is to say, something close to daily, for fifteen, thirty minutes at a time), meditation seems to be pretty good for your health, decreasing glucocorticoid levels, sympathetic tone, and all the bad stuff that too much of either can cause.

the studies are clear in showing physiological benefits while someone is meditating. It’s less clear that those good effects (for example, lowering blood pressure) persist for long afterward.

It is clearly a travesty to lead cancer patients or their families to believe, misinterpreting the power of the few positive studies in this field, that there is more possibility for control over the causes and courses of cancers than actually exists. Doing so is simply teaching the victims of cancer and their families that the disease is their own fault, which is neither true nor conducive to reducing stress in an already stressful situation.

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.

John Henryism is associated with a marked risk of hypertension and cardiovascular disease.

social support makes stressors less stressful, so go get some. Unfortunately, it’s not so simple.

marriage, on average, is associated with improved health. But that chapter also noted an obvious but important exception to this general rule: for women, being in a bad marriage is associated with immune suppression. So a close, intimate relationship with the wrong person can be anything but stress-reducing.

Throughout this section I have been emphasizing getting social support from the right person, the right network of friends, the right community. Often, one of the strongest stress-reducing qualities of social support is the act of giving social support, to be needed.