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

by Robert M. Sapolsky

absence of touch is seemingly one of the most marked developmental stressors that we can suffer.

stress dwarfism is reversible with a different environment. Studies have shown that the lifelong changes in glucocorticoid levels in prenatally stressed rats can be prevented with particular mothering styles postnatally. Much of preventative medicine is a demonstration that vast numbers of adverse health situations can be reversed—in fact, that is a premise of this book.

Yet I, like other adults, still secrete growth hormone into my circulation (although much less frequently than when I was an adolescent). What good is it in an adult?

Once the growth period of youth is finished and the edifice is complete, the hormones of growth mostly work at rebuilding and remodeling—shoring up the sagging foundation, plastering the cracks that appear here and there.

the hormones of stress wreak havoc with the trafficking of calcium, biasing bone toward disintegration, rather than growth. The main culprits are glucocorticoids. They inhibit the growth of new bone by disrupting the division of the bone-precursor cells in the ends of bones. Furthermore, they reduce the calcium supply to bone. Glucocorticoids block the uptake of dietary calcium in the intestines (uptake normally stimulated by vitamin D), increase the excretion of calcium by the kidney, and accelerate the resorption of bone.

These findings suggest that chronic stress can increase the risk of osteoporosis and cause skeletal atrophy.

an infant human or animal can be well fed, maintained at an adequate temperature, peered at nervously, and ministered to by the best of neonatologists, yet still not thrive. Something is still missing. Perhaps we can even risk scientific credibility and detachment and mention the word love

Something roughly akin to love is needed for proper biological development, and its absence is among the most aching, distorting stressors that we can suffer. Scientists and physicians and other caregivers have often been dim at recognizing its importance in the mundane biological processes by which organs and tissues grow and develop.

For physicians influenced by the likes of Holt, it was obvious and convenient—no need for mothers to visit hospitalized infants—anyone with a bottle would supply attachment needs. No need to worry about preemies kept antiseptically isolated in incubators—regular feeding suffices for human contact. No need for children in orphanages to be touched, held, noted as individuals.

Kids don’t love their mothers because Mom balances their nutritive intake, these results suggested. They love them because, usually, Mom loves them back, or at least is someone soft to cling to. “Man cannot live by milk alone. Love is an emotion that does not need to be bottle- or spoon-fed,” wrote Harlow.

repeated separations of infants from their mothers can predispose those individuals to depression when they are adults.

If a male goes through surgery, within seconds of the first slice of a scalpel through his skin, the reproductive axis begins to shut down. Injury, illness, starvation, surgery—all of these drive down testosterone levels. Anthropologists have even shown that in human societies in which there is constant energetic stress (for example, those of rural Nepalese villagers), there are significantly lower testosterone levels than among sedentary Bostonian controls.

But subtle psychological stressors are just as disruptive. Lower the dominance rank of a social primate and down go his testosterone levels.

Why do testosterone concentrations plunge with the onset of a stressor? For a variety of reasons. The first occurs at the brain. With the onset of stress,

Males who do extreme amounts of exercise, such as professional soccer players and runners who cover more than 40 or 50 miles a week, have less LHRH, LH, and testosterone in their circulation, smaller testes, less functional sperm. They also have higher levels of glucocorticoids in their bloodstreams, even in the absence of stress.

Up to half of competitive runners have menstrual irregularities, and highly athletic girls reach puberty later than usual. For example, in one study of fourteen-year-olds, approximately 95 percent of control subjects had started menstruating, whereas only 20 percent of gymnasts and 40 percent of runners had.

A decline in testosterone secretion is only half the story of what goes wrong with male reproduction during stress. The other half concerns the nervous system and erections.

for a male primate to have an erection, he has to divert a considerable amount of blood flow to his penis, engorging it.* This is accomplished by activating his parasympathetic nervous system. In other words, the guy has to be calm, vegetative, relaxed.

when you can’t take it anymore, the parasympathetic shuts off at the penis, the sympathetic comes roaring on, and you ejaculate.

if you’re stressed in that immediate situation? Well, obviously, if you’re nervous or anxious, you’re not calm or vegetative. First, it becomes difficult to establish parasympathetic activity if you are nervous or anxious. You have trouble having an erection. Impotency. And if you already have the erection, you get in trouble as well. You’re rolling along, parasympathetic to your penis, having a wonderful time. Suddenly, you find yourself worrying about the strength of the dollar versus the euro and—shazaam—you switch from parasympathetic to sympathetic far faster than you wanted. Premature ejaculation.

It is extremely common for problems with impotency and premature ejaculation to arise during stressful times.

loss of body fat leading to androgen buildup is one of the mechanisms by which reproduction is impaired in females who are extremely active physically.

this has been best documented in young girls who are serious dancers or runners, in whom puberty can be delayed for years, and in women who exercise enormous amounts, in whom cycles can become irregular or cease entirely.

Of all the hormones that inhibit the reproductive system during stress, prolactin is probably the most interesting. It is extremely powerful and versatile; if you don’t want to ovulate, this is the hormone to have lots of in your bloodstream. It not only plays a major role in the suppression of reproduction during stress and exercise, but it also is the main reason that breast feeding is such an effective form of contraception.

stress also disrupts female libido.

stress certainly suppresses estrogen secretion. As noted in chapter 3, Jay Kaplan has shown that the stressor of social subordinance in a monkey can suppress estrogen levels as effectively as removing her ovaries. Given these findings, it is relatively easy to see how stress disrupts sexual behavior in a female.

Stress can cause miscarriages in other animals as well. This may occur, for example, when pregnant animals in the wild or in a corral have to be captured for some reason (a veterinary exam) or are stressed by being transported.

Trouble seems to occur during stress as a result of repeated powerful activation of the sympathetic nervous system, causing increased secretion of norepinephrine and epinephrine. Studies of a large number of different species show that these two hormones will decrease blood flow through the uterus—dramatically, in some cases. Exposing animals to something psychologically stressful (for example, a loud noise in the case of pregnant sheep, or the entrance of a strange person into the room in which a pregnant rhesus monkey is housed) will cause a similar reduction in blood flow, decreasing the delivery of oxygen (called hypoxia) to the fetus.

there is an extraordinary array of mechanisms by which reproduction can be disrupted in stressed females—fat depletion; secretion of endorphins, prolactin, and glucocorticoids acting on the brain, pituitary, and ovaries; lack of progesterone; excessive prolactin acting on the uterus.

Moreover, possible blockage of implantation of the fertilized egg and changes in blood flow to the fetus generate numerous ways in which stress can make it less likely that a pregnancy will be carried to term.

the women in the Theresienstadt concentration camp, 54 percent of the reproductive-age women were found to have stopped menstruating. This is hardly surprising; starvation, slave labor, and unspeakable psychological terror are going to disrupt reproduction.

The point typically made is that, of the women who stopped menstruating, the majority stopped within their first month in the camps—before starvation and labor had pushed fat levels down to the decisive point. Many researchers cite this as a demonstration of how disruptive even psychological stress can be to reproduction.

Despite starvation, exhausting labor, and the daily terror that each day would be their last, only 54 percent of those women ceased menstruating. Reproductive mechanis...

psychoneuroimmunologist—who makes a living studying the extraordinary fact that what goes on in your head can affect how well your immune system functions.

tissue of the immune system turns out to be sensitive to (that is, it has receptors for) all the interesting hormones released by the pituitary under the control of the brain. The result is that the brain has a vast potential for sticking its nose into the immune system’s business.

there is a strong link between the nervous system and the immune system.

Such immune defenses are brought about by a complex array of circulating cells called lymphocytes and monocytes (which are collectively known as white blood cells; cyte is a term for cells).

Your immune system happily spends its time sorting out self from non-self: red blood cells, part of us. Eyebrows, our side. Virus, no good, attack. Muscle cell, good guy….

What if something goes wrong with the immune system’s sorting? One obvious kind of error could be that the immune system misses an infectious invader; clearly, bad news. Equally bad is the sort of error in which the immune system decides something is a dangerous invader that really isn’t.

Maybe it is something that you normally ingest, like peanuts or shellfish, or something airborne and innocuous, like pollen. But your immune system has mistakenly decided that this is not only foreign but dangerous, and kicks into gear. And this is an allergy.

In the second version of the immune system overreacting, a normal part of your own body is mistaken for an infectious agent and is attacked. When the immune system erroneously attacks a normal part of the body, a variety of horrendous “autoimmune” diseases may result. In multiple sclerosis, for example, part of your nervous system is attacked; in juvenile diabetes, it’s the cells in the pancreas that normally secrete insulin.

a period of stress will disrupt a wide variety of immune functions.

Stress will suppress the formation of new lymphocytes and their release into the circulation, and shorten the time preexisting lymphocytes stay in the circulation.

It will inhibit the manufacturing of new antibodies in response to an infectious agent, and disrupt communication among lymphocytes throu...

And it will inhibit the innate immune response, suppressing inflammation. All sorts of stressors do this—physical, psychological, in primates, rats, birds, e...

It turns out that during the first few minutes (say, up to about thirty) after the onset of a stressor, you don’t uniformly suppress immunity—you enhance many aspects of it (phase A on the accompanying graph). This is shown with all realms of immunity, but in particular for innate immunity. This makes sense—it may be helpful to activate parts of your immune system that are going to make some swell antibodies for you over the next few weeks, but it makes even more sense to immediately activate parts of the immune system that are going to help you out right now.

More immune cells are rushed into the circulation and, in the injured nervous system, more inflammatory cells infiltrate the site of injury.

Physical stressors, psychological stressors, all appear to cause an early stage of immune activation.

By the one-hour mark, more sustained glucocorticoid and sympathetic activation begins to have the opposite effect, namely, suppressing immunity. If the stressor ends around then, what have you accomplished with that immunosuppression? Bringing immune function back to where it started, back to baseline (phase B).

It is only with major stressors of longer duration, or with really major exposure to glucocorticoids, that the immune system does not just return to baseline, but plummets into a range that really does qualify as immunosuppressing (phase C). For most things that you can measure in the immune system, sustained major stressors drive the numbers down to 40 to 70 percent below baseline.