Why Zebra's Don't Get Ulcers

Why Zebra’s Don’t Get Ulcers.


There has been a revolution in medicine concerning how we think about the diseases that now afflict us. It involves recognizing the interactions between the body and the mind, the ways in which emotions and personality can have a tremendous impact on the functioning and health of virtually every cell in the body.


It is about the role of stress in making some of us more vulnerable to disease, the ways in which some of us cope with stressors, and the critical notion that you cannot really understand a disease in vacuo, but rather only in the context of the person suffering from that disease.


Some of the news in this book is grim—sustained or repeated stress can disrupt our bodies in seemingly endless ways. Yet most of us are not incapacitated by stress-related disease. Instead, we cope, both physiologically and psychologically, and some of us are spectacularly successful at it.


1-Why Don’t Zebras Get Ulcers?


It’s two o’clock in the morning and you’re lying in bed. You have something immensely important and challenging to do that next day—a critical meeting, a presentation, an exam.


You have to get a decent night’s rest, but you’re still wide awake. You try different strategies for relaxing—take deep, slow breaths, try to imagine restful mountain scenery—but instead you keep thinking that unless you fall asleep in the next minute, your career is finished.


Thus you lie there, more tense by the second. If you do this on a regular basis, somewhere around two-thirty, when you’re really getting clammy, an entirely new, disruptive chain of thought will no doubt intrude.


Suddenly, amid all your other worries, you begin to contemplate that nonspecific pain you’ve been having in your side, that sense of exhaustion lately, that frequent headache. The realization hits you—I’m sick, fatally sick! Oh, why didn’t I recognize the symptoms, why did I have to deny it, why didn’t I go to the doctor?


When it’s two-thirty on those mornings, I always have a brain tumor. These are very useful for that sort of terror, because you can attribute every conceivable nonspecific symptom to a brain tumor and justify your panic. Perhaps you do, too; or maybe you lie there thinking that you have cancer, or an ulcer, or that you’ve just had a stroke.


Our current patterns of disease would be unrecognizable to our great-grandparents or, for that matter, to most mammals. The diseases that plague us now are ones of slow accumulation of damage—heart disease, cancer, cerebrovascular disorders. While none of these diseases is particularly pleasant, they certainly mark a big improvement over succumbing at age twenty after a week of sepsis or dengue fever.


We have come to recognize the vastly complex intertwining of our biology and our emotions, the endless ways in which our personalities, feelings, and thoughts both reflect and influence the events in our bodies. One of the most interesting manifestations of this recognition is understanding that extreme emotional disturbances can adversely affect us. These intangibles can include emotional turmoil, psychological characteristics, our position in society, and how our society treats people of that position.


This book is a primer about stress, stress-related disease, and the mechanisms of coping with stress.


-How is it that our bodies can adapt to some stressful emergencies, while other ones make us sick?


-Why are some of us especially vulnerable to stress-related diseases, and what does that have to do with our personalities?


-How can purely psychological turmoil make us sick? What might stress have to do with our vulnerability to depression, the speed at which we age, or how well our memories work?


-What do our patterns of stress-related diseases have to do with where we stand on the rungs of society’s ladder?


-Finally, how can we increase the effectiveness with which we cope with the stressful world that surrounds us?


For animals like zebras, the most upsetting things in life are acute physical crises. These are extremely stressful events, and they demand immediate physiological adaptations if you are going to live. Your body’s responses are brilliantly adapted for handling this sort of emergency.


An organism can also be plagued by chronic physical challenges. The body’s stress-responses are reasonably good at handling these sustained disasters.


Critical to this book is a third category of ways to get upset—psychological and social disruptions. Regardless of how poorly we are getting along with a family member or how incensed we are about losing a parking spot, we rarely settle that sort of thing with a fistfight. Likewise, it is a rare event when we have to stalk and personally wrestle down our dinner.


Essentially, we humans live well enough and long enough, and are smart enough, to generate all sorts of stressful events purely in our heads.


Viewed from the perspective of the evolution of the animal kingdom, sustained psychological stress is a recent invention, mostly limited to humans and other social primates. We can experience wildly strong emotions (provoking our bodies into an accompanying uproar) linked to mere thoughts.


For the vast majority of beasts on this planet, stress is about a short-term crisis, after which it’s either over with or you’re over with. When we sit around and worry about stressful things, we turn on the same physiological responses—but they are potentially a disaster when provoked chronically.


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.


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.


Our human experience is replete with psychological stressors, a far cry from the physical world of hunger, injury, blood loss, or temperature extremes. When we activate the stress-response out of fear of something that turns out to be real, we congratulate ourselves that this cognitive skill allows us to mobilize our defenses early.


And these anticipatory defenses can be quite protective, in that a lot of what the stress-response is about is preparative. But when we get into a physiological uproar and activate the stress-response for no reason at all, or over something we cannot do anything about, we call it things like “anxiety,” “neurosis,” “paranoia,” or “needless hostility.”


Suppose there’s a water shortage in your body.

Homeostatic solution: kidneys are the ones that figure this out, tighten things up there, produce less urine for water conservation.


Allostatic solutions: brain figures this out, tells the kidneys to do their thing, sends signals to withdraw water from parts of your body where it easily evaporates (skin, mouth, nose), makes you feel thirsty.


Homeostasis is about tinkering with this valve or that gizmo. Allostasis is about the brain coordinating body-wide changes, often including changes in behavior.


Within this expanded framework, a stressor can be defined as anything that throws your body out of allostatic balance and the stress-response is your body’s attempt to restore allostasis.


During stress, digestion is inhibited—there isn’t enough time to derive the energetic benefits of the slow process of digestion, so why waste energy on it? If there is a tornado bearing down on the house, this isn’t the day to repaint the garage. Hold off on the long-term projects until you know there is a long term.


During stress, growth and tissue repair is curtailed, sexual drive decreases in both sexes; females are less likely to ovulate or to carry pregnancies to term, while males begin to have trouble with erections and secrete less testosterone.


Along with these changes, immunity is also inhibited. The immune system, which defends against infections and illness, is ideal for spotting the tumor cell that will kill you in a year, or making enough antibodies to protect you in a few weeks, but is it really needed this instant?


Energy is mobilized and delivered to the tissues that need them, i.e. muscles.


Finally, during stress, shifts occur in cognitive and sensory skills.


Walter Cannon, the physiologist considered the other godfather of the field, concentrated on the adaptive aspect of the stress-response in dealing with emergencies such as these. He formulated the well-known “fight-or-flight” syndrome to describe the stress-response, and he viewed it in a very positive light. Yet stressful events can sometimes make us sick. Why?


It has been believed that one becomes sick like an army that runs out of ammunition, suddenly we have no defenses left against the threatening stressor. It is very rare, however, as we will see, that any of the crucial hormones are actually depleted during even the most sustained of stressors. The army does not run out of bullets.


Instead, the body spends so much on the defense budget that it neglects education and health care and social services (okay, so I may have a hidden agenda here). 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 is a critical concept, because it underlies the emergence of much stress-related disease. If you experience every day as an emergency, you will pay the price. If you constantly mobilize energy at the cost of energy storage, you will never store any surplus energy. If you constantly turn off long-term building projects, nothing is ever repaired.


Sitting frustrated in traffic jams, worrying about expenses, mulling over tense interactions with colleagues. 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.


Stressors, even if massive, repetitive, or chronic in nature, do not automatically lead to illness. And the theme of the last section of this book is to make sense of why some people develop stress-related diseases more readily than others, despite the same stressor.


Moreover, by clarifying the progression between stressors and illness, it becomes easier to design ways to intervene in the process. Finally, it begins to explain why the stress concept often seems so suspect or slippery to many medical practitioners—clinical medicine is traditionally quite good at being able to make statements like “You feel sick because you have disease X,” but is usually quite bad at being able to explain why you got disease X in the first place.


Thus, medical practitioners often say, in effect, “You feel sick because you have disease X, not because of some nonsense having to do with stress; however, this ignores the stressors’ role in bringing about or worsening the disease in the first place.


2 -Glands, Gooseflesh, and Hormones


We all understand intellectually that the brain can regulate functions throughout the rest of the body, but it is still surprising to be reminded of how far-reaching those effects can be.


Hormones of the Stress-Response

As the master gland, the brain can experience or think of something stressful and activate components of the stress-response hormonally. Some of the hypothalamus-pituitary-peripheral gland links are activated during stress, some inhibited.


Two hormones vital to the stress-response, as already noted, are epinephrine and norepinephrine, released by the sympathetic nervous system. Another important class of hormones in the response to stress are called glucocorticoids. Glucocorticoids are steroid hormones. (Steroid is used to describe the general chemical structure of five classes of hormones: androgens—the famed “anabolic” steroids like testosterone that get you thrown out of the Olympics—estrogens, progestins, mineralocorticoids, and glucocorticoids.) Secreted by the adrenal gland, they often act, as we will see, in ways similar to epinephrine.


Epinephrine acts within seconds; glucocorticoids back this activity up over the course of minutes or hours. Because the adrenal gland is basically witless, glucocorticoid release must ultimately be under the control of the hormones of the brain.


When something stressful happens or you think a stressful thought, the hypothalamus secretes an array of releasing hormones into the hypothalamic-pituitary circulatory system that gets the ball rolling. The principal such releaser is called CRH (corticotropin releasing hormone), while a variety of more minor players synergize with CRH.* Within fifteen seconds or so, CRH triggers the pituitary to release the hormone ACTH (also known as corticotropin).


After ACTH is released into the bloodstream, it reaches the adrenal gland and, within a few minutes, triggers glucocorticoid release. Together, glucocorticoids and the secretions of the sympathetic nervous system (epinephrine and norepinephrine) account for a large percentage of what happens in your body during stress. These are the workhorses of the stress-response.


In addition, in times of stress your pancreas is stimulated to release a hormone called glucagon. Glucocorticoids, glucagon, and the sympathetic nervous system raise circulating levels of the sugar glucose. As we will see, these hormones are essential for mobilizing energy during stress.


Other hormones are activated as well. The pituitary secretes prolactin, which, among other effects, plays a role in suppressing reproduction during stress. Both the pituitary and the brain also secrete a class of endogenous morphine-like substances called endorphins and enkephalins, which help blunt pain perception, among other things. Finally, the pituitary also secretes vasopressin, also known as antidiuretic hormone, which plays a role in the cardiovascular stress-response.


Just as some glands are activated in response to stress, various hormonal systems are inhibited during stress. The secretion of various reproductive hormones such as estrogen, progesterone, and testosterone is inhibited. Hormones related to growth (such as growth hormone) are also inhibited, as is the secretion of insulin, a pancreatic hormone that normally tells your body to store energy for later use.


A Few Complications


It turns out that not all stressors produce the exact same stress-response. The sympathetic nervous system and glucocorticoids play a role in the response to virtually all stressors.


But, the speed and magnitudes of the sympathetic and glucocorticoid branches can vary depending on the stressor, and not all of the other endocrine components of the stress-response are activated for all stressors. The orchestration and patterning of hormone release tend to vary at least somewhat from stressor to stressor, with there being a particular hormonal “signature” for a particular stressor.


Sympathetic arousal is a relative marker of anxiety and vigilance, while heavy secretion of glucocorticoids is more a marker of depression. Furthermore, all stressors do not cause secretion of both epinephrine and norepinephrine, nor of norepinephrine from all branches of the sympathetic system.


In some cases, the stress signature sneaks in through the back door. Two stressors can produce identical profiles of stress hormone release into the bloodstream. So where’s the signature that differentiates them? Tissues in various parts of the body may be altered in their sensitivity to a stress hormone in the case of one stressor, but not the other. Finally, two identical stressors can cause very different stress signatures, depending on the psychological context of the stressors. Thus, every stressor does not generate exactly the same stress-response.


Chronic Stress and Cardiovascular Disease


If you sit and think about a major deadline looming next week, driving yourself into a hyperventilating panic, you still alter cardiovascular function to divert more blood flow to your limb muscles. Crazy. And, potentially, eventually damaging.


The first step in the road to stress-related disease is developing hypertension, chronically elevated blood pressure.* This one seems obvious: if stress causes your blood pressure to go up, then chronic stress causes your blood pressure to go up chronically. Task accomplished, you’ve got hypertension.


When you increase the force with which the fluid is moving through the system, turbulence increases and those outposts of wall are more likely to get damaged.

With the chronic increase in blood pressure that accompanies repeated stress, damage begins to occur at branch points in arteries throughout the body. Once this layer is damaged, you get an inflammatory response—cells of the immune system that mediate inflammation aggregate at the injured site.


Therefore, stress can promote plaque formation by increasing the odds of blood vessels being damaged and inflamed, and by increasing the likelihood that circulating crud (platelets, fat, cholesterol, and so on) sticks to those inflamed injury sites. But they’re not a great predictor; a surprising number of folks can tolerate high levels of bad cholesterol without cardiovascular consequences, and only about half of heart attack victims have elevated cholesterol levels.


In the last few years, it is becoming clear that the amount of damaged, inflamed blood vessels is a better predictor of cardiovascular trouble than is the amount of circulating crud. How can you measure the amount of inflammatory damage? A great marker is turning out to be something called C-reactive protein (CRP). It is made in the liver and is secreted in response to a signal indicating an injury.


CRP is turning out to be a much better predictor of cardiovascular disease risk than cholesterol, even years in advance of disease onset. As a result, CRP has suddenly become quite trendy in medicine, and is fast becoming a standard endpoint to measure in general blood work on patients. Thus, chronic stress can cause hypertension and atherosclerosis—the accumulation of these plaques.


Establish male monkeys in a social group, and over the course of days to months they’ll figure out where they stand with respect to one another. Once a stable dominance hierarchy has emerged, the last place you want to be is on the bottom: not only are you subject to the most physical stressors but to the most psychological stressors as well. Such subordinate males show a lot of the physiological indices of chronically turning on their stress-responses.


And often these animals wind up with atherosclerotic plaques—their arteries are all clogged up. As evidence that the atherosclerosis arises from the overactive sympathetic nervous system component of the stress-response, if doctors gave the monkeys at risk drugs that prevent sympathetic activity (beta-blockers), they didn’t form plaques.


Suppose you keep the dominance system unstable by shifting the monkeys into new groups every month, so that all the animals are perpetually in the tense, uncertain stage of figuring out where they stand with respect to everyone else. Under those circumstances, it is generally the animals precariously holding on to their places at the top of the shifting dominance hierarchy who do the most fighting and show the most behavioral and hormonal indices of stress. And, as it turns out, they have tons of atherosclerosis; some of the monkeys even have heart attacks (abrupt blockages of one or more of the coronary arteries).


(Insert the the perfectionist problem:)


In general, the monkeys under the most social stress were most at risk for plaque formation. But if you couple the social stress with a high-fat diet, the effects synergize, and plaque formation goes through the roof.


(Insert the the gut brain axis and fat diet experts)


Now it appears that, for someone at risk, trouble is occurring under all sorts of circumstances of psychological stress in everyday life, and you may not even know it. Once the cardiovascular system is damaged, it appears to be immensely sensitive to acute stressors, whether physical or psychological.


We’ve been focusing on the stress-related consequences of activating the cardiovascular system too often. What about turning it off at the end of each psychological stressor?


As noted earlier, your heart slows down as a result of activation of the vagus nerve by the parasympathetic nervous system. Back to the autonomic nervous system never letting you put your foot on the gas and brake at the same time—by definition, if you are turning on the sympathetic nervous system all the time, you’re chronically shutting off the parasympathetic. And this makes it harder to slow things down, even during those rare moments when you’re not feeling stressed about something.


How can you diagnose a vagus nerve that’s not doing its part to calm down the cardiovascular system at the end of a stressor? A clinician could put someone through a stressor, say, run the person on a treadmill, and then monitor the speed of recovery afterward.


It turns out that there is a subtler but easier way of detecting a problem. 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).


Therefore, the length of time between heartbeats tends to be shorter when you’re inhaling than exhaling. But what if chronic stress has blunted the ability of your parasympathetic nervous system to kick the vagus nerve into action? When you exhale, your heart won’t slow down, won’t increase the time intervals between beats. Cardiologists use sensitive monitors to measure interbeat intervals.


Large amounts of variability (that is to say, short interbeat intervals during inhalation, long during exhalation) mean you have strong parasympathetic tone counteracting your sympathetic tone, a good thing. Minimal variability means a parasympathetic component that has trouble putting its foot on the brake. This is the marker of someone who not only turns on the cardiovascular stress-response too often but, by now, has trouble turning it off.


(Insert the accessing the POLYVAGAL vagal nerve summary)


Personality and Cardiac Disease: A Brief Introduction


Two people go through the same stressful social situation. Only one gets hypertensive. Two people go through a decade’s worth of life’s ups and downs. Only one gets cardiovascular disease.


These individual differences could be due to one person already having a damaged cardiovascular system—for example, decreased coronary blood flow. They could also be due to genetic factors that influence the mechanics of the system—the elasticity of blood vessels, the numbers of norepinephrine receptors, and so on.


Faced with similar stressors, whether large or small, two people may also differ in their risk for cardiovascular disease as a function of their personalities. The risk of cardiovascular disease is increased by hostility, a Type-A personality, and by clinical depression. The bad news is that these personality risk factors are substantial in their impact. But the good news is that something can often be done about them.


In the face of a short-term physical emergency, the cardiovascular stress-response is vital. In the face of chronic stress, those same changes are terrible news. These adverse effects are particularly deleterious when they interact with the adverse consequences of too much of a metabolic stress-response.


Speaking of Metabolic stress-response:

It’s Thanksgiving, and you’ve eaten with porcine abandon. Your bloodstream is teeming with amino acids, fatty acids, glucose. It’s far more than you need to power you over to the couch in a postprandial daze. What does your body do with the excess?


Surplus energy is not kept in the body’s form of cash—circulating amino acids, glucose, and fatty acids—but stored in more complex forms. Enzymes in fat cells can combine fatty acids and glycerol to form triglycerides. Accumulate enough of these in the fat cells and you grow plump.


Meanwhile, your cells can stick series of glucose molecules together. These long chains, sometimes thousands of glucose molecules long, are called glycogen. Most glycogen formation occurs in your muscles and liver. Similarly, enzymes in cells throughout the body can combine long strings of amino acids, forming them into proteins.


The hormone that stimulates the transport and storage of these building blocks into target cells is insulin. Insulin is this optimistic hormone that plans for your metabolic future. Eat a huge meal and insulin pours out of the pancreas into the bloodstream, stimulating the transport of fatty acids into fat cells, stimulating glycogen and protein synthesis.


We secrete insulin when we are about to fill our bloodstream with all those nutritive building blocks: if you eat dinner each day at six o’clock, by five forty-five you’re already secreting insulin in anticipation of the rising glucose levels in your bloodstream. Logically, it is the parasympathetic nervous system that stimulates the anticipatory secretion, and this ability to secrete insulin in preparation for the glucose levels that are about to rise is a great example of the anticipatory quality of allostatic balance.


This grand strategy of breaking your food down into its simplest parts and reconverting it into complex storage forms is precisely what your body should do when you’ve eaten plenty. And it is precisely what your body should not do in the face of an immediate physical emergency. Then, you want to stop energy storage.


Turn up the activity of the sympathetic nervous system, turn down the parasympathetic, and down goes insulin secretion: step one in meeting an emergency accomplished. The body makes sure that energy storage is stopped in a second way as well. With the onset of the stressful emergency, you secrete glucocorticoids, which block the transport of nutrients into fat cells. This counteracts the effects of any insulin still floating around.


The syndrome-ness is a way of stating that if you have a subset of those symptoms, you’re probably heading toward the rest of them, since they’re all one or two steps away from each other. Have glucose levels above X, and it’s official, you have hyperglycemia. Have blood pressure levels above Z, you’re hypertensive. But how about if your glucose levels, blood pressure, HDL-cholesterol, and so on, are all in the normal range, but all of them are getting near the edge of where you have to start worrying?


Throw in some other measures as well—including resting levels of glucocorticoids, epinephrine, norepinephrine. This information was significantly predictive of who was going to have heart disease, a decline in cognitive or physical functioning, and mortality, far more predictive than subsets of those variables alone. This is the essence of that “allostasis” concept, of keeping things in balance through interactions among different, far-flung systems in the body.


This is also the essence of the wear-and-tear concept of allostatic “load,” a formal demonstration that even if there’s no single measure that’s certifiably wrong, if there are enough things that are not quite right, you’re in trouble. And, as the final, obvious point, this is also the essence of what stress does. No single disastrous effect, no lone gunman. Instead, kicking and poking and impeding, here and there, make this a bit worse, that a bit less effective. Thus making it more likely for the roof to cave in at some point.


It’s perfectly obvious where we’re heading in terms of appetite. You’re the zebra running for your life, don’t think about lunch. That’s the reason why we lose our appetites when we’re stressed. Except for those of us who, when stressed, eat everything in sight, in a mindless mechanical way.


And those who claim they’re not hungry, are too stressed to eat a thing, and just happen to nibble 3,000 calories’ worth of food a day. And those of us who really can’t eat a thing. Except for chocolate-chocolate chip hot fudge sundaes. With whipped cream and nuts.


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. So we can conclude with scientific certainty that stress can alter appetite. Which doesn’t teach us a whole lot, since it doesn’t tell us whether there’s an increase or decrease.


CRH helps to turn on the sympathetic nervous system, and it plays a role in increasing vigilance and arousal during stress. It also suppresses appetite. Glucocorticoids appear to stimulate appetite. What is really fascinating is that glucocorticoids don’t just stimulate appetite—they stimulate it preferentially for foods that are starchy, sugary, or full of fat—and we reach for the Oreos and not the celery sticks.


When a stressful event occurs CRH makes its effects felt within seconds, while glucocorticoids take minutes to hours to exert their actions. Finally, when the stressful event is over, it takes mere seconds for CRH to be cleared from the bloodstream, while it can take hours for glucocorticoids to be cleared.


Suppose that something truly stressful occurs, there will cumulatively be perhaps a twelve-minute burst of CRH and a two-hour burst of exposure to glucocorticoids (the roughly eight minutes of secretion during the stressor plus the much longer time to clear the glucocorticoids).


In contrast, suppose the stressor lasts for days, nonstop. In other words, days of elevated CRH and glucocorticoids, followed by a few hours of high glucocorticoids and low CRH, as the system recovers. The sort of setting where the most likely outcome is suppression of appetite.


“I am like, SO stressed, like totally, nonstop stressed, 24/ 7.” But that’s not really like totally nonstop stressed. What a person is actually experiencing is frequent intermittent stressors. And what’s going on hormonally in that scenario?


Frequent bursts of CRH release throughout the day. As a result of the slow speed at which glucocorticoids are cleared from the circulation, elevated glucocorticoid levels are close to nonstop. Guess who’s going to be scarfing up Krispy Kremes all day at work? So a big reason why most of us become hyperphagic during stress is our westernized human capacity to have intermittent psychological stressors throughout the day. The type of stressor is a big factor.


Another variable that helps predict hyperphagia or hypophagia during stress is how your body responds to a particular stressor. Put a bunch of subjects through the same experimental stressor and, not surprisingly, not everyone secretes the exact same amount of glucocorticoids.


The sources of these individual differences can be psychological—the experimental stressor may be an utter misery for one person and no big deal for another. Differences can also arise from physiology—one person’s liver may be pokier at breaking down glucocorticoids than the next person’s.


Lots of people eat not just out of nutritional need, but out of emotional need as well. These folks tend both to be overweight and to be stress-eaters. In addition, there’s a fascinating literature concerning the majority of us, for whom eating is a regulated, disciplined task.


At any given point, about two-thirds of us are “restrained” eaters. These are people who are actively trying to diet, who would agree with statements like, “In a typical meal, I’m conscious of trying to restrict the amount of food that I consume.” Mind you, these are not people who are necessarily overweight. Plenty of heavy people are not dieting, plenty of everyone else is at any point.


Restrained eaters are actively restricting their food intake. What the studies consistently show is that during stress, people who are normally restrained eaters are more likely than others to become hyperphagic.


Glucocorticoids not only increase appetite but, as an additional means to recover from the stress-response, also increase the storage of that ingested food. It turns out that when glucocorticoids stimulate fat deposition, they do it preferentially in the abdomen, promoting apple-shaped obesity.


This even occurs in monkeys. The pattern arises because abdominal fat cells are more sensitive to glucocorticoids than are gluteal fat cells; the former have more receptors that respond to glucocorticoids by activating those fat-storing enzymes. Furthermore, glucocorticoids only do this in the presence of high insulin levels.


It turns out that a large WHR is an even better predictor of trouble than being overweight is. Take some extremely applish people and some very peary ones. Match them for weight, and it’s the apples who are at risk for metabolic and cardiovascular disease.


Consuming lots of those comfort foods and bulking up on abdominal fat are stress-reducers. They tend to decrease the size of the stress-response (both in terms of glucocorticoid secretion and sympathetic nervous system activity). Not only do the Oreos taste good, but by reducing the stress-response, they make you feel good as well.


There seems to be a huge number of routes by which obesity can occur—too much or too little of this or that hormone; too much or too little sensitivity to this or that hormone.* But another route appears to involve being the sort of person who secretes too many glucocorticoids, either because of too many stressors, too many perceived stressors, or trouble turning off the stress-response. And thanks to that weird new regulatory loop discovered by Dallman, it appears as if abdominal fat is one route for trying to tone down that overactive stress-response.


When it comes to your GI tract, there’s no such thing as a free lunch. You’ve just finished some feast. You expect your gut to magically convert all that into a filtrate of nutrients in your bloodstream? It takes energy, huge amounts of it. All told, your run-of-the-mill mammals, including us, expend 10 to 20 percent of their energy on digestion.


Digestion is quickly shut down during stress. But why, to add insult to injury, is it so frequently diarrhea when you are truly frightened? Relatively large amounts of water are needed for digestion, to keep your food in solution as you break it down so that it will be easy to absorb into the circulation when digestion is done. Disaster strikes, run for your life, increase that large intestinal motility, and everything gets pushed through too fast for the water to be absorbed optimally. Diarrhea, simple as that.


Broadly, there are two types of gastrointestinal disorders. In the first, you feel terrible, something isn’t working right, and the doctors find something wrong. These are “organic” GI disorders. A gaping hole in the wall of your stomach, in other words, a peptic ulcer, counts as there being something demonstrably wrong. But suppose you feel terrible, something isn’t working right, and the docs can’t find a thing wrong. Congratulations, you now have a “functional” GI disorder.


The most common functional GI disorder, which will be considered here, is irritable bowel syndrome (IBS), which involves abdominal pain (particularly just after a meal) that is relieved by defecating and symptoms such as diarrhea or constipation, passage of mucus, bloating, and abdominal distention. Despite physicians checking you from every which end, they can’t find anything wrong, which qualifies IBS as a functional disorder. IBS is among the most common of stress-sensitive disorders.


Carefully conducted studies show that major chronic stressors increase the risk of the first symptoms of IBS appearing, and worsen preexisting cases. This makes sense. As we saw, what stress does is increase the contractions in the colon, getting rid of that dead weight. And IBS—also known as “spastic colon”—involves the colon being too contractile, an excellent way of producing diarrhea.


Another connection between stress and IBS concerns pain. Stress can blunt the sort of pain you feel in your skin and skeletal muscles while increasing the sensitivity of internal organs like the intestines to pain (something called “visceral” pain). And that is the profile seen in IBS patients—less sensitivity to skin (“ cutaneous”) pain, and more visceral pain.


Even more support for the stress/ IBS link is that people with IBS don’t typically have hypercontractility of their bowels when they are asleep. Gut spasticity is not something that’s going on all the time—only when the person is awake, amid the opportunities to be stressed.


So ongoing stress can be closely associated with IBS. Interestingly, traumatic stress early in life (abuse, for example) greatly increases the risk of IBS in adulthood. This implies that childhood trauma can leave an echo of vulnerability, a large intestine that is hyperreactive to stress, long afterward. Animal studies have shown that this occurs.


(Insert ACE Studies information)


An ulcer is a hole in the wall of an organ, and ulcers originating in the stomach or in the organs immediately bordering it are termed peptic ulcers. The ones within the stomach are called gastric ulcers; those a bit higher up than the stomach are esophageal, and those at the border of the stomach and the intestine are duodenal (the most common of peptic ulcers).


Most clinicians agree that there is a subtype of ulcers that forms relatively rapidly (sometimes over the course of days) in humans who are exposed to immensely stressful crises—hemorrhage, massive infection, trauma due to accident or surgery, burns over large parts of the body, and so on. Such “stress ulcers” can be life threatening in severe cases.


Helicobacter pylori turns out to be able to live in the acidic stomach environment, protecting itself by having a structure that is particularly acid-resistant and by wrapping itself in a coat of protective bicarbonate. And this bacterium probably has a lot to do with 85 to 100 percent of ulcers in Western populations (as well as with stomach cancer).


Nearly 100 percent of people in the developing world are infected with Helicobacter— it is probably the most common chronic bacterial infection in humans. The bacteria infect cells in the lining of the stomach, causing gastritis, which somehow compromises the ability of those cells lining the duodenum to defend themselves against stomach acids. Boom, under the right conditions, you’ve got a hole in that duodenal wall.


The trouble is that one bacterium can’t be the whole story. For starters, up to 15 percent of duodenal duodenal ulcers form in people who aren’t infected with Helicobacter, or with any other known bacterium related to it.


More damning, only about 10 percent of the people infected with the bacteria get ulcers. It’s got to be Helicobacter pylori plus something else. Sometimes, the something else is a lifestyle risk factor—alcohol, smoking, skipping breakfast habitually, taking a lot of nonsteroidal anti-inflammatory drugs like aspirin.


Maybe the something else is a genetic tendency to secrete a lot of acid or to make only minimal amounts of mucus to protect stomach linings from the acid. But one of the additional factors is stress. Study after study, even those carried out after the ascendancy of the bacteria, show that duodenal ulceration is more likely to occur in people who are anxious, depressed, or undergoing severe life stressors (imprisonment, war, natural disasters).


An analysis of the entire literature shows that somewhere between 30 and 65 percent of peptic ulcers have psychosocial factors (i.e., stress) involved. The problem is that stress causes people to drink and smoke more. So maybe stress increases the risk of an ulcer merely by increasing the incidence of those lifestyle risk factors.


But no—after you control for those variables, stress itself still causes a two-to threefold increase in the risk of an ulcer.


Peptic ulcers are what the physician Susan Levenstein, the wittiest person on earth writing about gastroenterology, has termed “the very model of a modern etiology.”* Stress doesn’t cause peptic ulcers to form. But it makes the biological villains that do cause ulcers to form more likely to occur, or more virulent, or impairs your ability to defend yourself against those villains. This is the classic interaction between the organic (bacteria, viruses, toxins, mutations) and the psychogenic components of disease.


It is time to look at how stress disrupts normal development. As we’ll see, this not only involves impairing skeletal growth (that is, how tall you grow to be), but also how stress early in life can alter your vulnerability to disease throughout your lifetime. I have to issue a warning to anyone who is a parent, or who plans to be a parent, or who had parents. There’s nothing like parenthood to make you really neurotic, as you worry about the consequences of your every act, thought, or omission. You only want perfection for the ones you love beyond words, so you get nutsy at times. This section will make you nutsier.


What is childhood about? It is a time when you make assessments about the nature of the world. For example, “If you let go of something, it falls down, not up.” Or, “If something is hidden underneath something else, it still exists.” Or, ideally, “Even if Mommy disappears for a while, she will come back because Mommy always comes back.”


(Insert Attachment Theory Summary)


Working with adults with severe early trauma histories almost always includes a process of sorting through complex and interrelated symptoms. This category of client often experiences what initially appear to be straightforward and separate physical issues: high blood pressure, autoimmune disorders, or diabetes, for example. But we now know that developmental trauma can trigger these somatic symptoms and conditions. Indeed, early trauma can activate genetic predispositions toward certain diseases, apparently “turning on” that genetic predisposition; it can alter the size of the developing brain; it can cause the immune system to create chronic inflammation; it can contribute to a wide range of physical, as well as psychological, disorders (Ellason, Ross, and Fuchs 1996; Felitti et al. 1998; Perry 2004a, 2006).


Often, these assessments shape your view of the world forever. It turns out that during development, beginning with fetal life, your body is also learning about the nature of the world and, metaphorically, making lifelong decisions about how to respond to the outside world. And if development involves certain types of stressors, some of these “decisions” cause a lifelong increase in the risk of certain diseases.


When you compare those who were heaviest versus lightest at birth, you see an approximate eight-fold difference in the risk of pre-diabetes, and about an eighteen-fold difference in the risk of Metabolic syndrome. Among both men and women, compare those whose birth weights were in the lowest 25 percent versus those in the highest 25 percent, and the former have a 50 percent higher rate of death from heart disease.


A smaller but fairly solid literature shows that prenatal stress programs humans for higher glucocorticoid secretion in adulthood as well. In these studies, low birth weight (corrected for body length) is used as a surrogate marker for stressors during fetal life, and the lower the birth weight, the higher the basal glucocorticoid levels in adults ranging from age twenty to seventy; this relationship becomes even more pronounced when low birth weight is coupled with premature birth.*


So now we have hypertension, diabetes, cardiovascular disease, obesity, and glucocorticoid excess in this picture. Let’s make it worse. Does prenatal stress in humans make for anxious adults? Seriously stress a pregnant rat and her offspring will grow up to be anxious. Now, how do you tell if a rat is anxious?


You put it in a new (and thus, by definition, scary) environment; how long does it take for it to explore?

Or take advantage of the fact that rats, being nocturnal, don’t like bright lights.

Take a hungry rat and put some food in the middle of a brightly lit cage; how long until the rat goes for the food?

How readily can the rat learn in a novel setting, or socially interact with new rats? How much does the rat defecate in a novel setting?


Prenatally stressed rats, as adults, freeze up when around bright lights, can’t learn in novel settings, defecate like crazy.


(Insert the brain that wires it self)


Anxiety revolves around a part of the brain called the amygdala, and prenatal stress programs the amygdala into a lifelong profile that has anxiety written all over it. The amygdala winds up with more receptors for (that is, more sensitivity to) glucocorticoids, more of a neurotransmitter that mediates anxiety, and fewer receptors for a brain chemical that reduces anxiety.


These tendencies can be passed down, not solely through genetic programs but also through shared gestation environments. So expose a fetus to lots of glucocorticoids and you are increasing its risk for obesity, hypertension, cardiovascular disease, insulin-resistant diabetes, maybe reproductive impairments, maybe anxiety, and impaired brain development. And maybe even setting up that fetus’s eventual offspring for the same.


Work done by Paul Plotsky at Emory University shows that maternal deprivation causes similar consequences in a rat as prenatal stress: increased levels of glucocorticoids during stress and an impaired recovery at the end of stress. More anxiety, and the same sorts of changes in the amygdala as were seen in prenatally stressed adults.


Michael Meaney of McGill University has looked at the lifelong consequences for rats of having had a highly attentive or highly inattentive mother. What counts as attentiveness? Grooming and licking. Infants whose mothers groomed and licked the least produced kids who were milder versions of rats who were maternally deprived as infants, with elevated glucocorticoid levels.


Though the subject is still poorly studied, childhood stress may produce the building blocks for the sort of adult diseases we’ve been considering. For example, when you examine children who had been adopted more than a year before from Romanian orphanages, the longer the child spent in the orphanage, the higher the resting glucocorticoid levels. Similarly, children who have been abused have elevated glucocorticoid levels, and decreased size and activity in the most highly evolved part of the brain, the frontal cortex.


A study that winds up in half the textbooks makes the same point, if more subtly. The subjects of the “experiment” were children reared in two different orphanages in Germany after World War II. Both orphanages were run by the government; thus there were important controls in place—the kids in both had the same general diet, the same frequency of doctors’ visits, and so on. The main identifiable difference in their care was the two women who ran the orphanages.


The scientists even checked them, and their description sounds like a parable. In one orphanage was Fräulein Grun, the warm, nurturing mother figure who played with the children, comforted them, and spent all day singing and laughing.


In the other was Fräulein Schwarz, a woman who was clearly in the wrong profession. She discharged her professional obligations, but minimized her contact with the children; she frequently criticized and berated them, typically among their assembled peers.


The growth rates at the two orphanages were entirely different. Fräulein Schwarz’s kids grew in height and weight at a slower pace than the kids in the other orphanage. Then, in an elaboration that couldn’t have been more useful if it had been planned by a scientist, Fräulein Grun moved on to greener pastures and, for some bureaucratic reason, Fräulein Schwarz was transferred to the other orphanage. Growth rates in her former orphanage promptly increased; those in her new one decreased.


This tells us something about which stress hormones shut down growth. It turns out to be touch, and it has to be active touching.


Separate a baby rat from its mother and its growth hormone levels plummet.


Allow it contact with its mother while she is anesthetized, and growth hormone is still low.


Mimic active licking by the mother by stroking the rat pup in the proper pattern, and growth normalizes.


In a similar set of findings, other investigators have observed that handling neonatal rats causes them to grow faster and larger.


The same seems to apply in humans. Studying premature infants in neonatology wards, they noted that the premature kids, while pampered and fretted over and maintained in near-sterile conditions, were hardly ever touched. So a crew went in and started touching them: fifteen-minute periods, three times a day, stroking their bodies, moving their limbs.


It worked wonders. The kids grew nearly 50 percent faster, were more active and alert, matured faster behaviorally, and were released from the hospital nearly a week earlier than the premature infants who weren’t touched. Months later, they were still doing better than infants who hadn’t been touched.


If this were done in every neonatology ward, this would not only make for a lot more healthy infants, but would save approximately a billion dollars annually. It’s rare that the highest technology of medical instrumentation—MRI machines, artificial organs, pacemakers—has the potential for as much impact as this simple intervention.


This holds true for adults. Feeling safe enough to be immobilized while being touched while relaxing, otherwise known as massage, is linked to a decrease in Depressive and anxious symptoms.


Next important question: How big are the effects? We’ve seen evidence that increasing amounts of fetal stress, over the normal range, predict increasing risk of Metabolic syndrome long afterward.


That statement may be true and describes the following scenario. For example, it could be that the lowest levels of fetal stress result in a 1 percent risk of Metabolic syndrome, and each increase in stress exposure increases the risk until an exposure to a maximal fetal stress results in a 99 percent chance.


Early stress and trauma seem to have a tremendous power in increasing the risk of various psychiatric disorders many years later. As discussed, 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.


Westernized societies and, in particular, the United States, out at the extreme in these cross-cultural measures, with our emphasis on individuality, independence, and self-reliance.


In our particular culture, how often is a child typically held by parents, by non-parents?


Do babies sleep alone ever and, if so, starting at what age?


What is the average length of time that a child cries in a particular culture before she is picked up and comforted?


This is our world of both parents working outside the home, of single-parent households, of day care and latchkey kids. There is little evidence that any of these childhood experiences leave indelible biological scars, in contrast to the results of horrific childhood trauma. But whatever style of child-rearing is practiced, it will have its consequences.


“Man cannot live by milk alone. Love is an emotion that does not need to be bottle-or spoon-fed,”- Harry Harlow of the University of Wisconsin, a renowned and controversial scientist.


Harlow helped to answer a seemingly obvious question in a non-obvious way. Why do infants become attached to their mothers? Because Mom supplies food. For behaviorists, this was obvious, as attachment was thought to arise solely from the positive reinforcement of food. For Freudians, it was also obvious—infants were thought to lack the “ego development” to form a relationship with any thing/ one other than Mom’s breast.


Harlow smelled a rat. He raised infant rhesus monkeys without mothers. Instead, he gave them a choice of two types of artificial “surrogate” mothers. One pseudo-mother had a monkey head constructed of wood and a wire-mesh tube resembling a torso. In the middle of the torso was a bottle of milk. This surrogate mother gave nutrition.


The other surrogate mother had a similar head and wire-mesh torso. But instead of containing a milk bottle, this one’s torso was wrapped in terry cloth. The behaviorists and the Freudians would be snuggling up to the milk-mom within seconds. But not the baby monkeys—they chose the terry-cloth mothers.


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.


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.


These studies have been extremely useful.


They have taught us the science of why we primates love individuals who treat us badly, why the mistreatment can at times increase the love.


They have taught us about why being abused as a child increases the risk of your being an abusive adult.


Other aspects of Harlow’s work have taught us how repeated separations of infants from their mothers can predispose those individuals to depression when they are adults.


Kidneys and pancreas and heart are important, but what we really want to know is why, when we are being stressed, our menstrual cycles become irregular, erections are more difficult to achieve, and we lose our interest in sex. As it turns out, there are an astonishing number of ways in which reproductive mechanisms may go awry when we are upset.


(Insert the founder well of sorrows articles)


With the onset of a stressor, the whole system is inhibited. LHRH concentrations decline, followed shortly thereafter by declines in LH and FSH, and then the testes close for lunch.


The result is a decline in circulating testosterone levels. The most vivid demonstrations of this occur during physical stress.


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 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. Put a person or a monkey through a stressful learning task and the same occurs.


In a celebrated study several decades ago, U.S. Officer Candidate School trainees who underwent an enormous amount of physical and psychological stress were subjected to the further indignity of having to pee into Dixie cups so that military psychiatrists could measure their hormone levels. Lo and behold, testosterone levels were down.


Obviously, if you don’t exercise at all, it is not good for you. Exercise improves your health. And a lot of exercise improves your health a lot. But that doesn’t mean that insanely large amounts of exercise are insanely good for your body.


At some point, too much begins to damage various physiological systems. Everything in physiology follows the rule that too much can be as bad as too little. There are optimal points of allostatic balance.


For example, while a moderate amount of exercise generally increases bone mass, thirty-year-old athletes who run 40 to 50 miles a week can wind up with decalcified bones, decreased bone mass, increased risk of stress fractures and scoliosis (sideways curvature of the spine)—their skeletons look like those of seventy-year-olds.


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. (A similar decline in reproductive function is found in men who are addicted to opiate drugs.)


With the onset of stress, LHRH secretion declines. In addition, prolactin, another pituitary hormone that is released during major stressors, decreases the sensitivity of the pituitary to LHRH.


A double whammy—less of the hormone dribbling out of the brain, and the pituitary no longer responding as effectively to it. Finally, glucocorticoids block the response of the testes to LH, just in case any of that hormone manages to reach them during the stressor (and serious athletes tend to have pretty dramatic elevations of glucocorticoids in their circulation, no doubt adding to the reproductive problems just discussed).


The other half concerns the nervous system and erections. Getting an erection to work properly is so incredibly complicated physiologically that if men ever actually had to understand it, none of us would be here.


In order 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.

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. Furthermore, this can be compounded by the fact that erectile dysfunction is a major stressor on its own, getting men into this vicious performance anxiety cycle of fearing fear itself.


A number of studies have shown that more than half the visits to doctors by males complaining of reproductive dysfunction turn out to be due to “psychogenic” impotency rather than organic impotency (there’s no disease there, just too much stress).


We now turn to female reproduction. Its basic outline is similar to that of the male. LHRH is released by the brain, which releases LH and FSH from the pituitary. The latter stimulates the ovaries to release eggs; the former stimulates ovaries to synthesize estrogen.


During the first half of the menstrual cycle, the “follicular” stage, levels of LHRH, LH, FSH, and estrogen build up, heading toward the climax of ovulation. This ushers in the second half of the cycle, the “luteal” phase.


Progesterone, made in the corpus luteum of the ovary, now becomes the dominant hormone on the scene, stimulating the uterine walls to mature so that an egg, if fertilized just after ovulation, can implant there and develop into an embryo.


Because the release of hormones has the fancy quality of fluctuating rhythmically over the menstrual cycle, the part of the hypothalamus that regulates the release of these hormones is generally more structurally complicated in females than in males.


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. As noted above, 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.


Overall, this is a logical mechanism. In the human, an average pregnancy costs approximately 50,000 calories, and nursing costs about a thousand calories a day; neither is something that should be gone into without a reasonable amount of fat tucked away.


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.


When a hunter-gatherer woman gives birth, she begins to breast-feed her child for a minute or two approximately every fifteen minutes. Around the clock. For the next three years. (Suddenly this doesn’t seem like such a hot idea after all, does it?)


When you breast-feed in this way, the endocrine story is very different. At the first nursing period, prolactin levels rise. And with the frequency and timing of the thousands of subsequent nursings, prolactin stays high for years. Estrogen and progesterone levels are suppressed, and you don’t ovulate.


Think about it over the course of her life span, she has perhaps two dozen periods. Contrast that with modern Western women, who typically experience hundreds of periods over their lifetime. Huge difference.


The hunter-gatherer pattern, the one that has occurred throughout most of human history, is what you see in nonhuman primates. Perhaps some of the gynecological diseases that plague modern westernized women have something to do with this activation of a major piece of physiological machinery hundreds of times when it may have evolved to be used only twenty times.


The majority of studies do show that the more stressed women (as determined by glucocorticoid levels, cardiovascular reactivity to an experimental stressor, or self-report on a questionnaire) are indeed less likely to have successful IVFs.



Psychoneuroimmunology, is a field that stresses that stress can increase the likelihood, the severity, or both of some immune-related diseases.


The halls of academe are filling with a newly evolved species of scientist—the psychoneuroimmunologist—who makes a living studying the extraordinary fact that what goes on in your head can affect how well your immune system functions.


Those two realms were once thought to be fairly separate—your immune system kills bacteria, makes antibodies, hunts for tumors; your brain makes you do the bunny hop, invents the wheel, has favorite TV shows.


Yet the dogma of the separation of the immune and nervous systems has fallen by the wayside. The autonomic nervous system sends nerves into tissues that form or store the cells of the immune system and eventually enter the circulation.


Furthermore, 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.


The evidence for the brain’s influence on the immune system goes back at least a century, dating to the first demonstration that if you waved an artificial rose in front of someone who is highly allergic to roses (and who didn’t know it was a fake), they’d get an allergic response.


Take some professional actors and have them spend a day doing either a depressing negative scene, or an uplifting euphoric one. Those in the former state show decreased immune responsiveness.


Robert Ader and Nicholas Cohen of the University of Rochester, scientists, experimented with a strain of mice that spontaneously develop disease because of overactivity of their immune systems. Normally, the disease is controlled by treating the mice with an immunosuppressive drug. Ader and Cohen showed that by using their conditioning techniques, they could substitute the conditioned stimulus for the actual drug—and sufficiently alter immunity in these animals to extend their life spans.


Studies such as these convinced scientists that there is a strong link between the nervous system and the immune system. It should come as no surprise that if the sight of an artificial rose or the taste of an artificially flavored drink can alter immune function, then stress can, too.


The primary job of the immune system is to defend the body against infectious agents such as viruses, bacteria, fungi, and parasites. The process is dauntingly complex. For one thing, the immune system must tell the difference between cells that are normal parts of the body and cells that are invaders—in immunologic jargon, distinguishing between “self” and “non-self.”


Somehow, the immune system can remember what every cell in your body looks like, and any cells that lack your distinctive cellular signature (for example, bacteria) are attacked. Moreover, when your immune system does encounter a novel invader, it can even form an immunologic memory of what the infectious agent looks like, to better prepare for the next invasion—a process that is exploited when you are vaccinated with a mild version of an infectious agent in order to prime your immune system for a real attack.


The immune system is distributed throughout the circulation. In order to sound immune alarms throughout this far-flung system, blood-borne chemical messengers that communicate between different cell types, called cytokines, have evolved.


The process of the immune system sorting self and non-self usually works well. 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.


In one version of this, some perfectly innocuous compound in the world around you triggers an alarm reaction. 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.


Suppose you’re exposed to some novel, dangerous pathogen, pathogen X, for the first time. Acquired immunity has three features. First, you acquire the ability to target pathogen X specifically, with antibodies and cell-mediated immunity that specifically recognize that pathogen.


But we also contain a simpler, more ancient branch of the immune system, one shared with species as distant as insects, called innate immunity. This generalized immune response tends to occur at the beachhead where a pathogen gets its first foothold, like your skin, or moist mucosal tissue, like in your mouth or nose.


As a first step, your saliva contains a class of antibodies that generically attack any sort of microbe that it encounters, instead of acquiring a means of targeting specific invaders. These antibodies are secreted and coat your mucosal surfaces like an antiseptic paint. In addition, at the site of infection, capillaries loosen up, allowing cells of the innate immune response to slip out of the circulation to infiltrate the immediate area of infection.


This gives us a broad overview of immune function. Time to see what stress does to immunity. Naturally, as it turns out, a lot more complicated things than used to be suspected.


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


Stress will inhibit the manufacturing of new antibodies in response to an infectious agent, and disrupt communication among lymphocytes through the release of relevant messengers.


And stress will inhibit the innate immune response, suppressing inflammation. All sorts of stressors do this—physical, psychological, in primates, rats, birds, even in fish. And, of course, in humans, too.


Sympathetic nervous system hormones, beta-endorphin, and CRH within the brain also play a role in suppressing immunity during stress. The precise mechanisms by which this happens are nowhere near as well understood as with glucocorticoid-induced immune suppression, and these other hormones have traditionally been viewed as less important than the glucocorticoid part of the story.


However, a number of experiments have shown that stressors can suppress immunity independently of glucocorticoid secretion, strongly implicating these other routes.


During stress it is logical for the body to shut down long-term building projects in order to divert energy for more immediate needs—this inhibition includes the immune system, which, while fabulous at spotting a tumor that will kill you in six months or making antibodies that will help you in a week, is not vital in the next few moments’ emergency.


However, 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. This boosting of immunity doesn’t occur only after some infectious challenge. 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.


If you fail to have phase B, if you don’t coast that activated immune system back down to baseline, you’re more at risk for an autoimmune disease. This idea has been verified in at least three realms. First, artificially lock glucocorticoid levels in the low basal range in rats and then stress them.


This produces animals that have phase A (mostly mediated by epinephrine), but there isn’t the rise in glucocorticoids to fully pull off phase B. The rats are now more at risk for autoimmune disease. Second, doctors have to occasionally remove one of the two adrenal glands (the source of glucocorticoids) from a patient, typically because of a tumor.


Immediately afterward, circulating glucocorticoid levels are halved for a period, until the remaining adrenal bulks up enough to take on the job of two. During that period of low glucocorticoid levels, people are more likely than normal to flare up with some autoimmune or inflammatory disease—there’s not enough glucocorticoids around to pull off phase B when something stressful occurs.


Finally, if you look at strains of rats or, weirdly, chickens, that spontaneously develop autoimmune diseases, they all turn out to have something wrong with the glucocorticoid system so that they have lower than normal levels of the hormone, or have immune and inflammatory cells that are less responsive than normal to glucocorticoids. Same for humans with autoimmune diseases like rheumatoid arthritis.


Insofar as autoimmune diseases involve over activation of the immune system (to the point of considering a healthy constituent of your body to actually be something invasive), the most time-honored treatment for such diseases is to put people “on steroids”—to give them massive amounts of glucocorticoids.


The logic here is obvious: by dramatically suppressing the immune system it can no longer attack your pancreas or nervous system, or whatever is the inappropriate target of its misplaced zeal (and, as an obvious side effect to this approach, your immune system will also not be very effective at defending you against real pathogens).


Thus, administration of large amounts of these stress hormones makes autoimmune diseases less damaging. Moreover, prolonged major stressors decrease the symptoms of autoimmune diseases in lab rats.


At the same time, it appears that stress can worsen autoimmune diseases. Stress is among the most reliable, if not the most reliable, factor to worsen such diseases.


This has often been reported anecdotally by patients, and is typically roundly ignored by clinicians who know that stress hormones help reduce autoimmunity, not worsen it. But some objective studies also support this view for autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, Grave’s disease, ulcerative colitis, inflammatory bowel disease, and asthma.


There have been only a handful of such reports, and they suffer from the weakness of relying on patient-reported retrospective data, rather than on prospective data. Nevertheless, their findings are relatively consistent—there is a subset of patients whose initial onset of an autoimmune disease and, to an even greater extent, their intermittent flare-ups of bad symptoms are yoked to stress. Moreover, there is, by now, a pretty hefty literature showing that stress can worsen autoimmunity in animal models of these diseases.


We’ve now seen two scenarios that increase the risk of autoimmune disease. First, it seems as if numerous transient stressors (that is, lots of phases A and B) increase the risk of autoimmunity—for some reason, repeated ups and downs ratchet the system upward, biasing it toward autoimmunity.


Is social isolation associated with damping down some aspect of immune function? There’s a lot of evidence for that: lonelier, more socially isolated individuals having less of an antibody response to a vaccine in one study; in another study of people with AIDS, having a faster decline in a key category of lymphocytes; in another, of women with breast cancer, having less natural killer cell activity.


For the same illness, people with the fewest social connections have approximately two-and-a-half times as much chance of dying as those with the most connections, after controlling for such variables as age, gender, and health status.


Relationships that are medically protective can take the form of marriage, contact with friends and extended family, church membership, or other group affiliations. The impact of social relationships on life expectancy appears to be at least as large as that of variables such as cigarette smoking, hypertension, obesity, and level of physical activity.


What does stress have to do with getting cancer?


Animal-experimentation literature shows that stress affects the course of some types of cancer.


The rate at which some tumors grow in mice can be affected merely by what sort of cages the animals are housed in—the more noisy and stressful, the faster the tumors grow.


If you expose rats to electric shocks from which they can eventually escape, they reject transplanted tumors at a normal rate. Take away the capacity to escape, yet give the same total number of shocks, and the rats lose their capacity to reject tumors.


Stress mice by putting their cages on a rotating platform (basically, a record player), and there is a tight relationship between the number of rotations and the rate of tumor growth.


Substitute glucocorticoids for the rotation stressor, and tumor growth is accelerated as well.


Once a tumor starts growing, it needs enormous amounts of energy, and one of the first things that tumors do is send a signal to the nearest blood vessel to grow a bush of capillaries into the tumor. Such angiogenesis allows for the delivery of blood and nutrients to the hungry tumor. Glucocorticoids, at the concentration generated during stress, aid angiogenesis.


Tumor cells are very good at absorbing glucose from the bloodstream. Your storehouses of energy, intended for your muscles, are being emptied and inadvertently transferred to the ravenous tumor instead.




Pain can hurt like hell, but it can inform us that we are sitting too close to the fire, or that we should never again eat the novel item that just gave us food poisoning. It effectively discourages us from trying to walk on an injured limb that is better left immobilized until it heals.


People who congenitally lack the ability to feel pain (a condition known as pain asymbolia) are a mess; because they can’t feel pain when they step down with too much force, their feet may ulcerate, their knee joints may disintegrate, and their long bones may crack; they burn themselves unawares; in some cases, they even lose a toe without knowing it.


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.


What is surprising is how malleable pain signals are—how readily the intensity of a pain signal is changed by the sensations, feelings, and thoughts that coincide with the pain.


The sensation of pain originates in receptors located throughout our body. Some are deep within the body, telling us about muscle aches, fluid-filled, swollen joints, or damage to organs. Or even something as mundane as a distended bladder. Others, in our skin, can tell us that we have been cut, burned, abraded, poked, or compressed.* Often, these skin receptors respond to the signal of local tissue damage.


(Insert P-PDTR and Mechano Receptors)


Sometimes pain consists of everyday sensations writ large. We may be pleased to have our thermal receptors stimulated by warm sunlight but not by boiling water.

Chronic, throbbing pain can be inhibited by certain types of sharp, brief sensory stimulation.


The most relevant dichotomy is between fibers that carry information about acute, sharp, sudden pain and those that carry information about slow, diffuse, constant, throbbing pain. Both project to spinal cord neurons and activate them, but in different ways.


As things are wired up, when a sharp, painful stimulus is felt, the information is sent on the fast fiber. This stimulates both neurons X and Y As a result, X sends a painful signal up the spinal cord, and an instant later, Y kicks in and shuts X off.


Thus the brain senses a brief, sharp burst of pain, such as after stepping on a tack. By contrast, when a dull, throbbing pain is felt, the information is sent on the slow fiber. It communicates with both neurons X and Y, but differently from the way it does on the fast fiber.


Once again the X neuron is stimulated and lets the brain know that something painful has occurred. This time, however, the slow fiber inhibits the Y neuron from firing.


Y remains silent, X keeps firing, and your brain senses a prolonged, throbbing pain, the type you’d feel for hours or days after you’ve burned yourself.


If someone pokes you over and over, you will continue to feel pain each time. Similarly, if you get an injury that causes days of inflammation, there are likely to be days of pain as well.


But sometimes, something goes wrong with pain pathways somewhere between those pain receptors and your spine, and you feel pain long after the noxious stimulus has stopped or the injury has healed, or you feel pain in response to stimuli that shouldn’t be painful at all.


Now you’ve got problems—allodynia, which is feeling pain in response to a normal stimulus.


Recall how when there is tissue injury, inflammatory cells infiltrate into the area and release chemicals that make those local pain receptors more excitable, more easily stimulated.


Now those inflammatory cells are pretty indiscriminate as to where they dump these chemicals, and some of them can leach over in the direction of receptors outside the area of injury, thereby making them more excitable. And suddenly the perfectly healthy tissue surrounding the injured area starts to hurt as well.


A scientist examined a decade’s worth of records at a suburban hospital, noting how many painkillers were requested by patients who had just had gallbladder surgery.


It turned out that patients who had views of trees from their windows requested significantly less pain medication than those who looked out on blank walls.


Other studies of chronic pain patients show that manipulating psychological variables such as the sense of control over events also dramatically changes the quantity of painkillers that they request.


Most of what the brain’s responses to pain are about is generating emotional responses and giving contextual interpretations about the pain. This is how being shot in the thigh, gasping in pain, can also leave you gasping in euphoric triumph—I’ve survived this war, I’m going home.


Three important things about the emotional ways the brain interprets and responds to pain: First, the emotional/ interpretative level can be dissociated from the objective amount of pain signal that is coursing up to the brain from the spine. In other words, how much pain you feel, and how unpleasant that pain feels, can be two separate things.


An elegant study shows it more explicitly. In it, volunteers dipped their hands into hot water before and after being given a hypnotic suggestion that they feel no pain.


During both hand dips, brain imaging was carried out to show which parts of the brain were becoming active. The sensation-processing part of the cortex (kind of a pain-ometer in this case) was activated to identical extents in both cases, reflecting the similar number of heat-sensitive pain receptors being triggered to roughly the equivalent extent in both cases.


But the more emotional parts of the brain activated only in the pre-hypnosis case. The pain was the same in both cases; the response to it was not.


As a second point, those more emotive parts of the brain not only can alter how you respond to pain information coming up the spinal cord; those areas of the brain can alter how the spinal cord responds to pain information. And the third point: this is where stress comes in big time.


Put a rat on a hot plate; then turn it on. Carefully time how long it takes for the rat to feel the first smidgen of discomfort, when it picks up its foot for the first time (at which point the rat is removed from the hot plate).


Now do the same thing to a rat that has been stressed—forced to swim in a tank of water, exposed to the smell of a cat, whatever. It will take longer for this rat to notice the heat of the plate: stress-induced analgesia.


Acupuncture stimulates the release of large quantities of endogenous opioids, for reasons no one really understands. The best demonstration of this is what is called a subtraction experiment: block the activity of endogenous opioids by using a drug that blocks the opiate receptor (most commonly a drug called naloxone). When such a receptor is blocked, acupuncture no longer effectively dulls the perception of pain.


Chinese veterinarians used acupuncture to do surgery on animals, thereby refuting the argument that the painkilling characteristic of acupuncture was one big placebo effect ascribable to cultural conditioning (no cow on earth will go along with unanesthetized surgery just because it has a heavy investment in the cultural mores of the society in which it dwells).


A placebo effect occurs when a person’s health improves, or the person’s assessment of their health improves, merely because they believe that a medical procedure has been carried out on them, regardless of whether it actually has.


Placebo effects are highly effective against pain. Not surprisingly, it turns out that they work by releasing endogenous opioids.


What about got stress-induced hyperalgesia. What is known about it makes perfect sense, in that stress-induced hyperalgesia does not actually involve more pain perception, and has nothing to do with pain receptors or the spinal cord. Instead, it involves more emotional reactivity to pain, interpreting the same sensation as more unpleasant. It’s the more emotional parts of the brain that are hyperreactive, the parts of the brain that are the core of our anxieties and fears.


This can be shown with brain-imaging studies, showing what parts of pain circuitry in the brain become overly active during such hyperalgesia. Moreover, anti-anxiety drugs like Valium and Librium block stress-induced hyperalgesia. People who score high on tests for neuroticism and anxiety are most prone toward hyperalgesia during stress. Amazingly, so are rat strains that have been bred for high anxiety.


Fibromyalgia. This is the mysterious syndrome of people having markedly reduced pain tolerance and multiple tender spots throughout the body, often paralyzing extents of pain, and no one can find anything wrong—no pinched nerve, no arthritis, no inflammation.


Mainstream medicine has spent decades consigning fibromyalgia to the realm of psychosomatic medicine (that is, “Get out of my office and go see a shrink”). It doesn’t help that fibromyalgia is more likely to strike people with anxious or neurotic personalities. There’s nothing wrong, is the typical medical conclusion. But this may not quite be the case.


(Insert the call for the BioPsychoSocail model)


For starters, sufferers have abnormally high levels of activity in parts of the brain that mediate the emotional/ contextual assessments of pain, the same areas activated in stress-induced hyperalgesia.


Chronic stress causes illness the stress-response doesn’t become depleted; instead, one gets sick because the stress-response itself eventually becomes damaging.


Stress can disrupt memory. By now, this dichotomy should seem quite familiar. If stress enhances some function under one circumstance and disrupts it under another.


Short-term stressors of mild to moderate severity enhance cognition, while major or prolonged stressors are disruptive. In order to appreciate how stress affects memory, we need to know something about how memories are formed (consolidated), how they are retrieved, how they can fail.


(Insert trauma and memory summary)


Memory is not monolithic, but instead comes in different flavors, short term, long term. Neuropsychologists are coming to recognize that there is a specialized subset of long-term memory.


Remote memories are ones stretching back to your childhood. Another important distinction in memory is that between explicit (also known as declarative) memory and implicit (which includes an important subtype called procedural memory) memory.


Explicit memory concerns facts and events, along with your conscious awareness of knowing them: I am a mammal, today is Monday, my dentist has thick eyebrows. Things like that.


In contrast, implicit procedural memories are about skills and habits, about knowing how to do things, even without having to think consciously consciously about them: shifting the gears on a car, riding a bicycle, doing the fox-trot. Memories can be transferred between explicit and implicit forms of storage. Memory can be dramatically disrupted if you force something that’s implicit into explicit channels.


Just as there are different types of memory, there are different areas of the brain involved in memory storage and retrieval. One critical site is the cortex, the vast and convoluted surface of the brain. Another is a region tucked just underneath part of the cortex, called the hippocampus.


If you want a totally simplistic computer metaphor, think of the cortex as your hard drive, where memories are stored, and your hippocampus as the keyboard, the means by which you place and access memories in the cortex.


There are additional brain regions relevant to a different kind of memory. These are structures that regulate body movements. What do these sites, such as the cerebellum, have to do with memory?


They appear to be relevant to implicit procedural memory, the type you need to perform reflexive, motor actions without even consciously thinking about them, where, so to speak, your body remembers how to do something before you do.


As an adolescent in the 1950s, “H.M.” had a severe form of epilepsy that was centered in his hippocampus and was resistant to drug treatments available at that time. In a desperate move, a famous neurosurgeon removed a large part of H.M.’ s hippocampus, along with much of the surrounding tissue.


The seizures mostly abated, and in the aftermath, H.M. was left with a virtually complete inability to turn new short-term memories into long-term ones—mentally utterly frozen in time.


Zillions of studies of H.M. have been carried out since, and it has slowly become apparent that despite this profound amnesia, H.M. can still learn how to do some things. Give him some mechanical puzzle to master day after day, and he learns to put it together at the same speed as anyone else, while steadfastly denying each time that he has ever seen it before.


Hippocampus and explicit memory are shot; the rest of the brain is intact, as is his ability to acquire a procedural memory.


(Insert link to neural path ways excerpt and link to NLP)


Neuroscientists have come to think of both learning and storing of memories as involving the “strengthening” of some branches rather than others of a network.

When a neuron has heard some fabulous gossip and wants to pass it on, when a wave of electrical excitation sweeps over it, this triggers the release of chemical messengers—neurotransmitters—that float across the synapse and excite the next neuron.


There are dozens, probably hundreds, of different kinds of neurotransmitters, and synapses in the hippocampus and cortex disproportionately make use of what is probably the most excitatory neurotransmitter there is, something called glutamate.


A professor drones on incomprehensibly in a lecture, a fact goes in one ear and out the other. It is repeated again—and, again, it fails to sink in. Finally, the hundredth time it is repeated, a lightbulb goes on, “Aha!” and you get it.


A little bit of neurotransmitter comes out of the first neuron and causes the second neuron to get a little excited; if a smidgen more neurotransmitter is released, there is a smidgen more excitation, and so on. In glutamatergic synapses, some glutamate is released and nothing happens.


A larger amount is released, nothing happens. It isn’t until a certain threshold of glutamate concentration is passed that, suddenly, all hell breaks loose in the second neuron and there is a massive wave of excitation. This is what learning something is about.


On a simplistic level, when you finally get it, that nonlinear threshold of glutamate excitation has just been reached.


Under the right conditions, when a synapse has just had a sufficient number of super-excitatory glutamate-driven “aha’s,” something happens. The synapse becomes persistently more excitable, so that next time it takes less of an excitatory signal to get the aha. That synapse just learned something; it was “potentiated,” or strengthened. The most amazing thing is that this strengthening of the synapse can persist for a long time.


There’s increasing evidence that the formation of new memories might also sometimes arise from the formation of new connections between neurons (in addition to the potentiating of pre-existing ones) or, even more radically, the formation of new neurons themselves. This latter, controversial idea is discussed below.


For the moment, this is all you need to know about how your brain remembers anniversaries and sports statistics and the color of someone’s eyes and how to waltz. We can now see what stress does to the process.


The first point, of course, is that mild to moderate short-term stressors enhance memory. This makes sense, in that this is the sort of optimal stress that we would call “stimulation”—alert and focused. This effect has been shown in laboratory animals and in humans. Memory for the emotional components is enhanced (although the accuracy isn’t necessarily all that good), whereas memory for the neutral details is not.


These changes are quite adaptive. When a stressor is occuring it is a good time to be at your best in memory retrieval (“ How did I get out of this mess last time?”) and memory formation (“ If I survive this, I’d better remember just what I did wrong so I don’t get into a mess like this again.”). So stress acutely causes increased delivery of glucose to the brain, making more energy available to neurons, and therefore better memory formation and retrieval.


As you go from no stress to a moderate, transient amount of stress—the realm of stimulation—memory improves. As you then transition into severe stress, memory memory declines.


There are also findings (although fewer in number) showing that stress disrupts something called “executive function.” This is a little different from memory. Rather than this being the cognitive realm of storing and retrieving facts, this concerns what you do with the facts—whether you organize them strategically, how they guide your judgments and decision making.


Stress can disrupt long-term potentiation in the hippocampus even in the absence of glucocorticoids (as in a rat whose adrenal glands have been removed), and extreme arousal of the sympathetic nervous system seems responsible for this.


Once glucocorticoid levels go from the range seen for mild or moderate stressors to the range typical of big-time stress, the hormone no longer enhances long-term potentiation, that process by which the connection between two neurons “remembers” by becoming more excitable.


Instead, glucocorticoids now disrupt the process. Furthermore, similarly high glucocorticoid levels enhance something called long-term depression, which might be a mechanism underlying the process of forgetting, the flip side of hippocampal aha-ing.


The hippocampus is one of only two sites in the brain where these new neurons originate. The rate of neurogenesis can be regulated. Learning, an enriched environment, exercise, or exposure to estrogen all increase the rate of neurogenesis, while the strongest inhibitors identified to date are, you guessed it, stress and glucocorticoids—as little as a few hours of either in a rat.


Within seconds of the onset of stress, glucose delivery throughout the brain increases. What if the stressor continues? By about thirty minutes into a continuous stressor, glucose delivery is no longer enhanced, and has returned to normal levels.


If the stressor goes on even longer, the delivery of glucose to the brain is even inhibited, particularly in the hippocampus. Delivery is inhibited about 25 percent, and the effect is due to glucocorticoids.


Post-traumatic stress disorder (PTSD) an anxiety disorder can arise from a variety of types of traumatic stressors. Work pioneered by Douglas Bremner of Emory University, replicated by others, shows that people with PTSD from repeated trauma (as opposed to a single trauma)—soldiers exposed to severe and repeated carnage in combat, individuals repeatedly abused as children—have smaller hippocampi. Again, the volume loss appears to be only in the hippocampus, and in at least one of those studies, the more severe the history of trauma, the more extreme the volume loss.


Major depression is utterly intertwined with prolonged stress, and this connection includes elevated glucocorticoid levels in about half the people with major depression. Yvette Sheline of Washington University and others have shown that prolonged major depression is, once again, associated with a smaller hippocampus.


The more prolonged the history of depression, the more volume loss. Furthermore, it is in patients with the subtype of depression that is most associated with elevated glucocorticoid levels where you see the smaller hippocampus.


When glucocorticoids cause the cables connecting neurons to shrivel up, it is not a permanent process—stop the glucocorticoid excess and the processes can slowly regrow.


For the moment, I think it is fair to say that there is decent but not definitive evidence that stress and/ or prolonged exposure to glucocorticoids can cause structural, as well as functional, changes in the hippocampus, that these are changes that you probably wouldn’t want to have happen to your hippocampus, and that these changes can be long-lasting.


We are now fifty, sixty years into thinking about ulcers, blood pressure, and aspects of our sex lives as being sensitive to stress. Most of us recognize the ways in which stress can also disrupt how we learn and remember.


Not getting enough sleep is a stressor; being stressed makes it harder to sleep.


Not surprisingly, the brain works differently in different stages of sleep. This can be studied by having people sleep in a brain scanner, while you measure the levels of activity of different brain regions.


Take some volunteers, sleep-deprive them for some godawful length of time, stick them in one of these imaging machines, poke them awake a little more while you get a measure of their brains’ activity when they’re awake, and then, snug as a bug in a scanner, let them go to sleep with the scanner running.


Sleep is not a monolithic process, a uniform phenomenon. Instead, there are different types of sleep—shallow (also known as stages 1 and 2) sleep, where you are easily awakened. Deep sleep (also known as stages 3 and 4, or “slow wave sleep”).


Rapid Eye Movement (REM) sleep, where the puppy’s paws flutter and our eyes dart around and dreams happen. There are not only these different stages, but a structure, an architecture to them. You start off shallow, gradually sleep your way down to slow wave sleep, followed by REM, then back up again, and then repeat the whole cycle about every ninety minutes.


During REM sleep. Overall, there’s an increase in activity. Some brain regions become even more metabolically active than when you’re awake. Parts of the brain that regulate muscle movement, brain stem regions that control breathing and heart rate—all increase their metabolic rate.


In a part of the brain called the limbic system, which is involved in emotion, there is an increase as well. The same for areas involved in memory and sensory processing, especially those involved in vision and hearing.


This is dreaming. That tells us something about how dream imagery arises. But something else that happens in the brain tells us something about the content of dreams.


During REM sleep, metabolism in the frontal cortex goes way down, disinhibiting the limbic system to come up with the most outlandish ideas. That’s why dreams are dreamlike—illogical, nonsequential, hyperemotional.


Even fruit flies die without sleep, just like you. Weirdly, another major reason to sleep is to dream. If you skip a night’s sleep, when you finally get to sleep the next night, you have more REM sleep than normal, suggesting that you’ve built up a real deficit of dreaming.


Some extremely difficult studies that make me queasy just to contemplate deprive people or animals of REM sleep preferentially, and the study subjects go to pieces much faster than they do for the equivalent amount of deprivation of other types of sleep. Thus, this begs the question of what dreaming is for.


Sleep plays a role in cognition. You don’t forget a phone number and then “sleep on it” to remember it. You do it for some complex, emotionally, ambiguous problem.


Both slow wave and REM sleep also seem to play roles in the formation of new memories, the consolidation of information from the previous day, even information that became less accessible to you while awake over the course of the day. One type of evidence supporting this is the fact that if you teach an animal some task and disrupt its sleep that night, the new information isn’t consolidated.


Being exposed to lots of new information during the day is associated with more REM sleep that night. Moreover, the amount of certain subtypes of sleep at night predicts how well new information is recalled the next day.


For example, lots of REM sleep during the night predicts better consolidation of emotional information from the day before, while lots of stage 2 sleep predicts better consolidation of a motor task, and a combination of lots of REM and slow wave sleep predicts better retention of perceptual information.


What should happen to sleep during stress?

Given a zebra-o-centric view of the world: lion coming, don’t nap (or, as the old joke goes, “The lion and the lamb shall lie down together. But the lamb won’t get much sleep.”). The hormone CRH seems to be most responsible for this effect. As you’ll recall, the hormone not only starts the glucocorticoid cascade by stimulating ACTH release from the pituitary, but it is also the neurotransmitter that activates all sorts of fear, anxiety, and arousal pathways in the brain.


The bodily consequences of sympathetic activation make sleeping hard. Not surprisingly about 75 percent of cases of insomnia are triggered by some major stressor. Moreover, many (but not all) studies show that poor sleepers tend to have higher levels of sympathetic arousal or of glucocorticoids in their bloodstream. So, lots of stress and, potentially, little sleep. But stress not only can decrease the total amount of sleep but can compromise the quality of whatever sleep you do manage.


Your sleep is dominated by more shallow sleep stages, meaning you wake up more easily—fragmented sleep. Moreover, when you do manage to get some slow wave sleep, you don’t even get the normal benefits from it.


When slow wave sleep is ideal, really restoring those energy stores, there’s a characteristic pattern in what is called the delta power range that can be detected on an EEG (electroencephalogram) recording. When people are stressed presleep, or are infused with glucocorticoids during sleep, you get less of that helpful sleep pattern during slow wave sleep. When it comes to what makes for psychological stress, a lack of predictability and control are at the top of the list of things you want to avoid.


The subject of one experiment is a rat that receives mild electric shocks (roughly equivalent to the static shock you might get from scuffing your foot on a carpet). Over a series of these, the rat develops a prolonged stress-response: its heart rate and glucocorticoid secretion rate go up, for example.


For convenience, we can express the long-term consequences by how likely the rat is to get an ulcer, and in this situation, the probability soars. In the next room, a different rat gets the same series of shocks—identical pattern and intensity; its allostatic balance is challenged to exactly the same extent.


But this time, whenever the rat gets a shock, it can run over to a bar of wood and gnaw on it. The rat in this situation is far less likely to get an ulcer. You have given it an outlet for frustration. Other types of outlets work as well—let the stressed rat eat something, drink water, or sprint on a running wheel, and it is less likely to develop an ulcer.


We humans also deal better with stressors when we have outlets for frustration—punch a wall, take a run, find solace in a hobby. We are even cerebral enough to imagine those outlets and derive some relief: consider the prisoner of war who spends hours imagining a golf game in tremendous detail. I have a friend who passed a prolonged and very stressful illness lying in bed with a mechanical pencil and a notepad, drawing topographic maps of imaginary mountain ranges and taking hikes through them.


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.


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. An extremely high percentage of primate aggression represents frustration displaced onto innocent bystanders.


Put a primate through something unpleasant: it gets a stress-response. Put it through the same stressor while in a room full of other primates and… it depends. If those primates are strangers, the stress-response gets worse. But if they are friends, the stress-response is decreased. Social support networks—it helps to have a shoulder to cry on, a hand to hold, an ear to listen to you, someone to cradle you and to tell you it will be okay.


Glucocorticoid levels are elevated among low-ranking baboons and among the entire group if the dominance hierarchy is unstable, or if a new aggressive male has just joined the troop. But if you are a male baboon with a lot of friends, you are likely to have lower glucocorticoid concentrations than males of the same general rank who lack these outlets. And what counts as friends? You play with kids, have frequent nonsexual grooming bouts with females (and social grooming in nonhuman primates lowers blood pressure).


People who are socially isolated have overly active sympathetic nervous systems. Given the likelihood that this will lead to higher blood pressure and more platelet aggregation in their blood vessels they are more likely to have heart disease—two to five times as likely, as it turns out. And once they have the heart disease, they are more likely to die at a younger age.


In the absence of any stressor, loss of predictability triggers a stress-response. During the onset of the Nazi blitzkrieg bombings of England, London was hit every night like clockwork. Lots of stress. In the suburbs the bombings were far more sporadic, occurring perhaps once a week. Fewer stressors, but much less predictability. There was a significant increase in the incidence of ulcers during that time. Who developed more ulcers? The suburban population.


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 flights, exchanging control: “Okay, you rest for a while, I’ll take over concentrating on keeping the pilot from having a stroke.”


Exercise can be a great stress reducer, but only so long as it is something that seems even remotely desirable. Amazingly, the same is seen in a rat—let a rat run voluntarily in a running wheel, and it makes it feel great. Force a rat to do the same amount of exercise and it gets a massive stress-response.


Endless studies have shown that the link between occupational stress and increased risk of cardiovascular and metabolic diseases is anchored in the killer combination of high demand and low control—you have to work hard, a lot is expected of you, and you have minimal control over the process.


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.


To understand some important subtleties of the effects of control on stress, we need to return to the paradigm of the rat being shocked. It had been previously trained to press a lever to avoid shocks, and now it’s pounding away like crazy on a lever.


The lever does nothing; the rat is still getting shocked, but with less chance of an ulcer because the rat thinks it has control. To introduce a sense of control into the experimental design decreases the stress-response because, in effect, the rat is thinking, “Ten shocks an hour. Not bad; just imagine how bad it would be if I wasn’t on top of it with my lever here.”


But what if things backfire, and adding a sense of control makes the rat think, “Ten shocks an hour, what’s wrong with me? I have a lever here, I should have avoided the shocks, it’s my fault.” If you believe you have control over stressors that are, in fact, beyond your control, you may consider it somehow to be your fault that the inevitable occurred. The effects of the sense of control on stress are highly dependent on context.


Best estimates are that from 5 to 20 percent of us will suffer a major, incapacitating depression at some point in our lives, causing us to be hospitalized or medicated or nonfunctional for a significant length of time. Its incidence has been steadily increasing for decades—by the year 2020, depression is projected to be the second leading cause of medical disability on earth.


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 to have persisted for at least two weeks.


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.”


Depression can be as tragic as cancer or a spinal cord injury. 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.


Cognitive therapists, like Aaron Beck of the University of Pennsylvania, even consider depression to be primarily a disorder of thought, rather than emotion, in that sufferers tend to see the world in a distorted, negative way.


Show a subject two pictures.

In the first, a group of people are gathered happily around a dinner table, feasting.

In the second, the same people are gathered around a coffin.

Show the two pictures rapidly or simultaneously; which one is remembered? Depressives see the funeral scene at rates higher than chance.

They are not only depressed about something, but see the goings-on around them in a distorted way that always reinforces that feeling. Their glasses are always half empty.


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.


Certain subtypes of depression have a rhythm. A manic-depressive may be manic for five days, severely depressed for the following week, then mildly depressed for half a week or so, and, finally, symptom-free for a few weeks. Then the pattern starts up again, and may have been doing so for a decade.


Good things and bad things happen, but the same cyclic rhythm continues, which suggests just as much deterministic biology as in the life cycle of the malarial parasite. 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.


Considerable evidence exists that something is awry with the chemistry of the brains of depressives. How strong the signal is in a synapse is a function both of how loudly the first neuron yells (the amount of neurotransmitter released) and of how sensitively the second neuron listens (how many receptors it has for the neurotransmitter).


Naturally, there’s a spate of other neurotransmitters that may be involved. One particularly interesting one is called Substance P. Decades of work have shown that Substance P plays a role in pain perception, with a major role in activating the spinal cord pathways. Remarkably, some recent studies indicate that drugs that block the action of Substance P can work as antidepressants in some individuals. What’s this about? Perhaps the sense of depression as a disease of “psychic pain” may be more than just a metaphor.


On an incredibly simplistic level, you can think of depression as occurring when your cortex thinks an abstract negative thought and manages to convince the rest of the brain that this is as real as a physical stressor. In this view, people with chronic depressions are those whose cortex habitually whispers sad thoughts to the rest of the brain. Thus, an astonishingly crude prediction: cut the connections between the cortex and the rest of a depressive’s brain, and the cortex will no longer be able to get the rest of the brain depressed.


Obviously, this is a simplified picture—no one actually disconnects the entire cortex from the rest of the brain. After all, the cortex does more than mope around feeling bad about the final chapter of Of Mice and Men. The surgical procedure, called a cingulotomy, or a cingulum bundle cut, actually disconnects just one area toward the front of the cortex, called the anterior cingulate cortex (ACC).


The ACC is turning out to have all the characteristics of a brain region you’d want to take offline in a major depression. It’s a part of the brain that is very concerned with emotions. Show people arrays of pictures: in one case, ask them to pay attention to the emotions being expressed by people in the pictures; in another case, ask them to pay attention to details like whether these are indoor or outdoor photographs.


In only the former case do you get activation of the ACC. And the emotions that the ACC is involved in seem to be negative ones. Induce a positive state in someone by showing something amusing, and ACC metabolism decreases. In contrast, if you electrically stimulate the ACC in people, they feel a shapeless sense of fear and foreboding.


Put a volunteer in a brain-imaging machine and, from inside, ask them to play some game with two other people, via a computer console. Rig up the flow of the game so that, over time, the other two (actually, a computer program) gradually begin just playing with each other, excluding the test subject.


Neuronal activity in the ACC lights up, and the more left out the person feels, the more intensely the ACC activates. How do you know this has something to do with that dread junior high school feeling of being picked last for the team? Because of a clever control in the study: set the person up to play with the supposed other two players.


Once again, it winds up that the other two only play against each other. The difference, this time, though, is that early on the subject is told there’s been a technical glitch and that their computer console isn’t working. Excluded because of a snafu in the technology, there’s no ACC activation.


Depression has a genetic component. As a first observation, depression runs in families. For a long time, that would have been sufficient evidence for some folks that there is a genetic link, but this conclusion is undone by the obvious fact that not only do genes run in families, environment does as well.


Growing up in a poor family, an abusive family, a persecuted family, can all increase the risk of depression running through that family without genes having anything to do with it.


Chronic illness that involves overactivation of the immune system (for example, chronic infections, or an autoimmune disease where the immune system has accidentally activated and is attacking some part of your body) is more likely to cause depression than other equally severe and prolonged illnesses that don’t involve the immune system.


People who secrete too little thyroid hormone can develop major depressions and, when depressed, can be atypically resistant to antidepressant drugs working. This is particularly important because many people, seemingly with depressions of a purely psychiatric nature, turn out to have thyroid disease.


With massive changes in hormone levels (a thousandfold for progesterone at the time of giving birth, for example), current speculation centers on the possibility that the ratio of estrogen to progesterone can change radically enough to trigger a major depression.


People who are prone to depression tend to experience stressors at a higher than expected rate. This is even seen when comparing them to individuals with other psychiatric disorders or health problems. Much of this appears to be stressors built around lack of social support.


This raises the potential for a vicious cycle to emerge. This is because if you interpret the ambiguous social interactions around you as signs of rejection, and respond as if you have been rejected, it can increase the chances of winding up socially isolated, thereby confirming your sense that you have been rejected….


Stress a lab rat, and it becomes anhedonic. Specifically, it takes a stronger electrical current than normal in the rat’s pleasure pathways to activate a sense of pleasure. The threshold for perceiving pleasure has been raised, just as in a depressive.


Genes are rarely about inevitability, especially when it comes to humans, the brain, or behavior. They’re about vulnerability, propensities, tendencies. In this case, genes increase the risk of depression only in certain environments: you guessed it, only in stressful environments. Share every single gene with someone who is depressive and you still have a 50 percent chance of not having the disease.


A far more common feature of depression is one of an overactive stress-response—somewhat of an overly activated sympathetic nervous system and, even more dramatically, elevated levels of glucocorticoids. This adds to the picture that depressed people, sitting on the edge of their beds without the energy to get up, are actually vigilant and aroused, with a hormonal profile to match—but the battle is inside them.


Those elevated glucocorticoid levels appear to have some other consequences as well. They may play a role, for example, in the fact that depressive patients often are at least mildly immunosuppressed, and are more prone to osteoporosis. Moreover, prolonged major depression increases the risk of heart disease about three-to fourfold, even after controlling for smoking and alcohol consumption, and the glucocorticoid excess is likely to contribute to that as well.


In one style of experiment, pioneered by the psychologists Martin Seligman and Steven Maier, animals are exposed to pathological amounts of psychological stressors:

A loss of control and of predictability within certain contexts

A loss of outlets for frustration

A loss of sources of support

A perception of life worsening

The result is a condition strikingly similar to a human depression.


For example, a rat may be subjected to a long series of frequent, uncontrollable, and unpredictable shocks or noises, with no outlets. After awhile, something extraordinary happens to that rat. This can be shown with a test.


Take a fresh, unstressed rat, and give it something easy to learn. Put it in a room, for example, with the floor divided into two halves. Occasionally, electricity that will cause a mild shock is delivered to one half, and just beforehand, there is a signal indicating which half of the floor is about to be electrified. Your run-of-the-mill rat can learn this “active avoidance task” easily, and within a short time it readily and calmly shifts the side of the room it sits in according to the signal. Simple.


Except for a rat who has recently been exposed to repeated uncontrollable stressors. That rat cannot learn the task. It does not learn to cope. On the contrary, it has learned to be helpless. Such helplessness extends to tasks having to do with its ordinary life, like competing with another animal for food, or avoiding social aggression.


Learned helplessness has been induced in rodents, cats, dogs, birds, fish, insects, and primates, including humans. It takes surprisingly little in terms of uncontrollable unpleasantness to make humans give up and become helpless in a generalized way.


In one study by Donald Hiroto, student volunteers were exposed to either escapable or inescapable loud noises (as in all such studies, the two groups were paired so that they were exposed to the same amount of noise). Afterward, they were given a learning task in which a correct response turned off a loud noise; the “inescapable” group was significantly less capable of learning the task.


Helplessness can even be generalized to nonaversive learning situations. Hiroto and Seligman did a follow-up study in which, again, there was either controllable or uncontrollable noise. Afterward the latter group was less capable of solving simple word puzzles. Giving up can also be induced by stressors far more subtle than uncontrollable loud noises.


In another study, Hiroto and Seligman gave volunteers a learning task in which they had to pick a card of a certain color according to rules that they had to discern along the way. In one group, these rules were learnable; in the other group, the rules were not (the card color was randomized).


Afterward, the latter group was less capable of coping with a simple and easily solved task. Seligman and colleagues have also demonstrated that unsolvable tasks induced helplessness afterward in social coping situations.


In the experiment involving inescapable noise, Hiroto had given the students a personality inventory beforehand. Based on that, he was able to identify the students who came into the experiment with a strongly “internalized locus of control”—a belief that they were the masters of their own destiny and had a great deal of control in their lives—and, in contrast, the markedly “externalized” volunteers, who tended to attribute outcomes to chance and luck.


In the aftermath of the uncontrollable stressor, the externalized students were far more vulnerable to learned helplessness. Transferring that to the real world, with the same external stressors, the more that someone has an internal locus of control, the less the likelihood of a depression.


(Insert fixed Vs growth mindset)


Collectively, these studies strike me as extremely important in forming links among stress, personality, and depression. Our lives are replete with incidents in which we become irrationally helpless.


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.


A major depression, these findings suggest, can be the outcome of particularly severe lessons in uncontrollability for those of us who are already vulnerable. This may explain an array of findings that show that if a child is stressed in certain ways—loss of a parent to death, divorce of parents, being a victim of abusive parenting—the child is more at risk for depression years later.


What could be a more severe lesson that awful things can happen that are beyond our control than a lesson at an age when we are first forming our impressions about the nature of the world? As an underpinning of this, Paul Plotsky and Charles Nemeroff of Emory University have shown that rats or monkeys exposed to stressors early in life have a lifelong increase in CRH levels in their brain.


This may explain an array of findings that show that if a child is stressed in certain ways—loss of a parent to death, divorce of parents, being a victim of abusive parenting—the child is more at risk for depression years later.


What could be a more severe lesson that awful things can happen that are beyond our control than a lesson at an age when we are first forming our impressions about the nature of the world?


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.


So differential incidences of depression can be explained by differences in the amount of stress, and/ or in stress histories. But even for the same stressors and the same history of stress, some of us are more vulnerable than others.


Why should some of us succumb more readily? To begin to make sense of this, we have to invert that question, to state it in a more world-weary way.


How is it that any of us manage to avoid getting depressed?


All things considered, this can be an awful world, and at times it must seem miraculous that any of us resist despair.


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.


Some folks are good at modulating stress in these ways, and others are terrible. These fall within the larger category of what Richard Davidson has called “affective style.” And this turns out to be a very important factor in understanding why some people are more prone toward stress-related diseases than others.


Animals are strongly individualistic, and when it comes to primates, there are astonishing differences in their personalities, temperaments, and coping styles.


These differences carry some distinctive physiological consequences and disease risks related to stress. This is not the study of what external stressors have to do with health. This is, instead, the study of the impact on health of how an individual perceives, responds to, and copes with those external stressors.


The lessons learned from some of these animals can be strikingly relevant to humans.


We are ecologically buffered and privileged enough to be stressed mainly over social and psychological matters. But, still a world filled with affiliation, friendships, relatives who support each other; and yet still a viciously competitive society as well.


Studies suggest two ways that a personality style might lead down the path to stress-related disease. In the first way, there’s a mismatch between the magnitude of the stressors they are confronted with and the magnitude of their stress-response—the most neutral of circumstances is perceived as a threat, demanding either a hostile, confrontational response or an anxious withdrawal.


At the most extreme they even react to a situation that most certainly does not constitute a stressor the same way as if it were a stressful misery. In their second style of dysfunction, the animal does not take advantage of the coping responses that might make a stressor more manageable they don’t grab the minimal control available in a tough situation, they don’t make use of effective outlets when the going gets tough, and they lack social support.


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. 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.Awful. And immensely stressful.


Not surprisingly, anxiety disorders are associated with chronically overactive stress-responses, and with increased risk of many of the diseases that fill the pages of this book (anxiety-prone rats, for example, have a shortened life span).


However, glucocorticoid excess is not the usual response. Instead, it’s too much sympathetic activation, an overabundance of circulating catecholamines (epinephrine and norepinephrine).


There are some things that mammals get anxious about that are innate. Bright lights for a rat. Being dangled up in the air if you are a terrestrial creature. Having your breathing obstructed for most any animal. But most things that make us anxious are learned. Maybe because they are associated with some trauma, or maybe because we’ve generalized them based on their similarity to something associated with a trauma.


This is implicit learning, where a certain autonomic response in your body has been conditioned. Thus, consider a woman who has suffered a traumatic assault, where her brain has become conditioned to speed up her heart every time she sees a similar-looking man.


Pavlovian learning—ring the bell associated with food, and the brain has learned to activate salivary glands; see a certain type of face, and the brain has learned to activate the sympathetic nervous system.


The conditioned memory can be elicited without you even being conscious of it. That woman finds herself in a crowded party, having a fine time, when suddenly the anxiety is there, she’s gasping, heart racing, and she hasn’t a clue why. It is not until a few seconds later that she realizes that the man talking just behind her has an accent just like the man. The body responds before there is consciousness of the similarity.


This implicit learned somatic response can happen with out any conscious memory available to the person. This learned response is automatic and involves the sensations from the environment and/or the internal feelings from the body that is associated with the implicit memory. Most good trauma therapy is working with the perception of the body to accomplish this. Often somatic interventions are the most effective at treating this.


(Insert somatic therapy workbook)


(Insert the Trauma and memory summary)


A mild transient stress enhances declarative learning, prolonged or severe stress disrupts it. But in the case of this pre-conscious, implicit, autonomic learning, any type of stress enhances it. For example, make a loud sound and a lab rat will have a startle response—in a few milliseconds, its muscles tense. Stress the rat beforehand with any type of stressor and the startle response is exaggerated and more likely to become a habitual, conditioned response. Same in us.


(Insert discussion about mono tasking as it relates to stress, overload ability to respond appropriately and with speed, sleep, drunk, multi tasking, predisposes you to injury physically and emotionally, and traumatically, And also inversely explains why having had past traumas on going in environments or in Identify leads to a higher probability of mono-tasking and learned helplessness).


Instead, anxiety and fear conditioning are the province of a related structure, the amygdala. To begin to make sense of its function, you have to look at brain areas that project to the amygdala, and where the amygdala projects to, in turn. One route to the amygdala is from pain pathways.


There’s pain and then there’s subjective pain interpretation.

The amygdala is about the latter.


The structure also gets sensory information. Remarkably, the amygdala gets sensory information before that information reaches the cortex and causes conscious awareness of the sensation—the woman’s heart races before she is even aware of the accent of the man.


The amygdala gets information from the autonomic nervous system. What’s the significance of this? Suppose some ambiguous information is filtering in, and your amygdala is “deciding” whether this is a time to get anxious. If your heart is pounding and your stomach is in your throat, that input will bias the amygdala to vote for anxiety. And, to complete the picture, the amygdala is immensely sensitive to glucocorticoid signals.


(Insert Hypoglycemia feelings paper)


(Insert the secret life of the brain)


(Insert POLYVAGAL theory)


Some of the most convincing work implicating the amygdala in anxiety comes from brain-imaging studies. Put people in a scanner, flash various pictures, see what parts of the brain are activated in response to each. Show a scary face, and the amygdala lights up. Make the pictures subliminal—flash them for thousandths of a second, too fast to be consciously seen (and too fast to activate the visual cortex), and the amygdala lights up.


People with anxiety disorders have exaggerated startle responses, see menace that others don’t. Give people some reading task, where they are flashed a series of nonsense words and have to quickly detect the real ones. Everyone slows down slightly for a menacing word, but people with anxiety disorders slow down even more. Commensurate with these findings, the amygdala in such a person shows the same hyperreactivity.


(Insert the body keeps the score about children that have survived trauma pictures excerpt)


Suppose a major traumatic stressor occurs, of a sufficient magnitude to disrupt hippocampal function while enhancing amygdaloid function. At some later point, in a similar setting, you have an anxious, autonomic state, agitated and fearful, and you haven’t a clue why—this is because you never consolidated memories of the event via your hippocampus while your amygdala-mediated autonomic pathways sure as hell remember. This is a version of free-floating anxiety.