2022-01-04 - Why Zebras Don't Get Ulcers by Robert Spolsky ========================================================== When i took a workshop on TRE (Trauma/Tension Releasing Exercises), Why Zebras Don't Get Ulcers was highly recommended reading. A family member loaned me the book and i finally got around to reading it. I really enjoyed the level of detail in this book, and yet it was quite accessible. What follows are excerpts that i found interesting while reading the book. Preface ======= 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 tremendous impact on the functioning of virtually every cell in the body. ... 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. Chapter 1 ========= Kind of stress: * acute physical crises: the body's responses are brilliantly adapted to this * chronic physical challenges: the body's stress-responses are reasonably good at handling these sustained disasters * psychological and social disruptions: these are recent inventions, in the evolutionary timescale 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... In the 1930s, Hans Selye formalized the concept of stress with two ideas: * The body has a surprisingly similar set of responses to a broad array of stressors. * If stressors go on for too long, they can make you sick. ... 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. For us vertebrates, the core of the stress-response is built around the fact that your muscles are going to work like crazy. One of the hallmarks of the stress-response is the rapid mobilization of energy... If your body has mobilized all that glucose, it also needs to deliver it to the critical muscles as rapidly as possible. Heart rate, blood pressure, and breathing rate increase... digestion is inhibited... growth and tissue repair is curtailed, sexual drive decreases, immunity is inhibited, pain becomes blunted, memory and senses sharpen. With prolonged stress, diseases emerge... The body spends so much on the defense budget that it neglects education, health care, and social services. With sufficient activation, the stress response can become more damaging to the stressor itself. The same systems of the brain that function more cleverly during stress can also be damaged by one class of hormones secreted for stress. It isn't really the case that stress makes you sick, or even increases your risk of being sick. Stress increases your risk of getting diseases that make you sick, or if you have such a disease, stress increases the risk of your defenses being overwhelmed by the disease. Chapter 2 ========= ANS: autonomic nervous system Half of this system is activated in response to stress, half is suppressed. The half of the ANS that is turned on is called the sympathetic nervous system. This is the part that activates goosebumps. UK: adrenaline US: epinephrine UK: noradrenaline US: norepinephrine The parasympathetic component mediates calm, vegetative activities: sleep, growth, energy storage, drowsiness after a large meal. Sympathetic: speeds up heart, divers blood to the muscles Parasympathetic: does the opposite the parts of the brain that activate on of the two branches typically inhibit the other. neurotransmitters go from cell to adjacent cell. hormones go through the blood stream. norepinephrine can be either a neurotransmitter or a hormone. the pituitary gland contains a whole array of hormones that run the show... it regulates what all the other glands do. In 1944, the physiologist Geoffrey Harris proposed that the brain was also a hormonal gland, that it released hormones that traveled to the pituitary and directed the pituitary's actions. Specifically, the hypothalamus. 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 glands are activated during stress, some inhibited. 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 * estrogens * progestins * mineralocorticoids * glucocorticoids Secreted by the adrenal gland, glucocorticoids often act in ways similar to epinephrine. Epinephrine acts within seconds; glucocorticoids back this activity up over the course of minutes or hours. When something stressful happens or you think stressful thoughts, the hypothalamus secretes an array of hormones that gets the ball rolling. The principal such releaser is called CRH (corticotropin releasing hormone)... 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. [male and female stress response differs. In addition to fight or flight, there is also tend and befriend. Oxytocin is secreted during stress in females.] Sympathetic arousal is a relative marker of anxiety and vigilance, while heavy secretion of glucocorticoids is more a marker of depression. Chapter 3 ========= Basically your heart is a pump and your blood vessels are hoses. The cardiovascular stress-response essentially consists of making them work harder for a while, and if you do that on a regular basis, they will wear out... The first step in the road to stress-related disease is developing hypertension, chronically elevated blood pressure. ... after controlling for age, having left ventricular hypertrophy is the single best predictor of cardiac risk. The branch points in the [blood] vessel wall where bifurcation occurs bear the brunt of the fluid pressure slamming into them. Thus, a simple rule: 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 the branch points in arteries throughout the body. The smooth inner lining of the vessel begins to tear or form little craters of damage. Once this layer is damaged, you get an inflammatory response--cells of the immune system that mediate inflammation aggregate around the injured site. Moreover, cells full of fatty nutrients, called foam cells, begin to form there too. In addition, during stress the sympathetic nervous system makes your blood more viscous. Specifically, epinephrine makes circulating platelets (a type of blood cell that promotes clotting) more likely to clump together, and these clumped platelets can get gummed up in these aggregates as well. As we'll see in the next chapter, during stress you're mobilizing energy into the bloodstream, including fat, glucose, and the "bad" type of cholesterol, and these can add to the aggregate. All sorts of fibrous gunk builds up there, too. You've now made yourself an atherosclerotic plaque. 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... sticks to those inflamed injury sites. 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). 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... But we're not done. Once you've formed those plaques, continued stress can get you in trouble another way. Again, increase stress and increase blood pressure, and, as blood moves with enough force, increase the chances of tearing that plaque loose, rupturing it. [This can] form what is called a thrombus, and that mobile hairball can now lodge in a much smaller blood vessel, clogging it completely. Clog up a coronary artery and you've got a myocardial infarct, a heart attack (and this thrombus route accounts for the vast majority of heart attacks). Clog up a blood vessel in the brain and you have a brain infarct (a stroke). But there's more bad news. If chronic stress has made a mess of your blood vessels, each individual new stressor is even more damaging, for an additional insidious reason. This has to do with myocardial ischema, a condition that arises when the arteries feeding your heart have become sufficiently clogged that your heart itself is partially deprived of blood flow and thus Oxygen and glucose. [In a healthy person the body has mechanisms to make sure the stress response does not starve the heart.[ But if you encounter an acute stressor with a heart that has been suffering from chronic myocardial ischema, you're in trouble. The coronary arteries, instead of vasodilating in response to the sympathetic nervous system, vasoconstrict. But one of the most striking and best know features of heart disease is how often that cardiac catastrophe hits during a stressor. The phenomenon is quite well documented. Embedded in the list of categories of precipitants of sudden cardiac death is a particularly interesting one: triumph or extreme joy. Extreme anger and extreme joy have different effects on [various body systems]; but with regard to the cardiovascular system, they have fairly similar effects. Chapter 4 ========= 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, stimulates the transport of fatty acids into fat cells, [and] stimulates glycogen and protein synthesis. We even 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, is is the parasympathetic nervous system that stimulates the anticipatory secretion... Stress response: * Turn up the activity of the sympathetic nervous system, turn down the parasympathetic nervous system, and down goes insulin secretion. * Secrete glucocorticoids, which block the transport of nutrients into fat cells. This counteracts the effects of any insulin still floating around. * Your body reverses all the storage steps through the release of the stress hormones: glucocorticoids, glucagon, epinephrine, norepinephrine. These cause triglycerides to be broken down in the fat cells and, as a result, free fatty acids and glycerol pour into the circulatory system. The same hormones trigger the degradation of glycogen to glucose in cells throughout the body, and glucose is then flushed into the bloodstream. These hormones also cause protein in non-exercising muscles to be converted back into individual amino acids. * Your body shunts the circulating amino acids into the liver, where they are converted to glucose. The liver can also generate new glucose, a process called gluconeogenesis... In effect, you are penalized if you activate the stress-response to often: you wind up expending so much energy that, as a first consequence, you tire more readily--just plain old everyday fatigue. As a second consequence, your muscles can waste away, although this rarely happens to a significant degree. Finally, [this puts more crud and LDL cholesterol into your bloodstream, which increases risks of cardiovascular disease.] Stress, including psychological stress, can wreak havoc with metabolism control in a juvenile diabetic. [Stress is also involved in increased risk of developing juvenile diabetes.] Therefore, this is a population in which successful stress management is critical. [Adult onset diabetes, type 2, insulin resistant diabetes involves] the failure of cells to respond to insulin. And if the adult-onset diabetes goes on for a while, an additional, miserable development can occur. Your body has become insulin resistant. Your pancreas responds by secreting even more insulin than usual. You're still resistant. So the pancreas secretes even more. Back and forth, your pancreas pumping out ever higher levels of insulin, trying to be heard. Eventually, this burns out the insulin-secreting cells in the pancreas, actually destroying them. [Thus type 2 diabetes can turn into type 1 diabetes.] What should be obvious over the last two chapters is that your metabolic and cardiovascular systems are intimately interconnected. Metabolic syndrome (also known as Syndrome X) is a new term recognizing this interconnection. Take more than a thousand study subjects, all over age 70, none of whom are certifiably sick--that is to say, where none of these [individual] measures are technically abnormal. Now, see how they're doing on all those Metabolic syndrome measures [put together]. Throw in some other measures as well... Combine the insights of these measures mathematically and, collectively, this information was significantly predictive of who was going to have heart disease, a decline in cognitive or physical functioning, and morality, far more predictive than subsets of those variables alone. Chapter 5 ========= The official numbers are that stress makes about two thirds of people hyperphagic (eating more) and the rest hypophagic. The confusing issue is that one of the critical hormones of the stress-response stimulates appetite, while another inhibits it. CRH inhibits 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. 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. Glucocorticoids not only increase appetite but, as an additional means to recover from the stress response, also increase the storage of the ingested food. It turns out that when glucocorticoids stimulate fat deposition, they do it preferentially in the abdomen... ... lots of fat is a predictor for Syndrome X. But it turns out that a large WHR (waist-hip ratio) is an even better predictor of trouble than being overweight [alone] is. run-of-the-mill mammals, including us, expend 10-20 percent of their energy on digestion. ["organic" gastro-intestinal disorders are caused by physical damage, i.e. ulcers] ["functional" gastro-intestinal disorders happen even though all the organs are in good shape.] The most common functional gastro-intestinal disorder is irritable bowel syndrome (IBS), which involves abdominal pain (particularly just after a meal) that is relieved by defecating... 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. 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 intestines are duodenal (the most common of peptic ulcers). And this bacterium [Heliobacter pylori] 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 Heliobacter--it is probably the most common chronic bacterial infection in humans. The trouble is that one bacterium can't be the whole story. For starters, up to 15 percent of duodenal ulcers form in people who aren't infected with Heliobacter, 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 Heliobacter pylori plus something else. An analysis of the entire literature shows that somewhere between 30 to 65 percent of peptic ulcers have psychosocial factors (i.e., stress) involved. ... after you control for [lifestyle risk factors such as drinking], stress itself still causes a two to threefold increase in the risk of an ulcer. Chapter 7 ========= 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 birth control. Breast feeding causes prolactin secretion. There is a reflex loop that goes straight from the nipples to the hypothalamus. If there is nipple stimulation for any reason (in males as well as females), the hypothalamus signals the pituitary to secrete prolactin. And as we now know, prolactin in sufficient quantities causes reproduction to cease. The problem with nursing as a contraceptive is how it is done in Western societies. During the six months or so that she breast-feeds, the average mother in the West allows perhaps half a dozen periods of nursing a day, each for 30 to 60 minutes. Each time she nurses, prolactin levels go up in the bloodstream within seconds, and at the end of the feeding, prolactin settles back to pre-nursing levels fairly quickly. This is not how most women on earth nurse. A prime example emerged a few years ago in a study of hunter-gatherer Bushmen in the Kalahari Desert of southern Africa. Bushmen males and females have plenty of intercourse, and no one uses contraceptives, but the women have a child only about every four years. Instead, the lengthy interval is probably due to their nursing pattern. This was discovered by a pair of scientists, Melvin Konner and Carol Worthman. 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. The young child is carried in a sling so he [or she] can nurse easily and frequently. At night, he [or she] sleeps his [or her] mother and will nurse every so often without even waking her. Once the kid can walk, he'll [or she'll] come running in from play every hour or so to nurse for a minute. 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. Chapter 8 ========= 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. Such acquired immunity is a pretty fancy invention, and it is found only in vertebrates. 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 involves generic antibodies that attack any microbe.] In chapter 1 ... I suggested that 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, [the immune system is not merely put on hold.] Instead, stress causes the active expenditure of energy in order to disassemble the preexisting immune system... you're PAYING, energetically, to take apart the immune system. During infections, the immune system releases the chemical messenger interleukia-1, which among other activities stimulates the hypothalamus to increase CRH. CRH stimulates the pituitary gland to release ACTH, which then causes adrenal release of glucocorticoids. These in turn suppress the immune system. In other words, under some circumstances, the immune system will ask the body to secrete hormones that will ultimately suppress the immune system. It is probably not just an accident. It turns out that during the first few minutes (say, up to about 30) after the onset of a stressor, you don't uniformly suppress immunity--you enhance many aspects of it. [But] when stress goes on longer... By the one-hour mark, more sustained glucocorticoid and sympathetic activation begins to have the opposite effect, namely, suppressing immunity. ... if you have a stressor that goes on for too long, an adaptive decline back to baseline can overshoot and you get into trouble. Thus, early on during exposure to a stressor, glucocorticoids and other stress-responsive hormones transiently activate the immune system, enhancing immune defenses, sharpening them, [and] redistributing immune cells to the scenes of infectious battle. Because of the dangers of the system's overshooting into autoimmunity, more prolonged glucocorticoid exposure begins to reverse these effects, bringing the system back to baseline. And during the pathological scenario of truly major, sustained stressors, immunity is suppressed below baseline. Insofar as autoimmune diseases involve overactivation of the immune system, the most time-honored treatment is to put people "on steroids"--to give them massive amounts of glucocorticoids [stress hormones--to suppress the immune system.] Stress is among the most reliable, if not the most reliable, factor to worsen autoimmune diseases. ... it seems as if numerous transient stressors increase the risk of autoimmunity--for some reason, repeated ups and downs ratchet the system upward, biasing it toward autoimmunity. [Also, having inadequate "cool-down" after each upswing] pushes the immune system upward into autoimmunity. The system apparently did not evolve for dealing with numerous repetitions of coordinating the various on-and-off switches, and ultimately something uncoordinated occurs, increasing the risk that the system becomes autoimmune. Herpes DNA contains a stretch that is sensitive to elevated glucocorticoid signals, and when levels are up, that DNA sensor activates the genes involved in coming out of latency. Epstein-Barr and varicella-zoster contain this glucocorticoid-sensitive stretch as well. [Stress accelerates tumor growth in lab animals.] Substitute glucocorticoids [for the stressors] and tumor growth is accelerated as well. And these glucocorticoids directly influence tumor biology through both immune and non-immune realms. The immune system contains a specialized class of cells (most notably, natural killer cells) that prevent the spread of tumors. Stress suppresses the numbers of circulating natural killer cells... 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. [angiogenesis] Glucocorticoids at the concentration generated during stress aid angiogenesis. When you rely on the rare prospective studies, there turns out not to be good evidence for a stress-cancer link. The cancer-prone personality, we're told, is one of repression--emotions held inside, particularly those of anger. This is a picture of an introverted, respectful individual with a strong desire to please--conforming and compliant. Hold those emotions inside and it increases the likelihood that out will come cancer, according to this view. Chapter 9 ========= Pain is useful to the extend that it motivates us to modify our behavior 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. Some pain receptors carry only information about pain (for example, the ones corresponding to cuts); others carry information about both pain and everyday sensations. A striking aspect of the pain system is how readily it can be modulated by other factors. The strength of a pain signal, for example, can depend on what other sensory information is funneled through the spine at the same time. This, it turns out, is why it feels so great to have a massage when you have sore muscles. The brain's interpretation of pain can be extremely subjective. This is because the brain is not a mindless pain-ometer, simply measuring units of ouchiness. But most of what the brain's responses to pain are about is generating emotional responses and giving contextual interpretations about the pain. How much pain you feel and how unpleasant that pain feels, can be two separate things. 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 [itself] responds to pain information. Soon they found exactly what they were looking for: endogenous compounds with chemical structures reminiscent of the opiate drugs. They turned out to come in three different classes: ekephalins, dynorphins, and the most famous of them all, endorphins (a contraction for "endogenous morphines"). (Opiate refers to analgesics not normally made by the body... Opioid refers to those made by the body itself.) Furthermore, scientists noted that Chinese veterinarians used acupuncture to do surgery on animals, thereby refuting the argument that the painkilling characteristic was one big placebo effect... Acupuncture stimulates the release of large quantities of endogenous opioids, for reasons no one really understands. Endogenous opioids turn out to be relevant to explaining placebos as well. In 1977 Roger Guillemin demonstrated that stress triggers the release of one type of endorphin, beta-endorphin, from the pituitary gland. [On the other hand, stress-induced hyperalgesia causes pain to seem worse. Hyperalgesia] 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. Stress-induced analgesia does not go on forever, and the best evidence ascribes this to depletion of opioids. You are not permanently out... but it takes a while for supply to catch up with demand. [The pain will return.] Chapter 10 ========== Stress can enhance memory. Stress can disrupt memory. Short-term stressors of mild to moderate severity enhance cognition, while major or prolonged stressors are disruptive. [Types of memory: short-term, long-term, and remote memory i.e. early childhood memories.] Explicit (also known as declarative) memory concerns facts and events, along with your conscious awareness of knowing them... Implicit memories can be used even without having to think consciously of them. Implicit procedural memories are about skills and habits, about knowing how to DO things. Memories can be transferred between explicit and implicit forms of storage. Memory can be dramatically disrupted if you force something that's implicit into the explicit channels. "muscle memory" is implicit procedural memory. The sympathetic nervous system pulls this off [during stress] by indirectly arousing the hippocampus into a more alert, activated state, facilitating memory formation. This involves the amygdala. [Memory formation uses a lot of energy.] The sympathetic nervous system helps by mobilizing glucose into the bloodstream and increasing the force with which blood is being pumped into the brain. In addition, a mild elevation in glucocorticoid levels helps memory as well. This occurs in the hippocampus, where those moderately elevated glucocorticoid levels facilitate long-term potentiation. Finally, there are some obscure mechanisms by which moderate, short-term stress makes your sensory receptors more sensitive. ... just a few days of high doses of synthetic glucocorticoids impairs explicit memory in healthy volunteers. It turns out that the hippocampus has large amounts of two different types of receptors for glucocorticoids. Critically, the hormone is about ten times better at binding to one of the receptors (thus termed a "high-affinity" receptor) than the other. What that means is that if glucocorticoid levels rise only a little bit, most of the hormone effect in the hippocampus will be mediated by that high-affinity receptor. In contrast, it is not until you are dealing with a major stressor that the hormone activates a lot of the "low-affinity" receptor. And, logically, it turns out that activation of the high-affinity receptor enhances long-term potentiation, while activation of the low-affinity one does the opposite. ... the amygdala plays a central role in the types of emotional memories involved in anxiety. Activation of [the amygdala during major stressors] seems to be a prerequisite for stress to disrupt hippocampal functionality. Actually, the evidence for new neurons in the adult brain [adult neurogenesis] was first reported in the 1960s by a handful of heretics who were generally ignored or hounded out of science. The field has finally caught up with them. The hippocampus is one of only two sites in the brain where these new neurons originate. The other region supplies new neurons to the olfactory system; for some strange reason, neurons that process odors constantly die off and have to be replaced. It turns out that there is a huge burst in the production of those new olfactory neurons early during pregnancy. They are fully on line just around the time of birth, and the scientists who discovered this speculated that these new olfactory neurons are tagged for the task of imprinting forever on the smell of your offspring... Finally, there is now evidence that truly prolonged exposure to stress or glucocorticoids can actually kill hippocampal neurons. Chapter 11 ========== Not getting enough sleep is a stressor; being stressed makes it harder to sleep. Yep, we've got a dread vicious cycle on our hands. Sleep is not a monolithic process... Instead, there are different types of sleep--shallow (also known as stages 1 and 2) sleep, where you are easily wakened. 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 90 minutes... [During slow wave sleep, parts of the brain slow down.] Interestingly, regions involved in the consolidation and retrieval of memories don't have much of a decrease in metabolism. ... deep slow wave sleep is when energy restoration occurs. Overall, there's an increase in activity [during REM sleep]. The frontal cortex is the nearest thing we have to a superego. The frontal cortex does all this disciplining you by inhibiting that frothy, emotional limbic system. [self-control] During REM sleep, metabolism in the frontal cortex goes way down, disinhibiting the limbic system to come up with the most outlandish ideas. Some extremely difficult studies that make me queasy just to contemplate deprive people or [other] animals of REM sleep preferentially, and the study subjects [fall apart] much faster than they do for the equivalent amount of deprivation of other types of sleep. The marked increase in metabolic activity during REM sleep, and in some of the most inhibited areas of the brain during waking, have suggested to some a sort of "use it or lose it" scenario in which dreaming gives some exercise to otherwise underutilized brain pathways. 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 [you might have thought was forgotten]. No one's sure what CIF (corticotropin inhibiting factor) is, or if it really exists, but there's some decent evidence that CIF is a brain chemical that helps bring on slow wave sleep (called "delta sleep-inducing factor"). Thus, sleep deeply, and you turn off glucocorticoid secretion. About an hour before you wake up, levels of CRH, ACTH, and glucocorticoids begin to rise. This is not just because merely rousing from slumber is a mini-stressor, but because those rising stress hormone levels play a role in terminating sleep. Chapter 12 ========== In many ways, aging can be defined as the progressive loss of the ability to deal with stress... This can be stated more rigorously by saying that many aspects of the bodies and minds of old organisms work fine, just as they do in young ones, so long as they aren't pushed. [If you give young and old people IQ tests] and give them lots of time to complete the test, there is little difference. As you stress the system--in this case, by making the subjects race against a time limit--scores fall... much further among older people. The bizarre thing is that this sequence of events not only occurs in five species of salmon, but also among a dozen species of Australian marsupial mice; cut out their adrenal glands, however, and they too keep living. Pacific salmon and marsupial mice are not close relatives. At least twice in evolutionary history, completely independently, two very different sets of species have come up with the identical trick: if you want to degenerate very fast, secrete a ton of glucocorticoids. The elevated glucocorticoid levels of old age, therefore, arise because of a problem with feedback regulation in the damaged hippocampus. Why are neurons damaged in the hippocampus? It's glucocorticoid exposure... Chapter 13 ========== We humans also deal better with stressors when we have outlets for frustration... A central feature of an outlet being effective is if it distracts from the stressor. But, obviously, more important is that it also be something positive for you... Another option is to take it out on an innocent bystander. * Social support networks and friends reduce stress. * Predictability makes stressors less stressful. * Control helps. Loss of control and lack of predictive information are closely related. The common theme is that the organism is subjected to novelty. * A perception of things worsening makes it more stressful. Chapter 14 ========== The defining feature of a major depression is loss of pleasure. Anhedonia [also known as dysphoria] is the inability to feel pleasure. The strikingly different subtypes of depression and their variability suggest not just a single disease, but [multiple] diseases that have different underlying biologies. The pleasure pathway seems to make heavy use of dopamine as a neurotransmitter. The strongest evidence for this is the ability of drugs that mimic dopamine, such as cocaine, to act as euphoriants. ACC: anterior cingulate cortex. And the emotions that the ACC is involved in seem to be negative ones. Induce a positive state in someone and ACC metabolism decreases. In contrast, if you electrically stimulate the ACC in people, they feel a shapeless sense of fear and foreboding. ...its resting level of activity tends to be elevated in people with a depression... Interestingly, the amygdala seems to be hyperactive in depressives as well. Specifically, activation of the left PFC (pre-frontal cortex) is associated with positive moods, and activation of the right PFC, with negative. [This is true in both humans and monkeys.] Glucocorticoid levels are typically abnormal in people who are clinically depressed. [It has been shown that adrenal steroidogenesis inhibitors lessen depression, but these drugs can have some nasty side-effects.] Chapter 15 ========== Thus among some male baboons, there are at least two routes for winding up with elevated basal glucocorticoid levels, independent of social rank--an inability to keep competition in perspective and social isolation. When it comes to psychological disorders, it seems that increases in the catecholamines have something to do with still trying to cope and the effort that involves, where the overabundance of glucocorticoids seems more a signal of having given up on attempting to cope. [Psychological stress seems to involve the hippocampus.] Instead, anxiety and fear conditioning are the province of a related structure, the amygdala. [The amygdala is about the interpretation of pain.] Remarkably, the amygdala gets sensory information before that information reaches the cortex and causes conscious awareness of the sensation... [Stress and glucocorticoids make the amygdala more excitable.] This final section is about a newly recognized version of an overactive stress-response. And it's puzzling. [These people are objectively pretty functional and well adjusted.] Yet, these people (comprising approximately 5 percent of the population) have chronically activated stress responses. The people in question are said to have "repressive" personalities, and we have all met someone like them. In fact, we usually regard these folks with a tinge of envy--"I wish i had their discipline; everything seems to come so easily to them. How do they do it?" These are the archetypal people who cross all their t's and dot all their i's. They describe themselves as planners who don't like surprises, who live structured, rule-bound lives... Not surprisingly, they don't like ambiguity and strive to set up their world in black and white... They keep a tight lid on their emotions. Stoic, regimented, hardworking, productive, solid folks who never stand out in a crowd... Intertwined with those characteristics is a peculiar lack of emotional expression. Yet even after you cross the anxious self-deceivers off the list, there remains a group of people with tight, constrained personalities who are truly just fine... But they have overactive stress responses. And these... exact a price. Davidson and Andrew Tomarken of Vanderbilt University have used electroencephalographic (EEG) techniques to show unusually enhanced activity in a portion of the frontal cortex of repressors... it takes a lot of [mental] work... Chapter 16 ========== Pleasure is the anticipation of a reward; from the standpoint of dopamine, the reward is almost an afterthought. [Dopamine fuels the behavior.] ...the strength of these pathways can change, just like any other part of the brain. This is how gratification postponement works--the core of goal-directed behavior is expectation. Soon we're foregoing immediate pleasure in order to get good grades in order to get into a good college in order to get a good job in order to get into the nursing home of our choice. [When there is simply a high probability of reward rather than certainty] there is even greater release of dopamine. [intermittent reinforcement] As we saw, experience moderate and transient stress, and memory, synaptic plasticity, and immunity are enhanced. Same thing here [with maximized dopamine release. Moderate but not excessive stress makes things more pleasurable.] We have a name for such transient stress. We call it "stimulation." If you flood a synapse with a gazillion times more of a neurotransmitter than is usually the case, the recipient neuron has to compensate by becoming less sensitive. This is the addiction cycle of escalating drug use. Early on, addiction is about "wanting" the drug, anticipating its effects, and about how high those dopamine levels are when they're pouring out in a drug-induced state. With time there's the transition to "needing" the drug, which is about how low the dopamine lows are without the addiction. The stranglehold of addiction is when it is no longer the issue of how good the drug feels, but how bad its absence feels. Chapter 17 ========== > Medicine is a social science, and politics nothing but medicine > on a large scale. Physicians are the natural attorneys of the > poor. --Rudolph Virchow The purpose of this chapter is to show how your place in society, and the sort of society it is, can leave an imprint on patterns of disease while you are alive, and to show that part of understanding this imprint incorporates the notion of stress. As a final variable, it is not just rank that is an important predictor of the stress-response, not just the society in which the rank occurs, or how a member of the society experiences both; it's also personality... If you want to see an example of chronic stress, study poverty. ... All these hardships suggest that low socioeconomic status (SES--typically measured by a combination of income, occupation, housing conditions, and education) should be associated with chronic activation of the stress-response. Only a few studies have looked at this, but they support this view. ...if you have a bunch of people of the same gender, age, and ethnicity and you want to make some predictions about who is going to live how long, the single most useful fact to know is each person's SES. If you want to increase the odds of living a long and healthy life, don't be poor. Findings such as these go back centuries. ...the diseases that people were dying of most frequently a century ago are dramatically different from the most common ones now. Different causes of death, but same SES gradient, same relationship between SES and health. Which tells you that the gradient arises less from disease than from social class. Thus the "roots [of the SES health gradient] lie beyond the reach of medical therapy." [Being poor sets you up for poor health more than poor health sets you up for being poor.] In the United States, poor people (with or without health insurance) don't have the same access to medical care as do the wealthy. As one example of this, a 1967 study showed that the poorer you are judged to be (based on the neighborhood you live in, your home, your appearance), the less likely paramedics are to try to revive you on the way to the hospital. In more recent studies, SES influenced your likelihood of receiving physical, occupational, or speech therapy, and how long you waited until undergoing surgery to repair the damaged blood vessel that cause the stroke. In a place like England, the SES gradient has gotten worse over this century, despite the imposition of universal health care allowing everyone equal health care access. It's not only the case that only poor people are less healthy than everyone else. Instead, for every step lower in the SES ladder, there is worse health, and the lower you get in the SES hierarchy, the bigger is each step of worsening health. ...the gradient [also] exists for diseases that have nothing to do with access [to health care. Perhaps this is related to the complete lack of preventative medicine.] Poorer people in westernized societies are more likely to drink and smoke excessively. These excesses take us back to the last chapter and having trouble "just saying no" when there are few yes's. [crap life syndrome] Moreover, the poor are more likely to have an unhealthy diet--in the developing world, being poor means having trouble affording food, while in the western world, it means having trouble affording HEALTHY food. Thanks to industrialism, fewer jobs in our society involve physical exertion and, when combined with the costs of membership in some tony health club, the poor get less exercise. They are more likely to live near a toxic dump, be mugged, have inadequate heat in the winter, live in crowded conditions (thereby increased exposure to infectious diseases). The list seems endless, and they all adversely impact health. Being poor is statistically likely to come with another risk factor--being poorly educated. Statistically, being better educated predicts that your community of friends and relatives is better educated as well, with those attendant advantages. [However] For the same risk factors and the same lack of protective factors, throw in poverty and you're more likely to get sick. So differential exposure to risk factors or protective factors does not explain a whole lot. ...the SES gradient is not really about a distribution that bottoms out at being poor. It's not about being poor. It's about feeling poor, which is to say, it's about feeling poorer than others around you. ...what someone thinks and feels their SES is their "subjective SES." [Subjective SES] is at least as good a predictor of these health measures as is one's actual SES, and, in some cases, it is even better. Adler shows that subjective SES is built around education, income, and occupational position, plus satisfaction with standard of living, and feeling of financial security about the future. But thanks to urbanization, mobility, and the media that makes for a global village, something absolutely unprecedented can now occur--we can now be made to feel poor, or poorly about ourselves, by people we don't even know. ...in societies that have more income equality, both the poor and the wealthy are healthier than their counterparts in a less equal society with the same average income. What Kawachi shows is that the more income inequality in a society, the lower the social capital, and the lower the social capital, the worse the health. Findings such as these make perfect sense to Wilkinson. In his writings, he emphasized that trust requires reciprocity, and reciprocity requires equality. In contrast, hierarchy is about domination, not symmetry and equality. By definition, you can't have a society with both dramatic income inequality and lots of social capital. So income inequality, minimal trust, [and] lack of social cohesion all go together. How does lots of social capital turn into better health throughout a community? Less social isolation. More rapid diffusion of health information. Potentially, social constraints on publicly unhealthy behaviors. Less psychological stress. Better organized groups demanding better public services (and, related to that, another great measure of social capital is how many people in a community bother to vote). ...the more economically unequal a society, the more crime. Critically, income inequality is consistently a better predictor of crime than poverty per se. ...poverty amid plenty predicts more crime--but not against the wealthy. The have-nots turn upon the have-nots. If you want to improve health and quality of life, and decrease the stress, for the average person in a society, you do so by spending money on public goods--public transit, safe streets, clean water, public schools, universal health care. The bigger the income inequality is in a society, the greater the financial distance between the wealthy and the average. The bigger [this distance], the less benefit the wealthy will feel from expenditures on the public good. This secession of the wealthy pushes toward private affluence and public squalor. And more public squalor means more of the daily stressors and allostatic load that drives down health for everyone. Agriculture is a fairly recent human invention, and in many ways it was one of the great stupid moves of all time. Hunter-gatherers have thousands of wild sources of food to subsist on. Agriculture changed all that, generating an overwhelming reliance on a few dozen domesticated food sources, making you extremely vulnerable to the next famine, the next locust infestation, the next potato blight. Agriculture allowed for the stockpiling of surplus resources and thus, inevitably, the unequal stockpiling of them--stratification of society and the invention of classes. Thus, it allowed for the invention of poverty. Chapter 18 ========== ...amid a population of, say, 50 subjects there have to be 6 subjects where Something Or Other is improving with age. Their kidney filtration rates have gotten BETTER, their blood pressures have DECREASED, they do BETTER on memory tests. This pattern used to be a statistical irritant to gerontologists. If a rat is handled [physical touch] during the first few weeks of its life, it secretes less glucocorticoids as an adult. Among this population [in George Vaillant's research], which subset has had the greatest health, contentment, and longevity in old age? A subset with an array of traits, apparently before the age of 50: no smoking, minimal alcohol use, lots of exercise, normal body weight, absence of depression, a warm, stable marriage, and a mature, resilient coping style (which seems built around extroversion, social connectedness, and low neuroticism). Findings like these have emerged from other studies. Another literature shows the tremendous gerontological benefits of being respected and needed in old age. [This reminds me of Malidoma Some's writing about tribal elders and children taking care of each other.] We can change the way we cope, both physiologically and psychologically. Examples: exercise and psychotherapy. Sheer repetition of certain activities can change the connection between your behavior and activation of your stress response. [Studies show that when you allow patients to self-medicate, the total amount of painkillers consumed decreases. Control and predictability help to manage the pain.] In one study, residents of a nursing home were given more responsibility for everyday decision making. They were made responsible for choosing their meals for the next day, signing up in advance for social activities, picking out and caring for a plant in their room... People became more active--initiating more social interactions--and describing themselves in questionnaires as happier. Their health improved, as rated by doctors unaware of whether they were in the increase-responsibility group or the control group. Most remarkable of all, the death rate in the former group was half that of the latter. [Even just a moderate increase in control produces great results.] When the staff present encouraged them, performance improved; when the staff present [merely] helped them, performance decline. These studies generated some simple answers to coping with stress that are far from simple to implement in everyday life. They emphasize the importance of manipulating feelings of control, predictability, outlets for frustration, social connectedness, and the perception of whether things are worsening or improving. "More control, more predictability, more outlets, more social support" is not some sort of mantra to be handed out indiscriminately, along with a smile button. * Exercise enhances mood and blunts the stress response only for a few hours to a day after the exercise session. * Exercise is stress reducing as long as it is something you actually want to do... * The studies are quite clear that aerobic exercise is better for your health. * Exercise needs to occur on a regular basis and for a sustained period. * Too much can be as bad as too little. When done on a regular, sustained basis (that is to say, something close to daily, for 15 to 30 minutes at a time), meditation seems to be pretty good for your health, decreasing glucocorticoid levels, sympathetic tone, ... An overabundance of information can be stressful as well. Having an illusory sense of control in a bad setting can be so pathological that one version of it gets a special name in the health psychology literature. As Sherman James defines it, John Henryism involves the belief that any and all demands can be vanquished, so long as you work hard enough. This is the epitome of individuals with an internal locus of control--they believe that, with enough effort and determination, they can regulate all outcomes. What's so wrong with that? Nothing, if you have the good fortune to live in the privileged, meritocratic world in which one's efforts truly do have something to do with the reward one gets, and in a comfortable, middle-class world, an internal locus of control does wonders. However, in a world of people born into poverty, John Henryism is associated with a market risk of hypertension and cardiovascular disease. Often, one of the strongest stress-reducing qualities of social support is the act of GIVING social support, to be needed. What's religiosity versus spirituality? The former is about an institutionalized system with a historical precedent and a lot of adherents; the latter is more personal. When comparing religious people with people who define themselves as spiritual but without a religious affiliation, the former tend to be older, less educated, and lower in socioeconomic status, with a higher percentage of men. So religiosity and spirituality can be very different things. But despite that, the health literature says roughly similar things about both... So religiosity is a tough subject to do real science on, something the best people readily point out. Another thing that folks like Sloan and Thoresen agree upon is that when you do see a legitimate link between religiosity and good health, you don't know which came first. [correlation versus causation] And once you've [controlled for lifestyle factors such as drinking and smoking], Thoresen and Sloan are still mostly in agreement, which is that religiosity does predict health to some extend in a few areas of medicine. Moreover, deeply religious people (by their own assessment) derive no more of what health benefits there are than the less deeply religious. [The effects] are more about healthy people staying healthy than sick people staying alive and recovering faster. In the face of some stressor, "coping" can take a variety of forms. Implicit in switching to the optimal strategy for the particular circumstance is having the cognitive flexibility to switch strategies. Coping responses built around fixed rules and flexible strategies. I would apple the 80/20 rule to stress management: 80 percent of the stress reduction is accomplished with the first 20 percent of effort. But once you sincerely want to change, the mere act of making an effort can do wonders. author: Sapolsky, Robert M. detail: LOC: QP82.2.S8 S266 tags: book,health,non-fiction,science title: Why Zebras Don't Get Ulcers Tags ==== book health non-fiction science