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       # 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.
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       tags:   book,health,non-fiction,science
       title:  Why Zebras Don't Get Ulcers
       
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