Stress and Health: Why Zebras Don't Get Ulcers

• “Basic, normal mammalian death: you drink some contaminated water and you’re dead from dehydration two days later. And what do we do? We spend 80 years having our bodies go to hell on us”
• Leading causes of death in 1900?
  • childbirth: women between 20-40 the single riskiest thing you could do was give birth
  • influenza, pneumonia, tuberculosis: In 1918, the worst winter of WWI, you had better chances of surviving if you were sent to the front lines than the chances you had if you caught the flu
• 20,000 years ago, typical big medical mistakes had a feedback cycle of death/illness within 3 days. Nowadays, the typical big mistakes may shorten your life by 20 years (or might not!)
• All these diseases that people die of nowadays are accrued over years of lifestyle choices, and all of these lifestyle choices (and the diseases themselves) are made worse by stress.
• [7:05] “Most of us in this room will have the profound westernized luxury of dropping dead someday of a stress-related disease.”
• Definitions
  • Homeostasis: being in balance (glucose levels, body temperature, …)
  • Stressor: anything in the outside world that knocks you out of homeostatic balance
• Stress responses try to restore homeostatic balance.
• In the animal kingdom, this can be when an animal is starving and needs the next hunt to be successful, or when the animal is under attack. So a radical stress response is almost always useful.
• A stressor can also be when your body thinks you’re about to be knocked out of homeostatic balance, and this can also be adaptive.
  • But if you think you’re about to be knocked out of homeostatic balance all the time, it’s maladaptive and there are medical terms to describe that behavior: you’re being neurotic, anxious, paranoid.
• “The critical point of the whole thing is we turn on the exact same stress response as that zebra running for its life or lion running for a meal, and we turn it for purely psychological reasons. And that’s the punchline of the entire field, that’s not what it evolved for. For 99% of beasts on this planet, stress is 3 minutes of screaming terror after which it’s either over with or you’re over with. And what do we do, we turn on the same stress response for 30 year mortgages.”
• “This is a system that evolved for dealing with short-term physical crises, and we turn it on for chronic psychosocial stress.”
• Why should your body turn on the same stress response no matter what kind of stressor you’re receiving? How is that better than a response tuned to the momentary need?
  • Originally researched by Hans Selye in the 1930s, who started the field
  • Was trying to research something about pancreas in rats. Discovered that all rats in his study had ulcers, and so do the control group.
  • It turns out he was just really bad at injecting rats, and chasing them to inject them was causing them major stress
  • He hypothesized there was some non-specific response of the body to generalized unpleasantries
  • So he ran new experiments where he kept exposing rats to different sorts of stressors, and found that indeed, rats experience the same kinds of symptoms as long as the circumstances are bad enough.
• How does this make sense?
  • Metabolic: The stress response mobilize as much energy as possible, trying to get glucose out of any place it’s stored
    • “It’s like you go to the bank and you empty out the savings accounts and turn it into cash”
  • Cardiovascular: In order to make the energy usable, it has to be dispersed. Increased cardiovascular tone, increase blood pressure, heart rate, increase breathing rate
  • Turn off all the long-term building projects (digestion, growth, reproduction and other “big optimistic things”)
    • “If there’s a tornado due this afternoon, you don’t spend the day outside gardening.”
    • “big, expensive, optimistic things to be doing with your body. And this is no time for it, you know. You’re running for your life, there’s a lion two steps behind you, you ovulate some other time. Don’t do it right now. Hit puberty next week. Grow antlers some other day. Don’t even think about sperm. With the onset of stress, you shut down growth, you shut down tissue repair, every sex hormone on Earth disappears from the bloodstream. Do it later, if there is a later.”
  • Immune defenses go up
  • Sharpening of cognition, alertness, sensual acuity, & pleasure. Memory is sharpened.
• There are syndromes where a stress response doesn’t happen
  • Somebody with undiagnosed Addison’s disease could go running for the commuter bus in the morning and fall dead from hypoglycemic shock
• So what if you’re turning the stress response on too often, for too long, for purely psychosocial reasons?
• Selye’s theory, which unfortunately was very wrong, dominated the field for 40 years
  • Stressor knocks you out of balance, you turn on the stress response, you reestablish homeostatic balance, but the stressor goes on too long and you enter the “exhaustion phase”, where your body has run out of the tools it needs to continue mounting a stress response
  • “No organism on earth has ever been so stressed that it runs out of adrenaline. You don’t deplete the stress response. The problem is that after a while it’s not that your military is running out of ammunition. After a while you’re spending so much on your military that you don’t do health care or social services or education oooooany of that stuff. And like, after a while the stress response is more damaging than the stressor. Especially if the stressor was some psychological nonsense. Everything you’re doing here is pennywise and dollar foolish, it’s inefficient, it’s less than optimal. All of this is built around, it’s an emergency, it’s an emergency, fix later, grow later, don’t do it right now. And if every day is an emergency, you pay a price for it.”
• Bad effects of chronically mobilizing energy out of your storage sites
  • myopathy: atrophy of muscle
  • inefficiency
  • increased severity of adult onset insulin-resistant diabetes
• Bad effects from cardiovascular ramp-up
  • Hypertension, atherosclerosis
• “What […] happens requires you to have, like, arcane knowledge of high-school physics explaining why, like, toilet bowl plumbing wears out after a while. You got a tube, and you got fluid moving through the tube. And by definition if the fluid is moving through with more force–elevated blood pressure–you begin to get fluid turbulence pounding away on the walls of your blood vessels, causing little bits of pitting and scarring and tearing and then you get inflammation there and then that’s exactly where like glucose and like cholesterol and fat wants to glom onto to clog your arteries. Where’s the glucose and cholesterol and fat coming from? That’s the stuff you’re mobilizing into your circulation in the previous slide. So you get this synergistic double-whammy here between the metabolic stress response and the cardiovascular, setting you up for the number one killer in this country, cardiovascular disease.”
• This link between stress and heart disease is so solid that it accounts for type A personalities
• Type A personalities
  • First described in 1950s by cardiologists Friedman and Rosen, people who are time-pressured, hostile, impatient, with low self-esteem, and joyless striving
  • If this was your personality, you were more at risk of heart disease
  • In the 1980s, it was finally established through studies as an objective personality factor.
  • And being Type A is a bigger risk factor than smoking, obesity, elevated cholesterol levels
  • It turns out that the subset of type A features that accounts for all the additional risk is “toxic hostility”
  • How did those guys first figure out about type A personalities?
  • Meyer Friedman had this cardiology practice, and they were spending a fortune reupholstering the armchairs in the waiting room.
  • One month the usual upholsterer is on vacation, and a substitute comes in and says “what is wrong with your patients, this isn’t a normal wear pattern or degree of wear”. All the wear-and-tear on these chairs was at the front edges.
  • “This is somebody with type A personality, this is what they do to a chair when they’re waiting in the waiting room with their cardiologist to hear if there’s bad news or not. This is not just figuratively, but literally, sitting on the edge of your seat and squirming and clawing and all of that.”
  • Friedman was too type A to listen to the guy, and 5 years later when working with psychologists he remembered the upholstery thing.
• [28:55] Bad effects of shutting down digestion
  • Increased risk of ulcers, and impaired capacity to repair ulcers (remember Selye’s rats?)
    • Helicobacter Pylorus bacteria is responsible for ~90% of ulcers in the west
    • Only about 10% of people with the bacteria get ulcers. Lifestyle factors like stress permit the bacteria to lead to damage, and result in ulcers.
  • Increased fat deposition
• [30:50] Bad effects of growth suppression
  • Psychogenic dwarfism/psychosocial dwarfism/stress dwarfism
    • “All kids are are big long-term building projects”
    • No growth hormone, and no response to synthetic growth hormone
    • But if you look at their home life the
    • “[Poke] around in their background and often out comes some appalling psychological stressor. And the amazing thing is, get them out of that stressful setting–technical term do a parentectomy on them–and growth will resume at that point.”
    • Example of kid brought into pediatric unit, after a few months forms a normal relationship with one of his nurses and growth has resumed. The nurse goes on vacation and suddenly his levels of growth hormone have shot back down to zero. When she comes back, he starts growing again.
      • “The rate at which this child was depositing calcium in his bones could be entirely predicted by how safe and loved he was feeling in the world.”
    • This condition is considered to be very rare because of the degree of stress required, although very common in warzones, cultures that do severe rites of passage.
    • Peter Pan is referenced in every book about growth. J.M. Barry (the author of Peter Pan) grew up in Victorian England in the 1870s, sees beloved older brother killed in front of him. For the next 10 years his mother shuts herself in her bedroom, and the only thing she ever talked to him about was her little boy David who died as her perfect little boy, who never grew up to become a man who didn’t need his mother anymore. He stopped growing at age 8, height of 4'10" until death at 80, unconsummated marriage.
  • Increased risk of diabetes, hypertension, and obesity due to fetal metabolic programming
  • Osteoporosis in adults
• [37:45] Bad effects of reproductive suppression
  • In females, irregular cycles, loss of cycles, failure of implantation of a fertilized egg
    • Females secrete a little bit of androgens (male sex hormones) into the blood stream from the adrenal glands, ~5% as much as males would have
    • Females bodies have to get rid of it
    • There’s an enzyme in fat cells that converts them to estrogens
    • If you’re stressed, your fat stores deplete and you can’t do this conversion. So you get too little estrogen, and too much androgens
    • This is why starvation (including anorexia), and too much exercise, can stop ovulation
    • One study on Romanian Olympic gymnasts found they started menstruating at 19 (12.5 is the western average)
  • In males, decreased testosterone, erectile dysfunction
    • “Testosterone turns out to be this vastly overrated hormone. Like, basically all you need is, like, a thimble full of the stuff and a couple of sperm and you’re in business. You’ve got to knock out like 90% of a guy’s testosterone levels to seriously impair fertility. Stress, what does it do at its worst, only about a 60% decline. The problem during stress is not that testosterone levels go down, the problem is that penises go down”
    • [48:10] How do erections work?
      • Spinal cord (and autonomic nervous system) do a bunch of automatic stuff. The autonomic nervous system has two halves that work in opposition with one another.
      • Sympathetic nervous system: emergency, arousal, adrenaline, stress response, all hell breaking loose
      • Parasympathetic nervous system: calm vegetative functions, like napping or digesting food
      • In order to get an erection, the parasympathetic nervous system needs to be active.
      • But during the act of sex, usually there’s exertion and excitement, which are activating the sympathetic system more and more, until at some point you turn off the parasympathetic system entirely and ejaculate.
      • A stressed person accelerates the process, resulting in either erectile dysfunction or premature ejactulation
    • How can you tell the difference between organic impotency and psychogenic?
      • Male primates get REM sleep erections (though nobody knows why), so you monitor if these are still happening.
      • There’s even a dumb, cheap way of doing this: take a long string of postage stamps, lick them at one end, and wrap them around the penis. If they’ve torn open in the morning, the guy got an erection
• Loss of libido
• [48:15] Bad effects of immune system suppression
  • Increased risk of some infectious diseases
  • But NO increased cancer risk
• [51:25] Bad effects of propping up cognition & mood
  • Memory loss, disconnection of neuronal networks, inhibition of the birth of new neurons, endangerment of existing neurons in the hippocampus
    • People with PTSD often have nonreversible atrophy of the hippocampus correlated with the amount of trauma.
  • Increased anxiety, amygdaloid expansion
    • Atrophy of the hippocampus is correlated with depression and anxiety
    • Hippocampus does learning and memory.
    • Next to the hippocampus is the amygdala, which does fear and anxiety
    • As stress atrophies the hippocampus, it stimulates and grows the amygdala
    • People with PTSD have bigger amygdalas. They’re more likely to associate things with fear that don’t make sense, less likely to receive signals of safety.
  • Dopamine depletion leads to anhedonia leads to depression
• [54:15] Another interested stress-related disease: Idiopathic Alopecia Areata - a very rare condition where someone is so traumatized by an event that over the next few days their hair turns white and falls out.
• [54:45] Why do some bodies and some psyches deal with stress better than others?
  • We have literature that shows us the building blocks of psychological stress
  • Put a rat in a cage, give him a shock, and give a mild shock every once in a while, and that rat gets ulcers.
  • Put a rat alone in a cage that gets these shocks, and in a second cage put one rat that gets the same shocks, and a 3rd rat that gets no shocks whatsoever. Every time that 2nd rat gets a shocked, it can go to the other side of the cage and attack the 3rd rat, and it doesn’t get ulcers. “He has an outlet.”
  • Same experiment, but instead of a 3rd rat, a block of wood it can attack, and it doesn’t get ulcers. “He has a hobby.”
  • Same experiment, but 10 seconds before the shock, a warning light comes on that only the 2nd rat can see, and the 2nd rat doesn’t get ulcers.
  • Similar experiment, but with a lever in the 2nd rat’s cage. Prior to the experiment, the rat has been given shocks, and prior to the experiment pressing the lever reduced the probability or severity of shocks. Although during the experiment the lever has been disconnected. The 2nd rat doesn’t get ulcers. “He thinks he has control”
  • Shock a rat and in its cage is a rat it knows and likes, and after the shock they groom each other, and it doesn’t get ulcers.
    • “Wow, science has finally proven that friends are good for your health.”
    • “When you look at all of behavioral medicine and all of health psychology, there are two of the biggest predictors out there as to mortality rates across all diseases. The first one taps into every one of the factors on the slide, which is never, ever make the mistake of being born into a poor family. Because your health is going to pay for it the rest of your life. The link between health and socioeconomic status is very heavily mediated by stress. The second biggest predictor is, if you gotta choice in the matter, don’t be socially isolated.”
      • “If you look at the extremes of social isolation versus social affiliation, […] for the same disease impact, almost a threefold difference in mortality rate, and that’s after you control for stuff […].”
• [1:00:15] Psychological modifiers of the stress response: outlets for frustration; sense of predictability; sense of control; belief that things will improve; social support

Q&A

Coping strategy: expecting the worst, is this a bad strategy

• Yes, it’s bad.
• Usually you’re not lowering expectations to the worst, but to a moderately bad outcome, which you’re now overexpecting.
• Forcing yourself to feel the world is unpredictable, if you’re actually successful, is going to induce stress.

Is there a general sense of well-being that is the inverse of chronic stress?

• Selye had an idea that there was something called eustress, that’s a good kind of stress. Getting on a rollercoaster or whatever.
• What is a good stressor?
  • Not too extreme (not risky)
  • Not going to last too long
  • Occurring in an overall benevolent environment
• “We love to give up control and predictability, because we love being surprised in safe settings. What do we call that? We call that play, we call it stimulation […]. I mean what are dogs doing when they play? The dominant one crouches down and says okay, for the next whatever length of time I’m gonna sort of eliminate our dominance relationship, so you can put your teeth on my throat or my privates or whatever, and it’s gonna be okay, you’re safe now. Come and surprise me, and I’ll try to surprise you too. What we call the optimal amount of stress is stimulation. And in that regard, the opposite of play is not work, the opposite of play is depression.”

What’s increasing the incidence of depression?

• [1:07:05] Given that population-wide depression is increasing faster than genetic mutation, what do you think is driving this?
• The main leading predictor for increase in depression is adolescents and young adults having a depressive episode [since that increases the chances of episodes continuing or recurring]
• So the question is, what part of life at this age is more prone to bring on a depressive episode?
• It’s hard to believe that a typical american adolescent has a harder life than in the dustbowl or a medieval peasant
• The stressors we have are largely inventions of our lifestyle
• We have less sources of support
  • Reduced family stability
  • American society is focusing on being more mobile and more anonymous, so it’s less likely you have a robust network of friends
    • Moving across the country, working 24/7, that makes Silicon Valley. But then along comes 9/11 and you don’t know the names of any of your neighbors.

Does social media help or hurt?

• [1:10:10] “All things considered, and as the father of two teenagers, I think it’s basically awful, what it does. Because it opens up all sorts of venues. People and circumstances and things you never even knew existed before can now make you feel crappy about yourself and diminished and insecure and not adequate and not up to measure. And what it also does is train you to mistake, like, the most, like, fruit fly level of model systems of what passes for, like, human sociality, for actual, real, like, connectiveness.”

What should we do to reduce psychosocial stress?

• [1:11:10] The one that’s gained most in prominence is social support
• Social support seems to be the most effective
• But it’s a double-edged sword, because we too easily confuse acquaintanceship with real sustained social affiliation.
• What is clear is that there’s no difference between a significant other, a small group, or a big community
• At the same time, there is nothing more corrosive than finding a source of social support was just an acquaintance after all.
• recent study published in PNAS, a big long longitudinal study looking at how much social isolation impacts health. The gist of it: it’s terrible for you lifelong, hurts you when you’re young and old
  • quantitative measures: how many people do you talk to on a regular basis, how many people could you borrow money from
  • qualitative measures: assess on some scale how much support they get from people closest to them, how much strain they get
  • the first finding was that quality trumps quantity tremendously
  • if you have a choice between making a new supportive friend, or getting rid of a high-maintenance/high-strain friend, the source of a strain was more of an adverse effect on health.

Antidepressants

• [1:14:35] Do they work, and will we ever understand why they do/don’t
• On average, 1/3 of major depression patients fail to respond to the medication, and another 1/3 respond but give up on the drugs because of the side effects.
• The average clinician thinks they’re better than average, and believe in their intuition about what kind of patients respond to what treatments.
• And what we’re trying to treat is sometimes rooted in genuine large trauma, so a complete treatment seems naive: the idea that a single chemical can undo the hurt of your parents having died in a car crash and you stewing in that pain for years to decades.

How do I tell if I’m stressed too much or not?

• [1:19:10] “Well, if you have to ask, you are, is one possible answer.”
• What are the canaries in the coalmine?
  • Gastrointestinal troubles, trouble sleeping, (for females) irregular menstrual cycles, mood disruption/depression/anxiety/poor concentration

Do you think the complexity of modern living is out of whack with what are brains are suited to?

• “the most fundamentally bizarre thing we do, as a primate, that makes the least sense to other primates, and is most impactful and foundational to all of this is, more than any other primate, we encounter strangers, and we have anonymous interactions. Like, every rule about brain size or primates versus body size suggests that humans should be living in communites of about 150 people which is about the average for hunter-gatherer extended fusion fission communities there, and, obviously, life is very different.”
• “We do something that no other primate does, we encounter more strangers standing on line at Starbucks than, like, our hunter-gatherer ancestors would do in a lifetime. And we have more capacity to be both the perpetrator and a victim of an anonymous act than any other species.”
• Ara Norenzayan at University British Columbia has noted that only cultures large enough to start having regular interaction with strangers that the cultures start inventing “Moralizing Gods”, gods which care about what humans are doing and punish bad acts
  • The idea is that in cultures this large, religion becomes a manner of bundling up norms. So that even if you meet a stranger, even though you don’t know their motives you retain more predictability about how they’ll treat you.