"Why Zebras Don't Get Ulcers: Stress and Health" by Dr. Robert Sapolsky

0:00 [MUSIC] So, Robert Sapolsky was my professor when we were students at Stanford University, many moons ago. And Robert made a huge influence on my wanting to be a scientist. He was simply the most influential and

0:46 outstanding, compelling professor at stanford, because of the way he connected with his students. And because of his incredible gift at lecturing, which you're all about to witness, and as you might imagine Robert has quite a number of impressive accomplishments in his career -- including the MacArthur Genius Fellow, loads of highly influential scientific articles, and research awards. But perhaps one of his greatest accomplishments are the books that have been so incredibly popular and so impactful to so many people that he's written. My personal favorites are "The Trouble with Testosterone: a Primates Memoir" and "Why Zebras Don't Get Ulcers," which is the topic of today's lecture. And so let's please all join me in welcoming Dr. Robert Sapolsky to the stage. [Applause]

1:40 Well, let me start off by saying actually these lights only give me a dim impression that there's a lot of primates out there. So i'm not entirely sure what I'm seeing here. But let me start off by thanking Justin and Peter. It is a delight to be here and a delight to see one's ex-students flourishing and all that sort of stuff, amid making me feel very elderly. Okay. So let me start off, I just got here a couple of hours ago. So I pretty much don't know anyone here. So i feel empowered to ask all sorts of invasive personal questions of you guys. Okay. How many of you here have a family history of heart disease, cancer, high blood pressure,

2:27 ulcers, stroke? Well, there's a hand there that's not even going down between the questions. Okay. That is not good. How many of you have a family history of somebody with a really bad case of leprosy? No hands. How about that cousin you're stuck sitting next to with thanksgiving, the one going to the bathroom every 10 minutes because of the dysentery? Not that either. How about that extra special relative who's just teeming with liver parasites the size of your fists? Not much there either. And, all things considered, this is not very surprising. Very few of us in this room seriously worry about smallpox or scarlet fever. Few of us gets malaria during the rainy season.

3:14 Few of our mothers died in childbirth. Nobody in this room is malnourished. We're not like normal animals. We don't get sick the way normal animals do. We don't die the way they do. 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. So we do. Oh great! I've got to listen to what for the next hour? This is actually fabulous news, because this is westernized disease for the most part. We are not plagued by infectious diseases, diseases of poor nutrition, poor hygiene. Instead, we live well enough and long enough to slowly fall apart over time. and this is a magnificent advance in the human experience

3:59 okay just to give you a sense of it like a little more than a century ago 1900 what do you think were the leading causes of death in the united states tuberculosis good what else childbirth if you were a woman between ages 20 and 40 the single medically riskiest thing you could do in 1900 was attempt to give birth what else was up there influenza pneumonia tuberculosis influenza number one on the list the flu nobody dies of the flu anymore 1918 worst winter world war one people being blown out of trenches all over europe and if you were sent to the war that winter your chances of surviving were better than if you got the flu eight million war deaths in world war one 40 million dead civilians that winter from the flu nobody under

4:46 age 100 dies of the flu anymore instead we die of these totally bizarre diseases that never used to exist on this planet in any sort of frequency totally weird diseases like heart disease and cancer and diabetes and alzheimer's and what you suddenly realize is this is a very novel realm we've entered in terms of making sense of which of us are sick and which are healthy okay 20 000 years ago you're some 20 year old hunter-gatherer and you have screwed up big time you've made a major medical mistake you've just eaten some reed buck riddled with anthrax and the medical outcomes absolutely clear you've got like a three-day life expectancy these days as a 20-year-old you make a major medical mistake you decide a

5:32 healthy diet consists of a lot of red meat and saturated fats and maybe a drink every other day or so and it's not at all clear what the outcome's going to be you may be dead in your grave at 50 or you may be running marathons with your grandkids when you're 85. and in lots of ways the central question for westernized medicine is so why do some of us last to 50 and some to 85. some of it's got to do with like nuts and bolts biology what your liver does with cholesterol or stuff like that but some of it's got to do with questions nobody ever had to ask before in medicine totally bizarre questions like what's your psychological makeup or what's your social status or how do people with your social status get treated in your society

6:18 or how about this one get the answer to this question and you will have done more good for the health of humanity than anyone since like jonas salk inventing the polio vaccine why is it that when we feel like nobody loves us we eat oreo cookies answer that one and you have just solved half the cases of diabetes in this country this is totally bizarre stuff that has something to do with which of us are healthy or sick that has everything to do with it and what we've entered is this very strange world when we look at the diseases that do us in these diseases of slow accumulation of damage from lifestyle over time these are predominantly diseases that can be caused by or be made worse by stress and most of us in this room

7:05 will have the profound westernized luxury of dropping dead someday of a stress-related disease so nonetheless amid that great news it's a good thing if that happens later rather than sooner so it's worth learning about this okay we start off with definitions i start off with a word i guarantee all of us had 9th grade biology with any luck you have not thought about this word since then do you remember homeostasis homeostasis having an ideal body temperature having an ideal level of glucose in your bloodstream having an ideal everything being in homeostatic balance a stressor is anything in the outside world that knocks you out of homeostatic balance your zebra a lion has left out ripped your stomach open and your injuries are dragging in the dust and you still need

7:51 to get out of there this counts as being out of homeostatic balance or you're that lion you're that lion who's half starved to death and if you don't chase down that zebra successfully you're not going to survive the night short-term physical crisis and what you do at that point is you turn on the stress response you secrete adrenaline 11d other hormones i won't torture you with what you do is you reestablish homeostatic balance that's all you need to know about the subject if you're a zebra or a lion if you're human though you got to expand the definition in a critical way yes a stressor can be when your body's been knocked out of homeostatic balance in addition a stressor can be when you think you're just about to be knocked out of homeostatic balance if it turns out that you're right that's great an anticipatory stress response

8:40 woo here comes the elephant maybe i'll increase my blood pressure now before it stomps me rather than after that could be very adaptive on the other hand if you think you're just about to be knocked out of homeostatic balance and you really aren't about to be and you think that way all the time there are medical ways of describing you you're being neurotic as hell you're being anxious you're being paranoid you're being hostile try to describe global warming to a hippo and it's going to have no idea what you're getting all upset about but that's the critical point we do the critical point of the whole thing is we turn on the exact same stress response as that zebra running for its life or a lion running for a meal and we turn it on for purely psychological reasons

9:26 and that's the punchline of the entire field that's not what it evolved for for 99 percent of beasts on this planet stress is three minutes of screaming terror after which it's either over whether you're over with and what do we do we turn on the same stress response for 30-year mortgages and that's not what it is for and what we see here is this is why we and other really cognitively sophisticated primates are the ones who get mowed over by stress-related disease this is a system that evolved for dealing with short-term physical crises and we turn it on for chronic psychosocial stress now listening to this description something should seem sort of questionable though i'm describing okay the stress response you turn this on if you're a zebra

10:14 you're injured you're bleeding you're hypotensive or if you're the lion you're starving you're hypoglycemic these are very different physical states and one of the things they pound into your head in biology is your body comes up with a very specific solution for a very specific challenge if you're hot you don't shiver your body does something very differently than that yet here's the stress response which does the exact same thing whether you're injured starving too hot or too cold why should you turn on the same stress response in all these circumstances and this was a question wrestled with by the guy who's officially sort of the godfather of stress and health this was an austrian physician in the 1930s named han selye who starred in the whole field because he was very smart and very intuitive and very insightful and very

11:01 creative and apparently he was totally lame at handling lab rats and this is how he started the field celie was this young assistant professor he's at mcgill university montreal and he was looking for some research project and some biochemist down the hall had isolated some hormone out of somebody's pancreas or something nobody knew what the stuff does so celia decides that's it i'm going to figure out the effects of this pancreatic stuff on the body so what do you do you go down the hall you get a bucket load of the pancreatic stuff from your body you come back and you start injecting lab rats and apparently celie simply was not very good at handling lab rats so he's in there every day with the rats injecting the rats and dropping the rats and chasing the rats and the rats chasing him and half the morning with a broom getting around from underneath the sink months of this goes by and he discovers

11:48 something amazing all of the rats have stomach ulcers celie is euphoric he's just discovered the effects of this pancreatic crud on the body it gives you a peptic ulcer now fortunately being a good scientist celie was also running a control group rats that he's injecting every day with saline instead of the pancreatic stuff so he's in there with the control rats injecting them and dropping them chasing them chasing him he checks out the control rats and they all have stomach ulcers okay so your average scientist at this point gives up and goes to business school but soviet thinks about this and he says this is totally screwed i'm seeing the exact same thing in the controls in the experimentals it's got nothing to do with the pancreatic stuff what do they have in common well i'm

12:34 pretty inept at handling these guys they can't be having such a hot time here maybe what i'm seeing is some sort of non-specific response of the body to generalized unpleasant trees and celie's insight was to at that point systematically expose rats to generalized unpleasant trees put some of them up in the roof of the building in the winter or down in the boiler rooms or rooms with loud noise or rooms filled with cat pee or who knows what and he always sees the same thing they get stomach ulcers we know exactly what soy had just discovered this was the tip of the iceberg of stress-related disease and celie was the guy who popularized what was this obscure term from metallurgy about torsional strain on metals he's the one who said these animals are under stress and they

13:20 turn on certain systems in their body that saves them from the stress but if they turn it on for too long you get sick everybody thought he was out of his mind because again you're trained your body solves specific challenges in very specific ways and here's celie with his imaginary stress response that gets turned on exactly the same if you're injured starving too hot too colder on a blind date why should you turn on the same exact stress response and all these circumstances and it turns out it makes a great deal of sense because whether you are that zebra or that lion if you're going to survive the crisis there's certain things you need to do with your body first off above all else you need energy not energy tucked away in your fat cells

14:05 for some building project next spring energy right now to hand to whichever muscles are going to save your neck and with the onset of stress you secrete adrenaline and a bunch of other hormones and they go to the storage sites in your body your liver your fat cells they mobilize energy at a storage form dump it into the circulation it's like you go to the bank and you empty out the savings accounts and turn it into cash circulating glucose and you hand it over to whichever muscles are going to save you makes wonderful sense whether you were that zebra or that lion the next thing you do makes perfect sense as well you've just done all this amazing biochemistry and dumped all this energy in your bloodstream you want to deliver it as fast as possible to your exercising muscles your heart speeds up your blood pressure increases your breathing rate you

14:54 increase your cardiovascular tone all as part of the strategy get that glucose get that oxygen to your thigh muscles in two seconds instead of three you're that much more likely to survive now the next things you do during stress make perfect sense which is you turn off all the long-term building projects if there's a tornado do this afternoon you don't spend the day outside gardening you don't worry about long-term projects until you know there's a long term you shut down everything that is not critical you shut down digestion by definition if you are that lion you are not staggering up from some all-you-can-eat buffet and if you are that zebra the energy you're mobilizing for your muscles you're ener mobilizing it from fat cells in just a couple of seconds digestion is slow it takes forever it costs a fortune

15:43 you're trying to avoid being somebody's lunch don't worry about digesting breakfast and we all know the first step of that suppose you get stressed speaking in public what happens your mouth gets dry you've stopped secreting saliva the first step of shutting down the whole gastrointestinal tract with the onset of stress you shut down growth you shut down reproduction 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 lie in 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

16:28 sex hormone on earth disappears from the bloodstream do it later if there is a later next so you're that zebra and your inners are dragging in the dust this might be a good time to perk up your immune system a little bit just in case of some effective stuff with the onset of stress immune defenses are enhanced finally a whole bunch of hormones secreted during stress get into your brain and short term their effects are fabulous they sharpen memory they increase glucose and oxygen delivery to your brain your sensory thresholds are sharper you even release this neurotransmitter dopamine which makes you feel good your memory is working that's that flash bulb memory where were you when you heard the news i'm willing to bet every single person

17:16 in this room no matter how long they live you will all remember exactly where you were when you heard the news that miley cyrus was joining the supreme court some stuff you just file away forever because it's important your brain needs to get a signal this one do not forget so what you see here is everything going on here is exactly what you want to do if you're that zebra or that line you're mobilizing energy you're delivering where it's needed you're shutting off on essentials you're fighting infections you're thinking more clearly all you have to do to appreciate that is look at a couple of weirdo human diseases where people can't do this one of them is called shy drager syndrome another one is addison's disease these are not diseases where oh you're now more at risk for certain cancers this is like somebody with undiagnosed

18:04 addison's goes running for the commuter bus one morning and drops dead from hypoglycemic shock so we've gotten our first critical take-home message here which is if you plan to get stressed like a normal mammal you had better turn on your stress response or else you got about a 30-second life expectancy for most of us though the far more important take-home message revolves around so what if you're turning on the stress response too often too long for purely psychological reasons and what you get there then is disease at the other end of it now celie was the first person to wrestle with this issue why is it that chronic stress makes us sick and he came up with an explanation in the 1930s and had dominated the field

18:50 for the next 40 years which was too bad because he was totally wrong okay here's what he thought was going on along comes the stressor knocks you out of homeostatic balance you turn on the stress response you re-establish homeostasis but the stressor goes on for too long and thus you enter what celie called the exhaustion phase you run out of the stress response your adrenals run out of adrenaline your pituitary runs out of its stress hormones it's like your military runs out of ammunition and you're just left defenseless there with the stressor pummeling you turns out this was totally imaginary there was no such thing as this exhaustion phase 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

19:38 military is running out of ammunition after a while you're spending so damn much in your military that you don't do health care or social services or education or any 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 layer don't do it right now and if every day is an emergency you pay the price for it at the metabolic level mobilize energy because the line's running after you no problem at all mobilize energy from your storage sites chronically because

20:24 you're chronically psychologically stressed and among other things your muscle mass decreases muscle is one of your main energy storage sites you get atrophy of muscle myopathy for extremely complex reasons you're using your energy really inefficiently for insanely complex reasons you're now more at risk for adult onset insulin resistant diabetes now adult onset diabetes is one of those interesting diseases that our great great great great grandparents never even dealt with this is a disease of getting older in a typically westernized way putting on weight getting more sedentary and everything down to the molecular level that goes wrong in your cells with adult onset diabetes stress exacerbates the process same punch line at the cardiovascular

21:13 level if a line is chasing you and your blood pressure is 180 over 120 you're not suffering from high blood pressure you're saving your life on the other hand if your blood pressure is 180 over 120 every time you're stuck in traffic or something you're not saving your life you are suffering from stress induced hypertension and you do that chronically enough and you're going to damage your cardiovascular system okay 30 seconds on stress and heart disease what's the scenario we all know about guy gets horrible news and he's wailing about something and he suddenly clutches his chest in pain kills over dead sudden cardiac arrest this has never happened this is like a movie plot this never occurs in real life instead what actually happens requires you to have like arcane knowledge of high school physics

21:58 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 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

22:45 cardiovascular disease now this link between stress and heart disease is so solid that it accounts for the most famous personality profile in all of medicine and it's one where basically if you're coming out to a lecture on a perfectly nice evening to be outside taking a walk instead i suspect it applies to like 80 percent of the people in this room which is those of us in here who have type a personality okay type a personality type a was first described in the 1950s by a pair of cardiologists in san francisco friedman and roseman here was their original formulation time pressured hostile impatient low self-esteem joyless striving okay like 90 of us

23:32 and what they observed back there in the 50s was if this was your personality profile you were more at risk for heart disease cardiologists hated these guys you're some like eisenhower cardiologist and all you're thinking about is like blood lipids and heart valves and here are these guys saying no you need to sit down you're patient and talk to them christ who wants to talk to their patients and talk to them and say okay so suppose you're in the supermarket and you pick the line that's moving slowly do you go berserk at that point that's got something to do with heart disease total resistance to the concept and it wasn't until the 1980s that enough studies had been done that it became clear type a is for real big time if you have type a personality you are more at risk for cardiovascular

24:20 disease than if you smoke than if you were overweight than if you have elevated cholesterol levels a huge risk factor now what became clear by the 80s was the critical component in the type a profile the piece that is the one that contributes to the cardiovascular disease and it's a term now that is used in the field if you have toxic hostility toxic hostility this attributional style where everything that happens around you is proof that they're out to get you they're out to get you more than everyone else and the only thing to do is watch your back 24 7 and keep a knife ready this is the style where you're in the supermarket and you've picked the slow line and you want to kill the son of a bitch kid behind the cash register come on come on how do you know i have a one o'clock

25:06 meeting trying to screw me up no don't ask the old lady how she is today come on come on come on i'm gonna die someday i get to you know if this is what you're doing instead of checking out the alpha sightings in the national enquirer your blood pressure is going to go up and if this is what you're doing every time somebody could have held the elevator door open for you but didn't if you're doing this 40 times a day you're going to pound away at your blood vessels set up for cardiovascular disease and these days the main question in that field is insofar as you were toxically hostile what's worse for your heart expressing those toxic emotions or keeping them repressed inside what's clear is expressing them is worse for everybody else's cardiovascular health but what is the cost of repressing strong physiological emotions so that's an area of a lot of ongoing research okay so that's stress and heart

25:55 disease actually how did those guys first figure out about type a personality given how much that was coming out of left field and i actually got to hear the story some years ago out of the horse's mouth himself meyer friedman the cardiologist who first described type a died a few years ago in his early 90s saw his last patient a week before he died was working full-time at a cardiology unit ucsf medical center as he used to say i'm still type a but i'm a type a tortoise now and here's the story he would tell in the 50s he and his partner had this cardiology practice everything was going great except for this one weird thing which is they were spending a fortune having to reupholster the armchairs in the waiting room what's this about who knows whatever

26:43 it's part of the overhead every month this upholsterer comes and there's a chair or two that needs to be fixed one month the upholsterer is out on vacation replacement upholstery comes in takes one look at the chairs and discovers type a personality he says what is wrong with your patients nobody wears out chairs this way and they have one of them left and as you can see here the front two inches of the armrests and the seat cushions are totally shredded and the rest of the chair is perfectly fine it's like every night there's like dwarf beavers in there clawing away the chair what is this this is the type a profile 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 cardiologists to hear if there's bad news or not this is not just figuratively but literally sitting on the edge of your

27:30 statement seat and squirming and clawing and all of that this is what somebody who's type a does to a chair in that circumstance okay so what happens at that point if science is working right and you know friedman should grab him like good god man what you've discovered were like like midnight conferences between upholsterers and cardiologists or or or teams of idealistic young upholsterers sweeping across america and coming back with the news that no you don't find chairs like these in podiatrists offices that's what should have happened what happens instead here's where 90 year old dr friedman starts looking all sheepish he says he says i told my nurse get this man out of here i'm this important cardiologist i can't waste my time with him give him this damn check

28:17 get him out of my face he was too type a to listen to the guy and it wasn't until about five years later that he collaborated with the psychologist and back came the type a profile they said oh my god the upholstery he was right to this day they have no idea who that guy was now let's see it is late afternoon in san francisco i'm willing to bet there's some bar in san francisco right now where there's like this 110 year old retired upholsterer and get this guy going and he's going to go on and on about how he discovered type a personality exactly what occurred so one of the dark chapters in my profession okay moving on digestion shut down your digestive system for two minutes running for your life it's not a big deal shut it down chronically and there's all sorts of

29:05 gastrointestinal disorders you're more at risk for most famously ulcers back to celie in the 1930s the first stress-related disease stress causes ulcer stress causes ulcers canonical knowledge everybody knows this and then about 25 years ago there's this revolution in ulcerology turns out there's a bacteria called helicobacter pylorus turns out the bacteria is responsible for about 90 percent of ulcers in the west it gets into your stomach it generates oxygen radicals and blows holes in the walls of your stomach it's a bacterial disorder this was an enormous contribution the two guys who discovered against the nobel prize amazing the evening this is announced every gastroenterologist on earth goes out that evening and celebrates

29:50 this is the greatest news they've ever heard because they're not going to have to sit down their patients and make eye contact and say if you have any stressful way it's got nothing to do with stress here's some antibiotics get out my office it's got nothing to do with stress it's got everything to do with stress because only 10 percent of people with the bacteria get the ulcer you've got to have the bacterial risk factor but you've got to have a lifestyle risk factor overlapping as well stress stress does not cause ulcers the bacteria does what does stress do when you got an ulcer beginning to start your stomach's reasonably good at repairing it and rebuilding the wall there before the ulcer gets troublesome unless you're chronically stressed and every day your stomach

30:36 walls are saying ah do it tomorrow do it tomorrow it feels like we're being chased by a predator psychological stress shuts down the reparations there so here we have a classic example of interactions between the organic causes of disease and the psychogenic stress is still very relevant to making sense of ulcers next growth shut down growth for three minutes while you're running for your life not a big deal our theme by now shut it down chronically this can be problematic especially if you were a kid all kids are are big long-term building projects and for reasons of psychological stress you keep saying do it tomorrow do it tomorrow you can impair growth and at an extreme you have one of the truly bizarre outposts of medicine

31:22 a disease of kids who stop growing for reasons purely of psychological stress known as psychogenic dwarfism psychosocial dwarfism stress dwarfism these are kids who are years behind the normal growth rates and there's no disease they're not malnourished there's no parasites you check their bloodstream there's like no growth hormone you give them synthetic growth hormone nothing happens the whole system is shut down and at that point you start poking 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 this is incredibly well understood how

32:08 this works open up any textbook of endocrinology go to the chapter on growth and i guarantee there will be the obligatory picture of the stressed dwarfism kid you know those pictures of stunted cues like naked in front of the growth chart with a rectangle over the eyes and turn the page and i guarantee there's the obligatory follow-up picture the kid in a different environment two years later he's like six foot fourteen he's playing for the nba it's everything's you know there's still the rectangle and nakedness but everything else gets better and what you see there is this is the system with an amazing capacity to recover remarkable cases of this for example this was a case report a few years ago this was a child brought in from an extremely abusive psychological setting into new york hospital with stress dwarfism and as

32:55 documented in the paper at the time he came into this pediatric unit zero growth hormone in his bloodstream over the next few months he became very close with one nurse there and this was like the first normal emotional relationship of his life after a couple of months normal growth hormone levels for his age at that point the nurse goes on vacation by the end of her two-week vacation he's back down to zero nurse comes back a week later he's back up to there think about this the rate at which this child was depositing calcium in his bones could be entirely predicted by how safe and loved he was feeling the world you can't ask for a much better example of what's going on here affects every outpost in the body

33:43 now the issue with stress dwarfism amid people understanding exactly which hormones are due or what the issue of course becomes how common is this disease if you were shorter than average and you were not obviously malnourished as a kid are you a victim of stress dwarfism did your parents do that to you no this is not like oh very stressful childhood we were moving all the time this is not like acrimonious divorce this is nightmare psychopathology this is the police and the social workers breaking down the door of an apartment and finding the kid chained to the radiator and smeared and excrement and just nightmare stuff and get the kid out of that setting and there's recovery the clinical consensus is this is a once in a career disease that you see extremely rare

34:28 except it's not so rare it pops up all over the place kids in war zones kids in areas of civil strife a research assistant of mine and i think we've got the data to show that kids who wound up in the japanese american internment camps in world war ii had mild stress dwarfism that pops up all over the place one classic study in the 60s looking at rites of passages from cultures all over the planet rights of passages in one culture they take you out of the desert and stake you down and cover you in poison ants and some other culture you play the piano for your grandmother and her friends or whatever's done in your tribe they did like 80 tribal comparisons they controlled for genetics back comes the finding stressful rites of passages during the first few years

35:14 of life two inches shorter as an adult big effect let me tell you about the single creepiest example of stress dwarfism i've ever heard of if for some inexcusable reason you ever find yourself reading chapter after chapter about growth hormone you're going to notice there's a weird thing which is a lot of the chapters make reference to peter pan some quote from peter pan or some snide comment about tinker bell i've seen this for years i had no idea what this was about until one day i stumbled on an explanation and this was a chapter about the psychological regulation of growth and was talking about stress dwarfism gave the following case history eight-year-old boy growing up in victorian england in the 1870s one day he sees his beloved older brother killed in front of him in an accident

36:01 this destroys the family there were no other siblings the father was like emotionally non-existent this was the mother's favorite child and this victorian swoon she takes to her bed with the shades drawn for the next 10 years this kid growing up in this horrible emotional isolation he goes into the bedroom with a tray of food for his mother and she's saying oh david david is that you david have you come to me have you david the dead son david are you finally oh it's only you growing up being only you apparently the only thing she ever spoke to him about was this idea she grabbed onto which was if david had to die he'll always be my perfect little boy who never grew up and became a man who didn't need his mother anymore he'll always be my perfect little boy because he didn't grow up and grow up and grow up this kid hears this with a

36:49 vengeance middle class family no evidence of disease or malnutrition boy stops growing there at age eight lives to age 60 4 foot 10 as an adult unconsummated marriage incredible example of stress dwarfism and then then the chapter concludes by informing us that as an adult this was the author of the much beloved children's classic peter pan this was j.m barry the guy who wrote peter pan who's incredibly screwed up this guy all he did was crank out book after play after novella about boys who die and come back as ghosts and marry their mothers his private journals were full of sadomasochistic fantasies about little boys this guy spent the rest of his life dealing very unsuccessfully with this

37:36 stress dwarfism so think about that the next time you see johnny depp up on a movie okay next next reproduction your gonads your gonads your gonads are not going to be working very well if you were chronically stressed if you were a female mammal of virtually any species if you were chronically stressed your cycles will become irregular lengthened they may stop all together stress induced amenorrhea stress-induced and ovulation and people understand exactly how those work which hormones are working at the brain at the pituitary at the ovaries of the uterus to shut things down let me tell you about one of those steps because it's got to do with a very weird thing that female mammals do including human females which is they secrete a certain amount of male

38:23 sex hormones into the bloodstream hormones that are related to testosterone androgen type hormones they come out of the adrenal glands not a ton of the stuff maybe five percent the levels you would see in the male nonetheless you got to get rid of it unfortunately female mammals come with this enzyme and fat cells that take circulating androgens and does biochemistry 101 and converts them to estrogens great perfect problem solved everyone lives happily ever after what if you're stressed what if you're stressed like the locusts have come and eaten your crops and you're subsisting on 800 calories a day what if you're slowly starving your fat stores are slowly getting depleted and at some point you have too little functional fat cells

39:09 to do the androgen to estrogen conversion one problem is there's now a little bit less estrogen in the bloodstream bigger problem is the androgen levels build up there and that shuts down every step in the system that's why starvation shuts down ovulation that's why voluntary starvation anorexia does the same and that's why some women who do massive massive amounts of exercise will stop ovulating as well because you get below a critical fat muscle ratio there now this is something that's been studied at length in girls for example it's always studies of very serious ballet dancers or gymnasts what you see is significant delay in the onset of puberty one study for example this was done on the olympic gymnastics squad from

39:55 romania you know those 60 pound 15 year olds getting the gold medals all over the place what was the average age of which these kids started menstruating 19. 12 and a half is the western average once hitting puberty women who do tons of athletics is best studied long distance runners women who run an average of 40 to 50 miles a week that's typically the range where fat stores are getting below threshold where you begin to have ovulatory irregularities i can tell you the exact same story about men men who run 40-50 miles a week sperm count goes down there's mild testicular atrophy okay wait a second i thought exercise was good for us exercise is good for us and in fact a lot of exercise is very good for us that doesn't mean though that an insane

40:42 amount of exercise is insanely good for us it means at some point too much of a good thing is just as bad as too little you've passed a point of homeostatic balance and all you need to do to get an appreciation for that is imagine you sit down some hunter gatherer from the kalahari desert and say you know where i come from we have so much food and so much free time that sometimes we'll just go run 26 miles in a day for the sheer pleasure and they're going to say are you crazy that's stressful i mean throughout hominid history if you're running 26 miles in a day either you are very intent on eating somebody or somebody's intent on eating you this is not normal physiology so we get a cautionary note here meanwhile over at the male end of things with the onset of stress down go testosterone levels anesthetize

41:31 a guy slice into his belly for surgery 10 minutes later testosterone is plummeting first year male medical students during exam periods down go testosterone drop the rank of a male baboon at a hierarchy down goes testosterone here's a stressor which thank god i have no personal experience with at all but apparently it's not fun to be in the marines apparently it's kind of a drag especially during basic training this was this classic study 1970 new england journal of medicine looking at military recruits during basic training were now on top of everything else they had to pee into little dixie cups for the psychiatrist and back comes the finding guys in the in the marines during their first couple of months of service they have the circulating androgen levels of like vatican choir boys that's how much the system is shut down

42:19 okay so people understand exactly which stress hormones are working at the brain the pituitary and the testes to shut down testosterone synthesis during stress the question you gotta ask at this point is so what are the consequences of testosterone levels declining during stress and amazingly enough the answer is there's no consequences at all testosterone turns out to be this vastly overrated hormone like basically all you need is like a thimble full of stuff and a couple of sperm and you're in business you've got to knock out like 90 percent of the guys testosterone levels to seriously impair fertility stress what does it do at its worst only about a 60 decline it's not suppressed enough that it makes a difference the problem during stress is not that

43:05 testosterone levels go down the problem is that penises go down okay am i allowed to talk about this in champaign urbana here okay finally we come to the first like useful point in this damn lecture so how do erections work okay so erections in order to i just saw somebody there pick up a pen for the first time okay so how do erections work in order to have an erection you gotta have a spinal cord now most of what your spinal cord does is totally boring and makes you shake hands and sign checks and foxtrot or who knows what but then there's the part that does the good stuff the stuff you normally don't have any control over stuff that is automatic like goose flesh and orgasms and pupillary contractions and blushing

43:53 things that are automatic and thus run by the automatic nervous system also known as the autonomic nervous system now the autonomic nervous system comes in two halves first half sympathetic nervous system emergency arousal adrenaline stress response all hell breaking loose second half the parasympathetic nervous system calm vegetative function you take a nap you turn on the parasympathetic nervous system you eat a big starchy meal you turn on the parasympathetic nervous system you get disemboweled by a lion you turn off the parasympathetic nervous system it works in opposition with a sympathetic okay so here's the rule in order to get an erection you've got to turn on the parasympathetic nervous system

44:38 you have to be calm and vegetative okay so you got your erection now what happens next maybe for some social reason having to do with the context that brought about the erection maybe you start feeling a little bit less calm and vegetative maybe your heart rate increases a little maybe your breathing rate maybe your muscles are starting to do some work slowly you're starting to turn on the sympathetic nervous system more time goes by your heart is racing your toes are curling you're sweating you're breathing fast all of that eventually you get to this point where your whole body is screamingly sympathetic except for this one lone outpost we are desperately holding on to parasympathetic tone as long as possible finally can't take anymore you turn off the parasympathetic turn on the sympathetic and ejaculate

45:25 okay so that's how erections work so what happens during stress what happens during stress you're not very calm and vegetative you can't get the erection stress induced imminency or you can have a second problem suppose you manage to get the erection and you think like oh no donald trump who knows why you accelerate the transition you accelerate the transition from parasympathetic to sympathetic the whole thing goes too fast either you can't get the erection or premature ejaculation incredibly easy for this to occur current estimates are 60 percent of the visits by men in this country going to doctors about erectile dysfunction turn out not to have an organic disease basis

46:11 but instead are psychogenic stress-related okay second useful piece of information so how do you tell the difference between a case of organic infancy and psychogenic so a guy comes to you says he hasn't been able to have an erection during sex in the last six months and you're wondering well is the stress related or does he have a pituitary tumor whatever you take advantage of a weird thing that male primates including human males do which is when they go into rem sleep rapid eye movement sleep they get erections i've no idea why i've talked to earth's penis experts nobody has an explanation for this nonetheless male primates get rem sleep erections so here's what you do the guy who hasn't been able to have an erection during six sex and months what you do is you give him this handy-dandy little penile pressure cuff

46:58 transducer thingy that he takes home and just before he goes to sleep he puts it on the base of his penis and wires it up and satellite relays and 24-hour operators in bangalore and the next day the next day you got your answer which is if this guy hasn't been able to have an erection during sex in the last six months but 30 seconds into his first rem stage he has a perfectly normal erection he doesn't have a pituitary tumor it's stress related that's how you distinguish between the two do you still get the nocturnal erections if that's the case it's stress related very easy to actually maybe this is not so easy because you got this electronic device and it's beeping and the wires and you're so sure it's going to electrocute you that's a stressor in and of itself this is what is done in the majority of sexual dysfunction clinics in this

47:45 country i kid you not you take a long string of postage stamps you lick them at one end and you wrap them around the guy's penis and the next morning if the stamps have been torn loose the guy had an erection during the night can you believe like how elegant this is like five bucks you get a lab result it's fabulous yeah oh of course insurance won't reimburse you for the stance but still you know maybe obamacare still has a chance okay so what we see here is another outpost of vulnerability and perhaps we should hurdle on before i embarrass myself further your immune system your immune system so as we heard before with the onset of stress you enhance your immune defenses with chronic stress something very different occurs with chronic stress

48:33 not only does the immune system go back to baseline you suppress immunity with chronic stress you become immune suppressed and this is the starting point for just this irresistible syllogism insofar as chronic stress chronically suppresses the immune system chronic stress should set you up for more infectious diseases and this is the basic premise behind this field that emerged about 25 years ago psychoneuroimmunology the notion that what's going on here is affecting your immune defenses in a quarter century into this field it's clear that's exactly how it works for all the boring stuff when you were under stress the common cold becomes more common you're at more risk for mononucleosis for herpes viral flare-ups reactivation what's far less

49:20 clear is what about bigger realms of infectious disease how about if you have aids your immune system declining if you're severely stressed does it decline even faster jury is out on that one it seems to have to do with personality type as an intervening variable how about the biggest one on everybody's list when it comes to worrying about disease so what's the relationship between stress and cancer and everybody knows the answer to that which is cancer is a stress related disease stress can cause you to have cancer stress can cause you to come out of remission from cancer stress can accelerate the growth of tumors everybody knows about this sufficiently so that some years ago there was a study in jama journal the american medical

50:05 association looking at women who had just gotten a metastatic breast cancer diagnosis where they were asked so what do you think is the cause of your cancer and by more than a two to one margin the most common answer was stress too much stress in my life stress has virtually nothing to do with cancer there has never been a decent prospective human study longitudinally that shows that stress increases the risk reoccurrence or growth rate of any type of tumor when they're well controlled there have been all sorts of studies showing how stress can accelerate tumor growth in lab rats we know how it works my lab did some of that work but it turns out these are types of cancers that are completely irrelevant to human cancer this is a realm where there's not much connection at all amid all those things on the right sides

50:54 of these charts you need to worry about this is one domain where you don't why is it important to emphasize this because of all of these highly credentialed quacks who are making a fortune off of cancer patients saying my special brand of stress therapy will slow down your cancer stop it reverse it credit cards accept it there's no science to support this bad medicine bad science bad ethics this is a domain where you don't have to worry okay so quickly let's hurtle back to domains where you do have to worry okay so back to stress in your brain we saw short term does all sorts of great stuff chronically bad news chronically stress will damage a part of your brain called the hippocampus which is essential for learning and

51:39 memory stress has something to do with failure of memory consolidation there shrinkage of neurons disconnecting of synapses at an extreme killing of neurons inhibition of the birth of new neurons there and this is turning out to be relevant to humans and a number of scary realms people with chronic stress due to ptsd post-traumatic stress disorder combat trauma or sexual abuse trauma and what you see there is atrophy of the hippocampus only the hippocampus the more severe the trauma history the more atrophy the more memory problems best evidence is this is not reversible second syndrome pertinent to the 10 to 15 percent of us in this room destined to have major clinical depression the

52:26 poster child and psychiatry of a stress related disorder it involves chronically elevated stress hormone levels and scads of studies now showing atrophy of the hippocampus only the hippocampus the more severe the depression history the more atrophy the more memory loss and as far as most studies show at this point this is not a reversible process meanwhile next door to the hippocampus is a brain region called the amygdala and in the amygdala things are real different hippocampus does learning and memory for you amygdala teaches you to be afraid it does fear it does anxiety and while stress is atrophying away those hippocampal neurons stress is making neurons and the amygdala work better than usual they expand their

53:14 connections the synapses become more excitable people with ptsd have amygdalas that grow larger than normal stress makes it easier for you to associate things with fear that are not actually valid and makes you harder to detect to detect safety signals this is the link between stress and anxiety meanwhile over in that part of the brain where you're releasing dopamine which has something to do with pleasure with the onset of stress chronic stress and you're depleted of dopamine what is this setting us up for explaining the link between stress and depression the defining symptom of depression is anhedonia hedonism the pursuit of pleasure and hedonia the inability to feel pleasure this is

54:01 the neurochemical link why chronic stress is a major precipitating factor for depression so okay if you're still awake at this point you should be depressed as hell okay so amid that it must seem like a miracle that any of us are still alive actually let me make this worse one last stress related disease this is like stress for 2000. how many of you have heard of a disease called idiopathic alopecia areata okay a few hands this is the profoundly rare state of somebody being so so traumatized by something that over the next few days their hair turns white and falls out this is for real people understand like what the immune system is doing the hair follicles there it's real it's a once in a career disease but nonetheless this is free

54:49 look at this you're chronically stressed you get high blood pressure you get diabetes you get flatulent your sex life is ruined your brain gets damaged and your hair falls out how is it any of us are still functioning here why haven't we all collapsed into puddles of stress-related disease and the critical thing is most of us don't most of us cope and what's been clear from the first day of the field with celie is some individuals cope with stress better than others what i want to spend the last couple of minutes on is how we understand this to work why do some bodies and more importantly some psyches deal better with stress than others okay so if we're talking about individual differences and stress responsiveness here we're not talking about physical stressors finish this lecture

55:36 go outside unexpectedly be gored by an elephant and you're gonna have a stress response there's no way you can't reframe your experience and grow from adversity or who knows what you're gonna have a stress response finish the lecture go outside and have kind of a tense ambiguous interaction with someone and only some of us will have a stress response what is it about that gray zone of psychosocial interactions that is more stressful for some individuals and others what we're asking here is what is it that makes psychological stress stressful and remarkably a massive literature stretching back decades shows what precisely are the building blocks of psychological stress okay here's a schematic summary of the gazillion studies what they would sort

56:22 of show take a lab rat put him in the cage every now and then he gets a shock mild shock and nonetheless with enough of them this is stressful blood pressure goes up heart rate goes up risk of ulcer goes up as shown here you're giving the rat a stress related disease now second line in a second cage there's another rat psychology jargon the second rat is yoked to the first rat every time the first rat gets a shock so does the second same intensity same duration same everything according to celie in 1930 both of their bodies are being knocked out of homostatic balance the exact same extent except for a critical difference which is every time that second rat gets a shock it can go over to the other side of the cage where there's another rat

57:09 and it can bite the crap out of it and you know what that rat's not going to get an ulcer the guy is biting isn't going to get one but this one doesn't he has an outlet for his frustration third line now we have in the second cage a second rat getting the same shock same duration same intensity same everything but each time he gets a shock he can go over and there's a bar of wood that he could gnaw on with his teeth and he doesn't get an ulcer he has a hobby okay now the next line what we have here is same shock same intensity same everything but 10 seconds before each shock the second rat a little warning light comes on and the rat doesn't get an ulcer for the same external stressor we are more protected when we get

57:55 predictive information when is it coming how bad is it going to be how long is it going to last and we all know that principle every time we ask the dentist how much more drilling and we all know the difference between the dentist that says two more bits and we're done on the one that says yeah it could be it could be weeks you're gonna be here and when the dentist says two more bits of drilling bad news you're not done yet good news the second that second bit of drilling is over with you're safe for the rat in the first line any second you can be a half second away from the next shock next line this is a rat that's been trained to press a lever by pressing the lever it decreases the likelihood of getting a shock today the rat is yoked to the first one getting the same shocks as the first guy but there's a lever in there the lever is disconnected the leverage has done nothing whatsoever but the rat doesn't

58:42 know what so he's in there pounding away the lever saying this is great just imagine how many stock you're getting otherwise he thinks he has control for the same external stressor a sense of control makes things less stressful jumping ahead to the final line shock a rat and now it goes over to the other side of the cage where there's a rat that it knows and likes and they groom each other and it doesn't have a stress response wow science has finally proven that friends are good for your health science has proven this big time 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

59:32 family because your health is going to pay for it the rest of your life the link between health and socioeconomic status very heavily mediated by stress the second biggest predictor is if you got a choice in the matter don't be socially isolated and you look at the extremes of social isolation versus social affiliation significant other others small group of friends community group you're intentionally involved with for the same disease impact almost a threefold difference in mortality rate and that's after you control for stuff like ooh people who live alone just eat cheetos for dinner and nobody reminded to take their meds control for that and social isolation is an aching stressor for every primate out there including us and a huge health risk factor so what is it that makes psychological stress

1:00:20 stressful for the same external misery you are more likely to feel subjectively stressed more likely to turn on a stress response and more at risk for stress-related disease if you feel like you have no control no predictability no outlets for the frustration if you interpret things as getting worse and you have nobody's shoulder to cry on and basically this is the place to stop because again none of us are getting ulcers because we're being chased by saber-toothed tigers none of us are ever gonna have to wrestle people for canned food items and bombed out supermarkets instead we are going to have this luxury of living well enough and long enough amid our psychological stressors to pay the medical cost and that's the critical point at the end to the extent that we are

1:01:08 smart enough to have invented these psychosocial stressors and then stupid enough to have fallen for them we all have the potential to instead be wise enough to keep them in perspective so on that note thank you for your attention and good luck with your stressors wow i see my mother did manage to call all of you before the lecture today

1:01:56 thank you he's still blushing from the erection topic so uh welcome back to that i wanted to ask you a question this is i have a strategy of coping and i'm not sure it's it's the best strategy um i so i i experience a lot of stress and so my here's my coping strategy i always am expecting the worst so basically you know when i'm applying for a grant or something i'm i'm expecting not to get it if i'm you know submitting a paper i'm expecting it to get rejected and this is a coping strategy for me because if uh you know if it turns out that i don't get the grant then i'm not really let down and that's in a way it helps me predict the stressor but on the other hand i'm thinking about it i'm thinking well then i'm always constantly thinking about the worst and it's kind of a pessimistic attitude

1:02:42 so basically my question is is this a bad strategy yes i would recommend first just taking out your adrenal glands that that will probably be more effective okay what we have here is the difference

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