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

0:00[MUSIC]

0:34So, Robert Sapolsky was my professor when we were students

0:38at Stanford University, many moons ago.

0:40And Robert made a huge influence on my

0:43wanting to be a scientist. He was simply the most influential and

0:46outstanding, compelling professor at stanford,

0:48because of the way he connected with his students. And because of his incredible

0:52gift at lecturing, which you're all about to witness,

0:54and as you might imagine Robert has quite a number of impressive

0:57accomplishments in his career -- including the MacArthur Genius Fellow,

1:00loads of highly influential scientific articles, and research awards.

1:04But perhaps one of his greatest accomplishments are the books that have

1:07been so incredibly popular and so impactful to so many

1:10people that he's written. My personal favorites are

1:11"The Trouble with Testosterone: a Primates Memoir" and "Why Zebras Don't Get Ulcers,"

1:13which is the topic of today's lecture. And so let's please all join me in

1:21welcoming Dr. Robert Sapolsky to the stage.

1:24[Applause]

1:40Well, let me start off by saying actually these lights only give me a dim

1:44impression that there's a lot of primates out there.

1:47So i'm not entirely sure what I'm seeing here. But let me start off by thanking

1:53Justin and Peter. It is a delight to be here

1:56and a delight to see one's ex-students flourishing and all that sort of stuff,

2:02amid making me feel very elderly.

2:04Okay. So let me start off, I just got here a couple of hours ago. So I pretty much

2:10don't know anyone here. So i feel empowered to ask all sorts of invasive

2:15personal questions of you guys. Okay. How many of you here have a family

2:19history of heart disease, cancer, high blood pressure,

2:27ulcers, stroke? Well, there's a hand there that's not even going down between the

2:32questions. Okay. That is not good. How many of you

2:35have a family history of somebody with a really bad case of leprosy?

2:43No hands. How about that cousin you're stuck sitting next to with thanksgiving,

2:47the one going to the bathroom every 10 minutes because of the dysentery?

2:51Not that either. How about that extra special relative

2:55who's just teeming with liver parasites the size of your fists?

3:00Not much there either. And, all things considered, this is not very surprising.

3:05Very few of us in this room seriously worry about smallpox or scarlet fever.

3:10Few of us gets malaria during the rainy season.

3:14Few of our mothers died in childbirth. Nobody in this room is malnourished.

3:18We're not like normal animals. We don't get sick the way normal animals do.

3:18We don't die the way they do. Basic, normal mammalian death.

3:22You drink some contaminated water and you're dead from dehydration two days later.

3:30And what do we do? We spend 80 years having our bodies go to hell on us.

3:35So we do. Oh great! I've got to listen to what for the next hour?

3:38This is actually fabulous news, because this is westernized disease

3:43for the most part. We are not plagued by infectious diseases,

3:47diseases of poor nutrition, poor hygiene. Instead, we live

3:51well enough and long enough to slowly fall apart over time.

3:55and this is a magnificent advance in the human experience

3:59okay just to give you a sense of it like a little more than a century ago 1900

4:03what do you think were the leading causes of death in the united states

4:08tuberculosis good what else childbirth if you were a woman between

4:14ages 20 and 40 the single medically riskiest thing you could do in 1900

4:18was attempt to give birth what else was up there

4:22influenza pneumonia tuberculosis influenza number one on the list

4:26the flu nobody dies of the flu anymore 1918 worst winter world war one people

4:32being blown out of trenches all over europe and if you were sent to the war

4:35that winter your chances of surviving were better

4:37than if you got the flu eight million war deaths in world war

4:41one 40 million dead civilians that winter from the flu nobody under

4:46age 100 dies of the flu anymore instead we die of these totally bizarre diseases

4:52that never used to exist on this planet in any sort of frequency

4:56totally weird diseases like heart disease

4:59and cancer and diabetes and alzheimer's and what you suddenly realize is

5:04this is a very novel realm we've entered in terms of making sense of which of us

5:09are sick and which are healthy okay 20 000 years ago you're some 20

5:14year old hunter-gatherer and you have screwed up big time you've

5:18made a major medical mistake you've just eaten some reed buck riddled

5:22with anthrax and the medical outcomes absolutely

5:25clear you've got like a three-day life expectancy

5:28these days as a 20-year-old you make a major medical mistake you decide a

5:32healthy diet consists of a lot of red meat and saturated fats and

5:36maybe a drink every other day or so and it's not at all clear what the outcome's

5:40going to be you may be dead in your grave at 50 or you may be running

5:44marathons with your grandkids when you're 85.

5:47and in lots of ways the central question for westernized medicine is

5:52so why do some of us last to 50 and some to 85.

5:55some of it's got to do with like nuts and bolts biology what your liver does

5:59with cholesterol or stuff like that but some of it's got to do with

6:02questions nobody ever had to ask before in medicine totally

6:07bizarre questions like what's your psychological

6:10makeup or what's your social status or how do

6:14people with your social status get treated in your society

6:18or how about this one get the answer to this question and you will have done

6:21more good for the health of humanity than anyone since like jonas salk

6:25inventing the polio vaccine why is it that when we feel like nobody

6:30loves us we eat oreo cookies answer that one and you have just solved half the

6:36cases of diabetes in this country this is totally bizarre stuff that has

6:41something to do with which of us are healthy or sick

6:44that has everything to do with it and what we've entered is this

6:48very strange world when we look at the diseases that do us in

6:51these diseases of slow accumulation of damage from lifestyle over time

6:56these are predominantly diseases that can be caused by

7:00or be made worse by stress and most of us in this room

7:05will have the profound westernized luxury of dropping dead someday of a

7:09stress-related disease so nonetheless amid that great news it's

7:13a good thing if that happens later rather than sooner so it's worth

7:17learning about this okay we start off with definitions

7:19i start off with a word i guarantee all of us had 9th grade biology

7:23with any luck you have not thought about this word since then do you remember

7:27homeostasis homeostasis having an ideal body temperature

7:33having an ideal level of glucose in your bloodstream having an ideal everything

7:37being in homeostatic balance a stressor is anything in the outside world that

7:44knocks you out of homeostatic balance your zebra a lion has left out ripped

7:48your stomach open and your injuries are dragging in the dust and you still need

7:51to get out of there this counts as being out of homeostatic

7:54balance or you're that lion you're that lion who's half starved to death and if

7:58you don't chase down that zebra successfully you're not going to survive

8:01the night short-term physical crisis and what you

8:05do at that point is you turn on the stress response you

8:09secrete adrenaline 11d other hormones i won't torture you

8:13with what you do is you reestablish homeostatic balance

8:17that's all you need to know about the subject if you're a zebra or a lion

8:21if you're human though you got to expand the definition in a critical way

8:25yes a stressor can be when your body's been knocked out of homeostatic balance

8:29in addition a stressor can be when you think you're

8:32just about to be knocked out of homeostatic balance

8:35if it turns out that you're right that's great an anticipatory stress response

8:40woo here comes the elephant maybe i'll increase my blood pressure

8:43now before it stomps me rather than after that could be very adaptive

8:46on the other hand if you think you're just about to be knocked out of

8:50homeostatic balance and you really aren't about to be and

8:53you think that way all the time there are medical ways of describing you

8:57you're being neurotic as hell you're being anxious you're being

9:01paranoid you're being hostile try to describe global warming

9:06to a hippo and it's going to have no idea what you're getting all upset about

9:10but that's the critical point we do the critical point of the whole thing is

9:16we turn on the exact same stress response

9:19as that zebra running for its life or a lion running for a meal

9:22and we turn it on for purely psychological reasons

9:26and that's the punchline of the entire field that's not what it evolved for

9:31for 99 percent of beasts on this planet stress is

9:34three minutes of screaming terror after which it's either over whether you're

9:38over with and what do we do we turn on the same stress response for 30-year

9:41mortgages and that's not what it is for and what

9:45we see here is this is why we and other really

9:49cognitively sophisticated primates are the ones who

9:52get mowed over by stress-related disease this is a system that evolved for

9:57dealing with short-term physical crises and we turn it on for chronic

10:02psychosocial stress now listening to this description

10:06something should seem sort of questionable though i'm describing

10:09okay the stress response you turn this on if you're a zebra

10:14you're injured you're bleeding you're hypotensive

10:17or if you're the lion you're starving you're hypoglycemic

10:20these are very different physical states and one of the things they pound into

10:24your head in biology is your body comes up with a very specific

10:28solution for a very specific challenge if you're

10:31hot you don't shiver your body does something very differently than that

10:34yet here's the stress response which does the exact same thing

10:38whether you're injured starving too hot or too cold

10:41why should you turn on the same stress response in all these circumstances

10:46and this was a question wrestled with by the guy who's officially sort of the

10:49godfather of stress and health this was an austrian physician in the

10:531930s named han selye who starred in the whole field

10:57because he was very smart and very intuitive and very insightful and very

11:01creative and apparently he was totally lame at handling lab rats and

11:05this is how he started the field celie was this young assistant professor

11:09he's at mcgill university montreal and he was looking for some research

11:13project and some biochemist down the hall

11:16had isolated some hormone out of somebody's pancreas or something nobody

11:20knew what the stuff does so celia decides that's it i'm going to

11:23figure out the effects of this pancreatic stuff on the body

11:26so what do you do you go down the hall you get a bucket load of the pancreatic

11:29stuff from your body you come back and you start injecting lab rats and

11:33apparently celie simply was not very good at handling lab

11:37rats so he's in there every day with the rats

11:39injecting the rats and dropping the rats and chasing the rats and the rats

11:42chasing him and half the morning with a broom getting around from underneath the

11:45sink months of this goes by and he discovers

11:48something amazing all of the rats have stomach ulcers

11:53celie is euphoric he's just discovered the

11:56effects of this pancreatic crud on the body it

11:59gives you a peptic ulcer now fortunately being a good scientist

12:03celie was also running a control group rats that he's injecting every day with

12:07saline instead of the pancreatic stuff so he's in there with the control rats

12:11injecting them and dropping them chasing them chasing him he checks out the

12:14control rats and they all have stomach ulcers

12:18okay so your average scientist at this point gives up and goes to business

12:23school but soviet thinks about this and he says this is totally screwed i'm

12:27seeing the exact same thing in the controls in the experimentals it's got

12:30nothing to do with the pancreatic stuff what do they have in common well i'm

12:34pretty inept at handling these guys they can't be having such a hot time

12:37here maybe what i'm seeing is some sort of

12:39non-specific response of the body to generalized unpleasant trees and celie's

12:46insight was to at that point systematically expose rats to

12:50generalized unpleasant trees put some of them up in the roof of the

12:53building in the winter or down in the boiler rooms or rooms with loud noise or

12:57rooms filled with cat pee or who knows what and he always sees the same thing

13:00they get stomach ulcers we know exactly what soy had just discovered this was

13:05the tip of the iceberg of stress-related disease and celie was

13:09the guy who popularized what was this obscure term from

13:13metallurgy about torsional strain on metals he's

13:16the one who said these animals are under stress and they

13:20turn on certain systems in their body that saves them from the stress but if

13:24they turn it on for too long you get sick everybody thought he was

13:29out of his mind because again you're trained your body

13:32solves specific challenges in very specific ways

13:35and here's celie with his imaginary stress response that gets turned on

13:39exactly the same if you're injured starving too hot too colder on a blind

13:42date why should you turn on the same exact

13:46stress response and all these circumstances and it turns

13:49out it makes a great deal of sense because whether you are that zebra or

13:54that lion if you're going to survive the crisis

13:57there's certain things you need to do with your body

14:00first off above all else you need energy not energy tucked away in your fat cells

14:05for some building project next spring energy right now to hand to whichever

14:10muscles are going to save your neck and with the onset of stress you secrete

14:14adrenaline and a bunch of other hormones and they go to the storage sites in your

14:18body your liver your fat cells they mobilize energy at a storage form

14:23dump it into the circulation it's like you go to the bank and you

14:27empty out the savings accounts and turn it into cash

14:30circulating glucose and you hand it over to whichever

14:33muscles are going to save you makes wonderful sense

14:37whether you were that zebra or that lion the next thing you do makes perfect

14:41sense as well you've just done all this amazing

14:43biochemistry and dumped all this energy in your bloodstream you want to deliver

14:47it as fast as possible to your exercising muscles

14:50your heart speeds up your blood pressure increases your breathing rate you

14:54increase your cardiovascular tone all as part of the strategy get that

14:58glucose get that oxygen to your thigh muscles in two seconds

15:02instead of three you're that much more likely to survive

15:06now the next things you do during stress make perfect sense

15:09which is you turn off all the long-term building projects

15:14if there's a tornado do this afternoon you don't spend the day outside

15:17gardening you don't worry about long-term projects until you know

15:20there's a long term you shut down everything that is not

15:23critical you shut down digestion by definition if you are that lion you

15:28are not staggering up from some all-you-can-eat buffet

15:31and if you are that zebra the energy you're mobilizing for your muscles

15:34you're ener mobilizing it from fat cells in just a couple of seconds

15:38digestion is slow it takes forever it costs a fortune

15:43you're trying to avoid being somebody's lunch don't worry about digesting

15:46breakfast and we all know the first step of that

15:49suppose you get stressed speaking in public what happens

15:52your mouth gets dry you've stopped secreting saliva the

15:56first step of shutting down the whole gastrointestinal tract

16:00with the onset of stress you shut down growth you shut down

16:04reproduction big expensive optimistic things to be doing with your body

16:09and this is no time for it you know you're running for your life there's a

16:12lie in two steps behind you you ovulate some other time don't do it

16:18right now hit puberty next week grow antlers some

16:21other day don't even think about sperm with the onset of

16:24stress you shut down growth you shut down tissue repair every

16:28sex hormone on earth disappears from the bloodstream do it later if there is a

16:32later next so you're that zebra and your

16:36inners are dragging in the dust this might be a good time to

16:39perk up your immune system a little bit just in case of some effective stuff

16:42with the onset of stress immune defenses are enhanced finally

16:48a whole bunch of hormones secreted during stress

16:52get into your brain and short term their effects are

16:55fabulous they sharpen memory they increase glucose and oxygen delivery to

17:00your brain your sensory thresholds are sharper you

17:04even release this neurotransmitter dopamine

17:07which makes you feel good your memory is working that's that flash bulb memory

17:12where were you when you heard the news i'm willing to bet every single person

17:16in this room no matter how long they live

17:19you will all remember exactly where you were when you heard the news that miley

17:24cyrus was joining the supreme court some stuff you just file away forever

17:30because it's important your brain needs to get a signal this

17:33one do not forget so what you see here is everything going

17:37on here is exactly what you want to do if you're that zebra or that line

17:40you're mobilizing energy you're delivering where it's needed you're

17:43shutting off on essentials you're fighting infections

17:46you're thinking more clearly all you have to do to appreciate that

17:49is look at a couple of weirdo human diseases where people can't do this

17:53one of them is called shy drager syndrome another one is addison's

17:57disease these are not diseases where oh you're

17:59now more at risk for certain cancers this is like somebody with undiagnosed

18:04addison's goes running for the commuter bus one morning

18:07and drops dead from hypoglycemic shock so we've gotten our first critical

18:12take-home message here which is if you plan to get stressed

18:15like a normal mammal you had better turn on your stress

18:18response or else you got about a 30-second life expectancy

18:23for most of us though the far more important take-home message revolves

18:27around so what if you're turning on the stress

18:29response too often too long for purely psychological

18:34reasons and what you get there then is disease

18:38at the other end of it now celie was the first person to wrestle with this issue

18:43why is it that chronic stress makes us sick

18:46and he came up with an explanation in the 1930s and had dominated the field

18:50for the next 40 years which was too bad because he was totally wrong

18:54okay here's what he thought was going on along comes the stressor

18:58knocks you out of homeostatic balance you turn on the stress response you

19:02re-establish homeostasis but the stressor goes on for too long

19:06and thus you enter what celie called the exhaustion phase

19:10you run out of the stress response your adrenals run out of adrenaline your

19:15pituitary runs out of its stress hormones

19:17it's like your military runs out of ammunition and you're just left

19:21defenseless there with the stressor pummeling you

19:23turns out this was totally imaginary there was no such thing as this

19:27exhaustion phase no organism on earth has ever been so stressed that it runs

19:31out of adrenaline you don't deplete the stress response

19:34the problem is that after a while it's not that your

19:38military is running out of ammunition after a while you're spending so damn

19:42much in your military that you don't do health care or social services

19:47or education or any of that stuff and like after a while the stress

19:53response is more damaging than the stressor

19:55especially if the stressor was some psychological nonsense everything you're

19:59doing here is pennywise and dollar foolish it's

20:02inefficient it's less than optimal all of this is

20:06built around it's an emergency it's an emergency fix

20:09later grow layer don't do it right now and if

20:11every day is an emergency you pay the price for it

20:15at the metabolic level mobilize energy because the line's running after you

20:20no problem at all mobilize energy from your storage sites chronically because

20:24you're chronically psychologically stressed

20:26and among other things your muscle mass decreases

20:30muscle is one of your main energy storage sites you get atrophy of muscle

20:34myopathy for extremely complex reasons you're using your energy

20:38really inefficiently for insanely complex reasons

20:42you're now more at risk for adult onset insulin resistant diabetes now

20:46adult onset diabetes is one of those interesting diseases

20:50that our great great great great grandparents never even dealt with

20:54this is a disease of getting older in a typically westernized way putting on

20:59weight getting more sedentary and everything down to the molecular

21:03level that goes wrong in your cells with adult onset diabetes

21:07stress exacerbates the process same punch line at the cardiovascular

21:13level if a line is chasing you and your blood pressure is 180 over 120

21:17you're not suffering from high blood pressure you're saving your life

21:20on the other hand if your blood pressure is 180 over 120 every time you're stuck

21:24in traffic or something you're not saving your life you are

21:27suffering from stress induced hypertension and you do that

21:31chronically enough and you're going to damage your

21:34cardiovascular system okay 30 seconds on stress and heart

21:38disease what's the scenario we all know about

21:40guy gets horrible news and he's wailing about something

21:44and he suddenly clutches his chest in pain kills over dead

21:47sudden cardiac arrest this has never happened this is like a movie plot this

21:51never occurs in real life instead what actually happens requires

21:55you to have like arcane knowledge of high school physics

21:58explaining why like toilet bowl plumbing wears out

22:01after a while you got a tube and you got fluid moving

22:05through the tube and by definition if the fluid is moving

22:09through with more force elevated blood pressure you begin to get

22:13fluid turbulence pounding away on the walls of your blood

22:16vessels causing little bits of pitting and scarring

22:19and tearing and then you get inflammation there and then that's

22:23exactly where like glucose and cholesterol and fat wants to glom onto

22:28to clog your arteries where's the glucose and cholesterol and

22:31fat coming from that's the stuff you're mobilizing into your circulation in the

22:35previous slide so you get this synergistic double

22:38whammy here between the metabolic stress response and the cardiovascular

22:42setting you up for the number one killer in this country

22:45cardiovascular disease now this link between stress and heart

22:50disease is so solid that it accounts for the most

22:53famous personality profile in all of medicine

22:57and it's one where basically if you're coming out to a lecture on a perfectly

23:01nice evening to be outside taking a walk instead

23:04i suspect it applies to like 80 percent of the people in this room

23:08which is those of us in here who have type a personality

23:13okay type a personality type a was first described in the 1950s

23:17by a pair of cardiologists in san francisco friedman and roseman

23:21here was their original formulation time pressured

23:25hostile impatient low self-esteem joyless striving okay like 90 of us

23:32and what they observed back there in the 50s was if this was your personality

23:37profile you were more at risk for heart disease

23:40cardiologists hated these guys you're some like

23:44eisenhower cardiologist and all you're thinking about is like

23:47blood lipids and heart valves and here are these guys saying

23:50no you need to sit down you're patient and talk to them christ who wants to

23:54talk to their patients and talk to them and say okay so suppose

23:58you're in the supermarket and you pick the line that's moving

24:01slowly do you go berserk at that point that's got something to do with heart

24:05disease total resistance to the concept and it wasn't until the 1980s that

24:10enough studies had been done that it became clear type a is for real

24:15big time if you have type a personality you are more at risk for cardiovascular

24:20disease than if you smoke than if you were overweight than if you

24:24have elevated cholesterol levels a huge risk factor now what became clear

24:29by the 80s was the critical component in the type a

24:32profile the piece that is the one that

24:35contributes to the cardiovascular disease

24:37and it's a term now that is used in the field if you have

24:41toxic hostility toxic hostility this attributional style

24:46where everything that happens around you is proof that they're out to get you

24:49they're out to get you more than everyone else and the only thing to do

24:52is watch your back 24 7 and keep a knife ready

24:55this is the style where you're in the supermarket

24:59and you've picked the slow line and you want to kill the son of a bitch kid

25:03behind the cash register come on come on how do you know i have a one o'clock

25:06meeting trying to screw me up no don't ask the old lady how she is today come

25:09on come on come on i'm gonna die someday i get to

25:11you know if this is what you're doing instead of checking out the alpha

25:14sightings in the national enquirer your blood pressure is going to go up

25:18and if this is what you're doing every time somebody

25:21could have held the elevator door open for you but didn't

25:24if you're doing this 40 times a day you're going to pound away at your blood

25:28vessels set up for cardiovascular disease and

25:32these days the main question in that field is

25:35insofar as you were toxically hostile what's worse for your heart

25:39expressing those toxic emotions or keeping them repressed inside what's

25:43clear is expressing them is worse for everybody else's cardiovascular health

25:47but what is the cost of repressing strong physiological emotions

25:51so that's an area of a lot of ongoing research okay so that's stress and heart

25:55disease actually how did those guys first figure

25:59out about type a personality given how much that was coming out of

26:03left field and i actually got to hear the story

26:06some years ago out of the horse's mouth himself meyer friedman the cardiologist

26:10who first described type a died a few years ago in his early 90s

26:14saw his last patient a week before he died was working full-time at a

26:18cardiology unit ucsf medical center as he used to say i'm still type a but

26:23i'm a type a tortoise now and here's the story he would tell in

26:28the 50s he and his partner had this cardiology

26:31practice everything was going great except for this one weird thing which is

26:35they were spending a fortune having to reupholster the

26:38armchairs in the waiting room what's this about who knows whatever

26:43it's part of the overhead every month this upholsterer comes and

26:46there's a chair or two that needs to be fixed

26:49one month the upholsterer is out on vacation replacement upholstery comes in

26:53takes one look at the chairs and discovers type a personality

26:56he says what is wrong with your patients nobody wears out chairs this way and

27:01they have one of them left and as you can see here the front two

27:06inches of the armrests and the seat cushions are totally

27:09shredded and the rest of the chair is perfectly fine it's like every night

27:12there's like dwarf beavers in there clawing away the chair what is this this

27:16is the type a profile this is somebody with type a personality

27:20this is what they do to a chair when they're waiting in the waiting room

27:23with their cardiologists to hear if there's bad news or not

27:26this is not just figuratively but literally sitting on the edge of your

27:30statement seat and squirming and clawing and all of that

27:33this is what somebody who's type a does to a chair in that circumstance

27:37okay so what happens at that point if science is working right and you know

27:43friedman should grab him like good god man what you've discovered

27:46were like like midnight conferences between upholsterers and cardiologists

27:51or or or teams of idealistic young

27:55upholsterers sweeping across america and coming back with the news that no

27:59you don't find chairs like these in podiatrists offices

28:02that's what should have happened what happens instead

28:06here's where 90 year old dr friedman starts looking all sheepish

28:09he says he says i told my nurse get this man out of here i'm this

28:14important cardiologist i can't waste my time with him give him this damn check

28:17get him out of my face he was too type a to listen to the guy and it

28:21wasn't until about five years later that he

28:25collaborated with the psychologist and back came the type a profile

28:28they said oh my god the upholstery he was right

28:32to this day they have no idea who that guy was

28:35now let's see it is late afternoon in san francisco i'm willing to bet there's

28:39some bar in san francisco right now where

28:42there's like this 110 year old retired upholsterer

28:45and get this guy going and he's going to go on and on about how he discovered

28:49type a personality exactly what occurred so one of the dark

28:53chapters in my profession okay moving on digestion shut down your

28:59digestive system for two minutes running for your life it's

29:02not a big deal shut it down chronically and there's all sorts of

29:05gastrointestinal disorders you're more at risk for

29:08most famously ulcers back to celie in the 1930s the first stress-related

29:13disease stress causes ulcer stress causes ulcers

29:16canonical knowledge everybody knows this and then about 25

29:19years ago there's this revolution in ulcerology

29:23turns out there's a bacteria called helicobacter pylorus

29:27turns out the bacteria is responsible for about 90 percent of ulcers in the

29:31west it gets into your stomach it generates

29:34oxygen radicals and blows holes in the walls of your stomach

29:37it's a bacterial disorder this was an enormous contribution the two guys who

29:42discovered against the nobel prize amazing the evening this is announced

29:46every gastroenterologist on earth goes out that evening and celebrates

29:50this is the greatest news they've ever heard

29:52because they're not going to have to sit down their patients and make eye contact

29:56and say if you have any stressful way it's got nothing to do

29:59with stress here's some antibiotics get out my office it's got nothing to do

30:03with stress it's got everything to do with stress

30:05because only 10 percent of people with the bacteria

30:08get the ulcer you've got to have the bacterial risk factor

30:12but you've got to have a lifestyle risk factor overlapping as well

30:17stress stress does not cause ulcers the bacteria does

30:21what does stress do when you got an ulcer beginning to start

30:25your stomach's reasonably good at repairing it

30:28and rebuilding the wall there before the ulcer gets troublesome

30:32unless you're chronically stressed and every day your stomach

30:36walls are saying ah do it tomorrow do it tomorrow it feels like we're being

30:39chased by a predator psychological stress shuts down the

30:43reparations there so here we have a classic example of

30:47interactions between the organic causes of disease

30:50and the psychogenic stress is still very relevant

30:54to making sense of ulcers next growth shut down growth for three

31:00minutes while you're running for your life not a big deal our theme by now

31:03shut it down chronically this can be problematic especially if you were a kid

31:07all kids are are big long-term building projects

31:11and for reasons of psychological stress you keep saying do it tomorrow do it

31:14tomorrow you can impair growth and at an extreme

31:18you have one of the truly bizarre outposts of medicine

31:22a disease of kids who stop growing for reasons purely of psychological stress

31:28known as psychogenic dwarfism psychosocial dwarfism stress dwarfism

31:33these are kids who are years behind the normal growth rates and

31:37there's no disease they're not malnourished there's no parasites

31:42you check their bloodstream there's like no growth hormone

31:45you give them synthetic growth hormone nothing happens the whole system is shut

31:49down and at that point you start poking

31:51around in their background and often out comes some appalling

31:55psychological stressor and the amazing thing is get them out of

31:59that stressful setting technical term do a parentectomy on them

32:02and growth will resume at that point this is incredibly well understood how

32:08this works open up any textbook of endocrinology go

32:11to the chapter on growth and i guarantee there will be the obligatory picture of

32:16the stressed dwarfism kid you know those pictures of

32:18stunted cues like naked in front of the growth chart with a rectangle over the

32:22eyes and turn the page and i guarantee

32:25there's the obligatory follow-up picture the kid in a different environment two

32:29years later he's like six foot fourteen he's playing for the nba

32:33it's everything's you know there's still the rectangle and nakedness but

32:36everything else gets better and what you see there is this is the

32:39system with an amazing capacity to recover remarkable cases of this for

32:45example this was a case report a few years ago

32:48this was a child brought in from an extremely abusive psychological setting

32:52into new york hospital with stress dwarfism and as

32:55documented in the paper at the time he came into this pediatric unit

33:00zero growth hormone in his bloodstream over the next few months

33:04he became very close with one nurse there and this was like the first normal

33:08emotional relationship of his life after a couple of months normal growth

33:12hormone levels for his age at that point the nurse goes on vacation

33:18by the end of her two-week vacation he's back down to zero

33:22nurse comes back a week later he's back up to there

33:26think about this the rate at which this child was depositing

33:30calcium in his bones could be entirely predicted by how safe and loved he was

33:35feeling the world you can't ask for a much better example

33:38of what's going on here affects every outpost in the body

33:43now the issue with stress dwarfism amid people understanding exactly which

33:47hormones are due or what the issue of course becomes how common

33:51is this disease if you were shorter than average and you

33:54were not obviously malnourished as a kid are you a victim of stress dwarfism did

33:58your parents do that to you no this is not like oh very stressful

34:02childhood we were moving all the time this is not like acrimonious divorce

34:06this is nightmare psychopathology this is the police and

34:10the social workers breaking down the door of an apartment

34:13and finding the kid chained to the radiator and smeared and

34:16excrement and just nightmare stuff and get the kid out of

34:20that setting and there's recovery the clinical consensus is this is a once

34:24in a career disease that you see extremely rare

34:28except it's not so rare it pops up all over the place

34:33kids in war zones kids in areas of civil strife

34:37a research assistant of mine and i think we've got the data to show

34:40that kids who wound up in the japanese american internment camps in world war

34:44ii had mild stress dwarfism that pops up

34:46all over the place one classic study in the 60s

34:51looking at rites of passages from cultures all over the planet

34:55rights of passages in one culture they take you out of the desert and stake you

35:00down and cover you in poison ants and some other culture you play the piano

35:03for your grandmother and her friends or whatever's done in your tribe they did

35:07like 80 tribal comparisons they controlled for genetics

35:10back comes the finding stressful rites of passages during the first few years

35:14of life two inches shorter as an adult big

35:18effect let me tell you about the single

35:21creepiest example of stress dwarfism i've ever heard of

35:24if for some inexcusable reason you ever find yourself

35:27reading chapter after chapter about growth hormone you're going to notice

35:31there's a weird thing which is a lot of the chapters make

35:34reference to peter pan some quote from peter pan or some snide

35:39comment about tinker bell i've seen this for years i had no idea

35:42what this was about until one day i stumbled on an explanation

35:45and this was a chapter about the psychological regulation of growth and

35:48was talking about stress dwarfism gave the following case history

35:52eight-year-old boy growing up in victorian england in the

35:561870s one day he sees his beloved older

35:59brother killed in front of him in an accident

36:01this destroys the family there were no other siblings the father was like

36:05emotionally non-existent this was the mother's favorite child and

36:09this victorian swoon she takes to her bed with the shades drawn for the next

36:1310 years this kid growing up in this horrible emotional isolation he goes

36:18into the bedroom with a tray of food for his mother

36:21and she's saying oh david david is that you david have you come to me have you

36:25david the dead son david are you finally oh it's only you growing up being

36:32only you apparently the only thing she ever spoke to him about

36:36was this idea she grabbed onto which was if david had to die he'll always be my

36:40perfect little boy who never grew up and became a man who didn't need his mother

36:44anymore he'll always be my perfect little boy

36:46because he didn't grow up and grow up and grow up this kid hears this with a

36:49vengeance middle class family no evidence of

36:51disease or malnutrition boy stops growing there at age eight

36:55lives to age 60 4 foot 10 as an adult unconsummated

37:00marriage incredible example of stress dwarfism

37:05and then then the chapter concludes by informing us that as an adult this was

37:10the author of the much beloved children's classic peter pan

37:14this was j.m barry the guy who wrote peter pan who's incredibly

37:18screwed up this guy all he did was crank out

37:22book after play after novella about boys who die and come back as ghosts and

37:26marry their mothers his private journals were full of

37:29sadomasochistic fantasies about little boys

37:32this guy spent the rest of his life dealing very unsuccessfully with this

37:36stress dwarfism so think about that the next time you see johnny depp

37:40up on a movie okay next next reproduction your gonads

37:47your gonads your gonads are not going to be working very well if you were

37:51chronically stressed if you were a female mammal of virtually any species

37:55if you were chronically stressed your cycles will become irregular

37:59lengthened they may stop all together stress induced amenorrhea stress-induced

38:04and ovulation and people understand exactly how those

38:07work which hormones are working at the brain at the pituitary at the

38:11ovaries of the uterus to shut things down

38:13let me tell you about one of those steps because it's got to do with a very weird

38:17thing that female mammals do including human females which

38:20is they secrete a certain amount of male

38:23sex hormones into the bloodstream hormones that are related to

38:27testosterone androgen type hormones they come out of the adrenal glands not

38:32a ton of the stuff maybe five percent the levels you would see in the male

38:35nonetheless you got to get rid of it unfortunately

38:38female mammals come with this enzyme and fat cells

38:42that take circulating androgens and does biochemistry 101 and converts

38:48them to estrogens great perfect problem solved

38:51everyone lives happily ever after what if you're stressed

38:54what if you're stressed like the locusts have come and eaten your crops

38:58and you're subsisting on 800 calories a day what if you're slowly starving

39:02your fat stores are slowly getting depleted

39:05and at some point you have too little functional fat cells

39:09to do the androgen to estrogen conversion

39:12one problem is there's now a little bit less estrogen in the bloodstream

39:15bigger problem is the androgen levels build up there and that shuts down every

39:19step in the system that's why starvation shuts down

39:22ovulation that's why voluntary starvation anorexia

39:27does the same and that's why some women who do

39:30massive massive amounts of exercise will stop ovulating as well

39:35because you get below a critical fat muscle ratio there now this is something

39:40that's been studied at length in girls for example it's always studies

39:44of very serious ballet dancers or gymnasts

39:47what you see is significant delay in the onset of puberty

39:51one study for example this was done on the olympic gymnastics squad from

39:55romania you know those 60 pound 15 year olds getting the gold

39:59medals all over the place what was the average age of which these kids started

40:02menstruating 19. 12 and a half is the western average

40:08once hitting puberty women who do tons of athletics

40:11is best studied long distance runners women who run an average of 40 to 50

40:16miles a week that's typically the range where fat

40:19stores are getting below threshold where you begin to have ovulatory

40:22irregularities i can tell you the exact same story about men

40:27men who run 40-50 miles a week sperm count goes down there's mild testicular

40:32atrophy okay wait a second i thought exercise

40:35was good for us exercise is good for us and in fact a

40:39lot of exercise is very good for us that doesn't mean though that an insane

40:42amount of exercise is insanely good for us

40:45it means at some point too much of a good thing is just as bad as too little

40:49you've passed a point of homeostatic balance

40:52and all you need to do to get an appreciation for that is imagine

40:55you sit down some hunter gatherer from the kalahari desert and say you know

40:59where i come from we have so much food and so much free time that

41:04sometimes we'll just go run 26 miles in a day for the sheer pleasure

41:07and they're going to say are you crazy that's stressful

41:11i mean throughout hominid history if you're running 26 miles in a day

41:15either you are very intent on eating somebody or somebody's intent on eating

41:18you this is not normal physiology so we get a cautionary note

41:23here meanwhile over at the male end of things

41:26with the onset of stress down go testosterone levels anesthetize

41:31a guy slice into his belly for surgery 10

41:33minutes later testosterone is plummeting first year male medical students during

41:38exam periods down go testosterone drop the rank of a male baboon at a

41:42hierarchy down goes testosterone here's a stressor which thank god i have

41:47no personal experience with at all but apparently it's not fun to be in the

41:51marines apparently it's kind of a drag

41:54especially during basic training this was this classic study

41:571970 new england journal of medicine looking at military recruits during

42:01basic training were now on top of everything else they

42:03had to pee into little dixie cups for the psychiatrist

42:06and back comes the finding guys in the in the marines during their first couple

42:10of months of service they have the circulating androgen

42:13levels of like vatican choir boys that's how much the system is shut down

42:19okay so people understand exactly which stress hormones are working at

42:24the brain the pituitary and the testes to shut down testosterone synthesis

42:28during stress the question you gotta ask at this point

42:32is so what are the consequences of testosterone levels declining during

42:36stress and amazingly enough the answer is

42:39there's no consequences at all testosterone turns out to be this vastly

42:44overrated hormone like basically all you need is like a

42:47thimble full of stuff and a couple of sperm and you're in business

42:50you've got to knock out like 90 percent of the guys testosterone levels to

42:54seriously impair fertility stress what does it do at its worst only

42:58about a 60 decline it's not suppressed enough that

43:02it makes a difference the problem during stress is not that

43:05testosterone levels go down the problem is that penises go down

43:10okay am i allowed to talk about this in champaign urbana here

43:14okay finally we come to the first like useful point in this damn lecture so how

43:19do erections work okay so erections in order to i just saw

43:25somebody there pick up a pen for the first time

43:30okay so how do erections work in order to have an erection

43:33you gotta have a spinal cord now most of what your spinal cord does is totally

43:36boring and makes you shake hands and sign checks and foxtrot

43:40or who knows what but then there's the part that does the good

43:42stuff the stuff you normally don't have any control over stuff that is

43:47automatic like goose flesh and orgasms and pupillary contractions and blushing

43:53things that are automatic and thus run by the

43:56automatic nervous system also known as the autonomic nervous system

44:00now the autonomic nervous system comes in two halves first half

44:04sympathetic nervous system emergency arousal adrenaline

44:08stress response all hell breaking loose second half

44:12the parasympathetic nervous system calm vegetative function you take a nap you

44:18turn on the parasympathetic nervous system

44:21you eat a big starchy meal you turn on the parasympathetic nervous system

44:25you get disemboweled by a lion you turn off the parasympathetic nervous system

44:28it works in opposition with a sympathetic

44:31okay so here's the rule in order to get an erection

44:35you've got to turn on the parasympathetic nervous system

44:38you have to be calm and vegetative okay so you got your erection now what

44:43happens next maybe for some social reason having to

44:48do with the context that brought about the erection maybe

44:51you start feeling a little bit less calm and vegetative

44:54maybe your heart rate increases a little maybe your breathing rate maybe your

44:58muscles are starting to do some work slowly you're starting to turn

45:02on the sympathetic nervous system more time goes by your heart is racing

45:06your toes are curling you're sweating you're breathing fast all of that

45:10eventually you get to this point where your whole body is screamingly

45:12sympathetic except for this one lone outpost we are desperately holding on to

45:16parasympathetic tone as long as possible finally can't take anymore you turn off

45:19the parasympathetic turn on the sympathetic and ejaculate

45:25okay so that's how erections work so what happens during stress what happens

45:30during stress you're not very calm and vegetative you can't get the

45:35erection stress induced imminency or you can have a second problem suppose

45:39you manage to get the erection and you think like oh no donald trump

45:43who knows why you accelerate the transition you accelerate the

45:50transition from parasympathetic to sympathetic the

45:53whole thing goes too fast either you can't get the erection

45:57or premature ejaculation incredibly easy

46:00for this to occur current estimates are 60 percent of the

46:03visits by men in this country going to doctors about erectile

46:07dysfunction turn out not to have an organic disease basis

46:11but instead are psychogenic stress-related

46:14okay second useful piece of information so how do you tell the difference

46:18between a case of organic infancy and psychogenic

46:21so a guy comes to you says he hasn't been able to have an erection during sex

46:25in the last six months and you're wondering well is the stress

46:28related or does he have a pituitary tumor whatever

46:31you take advantage of a weird thing that male primates

46:34including human males do which is when they go into rem

46:38sleep rapid eye movement sleep they get erections

46:42i've no idea why i've talked to earth's penis experts nobody has an explanation

46:46for this nonetheless male primates get rem sleep

46:49erections so here's what you do the guy who hasn't

46:52been able to have an erection during six sex and months what you do is you give

46:55him this handy-dandy little penile pressure cuff

46:58transducer thingy that he takes home and just before he goes to sleep he

47:02puts it on the base of his penis and wires it up and

47:05satellite relays and 24-hour operators in bangalore and the next day

47:11the next day you got your answer which is if this guy hasn't been able to have

47:14an erection during sex in the last six months but 30 seconds into his first rem

47:18stage he has a perfectly normal erection he doesn't have a pituitary tumor it's

47:22stress related that's how you distinguish between the

47:25two do you still get the nocturnal erections

47:28if that's the case it's stress related very easy to actually maybe this is not

47:32so easy because you got this electronic device

47:35and it's beeping and the wires and you're

47:37so sure it's going to electrocute you that's a stressor in and of itself

47:40this is what is done in the majority of sexual dysfunction clinics in this

47:45country i kid you not you take a long string of

47:48postage stamps you lick them at one end and you wrap

47:51them around the guy's penis and the next morning if the stamps have

47:54been torn loose the guy had an erection during the night

47:58can you believe like how elegant this is like five bucks

48:02you get a lab result it's fabulous yeah oh of course

48:07insurance won't reimburse you for the stance but

48:09still you know maybe obamacare still has a chance okay so

48:15what we see here is another outpost of vulnerability and perhaps we should

48:19hurdle on before i embarrass myself further your immune

48:22system your immune system so as we heard before with the onset of stress

48:25you enhance your immune defenses with chronic stress

48:29something very different occurs with chronic stress

48:33not only does the immune system go back to baseline you suppress immunity

48:38with chronic stress you become immune suppressed

48:41and this is the starting point for just this irresistible syllogism

48:45insofar as chronic stress chronically suppresses the immune system

48:49chronic stress should set you up for more infectious diseases

48:53and this is the basic premise behind this field that emerged about 25 years

48:56ago psychoneuroimmunology the notion that

49:00what's going on here is affecting your immune defenses in a

49:04quarter century into this field it's clear that's exactly how it works

49:08for all the boring stuff when you were under stress the common

49:12cold becomes more common you're at more risk for mononucleosis

49:16for herpes viral flare-ups reactivation what's far less

49:20clear is what about bigger realms of

49:23infectious disease how about if you have aids your immune

49:27system declining if you're severely stressed does it

49:30decline even faster jury is out on that one it seems to have

49:34to do with personality type as an intervening variable

49:38how about the biggest one on everybody's list

49:41when it comes to worrying about disease so what's the relationship between

49:44stress and cancer and everybody knows the

49:48answer to that which is cancer is a stress related

49:51disease stress can cause you to have cancer

49:54stress can cause you to come out of remission

49:57from cancer stress can accelerate the growth of tumors

50:00everybody knows about this sufficiently so that some years ago there was a study

50:04in jama journal the american medical

50:05association looking at women who had just gotten a metastatic breast cancer

50:09diagnosis where they were asked so what do you think is the cause of

50:12your cancer and by more than a two to one margin the most common answer was

50:17stress too much stress in my life stress has virtually

50:22nothing to do with cancer there has never been

50:25a decent prospective human study longitudinally

50:28that shows that stress increases the risk reoccurrence or growth rate of any

50:33type of tumor when they're well controlled there have

50:36been all sorts of studies showing how stress can accelerate tumor

50:40growth in lab rats we know how it works my lab did some of

50:43that work but it turns out these are types of cancers that are completely

50:46irrelevant to human cancer this is a realm where there's not much

50:50connection at all amid all those things on the right sides

50:54of these charts you need to worry about this is one domain where you don't why

50:58is it important to emphasize this because of all of these highly

51:02credentialed quacks who are making a fortune off of cancer

51:06patients saying my special brand of stress therapy will

51:10slow down your cancer stop it reverse it credit cards accept it

51:14there's no science to support this bad medicine bad

51:17science bad ethics this is a domain where you don't have to worry

51:22okay so quickly let's hurtle back to domains where you do have to worry okay

51:25so back to stress in your brain we saw short term

51:29does all sorts of great stuff chronically

51:32bad news chronically stress will damage a part of your brain called the

51:36hippocampus which is essential for learning and

51:39memory stress has something to do with failure of memory consolidation there

51:45shrinkage of neurons disconnecting of synapses

51:48at an extreme killing of neurons inhibition of the birth of new neurons

51:52there and this is turning out to be relevant

51:55to humans and a number of scary realms people with chronic stress due to ptsd

52:01post-traumatic stress disorder combat trauma or sexual abuse trauma and

52:06what you see there is atrophy of the hippocampus only the

52:09hippocampus the more severe the trauma history the

52:12more atrophy the more memory problems best evidence is this is not reversible

52:18second syndrome pertinent to the 10 to 15 percent of us in this room

52:23destined to have major clinical depression the

52:26poster child and psychiatry of a stress related disorder

52:30it involves chronically elevated stress hormone levels and

52:33scads of studies now showing atrophy of the hippocampus only the hippocampus

52:38the more severe the depression history the more atrophy

52:41the more memory loss and as far as most studies show at this point

52:45this is not a reversible process meanwhile next door to the hippocampus

52:50is a brain region called the amygdala and in the amygdala things are real

52:55different hippocampus does learning and memory for you

52:58amygdala teaches you to be afraid it does

53:02fear it does anxiety and while stress is atrophying away those hippocampal

53:08neurons stress is making neurons and the

53:10amygdala work better than usual they expand their

53:14connections the synapses become more excitable

53:18people with ptsd have amygdalas that grow larger than normal

53:22stress makes it easier for you to associate

53:26things with fear that are not actually valid and makes you harder to detect

53:31to detect safety signals this is the link between

53:34stress and anxiety meanwhile over in that part of the brain where

53:38you're releasing dopamine which has something to do with pleasure

53:42with the onset of stress chronic stress and you're depleted of dopamine what is

53:47this setting us up for explaining the link between stress and depression

53:52the defining symptom of depression is anhedonia hedonism the pursuit of

53:57pleasure and hedonia the inability to feel pleasure this is

54:01the neurochemical link why chronic stress is a major

54:05precipitating factor for depression so okay if you're still

54:09awake at this point you should be depressed as hell

54:12okay so amid that it must seem like a miracle that any of us are still alive

54:17actually let me make this worse one last stress related disease

54:20this is like stress for 2000. how many of you have heard of a disease called

54:24idiopathic alopecia areata

54:29okay a few hands this is the profoundly rare state

54:34of somebody being so so traumatized by something that over the next few days

54:39their hair turns white and falls out this is for real

54:42people understand like what the immune system is doing the hair follicles there

54:46it's real it's a once in a career disease but nonetheless this is free

54:49look at this you're chronically stressed you get high blood pressure you get

54:52diabetes you get flatulent your sex life is ruined your brain gets damaged and

54:56your hair falls out how is it any of us are still

54:59functioning here why haven't we all collapsed into puddles of stress-related

55:02disease and the critical thing is most of us

55:06don't most of us cope and what's been clear

55:10from the first day of the field with celie

55:12is some individuals cope with stress better than others

55:17what i want to spend the last couple of minutes on is how we understand this to

55:21work why do some bodies and more importantly some psyches deal

55:25better with stress than others okay so if we're talking about

55:29individual differences and stress responsiveness here

55:32we're not talking about physical stressors finish this lecture

55:36go outside unexpectedly be gored by an elephant and

55:39you're gonna have a stress response there's no way you can't reframe your

55:43experience and grow from adversity or who knows what

55:46you're gonna have a stress response finish the lecture go outside and have

55:49kind of a tense ambiguous interaction with someone and

55:54only some of us will have a stress response

55:57what is it about that gray zone of psychosocial interactions

56:01that is more stressful for some individuals and others

56:04what we're asking here is what is it that makes

56:07psychological stress stressful and remarkably a

56:11massive literature stretching back decades shows

56:14what precisely are the building blocks of psychological stress

56:18okay here's a schematic summary of the gazillion studies what they would sort

56:22of show take a lab rat put him in the cage every

56:25now and then he gets a shock mild shock and

56:29nonetheless with enough of them this is stressful blood pressure goes up

56:33heart rate goes up risk of ulcer goes up as shown here

56:36you're giving the rat a stress related disease

56:40now second line in a second cage there's another rat psychology jargon the second

56:47rat is yoked to the first rat every time the first rat gets a shock so does the

56:53second same intensity same duration same everything

56:56according to celie in 1930 both of their bodies are being knocked out of

56:59homostatic balance the exact same extent except for a critical difference which

57:03is every time that second rat gets a shock

57:06it can go over to the other side of the cage where there's another rat

57:09and it can bite the crap out of it and you know what that rat's not going to

57:13get an ulcer the guy is biting isn't going to get one but this one doesn't

57:16he has an outlet for his frustration third line now we have in the second

57:22cage a second rat getting the same shock same duration same intensity same

57:25everything but each time he gets a shock he can go over and there's a bar of wood

57:30that he could gnaw on with his teeth and he doesn't

57:33get an ulcer he has a hobby okay now the next line

57:39what we have here is same shock same intensity same everything

57:43but 10 seconds before each shock the second rat

57:46a little warning light comes on and the rat doesn't get an ulcer

57:50for the same external stressor we are more protected when we get

57:55predictive information when is it coming how bad is it going to be how long is it

57:59going to last and we all know that principle every

58:01time we ask the dentist how much more drilling

58:04and we all know the difference between the dentist that says two more bits and

58:07we're done on the one that says yeah it could be it could be weeks

58:09you're gonna be here and when the dentist says two more bits of drilling

58:13bad news you're not done yet good news the second that second bit of drilling

58:17is over with you're safe for the rat in the first

58:20line any second you can be a half second away from the

58:23next shock next line this is a rat that's been

58:28trained to press a lever by pressing the lever it decreases the

58:31likelihood of getting a shock today the rat is yoked to the first one

58:36getting the same shocks as the first guy but there's a lever in there the lever

58:40is disconnected the leverage has done nothing whatsoever but the rat doesn't

58:42know what so he's in there pounding away the lever saying this is

58:45great just imagine how many stock you're getting otherwise he thinks

58:48he has control for the same external stressor

58:51a sense of control makes things less stressful

58:55jumping ahead to the final line shock a rat and now it goes over to the other

58:59side of the cage where there's a rat that it knows and likes and they groom

59:03each other and it doesn't have a stress response wow

59:07science has finally proven that friends are good for your health

59:10science has proven this big time when you look at

59:13all of behavioral medicine and all of health psychology

59:16there are two of the biggest predictors out there

59:20as to mortality rates across all diseases the first one

59:23taps into every one of the factors on the slide which is

59:27never ever make the mistake of being born into a poor

59:32family because your health is going to pay for it the rest of your life

59:35the link between health and socioeconomic status very heavily

59:39mediated by stress the second biggest predictor is if you

59:43got a choice in the matter don't be socially isolated and you look

59:48at the extremes of social isolation versus social

59:51affiliation significant other others small group of

59:55friends community group you're intentionally involved with

59:57for the same disease impact almost a threefold difference in mortality rate

1:00:02and that's after you control for stuff like ooh people who live alone just eat

1:00:05cheetos for dinner and nobody reminded to take their meds

1:00:08control for that and social isolation is an

1:00:11aching stressor for every primate out there including us

1:00:15and a huge health risk factor so what is it that makes psychological stress

1:00:20stressful for the same external misery you are

1:00:24more likely to feel subjectively stressed

1:00:27more likely to turn on a stress response and more at risk for stress-related

1:00:32disease if you feel like you have no control no

1:00:35predictability no outlets for the frustration if you

1:00:39interpret things as getting worse and you have nobody's shoulder to cry on

1:00:43and basically this is the place to stop because again

1:00:47none of us are getting ulcers because we're being chased by saber-toothed

1:00:50tigers none of us are ever gonna have to

1:00:52wrestle people for canned food items and bombed out supermarkets

1:00:56instead we are going to have this luxury of living well enough and long enough

1:01:00amid our psychological stressors to pay the medical cost

1:01:04and that's the critical point at the end to the extent that we are

1:01:08smart enough to have invented these psychosocial stressors

1:01:11and then stupid enough to have fallen for them we all have the potential to

1:01:15instead be wise enough to keep them in

1:01:17perspective so on that note thank you for your attention and good

1:01:22luck with your stressors

1:01:51wow i see my mother did manage to call all of you before the lecture today

1:01:56thank you he's still blushing from the erection

1:01:59topic so uh welcome back to that i wanted to ask you a question this is i

1:02:04have a strategy of coping and i'm not sure it's it's the best

1:02:07strategy um i so i i experience a lot of stress and so

1:02:11my here's my coping strategy i always am expecting the worst so basically

1:02:18you know when i'm applying for a grant or something i'm i'm expecting not to

1:02:21get it if i'm you know submitting a paper i'm

1:02:23expecting it to get rejected and this is a coping strategy for me because

1:02:28if uh you know if it turns out that i don't get the grant then i'm not really

1:02:31let down and that's in a way it helps me predict

1:02:34the stressor but on the other hand i'm thinking about

1:02:36it i'm thinking well then i'm always constantly thinking about the

1:02:39worst and it's kind of a pessimistic attitude

1:02:42so basically my question is is this a bad strategy

1:02:46yes

1:02:50i would recommend first just taking out your adrenal glands that that will

1:02:53probably be more effective okay what we have here is the difference

1:02:56between bad outcomes and unpredictable outcomes

1:03:00the problem with over always expecting the worst

1:03:03is you're probably not really expecting the worst

1:03:06you're expecting maybe your grant won't get a good score you're not expecting to

1:03:10be disemboweled by your grant review committee

1:03:12so it's a moderately bad outcome that you're now over expecting

1:03:16that you're now expecting and the trouble is when something good happens

1:03:20it's good but what it also tells you is hey

1:03:23i thought i understood how the world worked and

1:03:26my model as to what cause and effect is about here is not quite so great

1:03:31and i blew it on expecting something good to happen maybe i'm blowing it also

1:03:34and expecting really bad stuff to happen the

1:03:37unpredictability there outweighs the goodness of it and various like

1:03:42classic studies have shown that under circumstances where you give

1:03:47rats more a bigger food pellet than they

1:03:50expected for this amount of level pressing

1:03:52good news but whoa they thought they understood how the world works within

1:03:57the right parameters that's more stressful because it's

1:04:01telling them they don't really understand how the

1:04:03world works that's fine for a bigger food pellet but what else don't i

1:04:06understand so you're saying when i get the grant

1:04:09then it's uh then you have to convince yourself why

1:04:14you knew you were going to all along yeah

1:04:17i have a question that maybe reframes the topic which is we

1:04:21look at stress and its consequences and there's the inverse of stress which is a

1:04:25sense of well-being or flourishing and i'm curious in your research if you look

1:04:30at that and um perhaps it's doing these four things

1:04:33really well but um is there a body of work that you can

1:04:37point to or are you motivated to to you know study around people who seem

1:04:41to be flourishing who live longer who seem to cope better

1:04:45okay this celie back in the 30s tried to introduce a word that never caught on

1:04:50which was eustress e-u-s-t-r-e-s which is good stress and somehow that

1:04:56never quite became popular but it was built

1:04:59around the fact that like a goal if you study stress

1:05:04biology or stress psychology or anything the goal is not to eliminate stress from

1:05:08our lives because the trouble is we love stress we love stress when it's

1:05:13the right kind when it's the right kind we pay good money for it we like push to

1:05:18see the front watch like what exciting tournament is

1:05:21happening we pay good money to get on roller coasters and get

1:05:24terrified we love stress when it's good so the question

1:05:28becomes what constitutes good stress and it turns out that it's within a

1:05:34fairly narrow parameter good stress consists of

1:05:37a stressor that's not too extreme you get on the roller coaster and you

1:05:42know there's a chance you're going to be made a little bit queasy afterward not

1:05:46decapitated it's not too long lasting it's not for

1:05:49nothing roller coaster rides aren't three weeks long

1:05:52so it's transient moderate and most of all it's occurring in what's overall a

1:05:56benevolent environment because when we're feeling safe we love

1:06:00to give up control and predictability because we

1:06:04love being surprised in safe settings what do we call that

1:06:07we call that play we call that stimulation we call it getting it to the

1:06:10optimum amount i mean what are dogs doing when they play

1:06:13the dominant one crouches down and says for the next whatever length of time i'm

1:06:18gonna i'm gonna sort of eliminate our

1:06:20dominance relationships so you can put your teeth on my throat

1:06:24or my privates or whatever and it's gonna be okay

1:06:26you're safe now come and surprise me and i'll try to surprise you too

1:06:30what we call the optimal amount of stress is stimulation

1:06:35and in that regard the opposite of play is not

1:06:38work the opposite of play is depression it's getting

1:06:41just the right amount of stress and of course what the gigantic challenge is is

1:06:46one person's version of just the right amount is what's like perforating

1:06:50somebody else's stomach there the enormous individual differences but

1:06:54what the successful aging people generally show

1:06:58is a capacity to respond to moderate stress responses

1:07:02and to be able to distinguish between those and the big persistent ones

1:07:08um so i i had a question about depression so

1:07:11we talked a little bit about this the other day depression has been increasing

1:07:15in our society now year after year and it doesn't appear to be due to a

1:07:20difference in the way we diagnose the illness it appears to be a true increase

1:07:24in the incidence of depression and it doesn't seem to be

1:07:28keeping pace with any possible genetic changes in our population so that means

1:07:32that there's something in our environment

1:07:34that's been changing over the years that's increasing the incidence of

1:07:38depression and the question for you is what do you

1:07:40think that is well you get some important hints when

1:07:44you sort of look at the demographics of the epidemiology

1:07:48epidemiology of that in more detail the increasing rate with each sort of decade

1:07:53or so is due to increased numbers of people

1:07:56who are getting their first depressions as

1:07:58adolescents or young adults in other words increasing number of

1:08:02people who have now joined the lifelong ranks of depressives

1:08:08so you sit there and like there's really no way that

1:08:11being like your typical american adolescent these days is truly more

1:08:15stressful than like being in the dust bowl or being a

1:08:18medieval peasant or who knows you you really can't make i mean be be a

1:08:23be a farmer in the developing world watching

1:08:26locusts doing your crops and like that sort of beats bullying in lots

1:08:31of ways but when you look at it it's not that we

1:08:34have more stressors this is the stressors we have are overwhelmingly

1:08:39inventions of our lifestyle where i think

1:08:42things have gone awry is we have less sources of support

1:08:46and i think that takes two forms one is i'm the last person on earth to start

1:08:50spouting norman rockwell sort of stuff but the rate of divorces and the

1:08:55disintegration of the traditional nuclear family or anything that clank

1:08:59falls for stability in a family that has to be a big factor

1:09:03the other is this incredibly american god-given right that we all expect

1:09:08which is to be able to be mobile and anonymous

1:09:11we are more than any country in the world we live

1:09:14further on the average than where we were born we move more frequently we

1:09:18have a lower likelihood of knowing the names of our neighbors

1:09:21and that's what makes silicon valley possible that's what makes

1:09:25you know maasai goat herders don't invent silicon valley

1:09:28people who are willing to go anywhere and work whatever and work 24

1:09:337 and who knows if they ever learn the name of their neighbor because that's

1:09:36not the point and you move on to the next one and

1:09:39along comes like a 911 and half of the country discovers they

1:09:42don't know the names of their neighbors and that's the trade-off all of us want

1:09:47this right we have more unlisted phone numbers back

1:09:50when that was something in common than in any other

1:09:52like country on earth more mobility we want to be able to move and we want to

1:09:57be anonymous and we want to be able to come up with a new persona

1:10:00and a new accent and a new name and a new who knows what

1:10:04and then we discover we have none of the traditional primate forms of social

1:10:07support i suspect that's where it's coming from

1:10:10what about social media though in social uh being having an online social

1:10:14presence does that does that influence this positively or negatively and in

1:10:17some ways it elevates your sense of where you are in the socio-economic

1:10:20status in other ways it may bring you closer um all things

1:10:24considered as the father of two teenagers i think it's basically awful

1:10:28what it does because it opens up all sorts of venues

1:10:32people and circumstances and things you never even knew existed before

1:10:36can now make you feel crappy about yourself and diminished

1:10:40and insecure and not adequate and not up to measure

1:10:43and what it also does is train you to mistake like

1:10:46the most like fruit fly level of model systems of what passes

1:10:52for like human sociality for actual real like connectiveness

1:10:59but how do i really feel about it

1:11:04many of you may not know i'm an investor in social media so

1:11:07i feel like this is um so along those lines you know it seems

1:11:15like the coping mechanisms here um are what many people might take away

1:11:19from tonight's talk which is you know how do you

1:11:21in the world that we live in apply this and

1:11:24i'm curious if any of these four things and maybe there's more

1:11:27have gained elevation in your mind in the last years and if others have lost

1:11:31elevation do you think we should be focused more

1:11:33on some versus others yep all things considered i think the one

1:11:38that has probably gained most improvements

1:11:41is social support if you got a choice in the matter amid

1:11:46all of those there more control over when your boss wastes

1:11:50your time with them like pointless meeting more predictabilities

1:11:53you know whatever more you know health club memberships as an outlet more

1:11:59walls to punch with your near frustration um

1:12:02the literature seems pretty clear that when it works right the social support

1:12:05is the one that's most effective is there a type of social support

1:12:08you know is it one good friend a group of kids which brings the next question

1:12:12at the same time the one that's lost the most sort of veneer

1:12:16is social support because of the enormous tendency people have to confuse

1:12:21like mere acquaintanceships or friday night whatever is with actual

1:12:25it's like hard it takes a long time it takes a great deal of patience it takes

1:12:29reciprocity and maturity and selflessness and all this stuff that all

1:12:33of us like fail miserably at at various points real real sustained

1:12:38social affiliation is like a very hard thing for primates

1:12:43to get good at including us what the studies tend to

1:12:46show though is there's no particular difference between

1:12:50a significant other a small group a community i mean

1:12:53they're all equally effective but within that i mean

1:12:57where the tarnishing comes from is nothing is more corrosive to us

1:13:02when we discover that a supposed source of social support was actually just

1:13:06an acquaintance after all and that it wasn't really there

1:13:11an interesting recent study published a couple of weeks ago

1:13:14in pnas a very prestigious journal in the country a little big

1:13:18long longitude longitudinal study looking

1:13:21at how much does social isolation impact health

1:13:25and does it do it during young adulthood as much as an old age and the general

1:13:29punch line was it's a terrible thing for you lifelong

1:13:32and this is like a standard finding in the

1:13:35literature quantitative measures how many people do you talk to on a

1:13:39regular basis how many people could you borrow money from

1:13:42how many organizations do you a quantitative measure what was unique

1:13:46about this study was they also took qualitative measures

1:13:49they asked people to assess on some scale

1:13:52how much support do you get from the people closest to you

1:13:57how much strain do you get from the people closest to you

1:14:01and that came the first finding which is the quality of the relationships

1:14:04trumped quantity far more in terms of impact on health

1:14:08but what was really the most interesting thing in the study was if you have the

1:14:11choice in the matter between making a new close supportive friend

1:14:15or getting rid of that high maintenance friend who's been like you've needed

1:14:18like a hole in the head for the last 30 years the source of

1:14:22strain was more of an adverse effect on health

1:14:25than source of support being a good thing on health which i thought was

1:14:28extremely interesting so i'm going to ask one last

1:14:32question and then what i'd like to ask the audience if they would like to ask a

1:14:35question to go to the microphones on other side my last

1:14:38question is uh about antidepressants so as you know um

1:14:43antidepressants are widely prescribed and many of the big

1:14:47clinical trials that have been done with these antidepressants like ssris as you

1:14:50know have failed suggesting that the antidepressants

1:14:53don't do any better than placebo however if you talk to any clinician or

1:14:57psychiatrist who prescribes these medications

1:14:59or people who take them they will swear that they work and so my question to you

1:15:03is one do they work and two

1:15:06is there any chance we're gonna get out of the dark ages in terms of how they

1:15:09work um yes and no i think the dark ages are

1:15:14going to be there for a long long time i think the reason why on on the average

1:15:19one-third of major depression patients

1:15:23fail to respond to antidepressants and another third respond would give up on

1:15:26them because of the severity of the side effects

1:15:29um so in other words there are oceans of clinically depressed people out there

1:15:34who are not being adequately helped by the best of current

1:15:37neuropsychopharmacology the question becomes why is that there's

1:15:41just a whole like menagerie of antidepressants

1:15:44out there working on by now five six different

1:15:47neurotransmitter systems where in most cases it's guesses as to

1:15:51how selectively it's actually working on one versus the other

1:15:54so there's like a gazillion different permutations of

1:15:58combinations and different dosages at the same time as with like every

1:16:02interesting human disease it's actually a whole bunch of different

1:16:05diseases and heterogeneous and people have such a poor sense at

1:16:09this point you get your average clinician of course

1:16:12thinks that they're better than the average clinician

1:16:15and what they also think is that they have a good intuition

1:16:18this kind of depression responds best to this combination

1:16:22have this much of drug a this much of drug whatever and

1:16:26this mixture and because i saw one fantastic response once

1:16:30and it's sheer well i'll try to find a good term for it

1:16:35it is it is a posteriori theorizing as to how these things work

1:16:41it's like an amazingly complex system like lose a parent to death when you

1:16:47were a child and 60 years later you were more at risk

1:16:50for this disease like throw one medication in there and

1:16:53you expect that to be able to do it it's going to be a long long time

1:16:57nonetheless amid that pessimism and amid the considerable side effects

1:17:02of these drugs and the fact that god knows what neurological costs we're

1:17:06going to discover down the line from 50 years of ssris or whatever and

1:17:10oh my god nonetheless an unmedicated major

1:17:14depression is one of the most life threatening

1:17:17diseases on earth the drugs with all their side effects are a really

1:17:21miserable solution these days but they're far better than the alternative

1:17:27so um in the last few minutes are there any questions on the side

1:17:30i can't see if people are over there or not we have one okay

1:17:48thank you for taking my question really enjoyed the talk

1:17:51um we have a 13 year old son at 13 years old who developed chronic nausea

1:17:57and had a multi-million dollar workup and tried all these meds and everything

1:18:02ultimately to make a long story short what ended up helping him was vagal

1:18:06nerve stimulation and ever since then i've been reading

1:18:11a lot about it and what i don't understand what i know is that it is

1:18:15fda approved for medicine for depression that is not responsive to

1:18:21medication why isn't it approved for depression

1:18:25at all and and let's do away with some of these meds

1:18:28um let's see i start off by pointing out that

1:18:32i know tons about like rats and monkeys and neurons and dishes but i'm

1:18:36not a clinician but my sense is that vagal nerve stimulation

1:18:40is upping the parasympathetic component of the common vegetative half

1:18:45and there's drugs that will do it as well and it happens to be more effective

1:18:48this way um i don't know why it's not used more

1:18:51broadly say for other realms but everybody out there is always looking

1:18:55for what termed off label novel uses for various

1:18:59techniques if it works someone's going to find it

1:19:02soon that it does

1:19:06thank you for the wonderful lecture and my question is how do i tell if i'm

1:19:10stressed too much or not

1:19:15well if you have to ask you are there's one possible answer

1:19:21more useful one maybe a different way of framing it is so what are

1:19:24amid all the different from common to incredibly arcane diseases that are

1:19:29stress sensitive what are the most vulnerable spots where

1:19:32the the canaries in the mine shaft varying from person to person tending to

1:19:37be gastrointestinal sensitivity which could range from

1:19:40everything from suppressed appetite to stimulated appetite to constipation to

1:19:44the runs and everything is so something's out of whack at the

1:19:47gastrointestinal level sleep disruption and females disruption

1:19:52of regular cycling and major mood disruption depression

1:19:57problems with concentration anxiety i mean maybe

1:20:01the most likely symptom for you would be if your hair turns white and falls out

1:20:05and otherwise you're just fine but for most people those are the most

1:20:08vulnerable spots

1:20:13also thank you very much for the talk and your fear and aggression lectures

1:20:16which i kind of stole off of youtube for something i was teaching so do you think

1:20:21there's a fundamental incompatibility between

1:20:24the brains we evolved with and the type of information we're required to hold on

1:20:27to and use to exist in a modern society and doesn't that sort of play into the

1:20:32unpredictability aspect i can't hold on to when i need to

1:20:35pay my accounts and what do i do with obamacare now that i'm

1:20:38going back to school and how will i lose my insurance

1:20:41these arbitrary rules and the tax code whatever very hard to hold on to very

1:20:44hard to predict would have huge impacts on what actually

1:20:47happens in your life and once you fall off the

1:20:50beaten path you know it can be very hard to get back into the functional part of

1:20:54society so that causes a lot of fear what do you think about that well i mean

1:20:59it's very easy to lament sort of modern life but

1:21:03you know the wheel and vaccines and a few other things like that are good

1:21:07things to have come up with so the the solution is not to sort of

1:21:12like we all go scarify ourselves and go wear loincloths or something

1:21:16um in that there are many benefits to it in terms of what are the sources of like

1:21:23our modern malaise and predicament in terms of

1:21:27westernized lifestyle industrial lifestyle urbanized

1:21:30in lots of ways what it comes down to i think

1:21:33the most fundamentally bizarre thing we do

1:21:36as a primate that makes the least sense to other primates and is sort of most

1:21:41impactful and foundational to all of this

1:21:43is more than any other primate we encounter strangers

1:21:47and we have anonymous interactions like every like rule about brain size or

1:21:53primates versus body size suggests that humans should be living in

1:21:57communities of about 150 people which is about the average for

1:22:00hunter-gatherer extended fusion fission communities there and obviously life is

1:22:06very different we do something that no other primate

1:22:10does we encounter more strangers standing online at

1:22:14starbucks than like our hunter-gatherer ancestors

1:22:17would do in a lifetime and we have more capacity to be both the

1:22:20perpetrator and a victim of an anonymous act

1:22:24than any other species one of the things we do

1:22:28is as a compensation skyara norenzayan at university british columbia

1:22:33has noted this really interesting thing it's only when

1:22:36cultures get large enough that people start having

1:22:39interactions with strangers that they invent what are called moralizing gods

1:22:44gods who care about what humans are doing and

1:22:48punish you what we do is hunter-gatherer gods could care less what humans are up

1:22:54to they're all feasting or goat hurting or who knows what

1:22:57but by the time you get to big anonymous interactions one of the things humans do

1:23:01is invent various forms of external monitoring but

1:23:05on the most fundamental level what happens when you are interacting

1:23:09very often with strangers is you don't understand what their motives

1:23:13are and on a certain level that's reduced to

1:23:17okay you're in trouble with the irs oh my god stressor what's stressful about

1:23:21it this person can make a decision that

1:23:24could either be benign for you or could make you miserable for years to come

1:23:27and you don't know who their grandparents were

1:23:30you don't know like what like circumcision ceremony

1:23:34they went through or what their and who knows what

1:23:37but mainly dealing with strangers means that you're dealing constantly where you

1:23:42don't know what people's motives are and the control and predictability

1:23:47aspects just come roaring to the forefront then i'm sorry

1:23:50we only have time for one more quick question

1:23:52and then justin you can wrap it up okay can we have one question peter's gonna

1:23:56say one question is that okay and then at

1:23:59the end of this um we do have a book signing outside if

1:24:02people want to meet robert so we'll take one more question

1:24:05here and then we'll finish with peter's question hi

1:24:07thank you i had a good time tonight it was fun coming

1:24:10um my question is in relation to procrastination so i'm a

1:24:14huge procrastinator i'm sure a lot of people here

1:24:18are and in part i really enjoy it because

1:24:21when i know that i'm under pressure i get things done

1:24:26and you know i'm able to write those papers faster for my students and so

1:24:31forth so i you know i'm wondering what the

1:24:34impact of that is on health outcomes

1:24:39my sense is only knowing how rats and baboons go about

1:24:43procrastinating for paper and deadlines but my sense is it pretty

1:24:49much takes two forms one is if someone is simply not very good at

1:24:54time budgeting or time discounting if i do

1:24:58this later instead of now it will seem that much

1:25:01less burdensome or whatever that you're just

1:25:04like not good at that um the other which i think is the much

1:25:08more pernicious less fixable version is if the procrastination is driven by

1:25:13anxiety i can't do it i can't do it i can't do

1:25:17it until all my pencils are sharpened i can't do it until

1:25:20i've done three more rounds of preparation because i really can't

1:25:23understand the stuff and i'm a fraud and they're going to find out

1:25:26i think the you're just not very good at like remembering how many days away one

1:25:30week is with deadlines is much less

1:25:34troublesome than when the procrastination is just

1:25:36secondary to a gnawing sense of dis ease and anxiety

1:25:41about the world so my final question is a personal one

1:25:45since you know we all are you're adoring fans and uh with the

1:25:50success you've had as a scientist to someone who's brought it to a popular

1:25:53stage i'm curious if you go back to robert

1:25:56zapolsky at age 21 what advice would you give him

1:25:59because some of that may be relevant for people at the beginning of their

1:26:01academic careers and

1:26:07okay

1:26:12two answers which are actually intertwined

1:26:16um and the first one will seem very sort of

1:26:20blindered in terms of the research um when i was 20 i started doing my field

1:26:25work in africa with baboons and for about 30 years afterward i spent my

1:26:28summers there back and forth going back to the same animals

1:26:30interested in what your social rank has to do with what stress-related diseases

1:26:35you have and when i was 21 if you asked me what

1:26:38explained baboon psychosocial health and thus

1:26:41humans was social dominance and social hierarchy

1:26:45and like you know i was like a sub-adult male

1:26:49primate so of course like hierarchical stuff

1:26:52seemed very important and it took me about 20 years in my work

1:26:54to realize the social support factors and the

1:26:58personality stuff was far far more important so

1:27:02it would have saved me about 20 years at work to have mentioned that to myself at

1:27:05that time um but in the broader sense what i think

1:27:10winds up being exactly the same answer is um

1:27:14i wish if i could talk to my 21 year old self

1:27:18and actually be convincing it would be to have been less ambitious

1:27:27mr robert supposedly thank you

1:27:42you