In this lecture, Professor Sapolsky talks about the effect of long term stress on human physiology. This video is modified from …
Robert Sapolsky was my professor when we
were students at Stanford University
many moons ago and Robert made a huge
influence on my my wanting to be a
scientist he was simply the most
influential and outstanding, compelling
professor at Stanford because of the way
he connected with the students and
because of his incredible gift at
lecturing which you're all about to
witness and as you might imagine
Robert has quite a number of impressive
accomplishments in his career including
a MacArthur Genius fellow, loads of
highly influential scientific articles
and research awards but perhaps one of
his greatest accomplishments are the
books that have been so incredibly
popular and so impactful to so many
people that he's written. My personal
favorites are the trouble with
testosterone, a primates memoir and why
zebras don't get ulcers which is the
topic of today's lecture and so let's
please all join me in welcoming Dr.
Robert Sapolsky to the stage.
Well let me start off by saying actually
these lights only give me a dim
impression that there's a lot of
primates out there. So I'm not entirely
sure what I'm seeing here but let me
start off by thanking Justin and Peter
it is a delight to be here and delight
to see one's ex-students flourishing and
all that sort of stuff amid and making
me feel very elderly. Okay. So let me
start off, I just got here a couple of
hours ago so I pretty much don't know
anyone here so I feel empowered to ask
all sorts of invasive personal questions.
if you guys okay how many of you here
have a family history of heart disease?
cancer, high blood pressure, ulcers, stroke,
well there's a hand there there's not
even going down between the questions.
okay, that is not good.
how many of you have a family history of
somebody with a really bad case of
no hands. How about that cousin you're
stuck sitting next to a Thanksgiving the
one going to the bathroom every 10
minutes because of the dysentery? Not
that either how about that extra-special
relative who is just teeming with liver
parasites the size your fists? not much
there either.
and all things considered this is not
very surprising, very few of us in this
room seriously worry about smallpox or
scarlet fever. few of us gets malaria
during the rainy season. few of our
mothers died in childbirth. nobody in
this room is malnourished.
we're not like normal animals. we don't
get sick the way normal animals do, we
don't die the way they do, basic normal
mammalian death you drink some contaminated water and
you are dead from dehydration two days later
and what do we do we spend 80 years
having our bodies go to hell on us. so we
– oh great I gotta listen to that for
the next hour. this is actually fabulous
news because this is westernize disease
for the most part we are not plagued by
infectious diseases, diseases a poor
nutrition, poor hygiene, instead we live
well enough and long enough to slowly
fall apart over time and this is a
magnificent advance in the human
experience. okay. just give you a sense of
it like a little more than a century ago
1900 what do you think were the leading
causes of death in the United States?
tuberculosis, good what else, childbirth,
if you were a woman between ages 20 and
40 the single medically riskiest thing
you could do in 1900 was attempt to give
birth. what else was up there? influenza,
pneumonia, tuberculosis, influenza number
one on the list. the flu. No body dies of the
flu anymore. 1918 worst winter
World War one people being blown out of
trenches all over Europe and if you were
sent to the war that winter your chances
of surviving were better than if you got
the flu. eight million more deaths in
World War one, 40 million dead civilians
that winter. From the flu nobody underage
a hundred dies of the flu anymore
instead, we die of these of these totally bizarre diseases that
never used to exist on this planet in
any sort of frequency. totally weird
diseases like heart disease and cancer
and diabetes and Alzheimer's and what
you suddenly realize is this is a very
novel realm we've entered in terms of
making sense of which of us are sick and
which are healthy. okay.
20,000 years ago you're some 20 year-old
hunter-gatherer and you have screwed up
big time you have made a major medical
mistake you've just eaten some read bark
riddled with anthrax and the Medical
Outcomes absolutely clear you've got
like a three-day life expectancy. these
days is a 20 year old you make a major
medical mistake you decide a healthy
diet consists of a lot of red meat and
saturated fats and maybe a drink every
other day or so and it's not at all
clear what the outcomes could it be. you
may be dead in your grave at 50 or you
may be running marathons with your
grandkids when you're 85 and in lots of
ways the central question for westernized
medicine is so why does some of us last
to 50 and some to 85. some of it's got to
do with like nuts and bolts biology, what
your liver does with cholesterol or
stuff like that. but some of it's got to
do with questions nobody ever had to ask
before in medicine? totally bizarre
questions like what's your psychological
makeup? or what's your social status? or
how do people with your social status
get treated in your society? or how about
this one get the answer to this question
and you will have done more good for the
health of humanity than anyone since
like Jonas Salk inventing the polio
vaccine. why is it that when we feel like
nobody loves us we eat Oreo cookies?
answer that one in you live just solve
half the cases of diabetes in this
country. this is totally bizarre stuff
that has something to do with which of
us are healthy or sick. that has
everything to do with it. and what we've
entered is this very strange world when
we look at the diseases that do us in
these diseases of slow accumulation of
damage from lifestyle over time. these
are predominantly diseases that can be
caused by or be made worse by stress and
most of us in this room will have the
profound westernized luxury of dropping
dead some day of a stress-related
disease. so nonetheless amid that great
news it's a good thing if that happens
later rather than sooner. so it's worth
learning about this. ok. start off with
definitions. I start off with a word I
guarantee all of us had a 9th grade
biology with any lucky you have not
thought about this word since then. Do
you remember homeostasis? Homeostasis
having an ideal body temperature, having
an ideal level of glucose in your
bloodstream, having an ideal everything
being in homeostatic balance. A stresser
is anything in the outside world that
knocks you out of homeostatic balance.
you are a zebra, a lion is lept out ripped
your stomach open and you are interest and
dragging on the dust and you still need
to get out of there. this counts as being
out of homeostatic balance or you are that
lion who is half starved to
death and if you don't chase down that
zebra successfully you're not going to
survive the night. Short term physical
crisis. And what you do at that point is
you turn on the stress response. you
secrete adrenaline and other
hormones I will torture you with what
you do is you re-establish homeostatic
balance. that's all you need to know
about the subject if you are a Zebra or a lion.
If you are a human though you got to
expand the definition in a critical way.
yes a stressor can be when your body's
been out of homeostatic balance in
addition a stressor can be when you
think you're just about to be knocked
out of homeostatic balance. if it turns
out that you're right that's great an
anticipatory stress response rule here
comes the elephant maybe I'll increase
my blood pressure now
before it stomps me rather than after
that could be very adaptive. On the other
hand if you think you're just about to
be knocked out of homeostatic balance
and you really aren't about to be and
you think that way all the time there
are medical ways of describing you.
you're being neurotic as hell. you're
being anxious, you're being paranoid
you're being hostile. try to describe
global warming to a hippo and it's kind
of no idea what you're getting all upset
about. but that's the critical point we
do. the critical point of the whole thing
is we turn on the exact same stress
response as that zebra running for its
life were a lion running for a meal and
we turned it on for purely psychological
reasons. And that's the punchline of the
entire field that's not what it evolves
for. For 99% of beasts on this planet
stress is three minutes of screaming
terror after which it's either over with
you're over with and what do we do we
turn on the same stress response for
30-year mortgages and that's not what it
is for. and what we see here is this is
why we and other really cognitively
sophisticated primates are the ones who
get mowed over by stress-related disease.
this is a system that evolved for
dealing with short-term physical crises
and we turn it on for chronic
psychosocial stress. now listening to
this description something should seem
sort of questionable. Though I'm
describing, ok the stress response you
turn this on if you're a zebra you're
injured you're bleeding you're
hypotensive or if you're the lion you're
starving, you're hypoglycemic these are
very different physical states and one
of the things they pound into your head
and biology is your body comes up with a
very specific solution for a very
specific challenge if you're hot you
don't shiver your body does something
very differently than that. yet here's
the stress response which does the exact
same thing whether you're injured,
starving, too hot or too cold. why should
you turn on the same stress response on
all these circumstances? and this was a
question wrestled with by the guy who's
officially sort of the godfather of
stress and health this was an Austrian
physician in the 1930s named Hans Selye
who started the whole field because it was
very smart and very intuitive and very
insightful and very creative and
apparently he was totally lame at
handling lab rats and this is how he
started the field. Selye was young assistant professor at McGill
University Montreal and he was looking
for some research project and some
biochemist down the hall had isolated
some hormone out of somebody's pancreas
or something nobody knew what this stuff
does. So Selye decides that's it, I'm gonna
figure out the effects of this pancreatic stuff on the body.
so what do you do? you go down the hall,
you get a bucket load of the pancreatic
stuff from your buddy, you come back and
you start injecting lab rats and
apparently Selye simply was not very
good at handling lab rats. so he's in
there every day with the rats, injecting
the rats and dropping the rats and
chasing the rats and the rest chasing
him and half the morning with a broom
getting out from underneath the sink.
months of this goes by and he discovers
something amazing. all of the rats have
stomach ulcers. Selye is euphoric. He's
just discover the effects of this
pancreatic crud on the body. it gives you
a peptic ulcer. Now fortunately being a
good scientist Selye was also running a
control group, rats that he's injecting
every day with saline instead of the
pancreatic stuff. so he's in there with
the control rats injecting them and
dropping them, chasing them, rats chasing him.
he checks out the control rats and they
all have stomach ulcers. okay, so your average scientists at this
point gives up and goes to business
school but Selye thinks about this and
says this is totally screwed, I'm seeing
the exact same thing of the controls and
the experimentals. it's got nothing to do
with a pancreatic stuff. what do they
have in common? well, I'm pretty inept at
handling these guys. they can't be having
such a hard time here. Maybe what I'm
seeing is some sort of nonspecific
response of the body to generalized
And Selye's insight was to, at that point,
systematically expose rats to
generalised unpleasantries. Put some of
them up on the roof of the building in
the winter, down the boiler rooms, rooms
with loud noise, or rooms filled with
cat pee or who knows what and he always
sees the same thing. they get stomach
ulcers. we know exactly what Selye had
just discovered. this was the tip of the
iceberg of stress-related disease and
Selye was the guy who popularized
what was thus obscure term from
metallurgy about torsional strain on
metals. he's the one who said these
animals are under stress and they turn
on certain systems in their body that
saves them from the stress but if they
turn it on for too long you get sick.
everybody thought he was out of his mind
because again you are trained, your body
solves specific challenges in very
specific ways and here's Selye with
his imaginary stress response that gets
turned on exactly the same if you're
injured, starving, too hot, too cold or on
a blind date. why should you turn on the
same exact stress response in all these
circumstances? and it turns out it makes
a great deal of sense. because whether
you are that zebra or that lion if
you're gonna survive the crisis there's
certain things you need to do with your
body. first off above all else you need
energy. Not energy tucked away in your
fat cells for some building project next
spring, energy right now to hand to
whichever muscles are good to save your
neck and with the onset of stress you
secrete adrenaline and a bunch of other
hormones and they go to the storage
sites in your body, your liver, your fat
cells they mobilize energy at a storage
form, dump it into the circulation. it's
like you go to the bank and you empty out the savings accounts
and turn it into cash. circulating glucose and you hand it over to
whichever muscles are going to save you.
makes wonderful sense whether you were
that zebra or that lion. The next thing
you do makes perfect sense as well
you've just done all this amazing
biochemistry and dumped all this energy
in your bloodstream. you want to deliver
it as fast as possible. you're exercising
muscles. your heart speeds up, your blood
pressure increases, your breathing rate
you increase your cardiovascular tone
all is part of the strategy get that
glucose, get that oxygen, to your thigh
muscles in two seconds instead of three
you're that much more likely to survive.
now the next things you do during stress
make perfect sense which is you turn off
all the long-term building projects. if
there's a tornado due this afternoon you
don't spend the day outside gardening.
you don't worry about long-term projects
until you know there's a long-term. you
shut down everything that is not
critical. you shut down digestion. by
definition if you are that lion you are
not staggering up from some
all-you-can-eat buffet and if you are
that zebra the energy you're mobilizing
for your muscles, you're mobilizing it from fat cells in just a
couple of seconds. digestion is slow, it
takes forever, it costs a fortune. you're
trying to avoid me somebody's lunch
don't worry about digesting breakfast.
And we all know the first step of that
suppose you get stressed speaking in
public what happens. your mouth gets dry.
You have stoped secreting saliva, the first step
of shutting down the whole
gastrointestinal tract. with the onset of
stress you shut down growth, you shut
down reproduction, being expensive
optimistic things to be doing with your
body and this is no time for it. you know
you're running for your life there's a
lion two steps behind you
you know, ovulate some other time don't do it right now. Hit puberty next week, grow antlers some
other day, don't even think about sperm.
with the onset of stress you shut down
growth, you shut down tissue repair, every
sex hormone on earth disappears from the
bloodstream do it later if there is a
later. Next, so you're that zebra and your
innards are dragging in the dust this
might be a good time to perk up your
immune system a little bit just in case
of some infective stuff. with the onset
of stress immune defenses are enhanced.
finally a whole bunch of hormones
secreted during stress get into your
brain and short-term their effects are
fabulous they sharpen memory they
increase glucose and oxygen delivery to
your brain, your sensory thresholds are
sharper, you even release this
neurotransmitter dopamine which makes
you feel good. your memory is working
that's that flashbulb memory where were
you when you heard that. I'm willing
to bet every single person in this room
no matter how long they live you will
all remember exactly where you were when
you heard the news that Miley Cyrus was
joining the supreme court. Some stuff
you just file away forever because it's
important your brain needs to get a
signal, this one do not forget. so what
you see here is everything going on here
is exactly what you want to do if you're
that zebra or that lion. you're
mobilizing energy. you're delivering
where it's needed. you're shutting off on
essentials. you're fighting infections.
you're thinking more clearly. all you
have to do to appreciate that is look at
a couple of weirdo human diseases where
people can't do this. one of them is
called shy-drager syndrome and other one
is Addison's disease. these are not
diseases where oh you're now more at
risk for certain cancers. this is like
somebody with undiagnosed Addison's goes
running for the commuter bus one morning
and drops dead from hypoglycemic shock.
so we've gotten our first critical
take-home message here, which is, if you
plan to get stressed like a normal
mammal you had better turn on your
stress response or else you got about a
30 second life expectancy. For most of us
though the far more important take home
message revolves around so what if
you're turning on the stress response
too often, too long, for purely
psychological reasons and what you get
there then is disease at the other end
of it. now Selye was the first person to
wrestle with this issue why is it that
chronic stress makes us sick? and he came
up with an explanation in the 1930s and
it dominated the field for the next 40
years which was too bad because he was
totally wrong. okay, here's what he
thought was going on. along comes a
stressor, knocks you out of homeostatic
balance, you turn on the stress response,
you reestablish homeostasis
but the stressor goes on for too long
and thus you enter what Selye called
the exhaustion phase. you run out of a
stress response, your adrenals run out of
adrenaline, your pituitary runs out of
it's stress hormones. it's like your
military runs out of ammunition and
you're just left defenseless there with
the stress or pummeling you. turns out
this was totally imaginary. there was no
such thing as this exhaustion phase. no
organism on earth has ever been so
stressed that it runs out of adrenaline.
you don't deplete the stress response
the problem is that half
while it's not that your military is
running out of ammunition, after a while
you're spending so damn much on your
military that you don't do health care,
or social services or education or any
of that stuff and like after a while the
stress response is more damaging than
the stressor. especially if the stressor
was some psychological nonsense.
everything you're doing here is penny
wise and dollar foolish, it's
inefficient. it's less than optimal. all
of this is built around. it's an
emergency. it's an emergency fix later,
grow layer, don't do it right now and if
every day is an emergency you pay the
price for it. at the metabolic level
mobilize energy because the Lions
running after you, no problem at all.
mobilize energy from your storage sites
chronically because you're chronically
psychologically stressed and among other
things your muscle mass decreases, muscle
is one of your main energy storage sites,
you get atrophy of muscle, myopathy, for
extremely complex reasons you're using
your energy really inefficiently for
insanely complex reasons you are now
more at risk for adult onset insulin
resistant diabetes. now adult onset
diabetes is one of those interesting
diseases that our great-great
great-great grandparents never even
dealt with. this is a disease of getting
older in a typically westernized way
putting on weight, getting more sedentary
and everything down to the molecular
level that goes wrong in your cells with
adult onset diabetes, stress exacerbates
the process. same punchline at the
cardiovascular level. if a Lion is
chasing you and your blood pressure is
180 over 120 you're not suffering from
high blood pressure, you're saving your
life. On the other hand if your blood
pressure is 180 over 120 every time
you're stuck in traffic or something
you're not saving your life you are
suffering from stress induced
hypertension and you do that chronically
enough and you're gonna damage your
cardiovascular system. okay 30 seconds on
stress and heart disease. what's the
scenario we all know about guy gets
horrible news and he's wailing about
something and he suddenly clutches his
chest in pain, keels over dead,
sudden cardiac arrest, this has never
happened, this is like a movie plot. it's
never occurs in real life. instead what
actually happens requires you to have
like arcane knowledge of high school
physics explaining why like toilet
bowl plumbing wears out after a while
you got a tube and you got fluid moving
through the tube and by definition if
the fluid is moving through with more
force elevated blood pressure you begin
to get fluid turbulence pounding away on
the walls of your blood vessels causing
little bits of pitting and scarring and
tearing and then you get inflammation
there and then that's exactly where like
glucose and cholesterol and fat wants to
glom onto to clog your arteries where's
the glucose and cholesterol and fat
coming from?
that's the stuff you're mobilizing into
your circulation in the previous slide.
so you get the synergistic double whammy
here between the metabolic stress
response and the cardiovascular setting.
you up for the number one killer in this
country cardiovascular disease. now this
link between stress and heart disease is
so solid that it accounts for the most
famous personality profile in all of
Medicine and it's one where basically if
you're coming out to a lecture on a
personally nice evening to be outside
technical walk instead
I suspect applies to like 80% of the
people in this room.
which is those of us in here who have
type A personality. Okay. Type A
personality. type A was first described
in the 1950s by a pair of cardiologists
in San Francisco Friedman and Rosalyn,
here was their original formulation
time-pressured, hostile, inpatient, low
self-esteem, joyless, striving okay like
90% of us and what they observed back
there in the 50s was if this was your
personality profile. you were more at
risk for heart disease. cardiologist
hated these guys. you're some like
Eisenhower cardiologist and all you're
thinking about is like blood lipids and
heart valves and here are these guys
saying no you need to sit down your
patient and talk to them. Christ, who wants
to talk to their patients and talk to
them to say okay so suppose you're in
the supermarket and you pick the line
that's moving slowly. Do you go beserk at
that point. that's got something to do
with heart disease. total resistance to
the concept and it wasn't until the
1980s that enough studies had been done
that it became clear type A is for real
big time. if you have type A personality
you are more at risk for cardiovascular
disease than if you smoked, than if you
were overweight, than if you have
elevated cholesterol levels a huge risk
factor. now what became clear by the 80s
was the critical component in the type A
profile. the piece that is the one that
contributes to the cardiovascular
disease and there's a term now that is
used in the field if you have toxic
hostility. toxic hostility this
attributional style where everything
that happens around you is proof that
there have to get you, there how to get
you more than everyone else and the only
thing to do is watch your back 24/7 and
keep a knife ready. this is the style
where you're in the supermarket and
you've picked the slow line and you want
to kill the son of a bitch, get behind
the cash register. come on, come on. how
do you know I have a one o'clock meeting
trying to scoop me up. no don't ask the
old lady how she used to make. come on, come on
I'm gonna die someday. I get that. you
know if this is what you're doing,
instead of checking out the Elvis
sightings in the National Inquirer your
blood pressure is going to go up and if
this is what you're doing every time
somebody could have held the elevator
door open for you but didn't. if you're
doing this 40 times a day you're gotta
pound away if your blood vessels set up
for cardiovascular disease and these
days the main question in that field is
insofar as you were toxically hostile
what's worse for your heart expressing
those toxic emotions or keeping them
repressed inside? what's clear is
expressing it was worse for everybody
else's cardiovascular health, what is the
cost of repressing strong physiological
emotions? so that's an area of a lot of
ongoing research. okay so that's stress
and heart disease. actually, how do those
guys first figure out about type A
personality given how much that was
coming at a left field and I actually
got to hear the story some years ago out
of the horse's mouth himself Meyer
Friedman the cardiologist who first
described Type A died a few years ago in
his early 90s saw his last patient a
week before he died, was working
full-time at a cardiology unit UCSF
Medical Center. as he used to say I'm
still type-A but I'm a type-A tortoise
now and here's the story he would tell.
in the 50s he and his partner had this
cardiology practice everything was going
great except for there's one weird thing
which is, they were spending a fortune
having to reupholster the armchairs in
the waiting room. what's this about , who
knows, whatever it's part of the overhead
every month this upholsterer comes and
there's a chair or two that needs to be
fixed. one month the upholsterer is out on
vacation replacement upholsterer comes
in takes one look at the chairs and
discovers type-A personality. he says what is
wrong with your patients, nobody wears
out chose this way and they have one of
them left and as you can see here in the
front two inches of the arm rests and
the seat cushions are totally shredded
and the rest of the chair is perfectly
fine. it's like every night there's like
dwarf beavers in there, clawing a chair. what
is this? this is the type A profile, this
is somebody with type A personality. this
is what they do to a chair when they're
waiting in the waiting room with their
cardiologist to hear if there's bad news
or not. this is not just figuratively but
literally sitting on the edge of your
seat and see them squirming and clawing
and all of that. this is what somebody's
type-a does to a chair in that
circumstance. okay, so what happens at
that point if science is working right
and Friedman should grab them like good
god man what you've discovered or like
like midnight conferences between
upholsterers and cardiologists or or
teams of idealistic young upholsterers
sweeping across America and coming back
with the news that no you don't find
chairs like these and podiatrists
offices that's what should have happened
what happens instead here's where 90
year old dr. Friedman starts looking all
sheepish. He says, I told my nurse
get this man out of here I'm an
important cardiologist I can't waste my
time with him getting this damn check
get him out of my face he was too
Type A to listen to the guy and it
wasn't until about five years later that
he collaborated with his psychologist
and back came the type-a profile and I
said oh my god the upholsterer he was
right. To this date they have no idea who
that guy was? now let's see it is late
afternoon in San Francisco I'm willing
to bet there's some bar in San Francisco
right now where there's like this
hundred ten year old retired upholsterer
and get this guy going and he's gonna go
on and on about how he discovered type A
personality exactly what occurred. so one
of the dark chapters in my profession. okay,
moving on, digestion shut down your
digestive system for two minutes running
for your life it's not a big deal shut
it down chronically and there's all
sorts of gastrointestinal disorders you
more at risk for, most famously ulcers
back to Selye in the 1930s the first
stress-related disease stress causes
ulcers, stress causes ulcers canonical
knowledge everybody knows this and then
about 25 years ago there's this
revolution in all serology. turns out
there's a bacteria called Helicobacter
pylori. Turns out the bacteria is
responsible for about 90% of ulcers in
the West. it gets into your stomach, it
generates oxygen radicals and blows
holes in the walls of your stomach. it's
a bacterial disorder. this was an
enormous contribution. the two guys who
discovered it gets the Nobel Prize.
amazing, the evening this is announced
every gastroenterologist on earth goes
out that evening celebrates. this is the
greatest news they've ever heard because
they're not gonna have to sit down their
patients and make eye contact and say they have any stress? it's got nothing to do
with stress, here's some antibiotics get
up my office. It has got nothing to do with
stress. It has got everything to do with
stress because only 10% of people with
the bacteria get the ulcer. you've got to
have the bacterial risk factor but
you've got to have a lifestyle risk
factor overlapping as well, stress. stress
does not cause ulcers, the bacteria does.
what does stress do when you got an
ulcer beginning to start your stomach's
reasonably good at repairing it and
rebuilding the wall there before the
ulcer gets troublesome unless you're
chronically stressed and every day your
stomach walls are saying that do it
tomorrow, do it tomorrow it feels like
we're being chased by a predator
psychological stress shuts down the
reparations there. so here we have a
classic example of interactions between
the organic causes of disease and the
psychogenic stress is still very
relevant to making sense of ulcers. Next
growth, you shutdown growth for three
minutes while you're running for life
not a big deal or theme by now shut it down chronically this can be problematic
especially if you were a kid. all kids
are are big long-term building projects
and if for reasons of psychological
stress you keep saying do it tomorrow, do
it tomorrow duties you can impair a
growth and at an extreme you have one of
the truly bizarre outposts of Medicine, a
disease of kids who stopped growing for
reasons purely of psychological stress
known as psychogenic dwarfism,
psychosocial dwarfism, stress tourism
these are kids who are years behind the
normal growth rate and there's no
disease. they're not malnourished
there's no parasites, you check their
blood stream there's like no growth
hormone, you give them synthetic growth
hormone nothing happens, the whole system
is shut down and at that point you start
poking around in their background and
often out comes some appalling
psychological stressor and the amazing
thing is get them out of that stressful
setting technical term do a parent
ectomy on them and growth will resume at
that point.
this is incredibly well understood how
this works. open up any textbook of
endocrinology go to the chapter on
growth and I guarantee there will be the
obligatory picture of the stressed dwarfism.
those picture is that stunted kids
like naked in front of the growth chart
with a rectangle over the eyes and turn
the page and I guarantee there's the
obligatory follow-up picture the kid in
a different environment two years later
he's like six foot fourteen, he's playing
for the NBA. it's everything you know,
there's still the rectangle and
nakedness but everything
else gets better and what you see there
is this is the system with the amazing
capacity to recover remarkable cases of
this for example, this was a case report
a few years ago this was a child brought
in from an extremely abusive
psychological setting into New York
Hospital with stress dwarfism and
there's documented in the paper at the
time he came into this pediatric unit
zero growth hormone was bloodstream. over
the next few months he became very close
with one nurse there and this was like
the first normal emotional relationship
in his life after a couple of months
normal growth hormone levels for his age.
at that point the nurse goes on vacation
by the end of her two-week vacation he's
back down to zero. nurse comes back a
week later he's back up to there. think
about this the rate at which this child
was depositing calcium in his bones
could be entirely predicted by how safe
and loved he was feeling. you
can't ask for a much better example of
what's going on here affects every
outpost in the body. now the issue with
stress dwarfism amid people
understanding exactly which hormones are
doing what. the issue of course becomes
how common is this disease. if you are
shorter than average and you were not
obviously malnourished as a kid, are you
a victim of stress dwarfism? did your
parents do that you? No, this is not
like a very stressful childhood we were
moving all the time
this is not like acrimonious divorce,
this is nightmare psychopathology, this
is the police and the social workers
breaking down the door of an apartment
and finding the kid chained to the
radiator and sneer at an excrement then
just lighten their stuff and get the kid
out of that setting and there's recovery
the clinical consensus is this is a
once-in-a-career disease that you see
extremely rare except it's not so rare
it pops up all over the place. kids in
war zones, kids in areas of civil strife,
a research assistant of mine and I think
we've got the data to show that kids who
line up into Japanese American
internment camps in World War two had
mild stressed dwarfism. it pops up all
over the place. one classic study, in the 60s looking at
rites of passages from cultures all over
the planet rites of passages in one
culture they take you out of the desert
and stake you down and cover you in
poison ants and some other culture you
play the piano for your grandmother and
her friends or whatever is done and you
are trying they did like 80 tribal
comparisons they control for genetics
back comes the finding stressful rites
of passages during the first few years
of life two inches shorter as an adult,
big effect. Let me tell you about the
single creepiest example of stress
dwarfism I've ever heard of. if for some
inexcusable reason you ever find
yourself reading chapter after chapter
about growth hormone, you're going to
notice there's a weird thing which is a
lot of the chapters make reference to
Peter Pan some quote from Peter Pan or
some snide comments about Tinkerbell. I
seen this for years I had no idea what
this was about until one day I stumbled
on an explanation and this was a chapter
about the psychological regulation the
growth and was talking about stress
dwarfism gave the following case history
eight-year-old boy growing up in
Victorian England in the 1870s one day
he sees his beloved older brother killed
in front of him in an accident this
destroys the family. there were no other
siblings. the father was like emotionally
non-existent. this was the mother's
favorite child and this Victorian swoon
she takes to her bed with the shades
drawn for the next ten years. this kid
growing up in this horrible emotional
isolation. he goes into the bedroom with
a tray of food for his mother and she's
saying, Oh David, David is that you? David
if you come to me, have you. David, the
dead son. David are you finally here? oh it's
only you. growing up being only you.
apparently the only thing she ever spoke
to him about was this idea she grabbed
on to which was if David had to die
he'll always be my perfect little boy
who never grew up and became a man who
didn't need his mother any more he'll
always be my perfect little boy because
he didn't grow up, didn't grow up, didn't
grow up. this kid hears this with a
vengeance. middle-class family no
evidence of disease or malnutrition boy
stops growing there at age 8.
reached the age sixty 4 foot 10 inch as an adult
unconsummated marriage, incredible
example of stress dwarfism. and then then
the chapter concludes by informing us
that as an adult this was the author of
the much beloved children's classic
Peter Pan.
this was JM Barrie the guy who wrote
Peter Pan who's incredibly screwed up
this guy all he did was crank out book
after, play after, novella my boys who die
and come back as ghosts and marry their
mothers. his private journals were full
of sadomasochistic fantasies about
little boys. this guy spent the rest of
his life dealing very unsuccessfully
with his store stressed dwarfism.
Think about that the next time you
see Johnny Depp up on a movie. okay. next
next reproduction. your gonads, your
gonads. your gonads are not going to
be working very well if you were
chronically stressed. if you were a
female mammal of virtually any species
if you were chronically stressed your
cycles will become irregular, lengthen,
they may stop altogether. stress induced
amenorrhea, stress induced ovulation
and people understand exactly how those
work. which hormones are working at the
brain, at the pituitary, at the ovaries, at
the uterus to shut things down. let me
tell you about one of those steps
because it's got to do with a very weird
thing that female mammals do including
human females. which is they secrete a
certain amount of male sex hormones into
the bloodstream. hormones that are
related to testosterone, androgen type
hormones. they come out of the adrenal
glands, not a ton of the stuff maybe 5%
the levels you would see in the male,
nonetheless you got to get rid of it.
unfortunately female mammals come with
this enzyme and fat cells that take
circulating androgens and does
biochemistry 101 and converts them to
estrogens. great. perfect.
problem solved. everyone was happily ever
after. what if you're stressed, what if
you're stressed like the locusts have
come and eaten your crops and you're
subsisting on 800 calories a day what if
you're slowly starving, yours fat stores
are slowly getting depleted and
some point you have two little
functional fat cells to do the androgen
to estrogen conversion. one problem is
there's now a little bit less estrogen
in the bloodstream, bigger problem is the
androgen levels build up there and that
shuts down every step in the system.
That's why starvation shuts down
ovulation. That's why voluntary
starvation, anorexia, does the same and
that's why some women who do massive
massive amounts of exercise will stop
ovulating as well. because you get below
a critical fat muscle ratio there. now
this is something that's been studied at
length and girls for example it's always
studies of very serious ballet dancers
or gymnasts what you see is significant
delay in the onset of puberty. one study,
for example, this was done on the Olympic
gymnastics squad from Romania you know
there's 60 pound 15 year olds getting
the gold medals all over the place. what
was the average age at which these kids
started menstruating? 19. Twelve and a half is
the Western average. once hitting puberty
women who do tons of athletics this best
study long-distance runners women who
run an average of 40 to 50 miles a week
that's typically the range where fat
stores are getting below threshold where
you begin to have ovulatory
irregularities. I can tell you the exact
same story about men. men who run 40 50
miles a week sperm count goes down,
there's mild testicular atrophy. okay
wait a second, I thought exercise is good
for us. exercise is good for us and in
fact a lot of exercise is very good for
us that doesn't mean though that an
insane amount of exercise is insanely
good for us. it means at some point too
much of a good thing is just as bad as
too little. you've passed a point of
homeostatic balance and all you need to
do to get an appreciation for that is
imagine you sit down some
hunter-gatherer from the Kalahari Desert
and say you know where I come from we
have so much food and so much free time
that sometimes we'll just go run 26
miles in a day for the sheer pleasure.
They are gonna say, are you crazy? that's
stressful. I mean throughout hominid
history if you're running 26 miles in
the day either you are very intent on
eating somebody or somebodies intent on
eating you. this is not normal physiology.
so we get a cautionary note here.
meanwhile over at the male end of things
with the onset of stress down go
testosterone levels. anesthetize a guy
slice into his belly for surgery ten
minutes later testosterone is plummeting
first-year male medical students during
exam periods down go testosterone, drop
the rank of a male baboon at a hierarchy
down goes testosterone, here's a stressor
which thank God I have no personal
experience with it all. But apparently
it's not fun to be in the Marines. Apparently it's kind of a drag.
especially during basic training. this
was this classic study 1970 New England
Journal of Medicine looking at military
recruits during basic training. we're now
on top of everything else. they had to
pee into little Dixie Cups for the
psychiatrist and back comes the fighting
guys in the Marines during
the first couple of months of service, they have the circulating androgen
levels of like Vatican choirboys and
that's how much the system is shut down.
okay. so people understand exactly which
stress hormones are working at the brain,
the pituitary, in the testes, to shut down
testosterone synthesis during stress. the
question you gotta ask at this point is
so what are the consequences of
testosterone levels declining during
stress? and amazingly enough the answer
is there's no consequences at all.
testosterone turns out to be this vastly
overrated hormone. like basically all you
need is like a thimble full of the stuff
and a couple of sperm and you're in
business. you got to knock out like 90
percent of the guy's testosterone levels
to seriously impaired fertility. stress
what does it do at its worst
only about a 60% decline. it's not
suppressed enough that it makes a
difference. the problem during stress is
not that testosterone levels go down. the
problem is that penises go down. am I
allowed to talk about this in the
champaign-urbana here. okay. finally we
come to the first like useful point in
this damned lecture. so how do erections
work? okay. so erections, in order to, I
just saw somebody there pick up a pen
for the first time. that's right.
okay. so how do erections work? in order
to have an erection you gotta have a
spinal cord. now most of what your spinal
cord does is totally boring and make you
shake hands and slide checks and Foxtrot
or who knows what but then there's the
part that does the good stuff. the stuff
you normally don't have any control over,
stuff that is automatic like goose flesh
and orgasms and pupillary contractions
and blushing. things that are automatic
and thus run by the automatic nervous
system also known as the autonomic
nervous system. now the autonomic nervous system comes
in two halves first half sympathetic
nervous system, emergency, arousal
adrenalin, stress response all hell
breaking loose. second half the
parasympathetic nervous system. calm,
vegetative function you take a nap you
turn on the parasympathetic nervous
system. you eat a big starchy meal you
turn on the parasympathetic nervous
system. you get disemboweled by a lion
you turn off the parasympathetic nervous
system. it works in opposition with a
sympathetic. okay. so here's the rule, in
order to get an erection you've got to
turn on the parasympathetic nervous
system, you have to be calm and
vegetative. okay. so you got your erection
now what happens next?
maybe for some social reason having to
do with the context that brought about
the erection maybe you start feeling a
little bit less calm and vegetative.
maybe your heart rate increases a little,
maybe your breathing rate, maybe your
muscles are starting to do some work,
slowly you're starting to turn on the
sympathetic nervous system. more time
goes by your heart is racing, your toes
are curling, you're sweating, you're
breathing fast, all of that eventually
get to this point where your whole body
is screamingly sympathetic except for
this one lung out coast reader desperately holding on to
parasympathetic tone as long as possible.
finally can't take anymore you turn off
the parasympathetic you turn on sympathetic and you ejaculate.
okay. so that's how erections work? so
what happens during stress? what happens
during stress, you're not very calm and
vegetative. you can't get the erection
stress induced impotency or you can have
a second problem suppose you managed to
get the erection and you think like no
Donald Trump who knows what you
accelerate, accelerate the transition. you
accelerate the transition from
parasympathetic to sympathetic the whole
thing goes too fast. either you can't get
the erection or premature ejaculation.
Incredibly easy for this to occur. current
estimates are 60% of the visit by men in
this country going to doctors about
erectile dysfunction turn out not to
have an organic disease basis but
instead are psychogenic stress-related.
okay. second useful piece of information
so how do you tell the difference
between a case of organic impotency and
psychogenic? so guy comes to you says he
hasn't been able to have an erection
during sex in the last six months and you're wondering well is the stress
related or does he have a pituitary
tumor whatever you take advantage of a
weird thing that male primates including
human males do which is when they go
into REM sleep, rapid eye movement sleep,
they get erections. I have no idea why
I've talked to Earth's penis experts
nobody has an explanation for this.
nonetheless male primates get REM sleep
erections. so here's what you do the guy
who hasn't been able to have an erection
during six months what you do is
you give him this handy dandy little
penile pressure cuff transducer thingy
that he takes home and just before he
goes to sleep he puts it on the base of
his penis and wires it up and satellite
relays and 24 hours
in Bangalore and the next day the next
day he got your answer which is if this
guy hasn't been able to have an erection
during sex in the last six months but
thirty seconds into his first REM stage
he has a perfectly normal erection. he
doesn't have a pituitary tumor it's stress-related. that's how you
distinguish between the two. do you still
get the nocturnal erections? if that's
the case it's stress-related. very easy.
actually maybe this is not so easy
because you got this electronic device
and it's beeping on the wires and you're
so sure it's cool electrocute you that's
a stressor in and of itself this is what
is done and the majority of sexual
dysfunction clinics in this country. I
kid you not you take a long string of
postage stamps you lick them at one end
and you wrap them around the guy's penis
and the next morning if the stamps have
been torn loose the guy had an erection
during the night. Can you believe like
how elegant this is? like five bucks you
get a lab results.
yes yeah oh of course insurance won't
reimburse you for the stems but still.
you know maybe Obamacare still has a
chance. okay. so what we see here is
another outpost of vulnerability and
perhaps we should her long before I
embarrass myself further. your immune
system, your immune system soon as we
heard before with the onset of stress
you enhance your immune defenses with
chronic stress something very different
occurs with chronic stress not only does
the immune system go back to baseline
you suppress immunity with chronic
stress you become immune suppressed and
this is the starting point for just this
irresistible syllogism. insofar as
chronic stress chronically suppresses
the immune system. chronic stress should
set you up for more infectious diseases.
and this is the basic premise behind
this field that emerged about 25 years
ago, psychoneuroimmunology. the notion
that what's going on here is affecting
your immune defenses. in a quarter
century into this field it's clear
that's exactly how it works for all the
boring stuff? when you were under stress
the common cold becomes more common. you
are at more risk for mononucleosis for
herpes viral flare-ups reactivation
what's far less clear is what about
bigger realms of infectious disease. how
about if you have AIDS your immune
system declining if you're severely
stressed does it decline even faster?
jury is out on that one it seems to have
to do with personality type is an
intervening variable. how about the
biggest one on everybody's list when it
comes to worrying about disease so
what's the relationship between stress
and cancer and everybody knows the
answer to that which is cancer is a
stress-related disease. stress can cause
you to have cancer. stress can cause you
to come out of remission from cancer.
stress can accelerate the growth of
tumors. everybody knows about the
sufficiently so that some years ago
there was a study in JAMA Journal
American Medical Association looking at
women who had just gotten a metastatic
breast cancer diagnosis where they were
asked so what do you think is the cause
of your cancer?
and by more than a two-to-one margin the
most common answer was stress too much
stress in my life. stress has virtually
nothing to do with cancer. there has
never been a decent prospective human
study longitudinally that shows that
stress increases the risk re occur into a
growth rate of any type of tumor. when
they're well controlled there have been
all sorts of studies showing how stress
can accelerate tumor growth and lab rats
we know how it works. my lab did some of
that work but it turns out these are
types of cancers that are completely
irrelevant to human cancer. this is a
realm where there's not much connection
at all. I made all those things on the
right sides of these charts. you need to
worry about this is one domain where you
don't. why is it important to emphasize
this because of all of these highly
credentialed quacks who are making a
fortune off of cancer patients saying my
special brand of stress therapy will
slow down your cancer, stop it, reverse it,
credit cards accepted. there's no science
to support this. bad medicine, bad science,
bad ethics. this is a domain where you
don't have to worry. okay. so quickly
let's hurdle back to domains where you
do have to worry. okay. so back to stress
in your brain we saw short-term there's
all sorts of great stuff. chronically, bad
news chronically stress will damage a
party or brain called the hippocampus
which is essential for learning and
memory. stress has something to do with
failure of memory consolidation. their
shrinkage of neurons, disconnecting of
synapses, at an extreme killing of
neurons, inhibition of the birth of new
neurons there and this is turning out to
be relevant to humans and a number of
scary realms people with chronic stress
due to PTSD post traumatic stress disorder
combat trauma or sexual abuse trauma and
what you see there is atrophy of the
hippocampus. only the hippocampus, the
more severe the trauma history the more
atrophy the more memory problems best
evidence says this is not reversible.
second syndrome pertinent to the 10 to
15 percent of us in this room destined
to have major clinical dipression.
the poster child and psychiatry of a
stress-related disorder and involves
chronically elevated stress hormone
levels and scads of studies now showing
atrophy of the hippocampus will leave
the hippocampus the more severe in the
depression history the more atrophy the
more memory loss and as far as most
studies show at this point this is not a
reversible process. meanwhile next door
to the hippocampus is a brain region
called the amygdala and then the
amygdala things are real different.
hippocampus does learning a memory for
amygdala teaches you to be afraid. it
does fear, it does anxiety and while
stress is atrophying away those
hippocampal neurons, stresses making
neurons and the amygdala work better
than usual. they expand their connections
the synapse has become more excitable.
people with PTSD have amygdalas that
grow larger than normal. stress makes it
easier for you to associate things with
fear that are not actually valid and
makes you harder to detect
safety signals. this is the link between
stress and anxiety. meanwhile over in
that part of the brain where you're
releasing dopamine which has something
to do with pleasure when the onset of
stress, chronic stress and you're
depleted of dopamine. what is this setting us up?
for explaining the link between stress and
depression. the defining symptom of
depression is anhadounia, hedonism the
pursuit of pleasure anhadounia the
inability to feel pleasure. this is the
neurochemical link why chronic stress is
a major precipitating factor for
depression. so okay if you're still awake
at this point you should be depressed as
so amid that it must seem like a miracle
that any of us are still alive. actually
let me make this worse one last
stress-related disease. This is like stress
for 2,000. how many of you've heard of a
disease called idiopathic alopecia
areata? okay a few heads this is the
profoundly rare state of somebody being
so so traumatized by something that over
the next few days their hair turns white
and falls out. this is for real
people understand like what the immune
system is doing into the hair follicles
there. it's real it's a once-in-a-career
disease but nonetheless this is for you.
look at this you're chronically stressed
you get high blood pressure, you get
diabetes, you get flatulent, your sex life
is ruined, your brain gets damaged and
your hair falls out. how is it any of us
are still functioning here? why haven't
we all collapsed into puddles of
stress-related disease and the critical
thing is most of us don't.
most of us cope and what's been clear
from the first day of the field with
Selye is some individuals cope with
stress better than others. what I want to
spend the last couple of minutes on is
how we understand this to work. why do
some bodies and more importantly some
psyches deal better with stress than
others? okay so if we're talking about
individual differences in stress
responsiveness here we're not talking
about physical stressors. finish this
lecture and go outside, unexpectedly be
gored by an elephant and you could have
a stress response there's no way you can't reframe your
experience and growth from adversity or
who knows. why you have a stress response
finish the lecture go outside and have
kind of a tense and big Lluis
interaction with someone and only some
of us will have a stress response. what
is it about that gray zone of psychosocial interactions that is more
stressful for some individuals and
others. what we're asking here is what is
it that makes psychological stress
stressful and remarkably a mass of
literature stretching back decades shows
what precisely are the building blocks
of psychological stress. okay. here's a
schematic summary of a gazillion studies
what they would sort of show. take a lab
put him in the cage, every now and then
he gets a shock, mild shock and
nonetheless with enough of them this is
stressful. blood pressure goes up, heart
rate goes up, risk of ulcer goes up as
shown here. you're giving the rat a
stress-related disease. now second line
in a second cage there's another rat
psychology jargon the second rat is
yoked to the first rat. every time the
first rat gets a shock so does the
second. same intensity, same duration, same
everything according to Selye 1930 both
of their bodies being knocked out of homeostatic
balance exact same extent
except for a critical difference which
is every time that second rat gets a
shock it can go over to the other side
of the cage where there's another rat
and it can bite the crap out of it and
you know what that rats not gonna get an
ulcer the guy he's biting is gonna get
one but this one doesn't he has an
outlet for his frustration. third line
now we have in the second cage, a second
rat getting the same shock, same duration
same intensity, same everything but each
time he gets a shock he can go over and
there's a bar of wood that he can bite
with his teeth and he doesn't get an
ulcer. he has a hobby. okay what we have
here is same shock, same intensity, same
everything but ten seconds before each
shock the second rat a little warning
light comes on and the rat doesn't get
an ulcer for the same external stressor
we are more protected when we get
predictive information when is it coming
how bad is it going to be, how long is it
going to last and we all love that
principle every time we ask the dentist
how much more drilling and we all know
the difference between the dentist that
says two more bits and we're done on the
one that says yeah it could be it could
be weeks
dentist says two more viscid drilling
bad news you're not done yet
good news the second that second bit of
drilling is over with you're safe for
the rat in the first line any second you
can be a half second away from the next
shock. next line this is a rat that's
been trained to press a lever by
pressing the lever it decreases the
likelihood of getting a shock, today the
rat is yoked to the first one getting
the same shocks as the first guy but
there's a lever in there the levers
disconnected the leverage has done
nothing whatsoever but the rat doesn't
know what so he's in there pounding away
the lever saying this is great just
imagine how many Stocking getting
otherwise he thinks he has control for
the same external stressor a sense of
control makes things less stressful.
jumping ahead to the final line shock a
rat and now it goes over to the other
side of the cage where there's a rat
that it knows and likes and they groom
each other and it doesn't have a stress
response. Wow science has finally proven that friends
are good for your health. science has
proven this big-time when you look at
all of behavioral medicine and all of
health psychology there are two of the
biggest predictors out there as to
mortality rates across all diseases. the
first one taps into every one of the
factors on the slide which is never ever
make them the state of being born into a
poor family. because your health is good
to pay for it the rest of your life the
link between health and socioeconomic
status very heavily mediated by stress.
the second biggest predictor is if you
go to choice in the matter
don't be socially isolated and you look
at the extremes of social isolation
versus social affiliation significant
other a very small group of friends,
community group you're intensely
involved with for the same disease
impact almost a three-fold difference in
mortality rate and that's after you
control for stuff like people will live
alone just each eaters for dinner and
nobody to remind them to take their meds
control for that and social isolation is
an aching stressor for every primate out
there including us and a huge health
risk factor. so what is it that makes
psychological stress stressful. for the
same external misery you are more likely
to feel subjectively stressed, more
likely to turn on a stress response and
more at risk for stress-related disease
if you feel like you have no control, no
predictability, no outlets for the
frustration. if you interpret things is
getting worse and you have nobody
shoulder to cry on and basically this is
the place to stop because again none of
us are getting ulcers because we're
being chased by saber-toothed Tigers
none of us are ever gonna have to
wrestle people for canned food items and
bombed out supermarkets. instead we are
gonna have this luxury of living well
enough and long enough amid our
psychological stressors to pay the
medical cost and that's the critical
point at the end. To the extent that we
are smart enough to have invented these
psychosocial stressors and then stupid
enough to have fallen for them. we all
have the potential to instead be wise
enough to keep them in perspective. so on
that note thank you for your attention
and good luck with your stressors.

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