Stanford University.
Variety of announcements,
tomorrow, office hours
are shifted because
at 4:30, there's
a really interesting
lecture over at Clark.
This guy is one of the
experts on the whole notion
that there are brain
metabolic abnormalities
in sociopathic humans,
violent criminals.
He's got the distinction
of having the world's only
portable MRI.
He has a big old Winnebago
with an MRI machine.
And he drives all
around the country
from one maximum security
prison to another,
trying to look at aspects of
frontal cortical dysfunction
in extremely
violent individuals.
I have no idea if he's
a good lecturer or not,
the material is going to
be really interesting.
So that's something
that probably should
be caught Friday,
again, is not going
to be videotape,
but just audiotape
for a number of reasons.
Finally, over next
year, I will be doing,
if anyone is interested,
some directed readings
with people that are--
that will be essentially
more of an exploration of some
of the topics in the course
here.
So if you are interested, do
not send me anything whatsoever
until it's the summer.
At that point, CV, transcript,
anything I need to know,
but it will be posted
on the coursework,
so as to more details about it.
So we pick up with the
homestretch here of language.
And what we got to just on
the edge of two days ago
is the now begin to look at
the genetics of language use.
In general, there's the
usual types of techniques
for behavior genetics.
The first is looking
for covariance
of certain language
abnormalities
in certain families.
And the evidence for that is
clear with Williams syndrome,
with the selective
language impairment.
Those tend to run
in families and they
tend to show classical
Mendelian inheritance,
very readily thought
of as genetically
influenced disorders.
Then, going to our
usual deal of looking
at adopted individuals, twins,
identical twins separated
at birth, that
whole armamentarium
of behavioral genetics
stuff, what does that show?
There's a fair degree
of heritability
of things like vocabulary
complexity, ability to spell,
skill at phonology,
things of that sort.
In general, the
evidence is pretty
poor for a strong genetic
load on dyslexias,
on learning disorders
of that type.
Of course, the
modern version of it
all is to start looking
at the actual genes,
the molecular biology of
language disorders, of language
in general.
First thing that
comes up is this gene
that has been at the center of
the whole field for years now,
a gene called FOXP2.
And it was originally
identified as having a mutation
in a family that had a very
specific linguistic problem
running through it,
language generation speech.
This family had severe
problems with it,
classic looking for
a genetic marker,
and eventually narrowing
down to the gene
itself, turning out to be this
mysterious gene FOXP2, which
turned out to be a
transcription factor,
and a mutation in
it in this family.
What immediately became
clear is this theme
over and over again
with language,
in so far as there's a
problem in this family,
is it at the cognitive
level of what language
is about symbolically or is
it just getting your lips
and tongues and articulating
and that much more
mechanical level.
It initially looked
like it was much more
the latter in this family.
It is apparently more
of a mixture of both,
just to make things
really confusing.
What you see is it
is preferentially
expressed in that
part of the brain
we heard about the other
day, the basal ganglia.
That area that's playing a
role in gesturing when you're
speaking, playing a
role in facial prosody,
that sort of stuff, motoric
stuff, and the fact that it was
found so heavily
expressed in there
was part of what got people
to think what's fundamentally
wrong with this family is motor
aspects of language production.
Again, it's gotten
messier since then
because these folks
have a variety
of cognitive impairments
in the realm of language.
So, of course, immediately,
what we need to be asking
is what's FOXP2 doing
in other species.
Does it occur in other species?
And it turns out that it
is all over the place.
You find FOXP2 in
birds and mammals
and all sorts of
things, large and small.
It is very, very widespread.
But, importantly, a
different version than you
find in humans.
It is immensely
conserved, which is
to say you see the
same version of FOXP2
ranging from apes to birds,
everything in between.
Nothing has changed
with that evolutionarily
in a long, long time.
So what does it do?
A handful of studies in animals
where the gene has been knocked
out, it has been removed,
where you now have
mice that do not have the gene.
And what you see is there
is less of vocalization
and simpler vocalization.
And that's back
to our whole world
of that subsonic
vocalizations that you
can't hear when
mice are giggling
and that sort of thing.
Knock out this gene, and
there's less vocalizing
and there's less
complexity to it.
So we're just doing something
or other that looks plausible.
And it's expressed
in motoric parts
of the brain preferentially
in these other species.
So this super
conservative version
of this gene, everybody
else has the same version.
And then you look
at the human version
and there's a bunch
of differences
and they emerged very
recently, best estimates
are the last couple
of 100,000 years.
Each one of the
changes extremely
positively selected for,
whatever this gene is about,
once it sort of went
on the human path,
it changed real fast under
major selective advantageous
conditions.
And thus, we've got a
real different version
from everyone else.
The next interesting
thing about it,
in so far as it is a
transcription factor, when
you look at the genes that
it regulates-- so this is now
taking her step further, our
old genetic network deal,
when you look downstream,
what genes it regulates,
they tend to be
fairly differentiated
from other primates and
to have differentiated
as a result of
positive selection.
So this is a whole
cluster of genes
that evolution was doing
some pretty stringent things
on in hominids in the last
couple of 100,000 years.
Now, what you do is one of the
all-time cool studies, which
was last year,
which you take mice
and you knock out
their FOXP2 gene.
And now, you stick
in the human version.
And, amazingly, what happens
is once these animals mature,
they speak just
like Mickey Mouse.
People were listening.
What you wind up seeing
is-- it's probably
the Disney people probably
are working on it,
and that's going to
be the end of life
as we know it when they
let those ones lose.
What you get when you
overexpress-- when you express
the human FOXP2 in
a mouse is a mouse
with more vocalizations
and more complex ones.
Whoa, that is mighty interesting
area of lots and lots of work
these days, trying to figure
out what this transcription
factor is about.
But, clearly, just
this screaming imprint
of major league selection
that has gone on
for the human version
and for the genes
that it regulates,
fairly recently, it
is no surprise that this
gene is central to such
a different unique
thing that we're doing.
More evidence for genetic
components of the language,
and this one is a
very indirect one
with this totally
interesting phenomenon that
has been shown in lots and
lots of different places
on the globe.
So you get some circumstance
where a whole bunch of people
are brought together
from different cultures,
with different language
groups, and why they're
having to deal with each other.
Classic version is you get,
for example, slave populations
brought from different
places in West Africa
to some of the
Caribbean islands.
You have, on some of
the Hawaiian Islands,
early in the last century,
people from all over Asia
are brought over to worth
the plantations there,
the fields, whatever.
What you have in
these cases, there's
a whole bunch of people
thrown together who
have languages from
every which way
who don't understand each other.
And what always
emerges, what has
been extremely
well-documented, is some sort
of fragmentary
communication system that
is made up of bits and pieces
of all the relevant languages,
which everybody can kind of
limp through and begin to be
understood with each other.
And what that is wounds up being
called is a pidgin language.
Pidgin, very simplistic version
that shows virtually nothing
in the way of complex
grammar, and it's basically
a vehicle for
getting individuals
who almost always,
in these cases,
are societally pretty under
the foot of powers that
be to deal with each other,
to work with each other,
working out this proto
proto communication system
with fragments of each language.
That's not surprising.
What is totally cool is what
happens next over the next one
to two generations, which
is this pidgin thing,
this committee glued
together amalgamation
of fragments of
different languages
within a generation
or two has evolved
into a real language,
which is then
known as a creole language.
Creole languages
are languages that
are a couple of generations
descended from pidgin.
And what you see is it winds
up being a real language.
That's fine, that's fine,
given that, two days ago, we're
hearing that it was
possible for kids
to come up and invent
Nicaragua in sign language
within a generation.
So you start with
this pidgin thing,
and within a couple
of generations,
it turns into a real
language, fits the rules,
grammar, all of that.
Here is the thing
that is so interesting
about this phenomenon, which
is all of the creoles have
the same grammatical structure.
What is that about?
Creoles from all
over the planet that
were built upon all
sorts of differing
hodgepodge of the original
languages in the pidgin, Creole
languages all have a similar
grammatical structure.
Easy explanation, easy
boring one, which is it's
very simple grammatical
structures and this
is a language that's
just getting off
its feet in each case.
No, in all these cases it
is grammatical structures
that are not necessarily
the simplest.
It's not just some
baby step languages.
It's languages that
all seem to come up
with the same graphical
structures there.
And what this has given
rise to is the notion
that there is a default
grammar built into humans.
Let humans go running with
a whole bunch of fragments
in different languages
and, not surprisingly, we
were able to turn it into
a real communicative system
within a generation or two.
And when pulling
language out of thin air,
humans always tend to
come up with the same sort
of grammatical structures
that are not necessarily
the simplest, argument there
being there is an innate,
there is a hard wire, there is
an ancient pattern of grammar
that humans use when they
come up with a language.
So totally interesting.
What you find, also,
with the sign languages,
as they get invented,
Nicaraguan sign language,
it went through a
first generation
of being pidgin, and soon
turned into a signing
equivalent of creole.
And it has some of the same
grammatical structures.
Even when humans are defaulting
into a new language that's
purely gestural, it shows
some of these constraints
that you see with
the creole languages.
Other features of this
that come through,
apparently, there's like
24 different ways that you
can put together objects,
and subjects, and rejects,
the participles, and whatever
it is, grammatical structures.
This guy, Joseph
Greenberg, linguist,
who was here at Stanford
until a few years ago when
he died, apparently,
incredible titan in the field,
he did some of this research.
There's 24 possible
different ways
languages can do this
object subject business,
and all across the earth,
all across the 6000 languages
there, you only see
15 of them used.
And the vast majority
of grammars on earth
only use four of them.
So the argument there
winds up being this
is a pretty nonrandom skew.
Again, we're seeing some kind
of prepared learning default
grammars, this very
imprecise sense of there's
something genetic
floating around here.
So that complementary
to the whole world
instead of looking
at things like FOXP2
and this mutations, the usual
two very different approaches.
That whole pidgin
to creole transition
is really, really interesting
and it really has this feel
in the undercurrents of it that
there is a basic human grammar
that floats around
there, a notion
that Chomsky has pushed
for a long, long time.
Jumping one box further
back, ecological factors
and language.
I'm going to touch on that only
briefly, but what you've got
is something similar to a theme
we heard a couple of weeks ago,
which is possibly not something
we heard a couple weeks ago
and we'll instead
hear on Friday.
But what you see is
diverse ecosystems,
very biodiverse ecosystems.
Rain forest ones,
for example, produce
cultures which have a great
deal of diversity in them.
What we're going
to see on Friday,
the version of
that, which I'm now
thinking I did mention before,
is that polytheistic cultures
are the things you tend to
see coming out of rain forest
settings, that notion that if
there's hundreds, if there's
a thousand different types of
edible plants in your world,
it doesn't take a great
leap to decide there's
a whole lot of different spurred
things in the world going
on there.
Polytheism, a very
similar theme,
great work done a few years ago,
a guy named William Sutherland
from the University of Dundee,
I think, where what he showed
was looking all over
the planet, looking
at the biodiversity
in different regions
on the planet, the more
ecological diversity,
the more linguistic diversity
you would find in that region.
The more different
languages, which, of course,
thus translates down into
small groups, small numbers
of speakers, this is an
interesting phenomenon,
which it's not completely clear
to me what to make of that.
But ecosystems that
are very diverse
generate an abundance
of theistic notions
and at above expected
rates and also produces
a whole lot more languages,
something on the diversity
there.
What his work then showed
is about everything else
I'm going to say in
this area, which is just
totally depressing stuff, which
is linguistic diversity is
going down the tubes
faster than biodiversity.
He shows that the rate
of language extinction
proportionately is faster
than the rate of extinction
of various species, plants, etc.
In these rain forest
ecosystems, totally grim,
depressing picture.
What seems to be the case,
given where things are heading,
is in the next century,
in this century,
90% of Earth's languages
will go extinct.
The vast majority of
humans on this planet
speak less than 10
different languages
out of the 6,000 existing ones.
How's this for depressing?
There's a couple of hundred
different languages that
are Inuit, and Northwest
Native American,
and some other
population as well.
And currently, only of
5% of those languages
have speakers who
are not elderly.
That's real depressing.
Also, and something that
strikes me as extraordinary
is, in each one of those
cases, somewhere along the way,
there's going to be
somebody in old age
who's the last person on earth
who understands their language.
There's not a single
other person alive
who will be able to talk in
their mother tongue with them.
Language is disappearing
left and right,
along with, of course,
cultural diversity
going down the
tubes, the process
of turning the whole
world into a lowest
common denominator of
McDonald's culture, blah, blah.
Along with that comes
a huge, huge loss
of language diversity.
Finally, jumping
to our last box,
if we're talking about
ecological factors,
thinking about
things like genes,
thinking about things
like highly, highly
driven positive selection
for genes like FOXP2
in humans, of course, we have to
talk about the evolutionary end
of things.
So evolution of language
and humans, general notion
is click languages, which you
tend to see in hunter gatherers
in Africa, that that might
have been the earliest
forms, the most ancient
types of languages on Earth.
And what you also see is
hunter gatherers are probably
the most ancient sort of
populations of humans that
live in Africa, with waves
of agriculturalists coming
from North Africa, the
Middle East, at later points,
pastoralists coming from
around there as well.
The original populations in
Africa were hunter gatherers.
And they have high frequencies
of these click languages.
That might be the starting
point for human language.
Interestingly, though, you
also see click languages
among a lot of aboriginal
groups in Australia.
What does that tell you?
Those became separately.
There was a huge gulf
of time between leaving
Africa and the first populations
winding up in Australia,
convergent evolution.
For some reason, click languages
is a very fundamental way
that people come up with
communication systems.
So selection issues
often run in with
our social biological notions
of language advantages,
it's easy to see what
the advantages are
of having a language system.
It is easier to store,
to archive, knowledge,
information.
It is easier to
coordinate hunts.
It is easier to figure out
what we did the last time there
was a famine, figuring out
things like that, all of those
facilitated by language.
In the memorable words of
Steve Pinker from Harvard,
"Language is how we
outsmart plants."
Language allows us to do all
sorts of organizational stuff.
Language evolution is
all about sequence.
We don't say a words
simultaneously.
It's all sequences.
And a number of
people have emphasized
that's what the construction
of tools are about also.
The whole process of careful
logical sequential transitions
of steps almost certainly
tool use and language use
is sequential processes
emerging in parallel.
Finally, obviously, you see all
sorts of room for cooperation
with kin selection, cooperation
with reciprocal altruism being
enhanced with communication.
But very importantly, for
our game theory world,
what language also
allows you to do
is lie, that whole
business from two days ago.
In human language, there's
that arbitrariness.
There's a dissociation between
the message and the messenger.
It's not like dogs
that have to put
the lid on their fear pheromones
by tucking their tale.
What you have is
the capacity to lie.
And, of course, running off
from that, a whole world
of evolutionary strategizing.
Pertinent to that, there's a
huge, huge disproportionate
share of neurons in the
motor system devoted
to facial expressions,
and mouth coordination,
and all that kind of world.
A really good thing
if you plan to lie
is to be able to
have good control
over your facial expressions.
Finally, formal
game theory models
showing when you have pairs
of individuals playing
against each other,
when you introduce,
when you allow the
emergence of communication
between two of the
players versus not
in the other group, you
immediately, no surprise,
have been getting
a big advantage.
If you allow them
semanticity, to have words
that they can communicate,
that is advantageous,
that improves outcome.
Even better is if you allow
semanticity and structure,
syntax, grammar, so
that they can have
more complex communication.
All of those wind
up being things
that facilitate winning
in game theory settings.
Finally, interesting
parallelism,
back to that
biodiversity stuff, which
is, when you look at all those
different possible grammatical
structures, the 24
of them, 15 of which
is the total of what
appears on Earth,
the rarest of the
grammatical structures
are the ones that are
closest to extinction.
The rarest not in terms
of the number of people
speaking it within a
population, but the structures
that have occurred the fewest
number of times in cultures
across the planet
are the ones that
are in cultures where
the languages are
most readily to be a lost,
some sort of connection there.
And thus, you've
got some sort of
weird grammatical
imperialism that
has emerged over the years.
Again, what strikes me as a
totally depressing number,
90% of Earth's languages will
disappear in the next century.
So now we jump.
We jump to our next
topic, which was
our first psychiatric disease.
And to remind you
from two days ago,
we're not going to have
a depression lecture.
The depression chapter
in the zebra's book
will tell all the same stuff in
much better, more clear terms,
I say, proving my point.
And what you should do is
read it with as much attention
to it as if it has
been a lecture subject.
It is an important
subject, enough hints.
So check that one out.
What we focus on today
though is schizophrenia.
And we're going to take
our same old strategy,
starting off with what
is the disease look like.
And as you will see, all
sorts of surprises in there,
and then what goes
on in the brain
just before early development,
prenatal, genes, evolution,
the whole deal there.
We know this drill once again.
So starting off, making
sense of schizophrenia,
as a bunch of
behaviorists, you've
got a challenge right
off the bat, which
is lots of people use the word
schizophrenic in an every day
sense that has no
resemblance whatsoever
to its actual technical use.
Schizophrenic, or schizian--
we all know that one.
We've thought, my God, I am
having such a schizi day.
I overslept, I missed my
first class, it was terrible.
I totally screwed up,
but then I found out
I got this great
grade on a midterm,
but then I had this
fight with a friend,
but then in the afternoon,
and then this crashed,
and, blah, blah.
God, what a schizoid
day I'm having.
No resemblance to how
the term's actually used.
That's not any sort of
real term in psychiatry.
Whatever the schizi
days are that we all
experience now and
then, schizophrenia
is something else.
On the most technical
level, schizophrenia
is a disease of people where,
when you start talking to them,
within two or three
sentences, you
realize there's something
strange with their thinking.
They're not thinking normally.
They're not
communicating normally.
On the most fundamental level,
that's what the disease is.
Obviously, far more precise
than that, schizophrenia,
disease of thought
disorder, disease
of inappropriate
emotion, disease
of inappropriate attribution
of things, and what you'll see
is this is not just some sort
of generic craziness in the way
that that word means
nothing whatsoever.
There are typical structures
to the ways in which things
are not working right in the
behavior of schizophrenics,
which we'll hear about in a bit.
Part of what begins
to bring that across
is the obvious fact
that there's no way
that schizophrenia
is just one disease,
because there's all
sorts of subtypes.
It is a bunch of
heterogeneous diseases.
You have a subtype
paranoid schizophrenia,
where what it's all about
is thought disorder built
around a sense of persecution.
You have catatonic
schizophrenia,
where the person is
in a frozen state,
immobile for long
periods of time.
You have schizoaffective
disorders,
which is kind of a mixture of
schizophrenia and depression
disorders.
It's not just one disease.
So the whole array of
behavioral symptoms
we're going to look at
now, remember, some of them
are more common in different
subtypes than others.
This is just the
first broad overpass.
So beginning to make
sense of the disease, what
it is, above all
else, is a disease
of cognitive abnormalities, of
abnormal sequential thought.
And the term that's given
for it is loose associations.
All of us can tell a story where
we have a pretty good ability
to put it sequentially and
have the facts go in a way
where it will make sense
to any other listener.
You do not see this
in schizophrenics.
Sequential thinking
is greatly impaired.
And instead of having logical
sequences of information
that they give, things
tangent all over the place,
bouncing around all over,
where, in retrospect, you
can kind of see how
they might have gotten
from A to Z, although most
people would have gone
from A to B at that point,
the tangential thinking
being another term for it,
the loose associations.
So what do you wind
up seeing there?
You get schizophrenics,
for example,
who get terribly
confused in a sentence,
whether when they are
hearing about boxers,
they are unable to keep
straight within one sentence
to separate out whether
they're talking about a dog
or they're talking
about an occupation.
Because they slip back
and forth between the two.
Confusion between
being a caddy, a caddy,
someone who a golf whatever,
and a Cadillac, short term
for that.
All sorts of ways in
which they can't hold on
to the sequential logic.
And, instead, there's
just this tangenting,
getting caught up in
the loose associations.
You're talking about a boxer,
if you were a schizophrenic,
you were talking about
a particular boxer,
you follow that sport
whatever, and, suddenly,
you are expressing
an opinion about how
that person would do in a
ring against a St. Bernard.
And you're often
talking about dogs
from there, just getting
caught by a loose association
between the sound of the word
and its multiple meanings,
going off the tracks on that,
so the loose associations.
Next, you have a
trouble, consistent one,
with abstraction.
All of us have a pretty
good intuitive sense,
when someone is
telling us a story,
is this meant to be
literal reporting of events
in a sequential way, is
this meant to be a parable,
is this meant to be a
somewhat secondhand,
through the grapevine story.
We have a very good
sense of how concrete
or how abstract the information
that we're getting is.
Schizophrenics are
terrible at that.
They have no intuition to get
the right level of abstraction.
And schizophrenics always
skew in the same direction,
which is to interpret
things far more concretely
than is actually the case.
And that's the term that's used
in the business, concreteness
of thought, which is having a
lot of trouble doing the more
abstract process
of seeing things
on a metaphorical level,
things of that sort.
So here, here's the
standard sort of test
you would give to someone if
you think they're schizophrenic.
You give them an
association task.
And you say something
like, OK, can you
tell me what do
these things have
in common, an apple, an
orange, and a banana.
And they'll say all of them
are multi-syllabic words.
You'll say, OK, well,
that's great, that's true.
But anything else
they have in common?
All of them have letters that
involved closed loops, just
getting caught up in the
most concrete possible level
of interpretations of it,
not able to step back and do
any sort of abstracting.
You see this in all
sorts of other ways.
Therapist role, meet the patient
and say something like so
what's on your mind
today, and they'll
say my hair in this very
literal sort of way.
Or you'll say can I take your
picture, holding a camera,
and they'll say, I don't
have a picture to give you,
this very literal sense again.
Or things like you would
sit down a schizophrenic
with a piece of paper
and a pen and say, just
as part of what
we're doing here,
can you write a sentence
for me, any sentence.
And then you look
at what they've
written which is a sentence
for me, any sentence.
And then you say, no,
no, no, actually, that's
not what I mean.
I mean can you come
up with a sentence.
And when you've thought of
that sentence, write it.
And they'll write the word
it because they can't get out
of the concreteness of saying
could you write a sentence, can
you write colon a sentence.
They're caught up in the
concrete level of that.
A way that that
always pops up, one
of the classic types
of tests that's done,
is called proverb tests.
Proverbs, by definition,
they are metaphorical.
They are parables,
they are abstract.
And we all know
intuitively that when
you're talking about birds
of a feather flock together,
you're doing something symbolic
about the well-known homogamy
of lips with people who
they choose to marry
and the similarities.
Yes, birds of a
feather flock together,
it's talking about like
tend to assort with like.
Give proverbs to
schizophrenics and they
can't get out of the
most concrete level
of interpretation of it.
So you're sitting down
and you say, OK, tell me
what this means.
A rolling stone gathers no moss.
And we all know that that's
people are on the move,
don't make an
emotional connections,
there is a detachment.
And they're often saying stones,
stones rolling down hills,
it's very hard for
plants to grow on them.
It's very hard because the
surface tends to be smooth.
And then on top of
it, if it's rolling,
you've got like this angular
motion that move to it.
So it's very hard for
moss to grow on stones.
In fact, I don't think
I've ever seen that happen.
And I've seen many stones.
And on the most
concrete possible level,
incapable of pulling it back
to the level of abstraction.
Consistent, consistent
feature of this.
Here, friend of mine
who's a psychiatrist
came up with what has to be one
of the all-time great proverb
tests for figuring
out if someone
has the remotest tendency
towards schizophrenic
concreteness.
There was a abstract
phrase, a proverb,
that was very popular, that was
very prevalent in the United
States during World War II.
It was up on posters and all the
post offices, places like that.
And it was a way of abstractly
telling people be careful
the information you put in
letters that you are sending
off to loved ones
who are off at war
because it may inadvertently
wind up in the wrong hands
and could carry information
that could be extremely damaging
to the war effort.
Do people know what it is?
Loose lips sink ships,
loose lips sink ships,
wonderfully abstract notion.
Try sitting down a
schizophrenic and saying
what does it mean when you
say loose lips sink ships.
And, suddenly,
there's this imagery
of ships being capsized
by big lips coming out
of the water and
things of that sort
because it can only be
dealt with on the very
concrete level.
What else?
More symptomatology, delusions,
belief in things that cannot
be, belief in having
participated in historical
events that cannot be.
You're sitting there
interviewing a schizophrenic
and they suddenly
say have you heard
of the Great Wall of China.
And you will say, well,
yes, in fact, I have.
And they'll say
my idea, my idea.
The generals came to
me at night with a map
and I said this
is where it goes.
This is probably
not what happened.
Delusional thought,
inserting yourself,
conversations with people
who no longer exist.
Related to that is
the paranoia, which,
of course, is most florid
in paranoid schizophrenia,
but it is a frequent theme.
What do apples, oranges,
and bananas have in common?
They're all wired for sound.
If the fruit is
listening to you,
this makes for a rather
disquieting life.
And almost certainly,
it has something
to do with if the world is
making so little sense to you,
it is a world that
is very threatening.
Along with that, most
famously, perhaps,
with schizophrenia, is
you get hallucinations.
Those are the defining features.
Somebody is trying to figure
out if somebody in an emergency
room has come in with some sort
of schizophrenic type disorder
and hear that the
person is hearing voices
and that pretty much
nails down the diagnosis.
For reasons that are
very poorly understood,
the vast majority of
hallucinations are auditory.
However, there's all sorts
of notions with that.
And one great theory coming from
our own Patrick House, given
two years ago, which is you get
auditory hallucinations more
often than visual
ones because we're
more accustomed to
visual stuff in the world
having fragmented visions or
seeing it across two mirrors,
reflections, things
of that sort.
We are more vulnerable towards
sounds not making sense.
Vast majority of
hallucinations in schizophrenia
are auditory hallucinations.
When we see in a little while
what the neurochemistry is
of hallucinations, by all
logic, what they should be
is just random splatters of
noise, and random visual dots,
and all of that.
Instead, they're structured.
They have content.
People hear voices,
rather than random sound.
People see very
structured hallucinations,
sufficiently so that
researchers can even do studies
as to which are the most common
voices heard by schizophrenics.
And, no surprise,
in Western cultures,
forever and ever, the number
one voice on the hit parade
is that of Jesus, the number two
voice, Satan, the number three,
typically, whoever
is the head of state
in the country at that point.
It's structure to that extent
that you can publish papers
about what the
hallucinations are like.
There's all sorts of
structure underneath.
It is not just
disordered thought,
it's loose associations,
and tangenting,
and concreteness, and
structured hallucinations.
What else?
Another feature of the
schizophrenic symptoms
is social withdrawal.
And schizophrenia,
everybody thinks
of as a disease of
abnormal thought,
it is a disease of abnormal
social affiliation.
You look at a-- you
look at a schizophrenic
in some village in who
knows where in the Amazon,
or in Bloomington, Indiana, and
this is going to be someone who
is somewhat ostracized and
socially disconnected, very
much alone.
It is not just the disease
of disordered thought.
More and more
people are realizing
the core with schizophrenia
is the disordered thought.
The standard view
has always been
to hone in on the most florid
feature of the disease.
Schizophrenia is the disease
where you hallucinate,
where you hear voices.
And the vast majority of the
neuropharmacology research
that's been done out
there on the disease
is meant to go and cure
the hallucinations.
But far less responsive
to any of the drugs
are the tangenting
thought, the concreteness,
the loose associations.
More and more
people are thinking
that that's really at the core
of what the disease is about.
Couple more features
of it, which
is the whole world of
the social withdrawal.
Apathy, what we're
beginning to see
is a dichotomy in the
business, positive symptoms
in schizophrenia, paranoia,
loose thoughts hallucination,
all of that.
Negative symptoms
of schizophrenia,
the absence of
social connectedness,
the absence of affect, a
very flat expressive style.
Physiologically,
you see some damping
of autonomic nervous systems in
schizophrenics, so the positive
and the negative
symptoms of the disease.
Last a couple of features
of it, one is the notion
that, of course,
schizophrenia has
something to do with violence.
Everybody knows that there is
the scenario lurking out there
that occurs endless
number of times which
is you have some psychiatrically
unstable individual turning out
to have schizophrenia who
winds up doing something
horribly violent, the danger
of schizophrenics cracking
and going postal.
And every now and then,
something like that happens.
20 years ago, there was
a horrifying incident
at Berkeley.
A student there who was
schizophrenic and probably
should not have been there at
the point because he was not
well-medicated,
something cracked and he
took a bunch of
Berkeley students,
women, hostage in
a bar at Berkeley,
did all sorts of horrific
sexually abusive things there
before he killed himself
after killing a few of them.
This is what happens
when something like that
occurs with a schizophrenic.
Oh, my God, so we've
got all these people
running around where that
could be happening any second.
Schizophrenics are
far less dangerous
than are normal
individuals in society.
The rates of violence
are extremely low,
with one exception,
which is schizophrenics
being violent and
damaging themselves.
Self-injury, a huge
feature of schizophrenia,
part of the delusions, part
of the thought disorder,
part of the despair, when
every now and then your head
clears enough to see what
the rest of it is like.
And there are even
studies as to which
are the most popular places
in the body that are mutilated
in schizophrenics.
Genitals are top on the list,
and going down from there.
Horrific thing that happened,
also about 20 years ago,
Columbia Medical
School, and this
was an individual,
a student there,
with a history of a lot of
psychiatric instability,
and schizophrenia, and somewhat
well-controlled with meds.
And somewhere in
the third year when
starting the clinical rotations,
the various stressors of it,
the person kind of unravelled.
Probably should not have been
there in the first place,
but, nonetheless, had
a schizophrenic break
and had withdrawn from med
school and was sitting at home.
Part of his paranoia,
part of his delusions
were that he was
satanically possessed.
And, specifically, the way
Satan was driving him to madness
was with obsessive
sexual thoughts.
So being a relatively
well-trained endocrinologist,
because we know better than
him at this point how it works,
he decides how do I make
those thoughts go away,
let me get rid of
my testosterone.
So he castrated himself.
But at least being well-trained
in one domain of endocrinology,
he knew that other
fact we've had
in here which is that
the adrenal glands also
make a certain degree
of testosterone.
And he proceeded to try to
adrenalectomize himself.
He sterilized with some alcohol.
He made an incision
with anesthetic.
He had a mirror
there, angled to be
able to see what he was doing.
And at one point, he hit a blood
vessel, which started bleeding.
And he went to the ER at
Columbia Presbyterian,
going in there, not saying
to his former classmates,
oh, my God, guys, can you
help me, look what I've done.
Saying instead, hi, guys, I'm
trying to take out my adrenals
and I'm having a
problem here with it,
can you give me a hand.
This is very disordered thought.
This is a very
elegant version of it
schizophrenic self-injury,
schizophrenic suicide,
is anything but clean.
Number one on the list,
genitals, number two
for women, female
schizophrenics, breasts, number
three, thighs, on it goes.
This brings up another
feature of the disease, which
is, back in the 1960s, when
all sorts of laudable things
happened along certain
cultural lines,
there amid that was
one horrifically
damaging idiotic
thing that emerged
in psychiatry at the
time, which was a minority
view in psychiatry, a
lunatic fringe view,
that, basically,
schizophrenia is not so bad.
Schizophrenia has all
sorts of hidden blessings.
And soon, it had
frameworks of things
like schizophrenia is
the disease of being
healthy in a crazy world.
Schizophrenia is the disease of
having insights into life that
other people can't.
And psychiatrists at
the time, one of them,
a man named Ronald
Laing, who became famous
for this, for arguing
it's not a disease,
we shouldn't be medicating,
we shouldn't be hospitalizing,
it's a bunch of blessings.
And it is even
continued to this day.
The quote that I put on the
top of the handout, Andrew
Wild, who is one of the gurus of
sort of complementary medicine,
and you'll see an absolutely
ridiculous statement
there along the lines
of the hidden blessings
of schizophrenia.
There were movies at
that time, King of Hearts
was one, very popular
one about somebody having
to hide from the police or who
knows what, and the asylum,
and eventually releasing
the schizophrenics who
were so much saner than
the other people around,
and heartwarming.
And all you need to do is be
schizophrenic or know someone
who is or have a family
member and you will see
there are no hidden blessings.
This is not a disease
of hidden compensations
and more insight into the world.
This is one of the most horrific
ways that biology can go wrong.
And one of the best
demonstrations of it
is half of schizophrenics
attempt suicide.
And the more often you
have periods of remission,
the more likely you
are to commit suicide.
What's the significance of that?
The more often you
have periods where
you're clear-headed enough
to see what your life is
like the rest of the
time, the more likely
you are to try to kill yourself.
A disease with no hidden
blessings whatsoever.
Other features of it,
there's an aging component,
two different forms.
First one is as schizophrenics
become older, elderly,
what you see is the positive
symptoms tend to disappear.
The hallucinations get
damp, the delusions,
the loose associations, and
the negative symptomatology
is what comes to the forefront,
this world of just flat affect
and withdrawal.
The other age feature of
it we will hear about it
in a bit, which is
real defining, which
is schizophrenia
is a disease where,
in the vast majority
of the sufferers,
it has late adolescence,
early adulthood onset.
It is a disease of
18 year olds who
come down with a diagnosis
for the first time.
If you make it to age 30
without schizophrenia,
you have virtually no
chance of ever having it.
It is a disease of
adolescent onset.
And this is going
to fit with two
things we'll be talking about.
One is the
epidemiological evidence
showing that what
schizophrenic attacks-- what
schizophrenic breaks typically
are at the very beginning
are in response to
major stressors.
These are individuals
who have always
been a little bit odd,
who, in elementary school,
had imaginary playmates far
later than most other kids did,
who had all sorts of
periods where they seemed
not to be paying attention and
lost in their own thoughts, who
had trouble making
friends, but they were OK.
They were sort of hanging on.
And then it was
late in high school
when they had the car accident,
or the first boyfriend was
so horrible to them,
or the parent died,
or whatever the crisis was,
and this person who was just
sort of holding on, that's
where the dip occurs,
and that's where it crashes.
Schizophrenia as an
adolescent onset disease
where stress plays a
major precipitating role.
The other piece that
we'll see is the fact
that schizophrenia almost
certainly is heavily
anchored in the frontal cortex.
Frontal cortex, you
remember the frontal cortex.
Frontal cortex, which
is not fully mature
until age 25 or so, the last
big burst of frontal maturation,
late adolescence
or early adulthood,
we'll see there's
lots of reasons
to think that schizophrenia
is a disease where,
around late adolescence,
a fragile, vulnerable
frontal cortex gets kicked
once too hard with something
or other.
And that's one where
the problems emerge.
A couple of other
features, demography
in every culture ever
looked at on Earth, 1% to 2%
of the population
comes down with it,
no gender differences,
no social economic status
differences in terms of
who becomes a friend.
But once you are, there
is the not very surprising
downward socioeconomic
spiral, which
is, no surprise, people
who are schizophrenic
do not make very good CEOs
of large corporations.
These are the street people.
These are the homeless.
The majority of people living
on streets in this country
are individuals who are
schizophrenic, not alcoholic.
That is the far more
common thing that you see.
So a disease of complete
collapse into some of the least
cared for sort of strata
of society, that is part
of the demographics as well.
So that's what the
disease looks like.
And if you're really thinking
about these symptoms,
at this point, you
should be jumping out
of your chair
because of something
really disturbing about
this collection of symptoms.
So what is schizophrenia?
It's a disease of
thinking abnormally.
This is a disease of thinking
differently from everyone else.
This is a disease of thinking,
in a way, that everyone
else thinks isn't right.
And, suddenly, we are skating on
thin ice of this transitioning
from a world of neuropsychiatric
disorders and medicine
into a world of all sorts
of hidden agendas of abuse.
And psychiatry has
been hand in hand
in bed with all sorts of
ideologues over the decades,
over the years, and willing
to hand out diagnoses
of schizophrenia to
political dissidents,
to people you want
to get rid of.
And this is a totally
loaded, loaded diagnosis,
when, most
fundamentally, this is
a disease of
everybody else thinks
you're not thinking normally.
Because, some of the
time, that describes
a florid psychiatric disease
that destroys your life.
And some of the time,
it describes people
who are just a pain in the ass.
And some of the
time, it describes
people who are going to
transform the world by thinking
differently.
How can you possibly
approach this disease
in an objective way
rather than it having just
shot through with ideology?
And one of the ways in
which this can happen,
one of the ways where you
get some grounding in it
is to look at what the disease
appears like in other cultures,
because you begin to
see the commonalities.
And this begins to impress
you with the notion
that there is, in fact, a
core set of dysfunctions
to the disease.
So let me tell you
about the one case
of cross-cultural schizophrenia
I have ever been exposed to.
And I was going to bring
slides, but I couldn't quite
figure out how to scan them.
So maybe eight
years from now, I'll
get together for
that technology.
But it has to do with the time
I spent in Africa and my nearest
neighbors.
Nearest neighbors there are
from a tribe called the Maasai.
These are nomadic pastoralists.
And these are not
the folks next door.
This is as different
of a culture
as you could find
on this planet.
Men, around puberty,
boys around puberty
become warriors, spend the
next 10 years in their warrior
clans, as we've heard about,
pillaging the neighbors,
getting killed in
return around age 25.
As elders, they settle down
and marry their first wife,
typically a 13 year old.
And, well, as soon as
they can, add on more.
This is a culture with,
up until recently,
a life expectancy in the 30s.
This is a culture where people
believe in all sorts of things
that we would view
as being paranormal.
This is a culture in which
people celebrate events
by drinking tureens
of cow blood.
This is a very different
bunch of folks.
Let me tell you about
the one schizophrenic
Maasai who I've ever seen.
And this was about 25 years ago.
And I was in my camp, which was
a few miles away from this one
village where I
knew a lot of folks,
and just sitting there
minding my own business.
And I had this
one woman in there
who was my-- closest friend
or whatever in the village.
And I suddenly see
she is running up
the mountain with a
bunch of the other women
from the village in this
completely agitated state.
They come roaring into my camp,
totally flummoxed and just
like completely agitated.
These are people who do not
get agitated over things very
readily.
These are people who,
as a puberty right,
have to go out and kill a
lion or don't come back.
So when Maasai are getting
all crazed about something,
this is something worth
paying attention to.
They're totally crazed and
they're saying somebody
in the village has done
something very wrong
and I need to come
and help them.
It turns out what they wanted
me to do was bring my car.
That's the way in which I
was going to be helpful.
So they impressed
me into doing this.
And we all pile into
the car and started
driving down and heading
towards the village.
And as we're getting
there, I'm beginning
to get some information.
And what I see is
them telling me
about a woman in
the village who's
done something
wildly inappropriate
and they've had it with her.
Now, I had been around that
area for about four years,
at that point, knew most of
the people in that village.
And this was someone who
I had never encountered.
A-ha, socially isolated,
living in the back of some hut
at the far corner of the
village, a first sort of hint.
So they're describing
to me that she has
done something inappropriate.
She has killed a goat.
You don't do that.
You don't do that
if you are a woman.
You don't do that if
it is not a ceremony.
You don't do it the
way she has done it.
She has grabbed
somebody's goat and ripped
its throat open with her teeth
and was now there with a goat.
And everybody had
had it with her.
So we're driving there
and I'm listening to this,
and I'm saying, whoa, this
sounds like a psychotic break.
This is going to be cool.
This is going to be
really interesting.
I wonder what it'll be
like to talk to the family
and find out what the
symptoms have been.
Or I wonder if she's
going to have any insight.
It's going to be fascinating
to talk to her about this.
So I get into the
village, and this person
I was now planning to have some
good heart to hearts with about
their tangential thinking, out
comes this huge naked woman
with a goat in her mouth by the
throat, covered in goat blood,
and goat urine, and goat shit.
And this woman gives this
howling yell, charges
across the village, knocks
me over, and attempts
to strangle me.
I'm a normal kind of
guy, normal fantasy life.
Never once in the darkest
recesses of my mind
did this strike me as
something that was appealing.
I'm lying there,
she's throttling me.
I'm thinking this is how
I'm going to wind up dying.
My poor parents
are going to have
to deal with the stigma of this
for the rest of their lives,
that this is-- he's
done in by someone
with a goat in her
mouth, and thinking that.
So, fortunately, everybody
else was much more clear-headed
and they pull her off me.
And what they proceed to do
is push her into my Jeep.
And they pile on top of
her and they say let's go.
So I collect myself and leap in
and we head off driving there.
And this woman was floridly
out of control of there.
But we're driving somewhere.
Where are we driving?
We're driving to the nearest
government clinic, which
was about 25 miles
away and consisted
of a wood shack
and a nurse there,
a government nurse, who
as a result of this three
weeks of training, gave
out malarial medication
for anything you came
to complain about.
And what they were
going to do was
they wanted to get rid of her.
So we go driving and we
eventually get to this clinic.
Well, what they proceed to
do is push her into the hut
and hammer the door closed.
So I'm sitting
there, at this point,
saying, OK, well,
we've containment.
So what do we now?
Do we-- do we talk to her?
Does the nurse talk to-- do
we go and get the family?
What are you-- so I
turned to my friends
there and say so
what do we do now.
And they say let's get
the hell out of here,
showing an important thing.
Even in a culture as
different from ours,
nobody has a whole lot of
tolerance for the mentally ill.
Let's get out of here.
So they persuade me to go.
We get into the vehicle and
start the long drive back.
After a while, the
car's aired out a bit
and everybody's
calming down a bit.
And I decide this was wonderful.
What a marvelous
opportunity to learn
about some cross-cultural
psychiatry or whatever.
So I turned to my friend
who's sitting next to me there
and I say so what do you think
was wrong with that woman.
And she looks at
me as I'm an idiot.
She says she's crazy.
And I said, well,
how do you know.
How do you know?
And she said she hears voices.
And I say, ha, you
guys hear voices.
Maasai hear voices,
they do trance dancing
before they do sort of these
around the clock cattle runs.
They hear voices of
ghosts, that sort of thing.
I say to her what's the
big deal, you hear voices.
And she says, no, no,
no, it's different.
Then I say, well, what
else was she doing wrong.
And she says she killed a goat.
And I say you guys kill goats.
But, again, this
wasn't how it's done.
There is an old longstanding
belief among Maasai men
that it is very bad luck to
have women observe eating meat,
so they get to go off on their
own and eat all the goat meat.
And it's done in a
certain ritualized way.
You do not kill a goat
if you are a woman,
if you are a naked,
yelling banshee
of a woman in the middle of the
village with your bare hands
and teeth.
You don't do this.
So I'm sitting there
and I'm saying, well,
do you know this-- it's
kind of hard for me
to tell the difference here.
And she says, in
the sense, idiot,
she hears voices
at the wrong time.
And that's the core,
ultimately, of the objectivity
that's needed in this disease.
In order to understand what
counts as abnormal thought,
you first have
the huge challenge
of understanding all
the different ways
that normal thought
can manifest itself.
And that is a classic problem in
training psychiatrists sitting
in some inner city
clinic recognizing
that the amount of
cultural variety there,
or the different ways in
which you can be normal,
is extraordinary and
extraordinarily challenging
at times.
You are on very
thin ice deciding
you know what counts
as abnormal thinking
before you have
a very wide sense
of what can count as normal.
So now let's take a
five minute break.
And all sorts of very
accomplished artists
over the years who've turned
out to be schizophrenic.
And schizophrenia is not what
made their creativity possible,
schizophrenia is what
destroyed their careers.
Other question is so what
happened to that woman.
And this was shortly before I
was coming back to the states.
And it was about nine months
later that I went back there.
And some point, when
seeing my friend,
saying whatever
happened to that woman.
And her response
was, oh, she died.
Maasai do not like to
stay indoors, she died.
That's all I ever
found out, once again,
as different to the culture
on Earth as you can imagine.
And they are no more tolerant
of the mentally ill than we are.
So now, beginning the
neurochemistry of it,
what's going on in
the brain, what's
going on with brain chemistry?
And for decades
and decades, there
has been one dominant model
for schizophrenia, which
is the dopamine hypothesis,
the notion that somewhere
in the brain, stay
tuned, there is
an excess of dopamine
winding up in the synapses.
What's the evidence for it?
First off, you do
things like look
at levels of dopamine breakdown
products in the bloodstream,
in the urine, in the
cerebral spinal fluid,
tending to be elevated
in schizophrenics.
Next, what you see is
the most important fact
which is all of the
classic drugs that
work with schizophrenia
block dopamine receptors.
Anti-psychotic
drugs, neuroleptics,
Haldol, Thorazine, when,
at some exciting moment
in the made for TV movie,
where the person has gone mad
in the ER and someone
yells for a syringe,
they're yelling for a syringe
of something that will
block the dopamine receptors.
If you give schizophrenics
dopamine or some drug that
activates dopamine
receptors, their symptoms
get worse, which kind
of makes you wonder who
approved that kind of study.
That doesn't sound very logical.
You look post-mortem at the
brains of schizophrenics
and there's elevated levels
of dopamine receptors
in the frontal cortex.
So we have a whole bunch of
ways that things can go wrong.
We can have too much
dopamine coming out,
for some reason or other.
We can have too many
dopamine receptors,
enhanced sensitivity.
We know another possible
way, which is dopamine
is then broken down
by this is enzyme.
And if this enzyme
isn't working very well,
levels are going to accumulate.
And there's a bit of
evidence of abnormalities
of this enzyme in
some individuals.
So one additional
interesting piece
of evidence for this
dopamine hypothesis,
which seemed absolutely
clear by now,
you have somebody
who's schizophrenic,
you give them a drug that
blocks dopamine receptors
and thus decreases the
dopaminergic signaling,
and they start getting better.
What's your
hypothesis have to be?
I bet you they had
too much dopamine.
This is shown in
another interesting way.
18 counties over in
the brain from where
dopamine's got something
to do with this,
dopamine serves another role.
In a motor system related
to the basal ganglia, all
of that, involved in fine motor
control, a part of the brain
called the substantia nigra.
And if you get a little
bit of damage there,
I think I mentioned
a couple extras ago,
you get the tremor of old age.
If you get a lot
of damage there,
you got yourself
Parkinson's disease.
And what occurs
in Parkinson's is
90% of the neurons in
the substantia nigra die.
And people are even
beginning to understand why.
These are dopaminergic neurons.
Parkinson's is a disease
of losing all the dopamine
signaling in this
part of the brain.
People began to figure
this out in the early '60s.
And out of that came one of
the first drug treatments
for any neurological disease.
What's the strategy?
These are people
who have too little
dopamine in this
part of the brain.
Give them replacement dopamine.
Turns out it's hard to
get dopamine in the brain,
so you would give
people one step earlier
in the biosynthesis
a drug called L-DOPA.
L-DOPA, which then gets
converted into dopamine,
and this was miraculous.
All sorts of people
who were just
paralysed with their
Parkinson's, L-DOPE
suddenly liberated them.
There's a movie 15
years ago or so,
called Awakenings
with Robin Williams,
which was based on a
book by Oliver Sacks,
based on his own
work, which had to do
with this rare disease that
emerged after World War I,
having something to do with
the influenza pandemic, then
a post-encephalitic
paralysis, which became
known as stiff man syndrome.
And people who were
essentially frozen in place,
and what we now know is it's
an autoimmune disorder that
targets something with
the dopamine system.
Sacks was a medical resident at
the time, was-- at that point,
the L-DOPA stuff was just
coming out with Parkinson's.
And Sacks was the one
who had the insight
to say I bet the
stiff man syndrome is
a case of the most extreme
severe Parkinson's that you
could possibly get.
And, thus, he was the first
one to try L-DOPA on people
with the syndrome, and thus
you had miraculous awakenings,
people moving voluntarily for
the first time in decades,
totally amazing.
But then, you have a downside.
And the downside
that we know sort
of the structure
of by now, you've
got a problem with dopamine
in the substantia nigra,
lower than normal levels.
Everywhere else in the brain,
you've got normal levels.
So you're trying to
fix up this depletion,
you give the person L-DOPA.
But you're not spritzing it
into their substantia nigra,
you're putting it in their
stomach or their bloodstream.
You are raising dopamine
levels in the substantia nigra
and things get better,
but you're also raising it
everywhere else in the brain.
And what you wind up seeing
is if you give a Parkinsonian
patient too much L-DOPA,
they become psychotic.
They are indistinguishable
from a schizophrenic.
And what was shown in the
movie was this character
played by Robert
De Niro wound up
having this florid paranoid
psychosis from the L-DOPA,
so, oh, that being
more evidence,
you give a drug that
raises dopamine levels
throughout the
brain and somebody
starts acting schizophrenic.
You give somebody a drug that
causes very rapid dumping
of dopamine, and
they will transiently
appear schizophrenic.
What's the drug?
That's what amphetamines do.
And you get somebody coming to
an ER who is loose associations
and hallucinating
delusions and all of that,
and most clinicians cannot tell
whether this was somebody with
an amphetamine psychosis
or schizophrenia.
Pump their stomach out.
If they suddenly start
making more sense,
it was probably
the amphetamines.
So this being more evidence.
Now, you should be thinking
what about the flip side.
So you have schizophrenics,
where you give them
these neuroleptic drugs to
block dopamine receptors
in the frontal cortex,
as it turns out.
But you're not injecting
it straight in there,
you're putting in the guts.
And, now, you've got
too much dopamine here.
You lower its levels,
but everywhere else it
gets a little lower than
normal-- not dopamine levels,
but dopamine signaling.
And, suddenly, you should
generate this prediction
that if you over
medicate schizophrenics,
they should start looking as if
they have Parkinson's disease.
And that's exactly
what you see as well,
a disorder called tardive
dyskinesia, kinetics,
body movement
dyskinesia, abnormal one.
And these are individuals
who look Parkinsonian.
Go into a state hospital,
go into the back ward,
and find somebody
sitting there who
is tremoring like this all over
their body the entire time.
And that's somebody
who was going
to have been taking these
drugs for 20, 25 years or so.
So, collectively, this
winds up telling you
all these different ways
of suggesting the problem
is that there is too much
dopamine in this disease.
However, just to
make life miserable,
there is at least one
anti-schizophrenic drug
out there which what it does is
it increases dopamine signaling
and people get better.
Bummer, nobody knows what to
make of this at this point.
So what's the excess
dopamine doing in there?
It's not having anything
to do with movement stuff.
That's substantia nigra.
It's not having anything
to do with pleasure.
That's dopamine in different
parts of the brain.
The best evidence
is this is dopamine
functioning in the
frontal cortex,
stimulating normal
executive function.
And what you've got
is a frontal cortex
that is not making a
whole lot of sense.
Loose associations,
that seems to be
where the dopamine
problem is played out.
Next neurotransmitter
that's been implicated,
serotonin, look at the chemical
structure of serotonin,
and then look at the
chemical structure of all
of the major hallucinogens,
LSD, mescaline, psilocybin,
they are all structurally
almost identical.
And all of those hallucinogens
fit into serotonin receptors
and activate them.
What is a hallucination
induced by a drug?
You've got some
serotonin synapse
where nothing's happening.
The pre-synaptic
neuron hasn't had
anything interesting
to say in weeks,
it hasn't released
any serotonin.
But, now, there's something that
kind of looks like serotonin
percolating its way into the
synapse, where it could then
bind to the serotonin receptors.
And as far as this
neuron thinks,
it just got a
message from there.
And it didn't come from there.
This neuron is hearing voices.
And the fact that that's how the
hallucinogens work immediately
generated all
sorts of hypotheses
that there are abnormalities
in serotonin in schizophrenia
as well having something to
do with the hallucinations.
Next, the
neurotransmitter glutamate
has also been implicated.
What's the evidence there?
When you take a drug
that wildly stimulates
one subtype of
glutamate receptor,
you begin to look a bit
like a schizophrenic.
What's the drug?
PCP, angel dust, phencyclidine.
That stimulates a subtype
of glutamate receptors.
And a lot of people
have argued this
has enough resemblance to
what schizophrenia looks like
that there has to be a
glutamate problem going on
in the disease.
Very, very little
bits of evidence
for that, the one thing
that has been shown in rats
is when you stimulate
the brain with PCP,
what you get is an increased
levels of receptors
for serotonin in some
interesting parts of the brain,
some kind of connection
running around there.
So very, very solid implication
of dopamine, some serotonin
thrown in there,
glutamate, eleventy other
neurotransmitters that
people are thinking about,
but these are the main ones.
And, overwhelmingly,
the dominant hypothesis
remains the dopamine hypothesis.
What about brain metabolism?
What's going on in the
brain, for example,
during a hallucination?
And what you essentially
get is wild activation
of everywhere in the brain
and you are hallucinating.
You get wild activation, people
who are in imaging studies
have taken these
drugs voluntarily,
you get wild activation
in the cortex,
except for, say,
the first couple
layers of the visual cortex,
or the first couple of layers
of the auditory cortex.
What's that about?
The cortex is seeing
things and hearing things
that did not come in from
the outside world, that
never stimulated the
primary sensory cortex.
Otherwise, during
hallucinations,
you see extremely high
levels of metabolism
throughout the brain.
The next interesting
thing in that realm,
you give schizophrenics
some standard declarative
memory tasks and metabolism
in the hippocampus
does not increase as much
as in other individuals.
So that brings us to structural
features of the disease.
Yeah?
Does the brain--
while hallucinating,
does the brain work
somewhat like when dreaming?
Good question.
Does the brain, in terms
of patterns of activation,
look somewhat like
during dreaming?
Yeah.
It's not the primary sensory
cortex regions that activate.
Frontal cortex is
relatively quiet.
And the rest of the
brain is going like mad,
and certainly makes sense.
So structural stuff,
there's all sorts
of structural abnormalities in
the brains of schizophrenics.
How do you learn this though?
Very difficult, because, for
the first couple of decades
in the field, it was all
post-mortem analysis, which
is you take out the
brain of a schizophrenic
and you go and
look at it, and you
see if there's anything weird.
So what's the
problems with that?
All sorts of things,
which is to try
to do post-mortem studies on
human brains, different brain
sit for different
lengths of time
before they're
autopsied and removed.
So that's a huge
piece of variability.
Moreover, you can get
post-mortem artifacts,
which is to say
you're pulling out
the brain and somebody
squeezes it too hard
and squishes something
in here and it's not
going to look normal afterward,
reflecting the handling of it.
And out of that has
come this whole world
of neuropsychiatry
types were what they
live for are rapid autopsies.
And a whole bunch
of medical centers
have rapid autopsy
teams connected
with their Alzheimer's
folk, connected
with some of the
psychiatric diseases,
where their idea is to
get in there as fast
as possible with
patients who have
or whose family have
given permission for that
and get the brain out
as fast as you can.
And I remember, a
few years ago, I
was down to Duke
Medical Center, and they
had one of these rapid
autopsy SWAT teams.
And they were bragging about
how they were getting brains out
in under 30 minutes from death.
So that solves a whole lot
of the post-mortem rotting
away lag time.
So all of those wind
up being problems.
More confounds,
very often you're
trying to understand the brains
of schizophrenics who have died
who are older, who are elderly.
And the confound there
is schizophrenics
have horrible diets.
You are seeing perhaps
the brain consequences
of malnutrition all those
years, rather than seeing
the consequences of
the disease itself.
Another problem that you've
got is you get someone
who's schizophrenic,
and, almost certainly,
what they have been doing
for a long time is taking
drugs for their schizophrenia.
And if you see something
different in the brain,
maybe it's due to
the schizophrenia
or maybe it's due to
the effect of the drugs.
And what that has generated
is the other thing
that people in this
business kill for, which
is unmedicated schizophrenics.
And researchers
love these people,
they can't get enough of them.
This is the teenager
who is brought
in for the first diagnosis.
And the family is no doubt
thinking finally we're
going to get some help.
And all the researcher
physician there is thinking
is they want to
centrifuge this kid
and do research
and find that out,
getting unmedicated
schizophrenics.
Finally, a big boon in the
field has been brain imaging.
So instead of trying to figure
out the normal size of things
after you've taken
the brain out,
you could image
the brain in situ,
while the person is still alive.
So given all of those
methodological constraints,
there's a number of
things that have come up.
Here's a cross-section
of the brain,
although I'm realizing this is
a cross-section of a rat brain.
And it also is a amusing face.
And what you have
are these things
that run through the brain
called the ventricles.
They are these caverns
running through, filled
with cerebral spinal fluid.
What you see in schizophrenia is
enlargement of the ventricles.
So the ventricles enlarge.
The skull isn't going
anywhere, and, thus,
if the ventricles
are getting bigger,
something else has to
be getting smaller.
There is contraction
compression of the cortex.
So you get cortical
compression in schizophrenics.
You get it particularly
so in the frontal cortex.
A-ha, that's kind
of interesting.
Meanwhile, over in the
hippocampus, what you have,
normally, are these very
characteristic cell fields,
where-- I just drew
them wrong, where
neurons that are called
pyramidal neurons that,
shockingly, are
pyramidally shaped.
And what they have is
they're organized in layers.
And they send all
of their projections
off to the next cell layer that
happens to be diamond shaped.
And that's how it works.
You look in the brains of
schizophrenics post-mortem
and there's fewer
hippocampal neurons.
And there's some of them
are facing the wrong way.
They've been flipped over.
They're sending projections
where they're not supposed to.
This is not going to make for
a whole lot of solid sequential
thought if you've
got neurons pointing
in the wrong direction.
So that's popped up
in the literature.
Then, of course,
frontal cortex, where
what's been seen as, in
some studies, fewer neurons,
in some studies, fewer
glia, in some studies,
fewer of both, what you see is,
also, lower levels of a protein
called reelin.
And what reelin has to do
is with cortical maturation.
There's lower levels of
it in the frontal cortex
of schizophrenics.
All of this begins to fit
in this picture of you're
not getting a normal final
burst of frontal maturation
late adolescence,
early adulthood.
You're seeing a lot
of problems there.
What else?
You also see a couple
of other minor things.
The thalamus tends
to be atrophied.
Nobody really knows
what's going on.
The sense is
hippocampus pointing
in the wrong direction,
frontal cortex, that's
getting compressed, because
it's got fewer neurons perhaps.
This is not going to
make for a normal brain.
So now switching one box
back, what about the genetics?
And you'll notice this is
one of our first topics
where there's nothing
been happening here
in terms of endocrine effects,
acute releasers not terribly
pertinent to this field.
So what about genetics?
Going back to all of our classic
behavior genetics approaches,
this has been the
psychiatric disease
where there was
the first evidence
for a genetic component to it.
The twin studies, the
Kety adoption studies
that we've heard all about,
and what they have suggested
was about 50% heritability
for schizophrenia.
And you are all over now
what heritability means
and what it doesn't mean.
What you see within families is
if you have an individual who
has schizophrenia and they
have an identical twin,
the twin has a 50%
chance of the disease.
If they have a full
sibling, about 25%
chance of a disease,
half sibling, about 12%.
Take a random person off
the street, 1% to 2%,
so there is a
large genetic load.
What you also see is in a
higher than expected number
of close relatives
of schizophrenics
are mild versions
of thought disorder.
And that's going to
come in on Friday
in a very interesting way.
What this is saying
right off the bat,
it is not saying that all
relatives of schizophrenics
have these abnormalities,
but they are occurring
at a higher than expected rate.
So that's old classical
behavior genetics.
Now, jumping forward a
decade's worth of technology,
how about molecular approaches
the version of just getting
genetic markers?
Not identifying the gene itself,
but you remember this approach
by now where you are
finding a stretch of DNA.
And inside that
stretch is a gene
that is very pertinent
to whatever it is,
and the folks with the disease
have a different version
than the other folks.
But you don't know what
the gene is or where it is.
So using this marker technique,
some of the first disease gene
markers came out in the
mid '80s, late '80s,
for schizophrenia.
And these were landmark studies.
And everybody was incredibly
excited about them.
And these were really,
really important.
And there was a problem,
which is somebody
would isolate a marker
for schizophrenia
in an Amish population.
People love studying the
Amish for things like this
because they've
got big families,
because they don't have a
whole lot of substance abuse,
because they have very
healthy lifestyles,
and, most importantly,
because men, Amish men who
say they are the father
of somebody or other
are probably the father
of the somebody or other.
There's not a lot of
messing around going on.
And that's kind of helpful.
You're trying to
understand genetics.
And if you don't even have
the right person pegged
as the father, that's going
to make for some messy data.
People love the Amish, people
love inbred Icelandic fishing
villages.
These are all the
folks who get studied.
And in those years,
out came some
of the first genetic markers.
And the problem was
each of the studies
was getting a different marker.
And nobody was coming
up with any replication,
a complete
uninformative mess that
was a major disappointment
in the field.
So very little happened in terms
of the genetic marker approach.
So we had to wait another
decade or two, and, now,
our current more
modern version, which
is forget a genetic marker,
what about actual genes?
Are there are genes that
have been implicated
in schizophrenia where
there are abnormalities,
where there are variances?
And then it comes from
two different flavors,
eight different
flavors, our usual deal.
We've already heard
about one of these,
which is variance in
versions of this gene
coding for this enzyme that
degrades dopamine carries
an association
with schizophrenia.
Nonetheless, very small effects.
Interesting finding, and
this was the last year,
these were three papers
back-to-back in science,
from three different
groups, all of whom
used a very
contemporary technique
for looking for genes,
which is a snip analysis.
And it's really interesting,
and not in a million years
could I describe it clearly.
But using this very
state of the art thing,
they all had huge populations
of schizophrenics,
thousands of people in
the study, great studies.
And the amazing
thing is they all
found genetic abnormalities,
and they all found one in common
with a huge effect, which
was very, very reassuring,
until you looked at
that the gene, which
made no sense at all.
All three of these
groups, superb scientists,
reported that, in
schizophrenia, you
have a higher than expected
rate of abnormalities
in genes of the major
histocompatibility complex.
What is that about?
The human equivalent,
wait, we're
back at pheromones, and
individual signatures,
and the immune system.
What is this about?
Nobody has a clue.
But a remarkable consistency
in these three studies,
they all found abnormalities in
these major histocompatibility
genes that have to do with cell
signatures and immune defenses,
all of that.
And these were big effects
in all three studies.
All the studies
were done superbly.
People are just beginning
to digest that one.
Nobody really has
a very clear idea.
Some other genes have popped
up as having mutations
or a lot of variants, where
one particular variant is more
associated with schizophrenia.
And there's this one gene
that's been found and replicated
called DISC1.
So does DISC1 do?
Nobody has a clue.
And just showing how pathetic
this whole finding is,
what does DISC,
D-I-S-C, stand for?
Disrupted in schizophrenia 1.
That sure tells you a lot
about what's going on.
Well, what happens
in schizophrenia?
You have abnormalities
in genes that
are abnormal in schizophrenia.
Let's party.
So you got DISC1, and people
trying to figure out it's
got something to do
with second messengers.
Nobody really knows.
There's not a whole
lot that has been
happening in this field
that counts as progress,
really frustrating.
People still need to make
sense of this finding.
One area, though, that's
getting a lot of traction
in the last few years goes back
to one of our weird mutations
from our macroevolution
type lectures,
that business of different
numbers of copies
of a gene, macro
mutations on that level,
transposable events, gene
duplications, a term we
got back then is
copy number variants.
How many copies of
particular genes?
And the one thing
that seems to be
consistent is all sorts
of genes in schizophrenia
are popping up with abnormal
numbers of copies of the gene
rather than abnormalities
in the gene itself.
So that's really exciting.
What's unexciting is
nobody's replicating
which the duplications are.
And most of the genes, nobody
has a clue what they do.
People are flailing
other than seeing
there's all sorts of different
genetic abnormalities
that are popping up.
How can that be?
How could they all be
relevant to this disease?
Back one hour,
it's not a disease.
It's a whole bunch of
heterogeneous ones,
and there's going
to be all sorts
of different genetic
components to it.
Now our next box,
early experience,
and what early experience
immediately translates into
is parenting style.
What does schizophrenia have
to do with parenting style?
We will see shortly,
which is my smooth way
of trying to say that I just
jumped a paragraph by accident.
So, of course, of
course, where we
begin is looking at the
role of early stress
in life, because
that's obviously
where you have to begin
discussing early experience
in schizophrenia.
It's that whole
stress model thing.
We already heard one version
of it, the adolescent stressor,
takes the kid who's just
barely holding on and dips him
way down.
Another version of it
that should seem plenty
logical to us by
now, prenatal stress.
People who were fetuses
during the Dutch Hunger Winter
have a higher than expected
rate of schizophrenia.
People who were fetuses
during a huge famine
in China, 1959 to 1961, higher
incidence of schizophrenia.
Rats, expose them prenatally
to lots of glucocorticoids,
and they wind up having
elevated dopamine levels
in their frontal cortex.
Have mechanical trauma at birth,
birth trauma, brief hypoxia,
any of those things, increased
incidence of schizophrenia.
This is very interesting.
Back to our business,
remember, identical twins,
they can either share
one single placenta
or have two of them,
monochorionic or bichorionic.
Monochorionic twins are
more likely to share
the trait of schizophrenia than
bichorionic identical twins.
Fetal environment,
stuff's going on there.
What else with that?
You wind up seeing a lot of
suggestions of interactions
between the
neurochemistry of stress,
and some of the
abnormalities here.
You know how this works.
Somewhere lurking out
there is a data set
that's going to wind
up looking like this,
bad version of the gene,
good version of the gene,
more and more stressful of
the developmental environment.
It hasn't been
identified yet, but it's
got to be something like that
because everything's like that.
So leading us now obviously
to discussing parenting style
and schizophrenia.
So where does that come in?
Take the best psychiatrists
in the field, the titans,
the grand poobahs
in 1950, and they
would know the
exact answer, which
is parenting style is the
cause of schizophrenia.
Abnormal parenting is the
cause of schizophrenia.
And out of this, of course,
since in those days,
fathers did no parenting, what
you were saying is abnormal
mothering is the cause
of schizophrenia.
And the great term
that was used there
was schizophrenogenic
mothering, mothering style
that generates schizophrenia.
What was schizophrenogenic
mothering about?
Well, it depends on whose
paper you're reading.
But, in general,
what they tended
to have were elements of
conflicting emotional messages,
conflicting, a double
bind is the phrase
that always ran through it.
The mother gets their son
two ties for his birthday,
he puts one of them on.
She says what's the matter,
you don't like the other tie
I got you, or, at the
more fundamental level,
saying you never say you love
me, you never say you love me,
you never say-- I love you.
How can that mean
anything to me when I just
forced you to say that?
There's no winning.
And, in that view,
what schizophrenia
was about was raising a kid
with distorted, contradictory,
fragmented emotional demands
from the schizophrenogenic
mother and out
comes schizophrenia.
Now, actually, by the early
'50s, people in the field
were feeling far more
broad in their thinking,
recognizing this
might be damaging,
in fact, to women who were
the mothers of schizophrenics.
And a much more
humane model came in,
which was recognizing the
possibility that fathers could
screw kids up in the same way.
What was more broadly
called this double bind
theory of schizophrenia,
it is caused by parenting.
It is caused by particular
parenting style.
And then, in the early '50s,
along came the very first drug
for schizophrenia,
the neuroleptics,
the dopamine receptor blockers.
And over the course
of the next few years,
90% of the hospital
beds in this country
for psychiatric patients
were emptied out,
the first medication
that effectively
treated schizophrenia.
And at that point, if one
had any sort of capacity
to face reality, all
of the proponents
of schizophrenogenic
mothering should
have been shocked and
stopped in their feet
at that point, saying, my
God, what have we done.
It's a biochemical disorder.
It is not a disorder of mothers
who are not competent mothers.
And it is fascinating to read
in the leading psychiatry
journals from that time, you
would get these editorials
from grand old men
in the field, where
they would be saying I have
spent my whole life researching
this disease, I
have spent my life
trying to fight this disease,
which is hell, which tragically
destroys lives.
I've been trying to
do the right thing.
I have been trying
to help people.
Look, what I have done instead.
This realization that
ran through the community
that parenting style has
nothing to do with it.
And it's half a century's
worth of mothers
bringing in their
late adolescents
for the first diagnosis and
being told, unfortunately,
it's this nightmare
of a disease.
How could this have happened?
Where does it come from?
You caused it.
You caused it with
your mothering style.
Endlessly, during the period
where modern biochemistry
sweeps into psychiatry,
over and over,
there are cases like this,
where the whole field has
to stop and say,
my God, what have
we done telling
people they caused it
through some parenting style,
something of that sort.
It's a biochemical disorder.
So this was a shocking
finding at the time
and transformed
the field in terms
of schizophrenogenic
mothering going down
the sink at that point.
Nonetheless, there is an
interesting literature
showing abnormalities
or oddities
in the way communication
works in the families
of schizophrenics.
And this is a field now that's
called communication deviance.
What you see is, on the average,
among first order relatives
of schizophrenics, parents,
siblings, immediate family,
what you see is, on the average,
an odd communicative style.
You see a very
fragmented communicating,
a very telescoped terse,
broken phrase sort of style.
This has been noted very often.
Again, this is not what is
seen in every close relative
of a schizophrenic, but
higher than an expected rate.
What you also see is all sorts
of realms of, in a sense,
private communication
between schizophrenics
and their close families.
And the way this is
shown is with things
like-- this was a
classic version.
You take schizophrenics
and you show them
a bunch of-- no,
that's not what you do.
You give them a
Rorschach print, one
of those ink symmetrical
things that's just
completely chaotic looking.
And they look at it
for a while, and then
you put it into a stack
of a dozen other ones,
and you mix them up.
And you give them to the
parents of the individual.
And the schizophrenic
or the healthy control
is now trying to describe to
the parents which one they
saw, how to find the
correct one in there.
Control healthy
individuals sitting
there trying to explain which
Rorschach block they saw,
like no accuracy whatsoever.
The schizophrenic
starts saying it
looks like a butterfly
with a Van Dyke beard
and ears on fire, and
the parents pull out
the right one instantly.
It works in the
opposite direction
as well, where the parents
are the ones trying
to describe the Rorschach test.
It only works within families.
The parents of the schizophrenic
are no better at chance
when doing it with
someone else's
child of a schizophrenic.
There seems to be this going on.
Logical interpretation,
this has nothing
to do with the emergence
of schizophrenia.
This is an obvious compensation.
You have a child, you
have a sibling who
is this thought
disordered, and there's
going to be a whole lot more
adventurous communication
in the family to try
to compensate for it.
Few other things in terms of
early experience, and this
is a whole other
domain of the disease,
which is being exposed to all
sorts of infectious thingies.
And this is a really interesting
provocative literature
floating around.
There's a far higher
than expected chance
rate of schizophrenics
whose mothers were exposed
to a number of different
viruses in third trimester
of pregnancy.
Ah, some sort
perinatal stressor,
pathogenic challenge
to the system.
And when you look at the
genomes of schizophrenics,
they have much higher than
expected rate of viral DNA
that has been inserted in there,
things called retroviruses.
Technical matters don't matter.
The main thing is more
evidence of higher exposure
to viral pathogens,
an elevated history
of neonatal viral infections.
And then, the
cruelest one of all,
which has to do with
a protozoan parasite,
not a virus or bacteria,
but this protozoa
called Toxoplasma gondii.
And not Gandhi in the
Gandhian sense, but probably
because it's even
pronounced differently.
How are you pronouncing
it these days?
Gondii.
Gondii.
Gondii, because there's
two Is at the end,
which the old Mahatma
never quite came up with.
But this parasite manages to get
more Is in there than he did.
So it's Toxoplasma gondii,
as everybody knows.
Toxoplasma is interesting.
It has this
interesting life cycle.
It reproduces in
the gut of cats.
It comes out in cat feces,
feces are eaten by rodents.
Now in rodents, and toxo's
evolutionary challenge
has been to figure
out how to get
rodents inside cats stomachs.
And toxo does this
amazing thing, which
my lab is doing some work
on, including Patrick,
and looking at the
thing that toxo does
is it makes rats begin to like
the smell of cats, and to go up
and check it out.
And soon, you are inside
the stomach of the cat
and completing
toxo's life cycle.
How it does it is
incredibly interesting
and slowly emerging.
So what's going on
with toxo in humans,
people who are
infected with toxo
have a higher than expected
rate of mild neuropsychological
disinhibition, a
little bit of problems
with frontal
regulation of behavior,
higher than expected rates
of serious car accidents,
higher than expected rates for
the same degree of depression,
of attempting suicide, a
picture of a certain degree
of impulsivity.
Not big effects, but,
nonetheless, it pops up there.
But parallel with
that, from day one,
there's also been a literature
showing that Toxoplasma
exposure increases the
risk of schizophrenia.
Individuals whose mothers
were exposed to toxo
during pregnancy or
looking at schizophrenics
and looking in their
blood and seeing higher
than anticipated levels of
antibodies against Toxoplasma,
evidence of this whole world
of a connection between cats
and schizophrenia,
and all sorts of hints
there, very, very
slowly emerging field.
It is a real finding and it
is a well-replicated one.
There's some connection there.
So where does these genes having
to do with immune function
come in?
Maybe this is
pertinent to this world
of viral correlates of
schizophrenia, parasitic ones.
Nobody knows.
Finally, what have we got?
This challenge that we're going
to have with-- when you read
the depression
chapter, all of that,
is how do you put
these pieces together.
How do you put together
adolescent stress
with prenatal viruses
with enlarged ventricles,
with funny genetic
abnormalities here?
There isn't a very
good integrated model
at this point to how to
put the pieces together.
The field has not
gotten that far.
So we're talking about genetic
abnormalities, blah, blah,
all of that.
And thus, you
know, our final box
has to be the evolution
of schizophrenia.
Where did schizophrenia
evolve from?
First question you would ask
is, well, do you see something
like schizophrenia
in other species.
And you don't.
You look at complex
primates and you
see things that look
like depression,
you see reactive depression,
you see melancholia,
you see, in some cases,
depression so severe
as to prove fatal.
You don't see animals
having to loose associations
with proverbs, and concrete
thought, and delusions,
and hallucinations.
Animals that start
acting schizophrenic
get eaten that evening.
So there's not a
whole lot of insight
from the zoological world.
There's not any animal
precedents for schizophrenia.
So how about in humans?
How did schizophrenia evolve?
We are now back to one
of our first lectures.
Why did giraffes
have long necks?
Because it's a good
thing that allows
them to pass on more
copies of their genes,
because it's an adaptive trait.
By the rules of Darwin,
schizophrenia is maladaptive.
Schizophrenics have a
lower reproductive rate
than their unaffected siblings.
By the math, that
is thus a trait
that should be being
selected against.
Yet, schizophrenia persists at
this 1% to 2% in every culture
out there.
Historical records
indicate things
that convincingly sound
like schizophrenia
have been there forever.
And, thus, one has to bring up
the question that always lurks
in a scenario like this, which
is are there circumstances
where schizophrenia is
in fact adaptive, where
it is advantageous,
where it increases
one's reproductive success.
The only domain where
that has had any evidence
at all in the literature
is schizophrenics
appear to have a lower incidence
of certain types of cancers,
in particular, lung and
throat, esophageal cancers.
And that's after controlling
for smoking rates, all of that.
Not a big effect, but
that causes people
to mumble something
about maybe schizophrenia
was selected for its anti-cancer
properties in the disease,
and balanced
selection, all of that.
However, there is another
possible adaptive thing
that's lurking around
in there, something
which causes some
of these traits
to not only no longer
be maladaptive,
but to be wildly useful
in certain contexts
of human society.
And what you'll see is it's
not full-blown schizophrenia,
it's the milder
versions that you
see in some of the relatives.
And thus, just to give you
a sense of where things
are heading, we'll talk about
that on Friday in the lecture
on--
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