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PROFESSOR: So today and next
time we're going to talk about

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psychopathology--

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people whose minds, brain, and
behavior are atypical more

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often than not.

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But we'll talk about
this in a moment.

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These people face struggles,
difficulties, and huge goals

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to try to help such
individuals.

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So we'll talk a little bit about
the history of ideas in

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psychiatry and psychopathology,
a little bit

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about the ideas of diagnosis
and labels.

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And I'll do a little film of a
patient with schizophrenia.

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But there's an intuition in some
places and some lives are

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led that psychopathology
is rare.

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Here's a list of not
all psychiatric

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diagnoses but some of them--

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schizophrenia; bipolar
disorder; depression;

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substance abuse (drugs and
alcohol); anxiety; panic

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disorder; phobia; developmental
ones like

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autism, ADHD, and dyslexia;
obsessive compulsive disorder.

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Tomorrow, I'm reviewing a lot
of research grants for

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anorexia and bulimia.

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So if we take this list that you
just saw and heard and ask

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how many of us in this
room know somebody

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that we care about--

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could be yourself,
could be a family

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member, could be a friend--

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know somebody who is touched
by one of these diagnoses?

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If you're willing to put up
your hand, who's touched?

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Look around the room.

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Right?

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An incredible number of people
are touched by this.

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And so it's a terribly important
topic to understand

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and to help individuals and
families who are struggling

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with these things.

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And in fact it's estimated--

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we'll talk about these labels
exactly-- that about half of

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all individuals, at some moment
in their life, will

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qualify, men or women, at least
for a brief period of

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meeting some psychiatric
disorder.

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It can be rare and
devastating.

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Like schizophrenia--

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1% of the population worldwide,
typically

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devastating in its
consequences.

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It can be potentially milder
like depression which ranges

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from very severe to somewhat
moderate and, interestingly,

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occurs considerably more often
in women than men.

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And we'll talk about
that next time.

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There was a recent survey done--
a public health survey,

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5,000 young adults, half of them
in college like you, have

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them out of college.

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They surveyed them and
talk with them.

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And about half qualified to have
some sort of psychiatric

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disorder within the last year.

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Whether they were in or out
of college didn't make a

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difference in this study.

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But fewer than a quarter of
those who met some criteria

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went and sought help.

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So how through recent history
have people thought about

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people who behave differently,
who are so depressed they

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can't get out of bed, who hear
hallucinations, who behave in

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agitated ways, and
bipolar disorder?

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And it's as much a history story
and a story of culture

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and tolerance and intolerance
as it is anything else.

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And so unusual or mad behavior,
behavior that's very

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disturbing, and atypical--

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now there's debates
about all of this.

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And so, for example, some
people have argued that

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everything that we call
psychiatric disorders is

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nothing but the labels we give
to behaviors that we find

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uncomfortable or unproductive.

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OK?

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It's nothing but that.

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It's just variation.

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Some people are taller
and shorter.

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Some people like vanilla
or chocolate ice cream.

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And some people do or do not
have bipolar disorder.

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All right?

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It's a label that's
given for just

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variation in human ability--

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and we'll talk about that--
or human performance.

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And there's many consequences
of that.

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Others think that there's
a humanitarian need to

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understand the disorders
to help people.

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So as you think about these two
sort of perspectives, you

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can think that when people
behaved very unusually--

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I'll show you a picture of this
that we think some time

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ago that people would literally
trephinate, that is,

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make a hole in the skull of
individuals to attempt to let

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out the demons.

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That was the interpretation
of the time.

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There's a thought that the witch
hunts in the 16th and

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17th centuries, the Salem trials
in the United States

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may have involved patients with
things like Huntington's

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or Tourette's.

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People didn't know how to
interpret unusual behavior.

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And so label it as possession
or label it as witchcraft or

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something like that.

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Insanity began to be understood
as some sort of a

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disease but without any approach
to treating it or

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helping individuals.

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Basically, the process was to
segregate individuals away.

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And you would have very large,
pretty scary institutions with

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people literally chained and
living in filthy conditions.

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There was nobody to care
or protect for them.

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In a London zoo you could go
pay a penny and watch the

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humans in the cages.

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They had not as many visitors
as are in London now for the

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royal wedding.

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But they had 96,000 in 1814.

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It wasn't a rare thing to go pay
your penny and look at the

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scary people.

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More recently we understand
there's an organic illness and

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a psychological illness.

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And we'll talk about all that.

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But all this is a huge point
that how we understand unusual

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behaviors and people is
tremendously influenced by the

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historical context
that you're in.

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And we'd like to think we're
making progress on this.

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I think we are.

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But a generation from now people
might look back and

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say, how sad that in 2011 people
at MIT were teaching

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stuff like this.

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Right?

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Because if they were that wrong,
how certain are we that

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we're that right?

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So one has to be a little
cautious about very strong

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positions on these
things, I think.

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Here are skulls that were
discovered with the

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trephination and some evidence
that the person actually

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survived this kind of radical
neurosurgery.

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But you understand at the time
when somebody behaved very,

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very unusually, people had tried
to explain what's going

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on and tried to do
what they can.

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Here's pretty monstrous looking
devices, heads in

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boxes and things kind of like
this, where people were trying

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to treat, if you want to call
it, or control individuals who

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were having very unusual
behaviors.

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Here's a huge hospital.

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It had thousands
and thousands.

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The name of the hospital
is Bedlam.

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And that's what led to the
word bedlam now, more

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generally used for sort of
wildness or craziness.

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And paintings like this one from
Goya showing a madhouse.

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Because at that time, don't
forget, when people-- there

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was no drug treatment, no
behavioral treatment.

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People were behaving
in scary ways.

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And they were sort of put off
to the side to be out of the

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range of disturbing
other people.

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Now the first step towards
teaching psychiatric diseases

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turns out to be a
giant misstep.

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But it took a long time for
that to be understood as a

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giant misstep.

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This is Egas Moniz who did
something that all of us as

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scientists would be happy
to have happen to us.

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He won the Nobel Prize
in physiology

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and medicine in 1949--

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the pinnacle of scientific
respect throughout the world.

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And he introduced what's now
called frontal lobotomies or

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prefrontal lobotomies as
a treatment for severe

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psychiatric disorders.

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And then in the United
States, Freeman and

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Watts picked it up.

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And they went around the country
taking basically ice

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picks, going inside,
and making various

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cuts inside the skulls.

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By 1942, there were 5,000 people
per year worldwide

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documented, probably
more than that.

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These were cases.

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And we now look at it
as a terrible idea.

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But at the time, this is
all they could imagine.

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And that seemed better than
putting people in boxes or

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cages was to attempt
to treat it.

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And even a kind of a nascent
understanding that very

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unusual behaviors went
with something

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to do with the brain.

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We now understand these front
frontal lobotomies or

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prefrontal lobotomies, surgery
to sever the connection to the

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frontal lobes, as not treating
the disorder but simply

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sedating and controlling
individuals.

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When you made a person who was
very agitated, hard to deal

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with, hard to control, hard
to reason with, you give a

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procedure like this, all of a
sudden they were easier to

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deal with for the doctors and
nurses and family members.

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And that seemed like progress.

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And we now understand that
simply making somebody behave

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in a sedated, controllable
way is not what we

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mean really by treatment.

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But we'll come back to this
in a minute because many

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individuals who get medications
don't like to take

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their medications.

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Some of you may have
that experience.

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They feel they're dulled
down in many cases,

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not themselves anymore.

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And so it's a really tricky
issue at what level some

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medications start to approach
that same issue of just making

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people behave in ways that other
people find comfortable.

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So a nice example of this or
challenging example of this is

00:09:37.230 --> 00:09:42.180
from your book where there's
a guy named Ray.

00:09:42.180 --> 00:09:44.330
He has Tourette's syndrome.

00:09:44.330 --> 00:09:47.090
So we classified that as a
neurological disorder but has

00:09:47.090 --> 00:09:48.660
a sort of psychiatric pieces.

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You know Tourette's syndrome.

00:09:51.080 --> 00:09:53.300
If you don't know from your own
life some way or another,

00:09:53.300 --> 00:09:54.540
you know it from movies.

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And TV shows love Tourette's
syndrome like law shows with

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courts because what do patients
with Tourette's

00:09:59.740 --> 00:10:01.120
syndrome do?

00:10:01.120 --> 00:10:03.480
They have involuntary
physical tics.

00:10:03.480 --> 00:10:07.800
And part of what they have is
they, during those tics, they

00:10:07.800 --> 00:10:13.110
curse in pretty horrific ways,
in an uncontrollable way.

00:10:13.110 --> 00:10:15.640
So that's ideal for television
plot lines.

00:10:15.640 --> 00:10:18.700
It's unbelievably hard for the
children and adults who have

00:10:18.700 --> 00:10:21.770
it because they're often
perceived as being scary and

00:10:21.770 --> 00:10:25.210
dangerous if they're not
in a controlled state.

00:10:25.210 --> 00:10:28.370
So here's a guy named Ray who
has tics every few seconds

00:10:28.370 --> 00:10:29.300
since age four.

00:10:29.300 --> 00:10:30.590
Imagine if you haven't been--

00:10:30.590 --> 00:10:32.750
maybe some of you have gone
through this or know somebody.

00:10:32.750 --> 00:10:36.360
It's very tough on children to
have that problem, tough on

00:10:36.360 --> 00:10:37.840
adults but really tough
on children.

00:10:37.840 --> 00:10:40.330
By the time he's an adult,
he's a weekend drummer.

00:10:40.330 --> 00:10:41.930
He loves to play ping-pong.

00:10:41.930 --> 00:10:44.570
But he's not doing too well
in terms of jobs.

00:10:44.570 --> 00:10:46.180
He loses his jobs
all the time.

00:10:46.180 --> 00:10:47.540
And his home life is
pretty miserable.

00:10:47.540 --> 00:10:51.710
He has a pretty miserable life
at work and at home.

00:10:51.710 --> 00:10:56.460
He tries Haldol which is a
drug that can help with

00:10:56.460 --> 00:10:57.330
Tourette's.

00:10:57.330 --> 00:10:58.120
And what happens to him?

00:10:58.120 --> 00:11:00.310
Is he instantly cured
of his tics and the

00:11:00.310 --> 00:11:03.090
happiest person around?

00:11:03.090 --> 00:11:06.840
Have any of you glanced
at this?

00:11:06.840 --> 00:11:07.310
Yeah?

00:11:07.310 --> 00:11:08.768
AUDIENCE: Life seemed
to slow down.

00:11:08.768 --> 00:11:10.712
And he keeps trying to
do things he used

00:11:10.712 --> 00:11:11.198
to do with his tics.

00:11:11.198 --> 00:11:14.114
And he hurts himself,
because his eyes--

00:11:14.114 --> 00:11:15.520
PROFESSOR: Yeah, because
it's slowing his--

00:11:15.520 --> 00:11:16.420
he feels slowed down.

00:11:16.420 --> 00:11:16.920
Exactly.

00:11:16.920 --> 00:11:19.220
So he comes back with a black
eye and a broken nose.

00:11:19.220 --> 00:11:21.480
So now, in a controlled,
voluntary way he

00:11:21.480 --> 00:11:23.490
curses at the doctor.

00:11:23.490 --> 00:11:25.520
And he says, like just trying
to go through a revolving

00:11:25.520 --> 00:11:29.200
door, his timing is so off
that he injures himself

00:11:29.200 --> 00:11:32.550
because the drug has changed,
in some sense, who he is.

00:11:32.550 --> 00:11:33.410
And he feels that.

00:11:33.410 --> 00:11:35.140
He's not himself anymore.

00:11:37.820 --> 00:11:41.210
He stays on the drug
for three months.

00:11:41.210 --> 00:11:43.280
It starts to work.

00:11:43.280 --> 00:11:45.545
Over the next nine years
he has a steady jobs.

00:11:45.545 --> 00:11:47.390
His familial relations
improve.

00:11:47.390 --> 00:11:49.440
He's successfully treated
by sort of

00:11:49.440 --> 00:11:51.010
every objective measure--

00:11:51.010 --> 00:11:54.170
happiness at home with your
family, holding a job, the

00:11:54.170 --> 00:11:56.160
sort of two practical things.

00:11:56.160 --> 00:11:58.810
But he likes to live
a life as two Rays.

00:11:58.810 --> 00:12:01.420
On the weekends, he likes to go
off his medication and be

00:12:01.420 --> 00:12:03.670
himself and be the fast drummer
and ping-pong player

00:12:03.670 --> 00:12:06.000
that he enjoyed for
his early life.

00:12:06.000 --> 00:12:08.380
And then he'll take the
medication and be the sober,

00:12:08.380 --> 00:12:11.800
slow, somewhat sedated
individual who is valued at

00:12:11.800 --> 00:12:13.710
the workplace and that can
work things out with this

00:12:13.710 --> 00:12:16.910
family more easily.

00:12:16.910 --> 00:12:18.640
It's always this interesting
thing about how you're

00:12:18.640 --> 00:12:20.820
changing people in order
to help them.

00:12:20.820 --> 00:12:24.040
And then, what's that line
between changing them to fit

00:12:24.040 --> 00:12:26.140
in versus helping them?

00:12:26.140 --> 00:12:27.130
So what is abnormal?

00:12:27.130 --> 00:12:29.680
And we mean in a very
statistical sense here, just

00:12:29.680 --> 00:12:31.050
being at the tail end
of distributions.

00:12:33.990 --> 00:12:37.680
Some things we value being
abnormal, at one end of the

00:12:37.680 --> 00:12:40.400
distribution in terms
of success in life.

00:12:40.400 --> 00:12:41.340
So what's a mental disorder?

00:12:41.340 --> 00:12:43.890
It's a clinically significant
behavioral or psychological

00:12:43.890 --> 00:12:46.620
syndrome or pattern that occurs
in a person and that is

00:12:46.620 --> 00:12:51.320
associated with present distress
or disability or with

00:12:51.320 --> 00:12:53.070
significantly increased risk
of suffering death, pain,

00:12:53.070 --> 00:12:54.550
disability, or important
loss of freedom.

00:12:54.550 --> 00:12:56.940
So when I talk with
psychiatrists-- and I

00:12:56.940 --> 00:12:58.800
collaborate a lot with
them on research--

00:12:58.800 --> 00:13:01.910
they emphasize, again, the
functional consequence.

00:13:01.910 --> 00:13:05.230
Can you lead a happy
personal life?

00:13:05.230 --> 00:13:09.150
Can you lead a reasonably
successful professional life?

00:13:09.150 --> 00:13:10.690
And that's almost the
most important

00:13:10.690 --> 00:13:13.400
thing beyond anything.

00:13:13.400 --> 00:13:16.590
And there's amazing stories
that make you think about

00:13:16.590 --> 00:13:21.290
sources of apparent madness
or insanity.

00:13:21.290 --> 00:13:26.970
And a powerful story for me is
the story of Semmelweis.

00:13:26.970 --> 00:13:32.150
So he noticed, as a physician
in 1840's, that the rate of

00:13:32.150 --> 00:13:36.320
death of childhood fever in a
ward served by physicians was

00:13:36.320 --> 00:13:39.370
four times as high as mothers in
a ward in the same hospital

00:13:39.370 --> 00:13:41.090
served by midwives.

00:13:41.090 --> 00:13:43.840
At that time practically every
physician was a male.

00:13:43.840 --> 00:13:46.270
And every midwife
was a female.

00:13:46.270 --> 00:13:48.300
But you were four times
more likely to die.

00:13:48.300 --> 00:13:52.176
That's a big increase in his
death if you were in a ward

00:13:52.176 --> 00:13:55.500
that physicians served
compared to midwives.

00:13:55.500 --> 00:13:57.830
So he wondered what
that was about.

00:13:57.830 --> 00:13:59.790
And he tended to know,
furthermore, that the deaths

00:13:59.790 --> 00:14:03.090
tended to occur in women
serially who were in one bed

00:14:03.090 --> 00:14:03.700
next to the other.

00:14:03.700 --> 00:14:06.370
There were physical
clusters of these.

00:14:06.370 --> 00:14:08.770
And so he began to think, well,
for example, if the

00:14:08.770 --> 00:14:10.940
priest comes to give the last
rites to this person, does

00:14:10.940 --> 00:14:14.780
that psychologically discourage
the next person?

00:14:14.780 --> 00:14:19.120
And he also found out that
didn't seem to tell the story.

00:14:19.120 --> 00:14:20.930
And then he asked, was
the same doctor

00:14:20.930 --> 00:14:22.500
going from bed to bed?

00:14:22.500 --> 00:14:23.910
And the answer was yes.

00:14:23.910 --> 00:14:24.720
It makes sense, right?

00:14:24.720 --> 00:14:28.646
Bed to bed, the same doctors
going down the line of women.

00:14:28.646 --> 00:14:31.350
And what he began to notice is
that the physicians we're

00:14:31.350 --> 00:14:33.800
reluctant to wash their hands.

00:14:33.800 --> 00:14:35.660
Now this sounds ridiculous.

00:14:35.660 --> 00:14:38.270
But this is 1840 medicine.

00:14:38.270 --> 00:14:41.100
And when he asked them why they
didn't wash their hands,

00:14:41.100 --> 00:14:43.090
which we would now consider
pretty fundamental in a

00:14:43.090 --> 00:14:44.570
medical environment.

00:14:44.570 --> 00:14:47.510
The basic response was
that it was unmanly.

00:14:47.510 --> 00:14:49.530
Like, men didn't wash
their hands.

00:14:49.530 --> 00:14:50.040
I'm a doctor.

00:14:50.040 --> 00:14:50.380
I'm a man.

00:14:50.380 --> 00:14:51.130
I don't wash my hands.

00:14:51.130 --> 00:14:53.720
I'll come back to this
in a couple minutes.

00:14:53.720 --> 00:14:55.700
So he asked them to wash their
hands in a solution of

00:14:55.700 --> 00:14:57.040
chlorine and lime.

00:14:57.040 --> 00:15:01.570
The deaths fell from 12% to
about 1% in 15 months.

00:15:01.570 --> 00:15:04.360
All right, many lives were saved
because the physicians

00:15:04.360 --> 00:15:08.110
simply washed their hands and
did not carry infections from

00:15:08.110 --> 00:15:14.760
one person to another down the
row of child-bearing women.

00:15:14.760 --> 00:15:15.510
1848--

00:15:15.510 --> 00:15:17.640
there's a revolution
in Austria.

00:15:17.640 --> 00:15:19.460
He's fired from his job.

00:15:19.460 --> 00:15:20.920
The doctors--

00:15:20.920 --> 00:15:22.860
you would think this would be
better world-- but the doctors

00:15:22.860 --> 00:15:24.710
immediately are happy
they no longer have

00:15:24.710 --> 00:15:26.020
to wash their hands.

00:15:26.020 --> 00:15:28.760
And the death rate goes
right back up.

00:15:28.760 --> 00:15:31.595
Joseph Lister in 1880 figured
out the formula of Listerine.

00:15:31.595 --> 00:15:33.290
But Lister--

00:15:33.290 --> 00:15:36.740
what was going on in terms of
cleanliness and sanitation.

00:15:36.740 --> 00:15:41.015
Semmelweis in Austria
becomes crazy.

00:15:41.015 --> 00:15:44.300
He runs around to people in the
street, telling them to

00:15:44.300 --> 00:15:46.800
wash their hands and
avoid physicians.

00:15:46.800 --> 00:15:50.566
And he dies in a mental
institution in 1865.

00:15:50.566 --> 00:15:52.530
And imagine if you were
walking here.

00:15:52.530 --> 00:15:54.710
And sometimes when you do walk
on the street, you run into

00:15:54.710 --> 00:15:56.280
people with psychiatric
difficulties.

00:15:56.280 --> 00:15:57.980
And it can be a bit scary.

00:15:57.980 --> 00:16:02.600
Imagine somebody runs up to you
and tells you, God sakes,

00:16:02.600 --> 00:16:05.760
avoid physicians and please
wash your hands.

00:16:05.760 --> 00:16:07.190
Most of us would shrink
back a little bit.

00:16:07.190 --> 00:16:09.270
It would be unusually slightly
scary, right?

00:16:09.270 --> 00:16:12.290
But is he-- who's the
crazy person, right?

00:16:12.290 --> 00:16:14.430
And he's tragically feeling
that if he could just tell

00:16:14.430 --> 00:16:17.570
doctors to wash their hands, he
would save lives that day

00:16:17.570 --> 00:16:18.970
and into the future.

00:16:18.970 --> 00:16:23.040
So but more recently there's
a compelling story for

00:16:23.040 --> 00:16:23.990
checklists.

00:16:23.990 --> 00:16:25.760
I don't know if any of you
have seen this book.

00:16:25.760 --> 00:16:28.750
So in an emergency room-- you
think, OK, that's 1840.

00:16:28.750 --> 00:16:30.660
But now we're modern-day USA.

00:16:30.660 --> 00:16:33.020
We know what we're doing and
doctors do and other

00:16:33.020 --> 00:16:34.220
professionals wash
their hands.

00:16:34.220 --> 00:16:37.620
More recently there's a best
seller, couple years ago about

00:16:37.620 --> 00:16:38.970
checklists.

00:16:38.970 --> 00:16:41.700
So this is what's done
in emergency rooms.

00:16:41.700 --> 00:16:43.890
And you may know that there's an
unfortunately high rate of

00:16:43.890 --> 00:16:46.550
errors in hospitals, even
among highly skilled

00:16:46.550 --> 00:16:49.370
physicians in the best of
academic hospitals.

00:16:49.370 --> 00:16:51.870
There's just miscommunications
between doctors and nurses,

00:16:51.870 --> 00:16:53.160
changes of shifts, and so on.

00:16:53.160 --> 00:16:54.620
Mistakes happen.

00:16:54.620 --> 00:16:58.790
And they began to use, as an
experiment, a small checklist,

00:16:58.790 --> 00:16:59.580
like five items.

00:16:59.580 --> 00:17:02.550
Did you do the following five
things about the catheter or

00:17:02.550 --> 00:17:04.560
replacing needles or so on?

00:17:04.560 --> 00:17:07.410
And almost instantly, there
was opposition from the

00:17:07.410 --> 00:17:07.970
physicians.

00:17:07.970 --> 00:17:10.020
They said, we're doctors.

00:17:10.020 --> 00:17:12.030
And some of this was at Johns
Hopkins which is, as you know,

00:17:12.030 --> 00:17:13.130
a famous academic place.

00:17:13.130 --> 00:17:14.950
But I think it would apply
at every hospital.

00:17:14.950 --> 00:17:16.730
We're doctors-- now men
and women doctors.

00:17:16.730 --> 00:17:17.880
OK?

00:17:17.880 --> 00:17:20.089
We don't need a checklist.

00:17:20.089 --> 00:17:20.869
I went to college.

00:17:20.869 --> 00:17:21.690
I went to medical school.

00:17:21.690 --> 00:17:22.490
I've been through
my residency.

00:17:22.490 --> 00:17:24.319
I got my specialty
and my boards.

00:17:24.319 --> 00:17:26.069
I don't need a checklist.

00:17:26.069 --> 00:17:28.010
That's for the intern, right?

00:17:28.010 --> 00:17:29.440
So they really opposed it.

00:17:29.440 --> 00:17:33.400
But they got almost instantly
far better results of safety.

00:17:33.400 --> 00:17:35.750
And including saving lives
almost instantly from the

00:17:35.750 --> 00:17:38.070
checklists.

00:17:38.070 --> 00:17:39.270
But the physicians still
don't like it

00:17:39.270 --> 00:17:40.670
because it seems childish.

00:17:40.670 --> 00:17:45.370
So even to this day, it's a
bit of a challenge to get

00:17:45.370 --> 00:17:47.590
professionals with pride to do
certain things that go against

00:17:47.590 --> 00:17:50.870
the grain, even if it helps
people's health.

00:17:50.870 --> 00:17:53.230
So, again, we talked about that
some people think that

00:17:53.230 --> 00:17:56.390
mental illness is nothing but
labeling that which we find

00:17:56.390 --> 00:17:59.560
unpleasant or difficult,
non-conforming, or deviant.

00:17:59.560 --> 00:18:01.200
On the other hand, there's
two things.

00:18:01.200 --> 00:18:03.510
One is-- again, so many
hands were up.

00:18:03.510 --> 00:18:06.440
I think if you're around it, you
know that for many, many

00:18:06.440 --> 00:18:10.270
psychiatric diagnoses there's
a lot of misery involved for

00:18:10.270 --> 00:18:12.130
the patient, for the family.

00:18:12.130 --> 00:18:14.390
It's not just a conceptual
argument.

00:18:14.390 --> 00:18:16.730
And then for many diseases,
like for schizophrenia for

00:18:16.730 --> 00:18:19.810
example, in very different
cultures around the world the

00:18:19.810 --> 00:18:23.190
rates are strikingly
similar around 1%.

00:18:23.190 --> 00:18:25.510
We'll talk about disorders like
autism and ADHD where the

00:18:25.510 --> 00:18:26.360
numbers have gone up.

00:18:26.360 --> 00:18:28.870
But in schizophrenia, for as
long as people have roughly

00:18:28.870 --> 00:18:31.200
had a definition, around
the world is roughly

00:18:31.200 --> 00:18:32.740
1%, which is a lot--

00:18:32.740 --> 00:18:38.090
1 out of 100 for a very, very
severe, life-altering disease.

00:18:38.090 --> 00:18:42.420
So the challenges of diagnosis
are huge because no brain

00:18:42.420 --> 00:18:45.540
disorder for all these
neuropsychiatric disorders

00:18:45.540 --> 00:18:48.995
that affect so many people can
be spotted by a blood test or

00:18:48.995 --> 00:18:49.810
a brain image.

00:18:49.810 --> 00:18:51.090
None, zero to this day.

00:18:51.090 --> 00:18:53.700
Everybody's working on
it for many years.

00:18:53.700 --> 00:18:55.210
And that corner may turn.

00:18:55.210 --> 00:18:56.330
Or a genetic test--

00:18:56.330 --> 00:18:57.490
none.

00:18:57.490 --> 00:19:00.830
So everything is a discussion
between the physician and the

00:19:00.830 --> 00:19:02.490
patient and the family.

00:19:02.490 --> 00:19:04.550
Everything's a discussion
like that.

00:19:04.550 --> 00:19:06.470
You can use your common sense
and do a good job.

00:19:06.470 --> 00:19:07.130
But there's risks.

00:19:07.130 --> 00:19:09.460
So here's a famous study
that psychiatrists

00:19:09.460 --> 00:19:10.710
get really mad about.

00:19:10.710 --> 00:19:11.740
I'll tell you, OK?

00:19:11.740 --> 00:19:13.240
And you'll hear why
in a moment.

00:19:13.240 --> 00:19:15.870
So this is David Rosenhan, a
psychologist at Stanford.

00:19:15.870 --> 00:19:19.000
And what he did is he and his
graduate students became

00:19:19.000 --> 00:19:19.910
pseudopatients.

00:19:19.910 --> 00:19:23.530
They pretended to hear voices,
which is one of the signal

00:19:23.530 --> 00:19:25.510
symptoms of schizophrenia,
to hear

00:19:25.510 --> 00:19:28.130
voices telling you things.

00:19:28.130 --> 00:19:31.020
And of course if you go to an
emergency room and say you're

00:19:31.020 --> 00:19:34.650
hearing voices telling you to
do things, you get admitted.

00:19:34.650 --> 00:19:37.140
You get a psych consult.

00:19:37.140 --> 00:19:39.020
And then what they did is once
they were admitted into a

00:19:39.020 --> 00:19:42.730
psychiatry ward, they just
became themselves again.

00:19:42.730 --> 00:19:43.620
OK?

00:19:43.620 --> 00:19:47.740
But now they had the label that
they had a behavior at

00:19:47.740 --> 00:19:50.530
the check-in at the moment of
admission that look like

00:19:50.530 --> 00:19:51.980
schizophrenia.

00:19:51.980 --> 00:19:54.560
Seven of eight of these people
were diagnosed as

00:19:54.560 --> 00:19:55.780
schizophrenia by the
physicians and

00:19:55.780 --> 00:19:57.020
nurses who saw them.

00:19:57.020 --> 00:20:00.840
And it took them anywhere from
three weeks to two months to

00:20:00.840 --> 00:20:03.250
be released.

00:20:03.250 --> 00:20:05.520
And every behavior they did--

00:20:05.520 --> 00:20:07.680
like taking notes because
they were doing it for

00:20:07.680 --> 00:20:09.070
the research paper--

00:20:09.070 --> 00:20:12.760
they were frequently interpreted
as another sign of

00:20:12.760 --> 00:20:17.970
their disorder like abnormal
writing behavior.

00:20:17.970 --> 00:20:19.380
And if they got a little bit
better they would say

00:20:19.380 --> 00:20:21.360
schizophrenia but now in
remission because, you

00:20:21.360 --> 00:20:25.280
understand, once you have that
perspective on somebody then

00:20:25.280 --> 00:20:28.660
every behavior can be
interpreted as a momentary

00:20:28.660 --> 00:20:30.470
abatement or, if you're sitting
there scribbling

00:20:30.470 --> 00:20:33.770
something, unusual
writing behavior.

00:20:33.770 --> 00:20:35.980
So one pseudopatient described
that he had a close

00:20:35.980 --> 00:20:38.750
relationship with his mother but
was rather remote from his

00:20:38.750 --> 00:20:40.440
father during early childhood.

00:20:40.440 --> 00:20:42.890
During adolescence and beyond,
his father became a close

00:20:42.890 --> 00:20:45.660
friend while his relationship
cooled with his mother.

00:20:45.660 --> 00:20:48.860
OK, so that happens, right?

00:20:48.860 --> 00:20:50.660
His present relationship
with his wife was

00:20:50.660 --> 00:20:52.170
characteristically
close and warm.

00:20:52.170 --> 00:20:54.520
Apart from occasional
angry exchanges,

00:20:54.520 --> 00:20:55.770
friction was minimal.

00:20:55.770 --> 00:20:57.820
The children had rarely
been spanked.

00:20:57.820 --> 00:20:58.860
This is what he told them.

00:20:58.860 --> 00:20:59.890
This is the truth.

00:20:59.890 --> 00:21:01.670
Nothing's remarkable in
this story, right?

00:21:01.670 --> 00:21:02.360
OK.

00:21:02.360 --> 00:21:06.840
But because you're a health
professional who's now trying

00:21:06.840 --> 00:21:10.960
to figure out why did this
person hear voices, the notes

00:21:10.960 --> 00:21:14.560
were this white 39-year-old male
manifests a long history

00:21:14.560 --> 00:21:17.730
of considerable ambivalence and
close relationships which

00:21:17.730 --> 00:21:19.660
began in early childhood.

00:21:19.660 --> 00:21:22.130
A warm relationship with his
mother cools during his

00:21:22.130 --> 00:21:22.760
adolescence.

00:21:22.760 --> 00:21:24.880
A distant relationship to his
father is described as

00:21:24.880 --> 00:21:26.960
becoming very intense.

00:21:26.960 --> 00:21:29.720
Affective stability is absent.

00:21:29.720 --> 00:21:31.960
His attempts to control
emotionality with his wife and

00:21:31.960 --> 00:21:34.800
children are punctuated by angry
outbursts and, in the

00:21:34.800 --> 00:21:37.060
case of children, spankings.

00:21:37.060 --> 00:21:38.250
I mean, this is human.

00:21:38.250 --> 00:21:38.820
This is not--

00:21:38.820 --> 00:21:39.390
OK?

00:21:39.390 --> 00:21:42.620
Because once you have a take
on somebody, you keep

00:21:42.620 --> 00:21:43.970
connecting the dots.

00:21:43.970 --> 00:21:47.370
And while he says that he has
several good friends, one

00:21:47.370 --> 00:21:49.820
senses considerable ambivalence
embedded in those

00:21:49.820 --> 00:21:51.090
relationships also.

00:21:51.090 --> 00:21:52.500
OK, you understand that
the interpret--

00:21:52.500 --> 00:21:54.530
and you could say, but this
is just the problem of

00:21:54.530 --> 00:21:55.740
psychiatric diagnoses--

00:21:55.740 --> 00:21:59.960
all discussion and
interpretation.

00:21:59.960 --> 00:22:01.700
Finally, they were remitted.

00:22:01.700 --> 00:22:05.780
Patient resumes writing
behavior, oral fixation.

00:22:05.780 --> 00:22:07.330
It's a little too good
to be almost true.

00:22:07.330 --> 00:22:09.540
But there's some stories where
other patients were skeptical.

00:22:09.540 --> 00:22:11.460
One patient said quote,
"You're not crazy.

00:22:11.460 --> 00:22:13.030
You're a journalist
or professor--

00:22:13.030 --> 00:22:15.010
referring to the continual
note-taking.

00:22:15.010 --> 00:22:17.740
You're checking up on the
hospital." As if the freed-up

00:22:17.740 --> 00:22:18.270
up patients.

00:22:18.270 --> 00:22:21.580
Now this is a little bit of a
fable because this makes a

00:22:21.580 --> 00:22:23.830
psychiatric disorder sound like
we have a better sense of

00:22:23.830 --> 00:22:24.800
reality on the world.

00:22:24.800 --> 00:22:27.180
And I don't think anybody thinks
that in a deep way.

00:22:27.180 --> 00:22:30.030
But it just shows you how
far off the health

00:22:30.030 --> 00:22:31.140
professionals were.

00:22:31.140 --> 00:22:33.590
So you tell this story to
psychiatrists, and they get

00:22:33.590 --> 00:22:35.030
really mad at you.

00:22:35.030 --> 00:22:36.600
I mean, it's a true story.

00:22:36.600 --> 00:22:39.470
It shows you the difficulty
of diagnosis.

00:22:39.470 --> 00:22:42.010
The psychiatrists I talk with
say, well, they could fake any

00:22:42.010 --> 00:22:45.310
disease they wanted to and go
pretty far because if you know

00:22:45.310 --> 00:22:47.380
the medical symptoms and you
go and tell doctor those

00:22:47.380 --> 00:22:50.280
things, a non-psychiatric
disease, you could get pretty

00:22:50.280 --> 00:22:51.900
far in terms of treatment
before they figure out

00:22:51.900 --> 00:22:54.350
something's not there, if
you know what to say.

00:22:54.350 --> 00:22:56.190
So they just think it's
nothing specific about

00:22:56.190 --> 00:22:58.190
psychiatry.

00:22:58.190 --> 00:22:59.620
But, in any case, diagnosis--

00:22:59.620 --> 00:23:03.230
so what are the criteria for
diagnostic categories?

00:23:03.230 --> 00:23:06.180
Signs are what the examiner
sees in symptoms, what the

00:23:06.180 --> 00:23:07.460
patient says.

00:23:07.460 --> 00:23:10.320
And a syndrome is a cluster
of signs and symptoms.

00:23:10.320 --> 00:23:12.540
Everyone neuropsychiatric
psychiatric disorder is

00:23:12.540 --> 00:23:14.860
basically a syndrome.

00:23:14.860 --> 00:23:17.670
It's a cluster of things that
tend to go together.

00:23:17.670 --> 00:23:20.330
But individual patient,
individual patient, individual

00:23:20.330 --> 00:23:24.830
patient, shows a different
picture than other people.

00:23:24.830 --> 00:23:27.400
They want diagnosis that can
be relatively reliably

00:23:27.400 --> 00:23:29.420
assessed, consistently
assessed.

00:23:29.420 --> 00:23:31.490
Some sense that there's
some validity to this.

00:23:31.490 --> 00:23:34.130
But all of this is sort of
thinking things through.

00:23:34.130 --> 00:23:36.160
And then finally all these
thoughts are organized by

00:23:36.160 --> 00:23:39.000
experts meeting in hotel rooms
around the country in

00:23:39.000 --> 00:23:40.080
conferences.

00:23:40.080 --> 00:23:42.590
And they produce a book called
the Diagnostic and Statistical

00:23:42.590 --> 00:23:44.910
Manual of the American
Psychiatric Association--

00:23:44.910 --> 00:23:46.430
DSM-IV.

00:23:46.430 --> 00:23:50.850
DSM-V is about to come
out in a little bit.

00:23:50.850 --> 00:23:52.560
This is the official
list of diagnoses.

00:23:52.560 --> 00:23:55.390
These are the lists that all
doctors use, school systems

00:23:55.390 --> 00:23:57.130
use, health insurers use.

00:23:57.130 --> 00:23:59.510
You have to meet the
criteria in this

00:23:59.510 --> 00:24:01.350
book to get a diagnosis.

00:24:01.350 --> 00:24:02.680
It looks like that.

00:24:02.680 --> 00:24:05.670
People like to point out that
if you pile up the original

00:24:05.670 --> 00:24:10.180
DSMs with each version, the
lists get bigger and bigger.

00:24:10.180 --> 00:24:15.900
All of these lists are debated
in various ways.

00:24:15.900 --> 00:24:19.530
Let me give you a sense of
a couple of the ones.

00:24:19.530 --> 00:24:21.830
And you can see the
ambivalence and

00:24:21.830 --> 00:24:23.630
the dangers of this.

00:24:23.630 --> 00:24:28.080
So psychiatrists in the Soviet
Union, before the Soviet Union

00:24:28.080 --> 00:24:31.830
fell, were thrown out of the
worldwide psychiatric

00:24:31.830 --> 00:24:34.620
associations because they
would regularly diagnose

00:24:34.620 --> 00:24:40.550
protesters of the Soviet Union
as being crazy and had to be

00:24:40.550 --> 00:24:43.130
put into mental institutions
and given anti-psychotic

00:24:43.130 --> 00:24:46.140
medications because only a crazy
person would fail to

00:24:46.140 --> 00:24:49.800
recognize the correctness of
Marxist principles in the

00:24:49.800 --> 00:24:53.140
Soviet Union and the
incorrectness of all other

00:24:53.140 --> 00:24:54.220
competing systems.

00:24:54.220 --> 00:24:54.750
All right?

00:24:54.750 --> 00:24:57.120
Now that's what we consider to
be politically abusive, in the

00:24:57.120 --> 00:24:59.000
worst sense.

00:24:59.000 --> 00:25:01.130
I think some of that is thought
to go on a bit in

00:25:01.130 --> 00:25:03.190
China still and other
countries.

00:25:03.190 --> 00:25:05.770
But it was manifest in
the Soviet Union.

00:25:05.770 --> 00:25:08.390
So that we can throw
out as really bad.

00:25:08.390 --> 00:25:11.000
But it just shows you that the
dominant powers in a culture

00:25:11.000 --> 00:25:12.750
could make these decisions.

00:25:12.750 --> 00:25:16.540
About 20 years ago, if you were
a homosexual, you had a

00:25:16.540 --> 00:25:22.440
diagnosis in this book as
a psychiatric disorder.

00:25:22.440 --> 00:25:23.910
On a lighter side people--

00:25:23.910 --> 00:25:25.270
not always lighter
side, maybe--

00:25:25.270 --> 00:25:28.750
people would have debated
whether video game addiction

00:25:28.750 --> 00:25:30.630
should count as a
real addiction.

00:25:30.630 --> 00:25:31.600
People debate all the time.

00:25:31.600 --> 00:25:34.140
What is the borderline between
addictions that almost

00:25:34.140 --> 00:25:37.100
everybody agrees in terms of
alcoholism and drug dependency

00:25:37.100 --> 00:25:40.260
count as full-scale addictions
versus other things.

00:25:40.260 --> 00:25:43.160
What would it take for a person
not to leave the room

00:25:43.160 --> 00:25:47.920
ever playing video games to
count as an addiction?

00:25:47.920 --> 00:25:51.530
There's debates now in autism
spectrum disorders.

00:25:51.530 --> 00:25:53.580
They're about to eliminate
the separate

00:25:53.580 --> 00:25:56.770
listings of two diagnoses.

00:25:56.770 --> 00:26:00.390
One of them called Asperger's
which is sort of the milder

00:26:00.390 --> 00:26:02.530
form of autism, in general.

00:26:02.530 --> 00:26:04.670
They're about to eliminate
that distinction.

00:26:04.670 --> 00:26:06.110
Many patients and families with

00:26:06.110 --> 00:26:08.070
Asperger's don't like that.

00:26:08.070 --> 00:26:10.330
And also something called--
here's a bad label--

00:26:10.330 --> 00:26:15.410
PDD-NOS, pervasive developmental
disorder not

00:26:15.410 --> 00:26:16.460
otherwise specified.

00:26:16.460 --> 00:26:18.020
Imagine if you have a child
with difficulty.

00:26:18.020 --> 00:26:20.390
And the doctor tells you,
your child has pervasive

00:26:20.390 --> 00:26:23.370
developmental disorder not
otherwise specified.

00:26:23.370 --> 00:26:25.910
That's a child, basically,
who has two of the three

00:26:25.910 --> 00:26:30.330
components of a diagnosis
for autism.

00:26:30.330 --> 00:26:31.770
So why draw the line there?

00:26:31.770 --> 00:26:34.290
And so psychiatrist, I think,
reasonably are saying, we

00:26:34.290 --> 00:26:35.410
don't really understand
the lines.

00:26:35.410 --> 00:26:36.340
We're going to call
all of these

00:26:36.340 --> 00:26:39.120
autism spectrum disorders.

00:26:39.120 --> 00:26:41.050
But you could see these things
are shifting over time.

00:26:41.050 --> 00:26:43.920
These labels move as people
think about things.

00:26:43.920 --> 00:26:46.530
And there's no definitive
evidence one way or the other

00:26:46.530 --> 00:26:49.100
besides best attempts by
people to figure out

00:26:49.100 --> 00:26:49.640
what's going on.

00:26:49.640 --> 00:26:51.080
And not everybody agrees.

00:26:51.080 --> 00:26:51.660
Also--

00:26:51.660 --> 00:26:53.060
I'll talk about this
next time--

00:26:53.060 --> 00:26:56.290
when one DSM switched to
another, for example, the

00:26:56.290 --> 00:26:59.590
number of children in Germany
who qualified for ADHD

00:26:59.590 --> 00:27:03.430
diagnosis doubled overnight
because the diagnostic

00:27:03.430 --> 00:27:04.980
criteria changed.

00:27:04.980 --> 00:27:06.570
That doesn't mean that the--

00:27:06.570 --> 00:27:07.810
which is the better one.

00:27:07.810 --> 00:27:09.320
You couldn't even begin
to prove which

00:27:09.320 --> 00:27:10.580
is the better one--

00:27:10.580 --> 00:27:12.640
the original or the one
that had admitted more

00:27:12.640 --> 00:27:13.790
children into it.

00:27:13.790 --> 00:27:15.400
So these are tough calls.

00:27:15.400 --> 00:27:17.100
And you could say, well it's
all kind of a little bit

00:27:17.100 --> 00:27:18.110
arbitrary and a bit
subjective.

00:27:18.110 --> 00:27:19.680
And it's true.

00:27:19.680 --> 00:27:21.460
On the other hand, you've
got to help people.

00:27:21.460 --> 00:27:23.870
So why have these labels if
there's all kinds of issues?

00:27:23.870 --> 00:27:26.250
Well first, allocation
of resources.

00:27:26.250 --> 00:27:30.460
If a person usually needs such
a diagnostic label to get

00:27:30.460 --> 00:27:34.300
services at school, to get
medical services in hospitals,

00:27:34.300 --> 00:27:36.780
to have insurers support them,
and that's independent of the

00:27:36.780 --> 00:27:38.850
kind of medical service
you have.

00:27:38.850 --> 00:27:39.980
Right?

00:27:39.980 --> 00:27:43.840
Second, if you have a label
that's somewhat useful for--

00:27:43.840 --> 00:27:45.680
that helps you know what kind
of service is needed,

00:27:45.680 --> 00:27:49.090
different services are needed
for a child with ADHD versus

00:27:49.090 --> 00:27:51.200
an adult with depression or
an adult with obsessive

00:27:51.200 --> 00:27:52.330
compulsive disorder.

00:27:52.330 --> 00:27:53.330
Different things are needed.

00:27:53.330 --> 00:27:55.160
A label is needed to even
begin to figure out

00:27:55.160 --> 00:27:56.680
which way to go.

00:27:56.680 --> 00:27:58.490
And then people also want to
understand a little bit what

00:27:58.490 --> 00:28:00.720
can they predict about the
future course of that person--

00:28:00.720 --> 00:28:03.300
a little bit of treatment and
their fine, a lot of treatment

00:28:03.300 --> 00:28:04.970
and monitoring needed?

00:28:04.970 --> 00:28:06.200
You have to do something
practical.

00:28:06.200 --> 00:28:08.440
And the labels help you organize
around that with all

00:28:08.440 --> 00:28:10.970
the risks of these labels.

00:28:10.970 --> 00:28:14.055
So we're going to focus a little
bit on schizophrenia.

00:28:14.055 --> 00:28:15.430
And I'll describe
it a little bit.

00:28:15.430 --> 00:28:17.170
And then we'll see a film.

00:28:17.170 --> 00:28:20.120
So sometimes the word
schizophrenia is used in kind

00:28:20.120 --> 00:28:22.750
of a medically incorrect way
which is like multiple

00:28:22.750 --> 00:28:23.790
personality disorder.

00:28:23.790 --> 00:28:25.690
That's not what schizophrenia
is.

00:28:25.690 --> 00:28:28.000
It was described by Bleuler
as a splitting of mental

00:28:28.000 --> 00:28:30.000
functions; disintegration
of emotions,

00:28:30.000 --> 00:28:32.160
thoughts, and actions.

00:28:32.160 --> 00:28:36.820
About 1% worldwide, another 2%
to 3% have a partial version

00:28:36.820 --> 00:28:38.110
of schizophrenia.

00:28:38.110 --> 00:28:41.550
Practically for every disorder
there's patients

00:28:41.550 --> 00:28:42.450
who meet the disorder.

00:28:42.450 --> 00:28:44.900
And there's patients
who come close.

00:28:44.900 --> 00:28:47.400
And what that exact dividing
line should be and what the

00:28:47.400 --> 00:28:51.110
value of it is is constantly
struggled with.

00:28:51.110 --> 00:28:53.330
Similar around the world, a
slight tendency from birth in

00:28:53.330 --> 00:28:54.410
winter or spring--

00:28:54.410 --> 00:28:55.770
people don't know why
schizophrenia happens.

00:28:55.770 --> 00:28:58.580
It makes them think about a
virus as part of the story.

00:28:58.580 --> 00:29:00.270
Patients with schizophrenia
are defined as having

00:29:00.270 --> 00:29:02.740
psychosis, an alteration in
thoughts, perception, and

00:29:02.740 --> 00:29:03.870
consciousness.

00:29:03.870 --> 00:29:06.170
The thoughts are disconnected
and loose.

00:29:06.170 --> 00:29:08.160
They've unusual beliefs
or delusions, often of

00:29:08.160 --> 00:29:09.920
persecution.

00:29:09.920 --> 00:29:12.070
Somebody else is possessing
their thought.

00:29:12.070 --> 00:29:14.100
They can have abnormal
experiences in terms of

00:29:14.100 --> 00:29:18.990
auditory hallucinations, mood
disorders, motor alteration.

00:29:18.990 --> 00:29:21.720
You'll see in the movie, it was
a restless, purposeless

00:29:21.720 --> 00:29:23.480
overactivity.

00:29:23.480 --> 00:29:25.460
Can have impoverished
social function.

00:29:25.460 --> 00:29:28.165
For a while, people thought a
really important distinction

00:29:28.165 --> 00:29:31.070
of schizophrenia was between
what they called negative and

00:29:31.070 --> 00:29:32.940
positive symptoms.

00:29:32.940 --> 00:29:35.860
So the negative ones were they
did less of what a person

00:29:35.860 --> 00:29:36.840
typically does--

00:29:36.840 --> 00:29:40.610
poverty of speech, poor
attention, flat affect, lack

00:29:40.610 --> 00:29:42.540
of motivation.

00:29:42.540 --> 00:29:43.240
Sorry, that's negative.

00:29:43.240 --> 00:29:45.260
And the positive were active
things that people don't

00:29:45.260 --> 00:29:47.410
usually do-- delusions,
hallucinations, bizarre or

00:29:47.410 --> 00:29:49.220
disorganized behaviors.

00:29:49.220 --> 00:29:51.390
Biologically, it's been hard to
show that that's kind of a

00:29:51.390 --> 00:29:53.940
distinction that matters.

00:29:53.940 --> 00:29:57.380
And so what happens with
patients with schizophrenia,

00:29:57.380 --> 00:30:02.100
very mysteriously the clinical
onset in most cases is late

00:30:02.100 --> 00:30:03.640
adolescence and early
adulthood.

00:30:03.640 --> 00:30:06.360
And nobody understands this.

00:30:06.360 --> 00:30:11.110
So typically it's in your
18, 20, 22, 24.

00:30:11.110 --> 00:30:15.380
How is that such a psychiatric
disorder waits that long and

00:30:15.380 --> 00:30:18.410
not much longer in the vast
majority of cases?

00:30:18.410 --> 00:30:22.050
What biological thing is ticking
in a person that will

00:30:22.050 --> 00:30:24.850
lead to a psychotic break
with reality?

00:30:24.850 --> 00:30:27.280
A huge amount of research
now is to try to look at

00:30:27.280 --> 00:30:32.310
individuals who are in their
teens and step in and stop

00:30:32.310 --> 00:30:35.050
somebody before they have
a psychotic episode.

00:30:35.050 --> 00:30:37.890
The positive symptoms are most
evident in this acute

00:30:37.890 --> 00:30:38.960
schizophrenic episode.

00:30:38.960 --> 00:30:41.530
Negative symptoms often
predominate in the long run.

00:30:41.530 --> 00:30:44.440
Huge variability from one
person to the other.

00:30:44.440 --> 00:30:46.680
In terms of outcome, the
outcome often responds

00:30:46.680 --> 00:30:49.210
positively to anti-psychotic
drugs.

00:30:49.210 --> 00:30:52.030
It's estimated about a quarter
of patients make a pretty

00:30:52.030 --> 00:30:52.990
strong recovery.

00:30:52.990 --> 00:30:55.060
About a quarter remain
very disturbed.

00:30:55.060 --> 00:30:58.160
And about half are going
back and forth,

00:30:58.160 --> 00:30:59.520
fluctuating over the years.

00:30:59.520 --> 00:31:02.250
So a picture that people will
use is there's premorbid

00:31:02.250 --> 00:31:04.950
functioning, and then somewhere
in the late teens,

00:31:04.950 --> 00:31:08.650
early 20s some dramatically bad
thing happens, and then

00:31:08.650 --> 00:31:12.860
some sort of stable condition
with occasional relapses.

00:31:12.860 --> 00:31:15.330
And a lot has to do with the
challenge of individuals like

00:31:15.330 --> 00:31:18.490
this taking their medications,
partly being organized enough

00:31:18.490 --> 00:31:23.430
to take them, partly again
feeling like their real selves

00:31:23.430 --> 00:31:28.000
often is not what the
medicated self is.

00:31:28.000 --> 00:31:31.880
You may know the movie Beautiful
Mind with John Nash.

00:31:31.880 --> 00:31:36.780
And it's just an example how
psychiatric disorders

00:31:36.780 --> 00:31:40.680
challenge people of every
mental caliber.

00:31:40.680 --> 00:31:45.240
So he won the 1994 Nobel
Prize in Economics.

00:31:45.240 --> 00:31:46.470
And if you've seen the movie--

00:31:46.470 --> 00:31:48.080
although it's interesting if
you've seen the movie, also

00:31:48.080 --> 00:31:50.500
you could go up on YouTube and
see him talking about the

00:31:50.500 --> 00:31:55.310
movie because they sanitized him
somewhat to make him more

00:31:55.310 --> 00:32:00.340
popular with the movie-going
public because they made it a

00:32:00.340 --> 00:32:03.730
more charming disorder than
everybody says it was,

00:32:03.730 --> 00:32:05.690
including himself.

00:32:05.690 --> 00:32:09.270
But he had a terrific aptitude
for math, went to the Carnegie

00:32:09.270 --> 00:32:12.580
Mellon, Princeton for his Ph.D.,
famous for bargaining

00:32:12.580 --> 00:32:17.350
problem and non-cooperative
games theory, came to MIT in

00:32:17.350 --> 00:32:19.970
1951 as an instructor.

00:32:19.970 --> 00:32:22.185
And then, after doing his
fantastic work that won him

00:32:22.185 --> 00:32:26.130
the Nobel Prize, developed
acute schizophrenia.

00:32:26.130 --> 00:32:27.530
So why don't we watch
the movie.

00:32:27.530 --> 00:32:28.410
Tyler, can we do that?

00:32:28.410 --> 00:32:28.860
Let me do this.

00:32:28.860 --> 00:32:31.720
So here's a fairly
typical patient.

00:32:42.588 --> 00:32:44.070
Yeah?

00:32:44.070 --> 00:32:46.540
AUDIENCE: [INAUDIBLE]

00:32:46.540 --> 00:32:47.034
PROFESSOR: Sorry?

00:32:47.034 --> 00:32:48.284
AUDIENCE: [INAUDIBLE]

00:32:52.500 --> 00:32:53.985
PROFESSOR: I have no idea.

00:32:53.985 --> 00:32:56.770
Is there any different rate of
schizophrenia in people who--

00:32:56.770 --> 00:32:58.227
AUDIENCE: I was just wondering
about the voices, hearing

00:32:58.227 --> 00:32:59.100
voices in their head.

00:32:59.100 --> 00:33:01.530
But if you--

00:33:01.530 --> 00:33:02.716
PROFESSOR: That's a--

00:33:02.716 --> 00:33:03.670
that's a good--

00:33:03.670 --> 00:33:08.180
somebody who were deaf, would
they hear voices in their

00:33:08.180 --> 00:33:08.950
schizophrenia?

00:33:08.950 --> 00:33:10.890
AUDIENCE: [INAUDIBLE]

00:33:10.890 --> 00:33:11.820
PROFESSOR: It's a fascinating
question

00:33:11.820 --> 00:33:12.370
because I have no idea.

00:33:12.370 --> 00:33:15.760
I've never thought about that.

00:33:15.760 --> 00:33:16.455
It's rare.

00:33:16.455 --> 00:33:18.730
Its combination of the two
are moderately rare,

00:33:18.730 --> 00:33:19.690
just numbers wise.

00:33:19.690 --> 00:33:21.130
But that'd be an interesting
question.

00:33:21.130 --> 00:33:22.690
I don't know.

00:33:22.690 --> 00:33:23.120
Any other?

00:33:23.120 --> 00:33:26.580
I saw another hand, or no?

00:33:26.580 --> 00:33:29.010
OK.

00:33:29.010 --> 00:33:32.490
So we know one thing that
practically for every

00:33:32.490 --> 00:33:35.220
neuropsychiatric disorder,
there's strong familial

00:33:35.220 --> 00:33:38.200
evidence that there's a genetic
component to the

00:33:38.200 --> 00:33:40.930
disorder and a big one.

00:33:40.930 --> 00:33:42.310
So here are four--

00:33:42.310 --> 00:33:44.880
this is a very touching
picture, in a way.

00:33:44.880 --> 00:33:48.330
These are identical quadruplets,
four girls, who

00:33:48.330 --> 00:33:49.970
all grew up to have
schizophrenia.

00:33:53.420 --> 00:33:55.450
Not every identical
twin will do that.

00:33:55.450 --> 00:34:01.200
So if one twin has
schizophrenia, half the time

00:34:01.200 --> 00:34:04.660
the second twin will
have schizophrenia.

00:34:04.660 --> 00:34:07.380
If it's dizygotic, it's
still higher than 1%.

00:34:07.380 --> 00:34:09.310
But it gets down to 15%.

00:34:09.310 --> 00:34:12.790
But I think people have
rethought this because very

00:34:12.790 --> 00:34:18.290
often the sibling or the twin,
if you look a little bit more

00:34:18.290 --> 00:34:21.159
carefully, they won't meet
the diagnostic criteria.

00:34:21.159 --> 00:34:24.120
But they often have struggles
of some kind, as well.

00:34:24.120 --> 00:34:26.580
The lifetime probability in
a first degree relative

00:34:26.580 --> 00:34:28.560
is 10% versus 1%.

00:34:28.560 --> 00:34:31.659
If one parent is 13%,
two parents 50%.

00:34:31.659 --> 00:34:34.300
So all this is lots of
suggestions that there's a

00:34:34.300 --> 00:34:36.679
genetic basis.

00:34:36.679 --> 00:34:39.055
Concordance rates for
monozygotic twins, for

00:34:39.055 --> 00:34:41.360
identical twins, is almost
identical whether they're

00:34:41.360 --> 00:34:43.710
reared together or apart--
again, suggesting a very

00:34:43.710 --> 00:34:46.989
strong genetic basis.

00:34:46.989 --> 00:34:48.820
Being adopted away from
relatives does

00:34:48.820 --> 00:34:51.239
not reduce the risk.

00:34:51.239 --> 00:34:54.449
Having said that, if it's not
100% concordance, there's got

00:34:54.449 --> 00:34:55.969
to be something else going
on besides the

00:34:55.969 --> 00:34:58.860
simple genes at birth.

00:34:58.860 --> 00:35:01.450
It is higher in urban areas,
areas that we think have more

00:35:01.450 --> 00:35:03.390
stress in them.

00:35:03.390 --> 00:35:04.870
People have noticed
that often times

00:35:04.870 --> 00:35:06.520
when people move cultures--

00:35:06.520 --> 00:35:09.900
for example, African communities
in London were of

00:35:09.900 --> 00:35:11.690
recent immigres.

00:35:11.690 --> 00:35:14.350
They kind of seemed to notice a
higher rate, as well, as if

00:35:14.350 --> 00:35:17.200
a big cultural move can
put you at risk.

00:35:17.200 --> 00:35:20.020
And so everybody pretty much
agrees that there's what

00:35:20.020 --> 00:35:21.540
people would call
multifactorial

00:35:21.540 --> 00:35:23.360
polygenic-environmental
threshold model.

00:35:23.360 --> 00:35:25.480
That is, there's a lot of
different genes, plus

00:35:25.480 --> 00:35:27.850
environmental stressors that
come together in some way we

00:35:27.850 --> 00:35:29.100
don't understand.

00:35:31.340 --> 00:35:35.270
And you would think that with
the human genome decoded to a

00:35:35.270 --> 00:35:38.770
large extent and so on, that we
have some clarity on this.

00:35:38.770 --> 00:35:41.330
It's been-- you can
debate this.

00:35:41.330 --> 00:35:44.190
And certainly identifying the
genes that put you at risk for

00:35:44.190 --> 00:35:47.270
these disorders is a hugely
important topic.

00:35:47.270 --> 00:35:49.880
The progress in identifying
certain genes for any of these

00:35:49.880 --> 00:35:54.050
psychiatric disorders
has been horrible.

00:35:54.050 --> 00:35:56.390
Genes are identified one year
and the next five studies

00:35:56.390 --> 00:35:57.970
don't replicate it and so on.

00:35:57.970 --> 00:35:59.940
So people at the Broad Institute
across the street

00:35:59.940 --> 00:36:03.120
now say for them to believe that
a gene is associated with

00:36:03.120 --> 00:36:07.300
schizophrenia, they think you
have to have samples of 10,000

00:36:07.300 --> 00:36:11.230
patients with schizophrenia and
10,000 people without it.

00:36:11.230 --> 00:36:12.950
What does that mean?

00:36:12.950 --> 00:36:16.350
That means there's nothing
like a smoking gun gene--

00:36:16.350 --> 00:36:18.980
10,000 to have enough statistics
to support a

00:36:18.980 --> 00:36:19.940
difference.

00:36:19.940 --> 00:36:24.860
That means many, many of the
10,000 don't have that gene

00:36:24.860 --> 00:36:26.520
who have schizophrenia.

00:36:26.520 --> 00:36:29.500
If it were one gene, one
disorder you don't need 10,000

00:36:29.500 --> 00:36:30.750
people to get a statistic.

00:36:30.750 --> 00:36:32.750
You need five people.

00:36:32.750 --> 00:36:38.440
So it's been a shock to people
that there's been so slow

00:36:38.440 --> 00:36:40.940
progress, given that all the
things they can decode the

00:36:40.940 --> 00:36:44.240
genome, to find the genes
that are at the heart of

00:36:44.240 --> 00:36:45.520
psychiatric diseases.

00:36:45.520 --> 00:36:49.120
And that's true for practically
all of them.

00:36:49.120 --> 00:36:51.920
So there's something complex
about genes and environment

00:36:51.920 --> 00:36:54.390
and people that far exceeds
their understanding at the

00:36:54.390 --> 00:36:57.260
moment at every level.

00:36:57.260 --> 00:36:59.060
And so people could be modelled
like this because it

00:36:59.060 --> 00:36:59.920
makes us feel better.

00:36:59.920 --> 00:37:02.260
And there's something probably
right about it.

00:37:02.260 --> 00:37:04.850
There's an amount of stress in
your life that can come up

00:37:04.850 --> 00:37:08.640
from socioeconomic risk,
health problems, family

00:37:08.640 --> 00:37:09.740
situations.

00:37:09.740 --> 00:37:12.500
There's a predisposition that's
genetically based.

00:37:12.500 --> 00:37:16.770
And some combination of them
determines whether you

00:37:16.770 --> 00:37:19.910
manifest the disorder
or don't.

00:37:19.910 --> 00:37:22.970
So we said there's no definitive
biological marker

00:37:22.970 --> 00:37:26.260
for schizophrenia, as there
isn't for every other

00:37:26.260 --> 00:37:27.160
psychiatric disease.

00:37:27.160 --> 00:37:29.990
There's no blood test, no brain
test, no nothing that

00:37:29.990 --> 00:37:32.720
definitively tells you if a
person has a diagnosis.

00:37:32.720 --> 00:37:35.590
But people have been studying
things that are, on average,

00:37:35.590 --> 00:37:36.540
different in brains.

00:37:36.540 --> 00:37:40.110
And I'll show you some of the
most consistent findings about

00:37:40.110 --> 00:37:43.190
ventricles, about hippocampal
involvement, PET scans.

00:37:43.190 --> 00:37:44.120
I'll show you this.

00:37:44.120 --> 00:37:47.030
And I'll show you a few examples
in schizophrenia.

00:37:47.030 --> 00:37:49.540
So one thing people have
noticed is that if they

00:37:49.540 --> 00:37:52.360
compare-- these are
identical twins.

00:37:52.360 --> 00:37:54.910
And you can see the ventricle,
the fluid filled space, is

00:37:54.910 --> 00:37:56.360
somewhat larger in
the twin with the

00:37:56.360 --> 00:37:58.900
diagnosis than without.

00:37:58.900 --> 00:38:00.920
That's about the least
specific brain marker

00:38:00.920 --> 00:38:01.710
we could ever have.

00:38:01.710 --> 00:38:03.490
The ventricle just means
that there's tissue

00:38:03.490 --> 00:38:04.740
missing around it.

00:38:04.740 --> 00:38:05.360
OK?

00:38:05.360 --> 00:38:06.890
It's just this fluid-filled
space.

00:38:06.890 --> 00:38:08.200
There should be a
bit more tissue.

00:38:08.200 --> 00:38:09.830
It's very far from any specific

00:38:09.830 --> 00:38:10.970
biology of the disorder.

00:38:10.970 --> 00:38:14.800
And here's the actual twins
with their actual MRIs.

00:38:14.800 --> 00:38:16.780
So we don't think it's the
size of the ventricle.

00:38:16.780 --> 00:38:17.760
That makes no sense.

00:38:17.760 --> 00:38:20.690
But that somehow roughly
correlated over the brain

00:38:20.690 --> 00:38:22.700
basis of the disorder is.

00:38:22.700 --> 00:38:24.530
And then people have shown--
and these are relatively

00:38:24.530 --> 00:38:26.790
extreme examples, post-mortem
samples.

00:38:26.790 --> 00:38:29.510
Here's the hippocampus in
healthy individuals.

00:38:29.510 --> 00:38:32.870
Here you can see a somewhat
shrunken in patients with a

00:38:32.870 --> 00:38:36.750
diagnosis of schizophrenia.

00:38:36.750 --> 00:38:38.470
And if you look at those
pictures that are kind of

00:38:38.470 --> 00:38:40.490
picked, you could say,
well that's easy.

00:38:40.490 --> 00:38:43.480
Give me the MRI and I'll
tell you who has it.

00:38:43.480 --> 00:38:45.410
But statistically it doesn't
work that way at all.

00:38:45.410 --> 00:38:48.380
There's tremendous overlap in
the size of the hippocampus

00:38:48.380 --> 00:38:51.070
between people without a
diagnosis and people with

00:38:51.070 --> 00:38:51.690
schizophrenia.

00:38:51.690 --> 00:38:54.310
So it's a statistical thing.

00:38:54.310 --> 00:38:56.160
People have also noticed the
cellular organization

00:38:56.160 --> 00:39:00.830
sometimes looks somehow better
in the typical people than

00:39:00.830 --> 00:39:01.690
people with schizophrenia.

00:39:01.690 --> 00:39:04.500
Again, a suggestion about
a developmental history

00:39:04.500 --> 00:39:06.700
underlying this for
the risk but

00:39:06.700 --> 00:39:09.250
without any kind of certainty.

00:39:09.250 --> 00:39:12.970
When they've done studies
looking at resting scanning

00:39:12.970 --> 00:39:13.830
metabolism--

00:39:13.830 --> 00:39:15.250
you just laying there.

00:39:15.250 --> 00:39:16.160
This is a PET scan.

00:39:16.160 --> 00:39:19.010
It's just where is the
blood flowing.

00:39:19.010 --> 00:39:20.920
You can see that this
is a healthy person.

00:39:20.920 --> 00:39:23.930
A lot of our blood flows
as we sit there

00:39:23.930 --> 00:39:25.560
to the frontal cortex.

00:39:25.560 --> 00:39:28.210
And you can see it's kind of
diminished in schizophrenia.

00:39:28.210 --> 00:39:31.100
But, again, you cannot put
a patient in and say this

00:39:31.100 --> 00:39:33.670
patient has schizophrenia
because many patients will

00:39:33.670 --> 00:39:36.690
look like many controls.

00:39:36.690 --> 00:39:38.850
But the average can
look like this.

00:39:38.850 --> 00:39:42.830
Here's a task now of a
working memory task.

00:39:42.830 --> 00:39:45.220
So people see in the
easy condition,

00:39:45.220 --> 00:39:46.560
letters are running along.

00:39:46.560 --> 00:39:48.410
And every time there's an
X, they push a button.

00:39:48.410 --> 00:39:49.980
That's the easy condition.

00:39:49.980 --> 00:39:51.640
Here, letters are presented
rapidly.

00:39:51.640 --> 00:39:53.750
And every time the current
letter is identical to the one

00:39:53.750 --> 00:39:55.850
you saw two letters ago,
you push a button.

00:39:55.850 --> 00:40:00.980
So this is harder mental work,
harder working memory demands.

00:40:00.980 --> 00:40:04.860
And then here's what you
see in one data set.

00:40:04.860 --> 00:40:08.960
So as they're doing this task,
they turn on a lot of frontal

00:40:08.960 --> 00:40:10.550
cortex, working memory,
thinking.

00:40:10.550 --> 00:40:11.730
You're used to that.

00:40:11.730 --> 00:40:13.150
Here's controls--

00:40:13.150 --> 00:40:16.290
how much they turn it on,
the front of the brain

00:40:16.290 --> 00:40:17.750
viewed from the top.

00:40:17.750 --> 00:40:21.150
Here's relatives who don't
have the diagnosis.

00:40:21.150 --> 00:40:23.320
And here's patients who
do have the diagnosis.

00:40:23.320 --> 00:40:25.650
These are relatives
of these patients.

00:40:25.650 --> 00:40:26.600
And take a look at it.

00:40:26.600 --> 00:40:27.990
You can see they're growing.

00:40:27.990 --> 00:40:29.370
So this is this issue
of is more

00:40:29.370 --> 00:40:30.670
activation better or worse?

00:40:30.670 --> 00:40:31.880
Well it all depends.

00:40:31.880 --> 00:40:35.370
The way we interpret this is for
a typical person, here's

00:40:35.370 --> 00:40:39.800
how much they have to push the
pedal to accomplish that

00:40:39.800 --> 00:40:41.390
working memory task.

00:40:41.390 --> 00:40:43.520
If you're a patient, you
have to push it a lot

00:40:43.520 --> 00:40:45.220
more to do the task.

00:40:45.220 --> 00:40:48.190
And you still make
more mistakes.

00:40:48.190 --> 00:40:51.830
If you are a relative without a
diagnosis of schizophrenia,

00:40:51.830 --> 00:40:53.900
you're somewhere in between.

00:40:53.900 --> 00:40:57.040
And those relatives are
accurate as controls.

00:40:57.040 --> 00:40:59.400
But they perform somewhat
more slowly.

00:40:59.400 --> 00:41:00.920
This is a kind of interesting
thing.

00:41:00.920 --> 00:41:04.680
And practically every disorder,
if you take the

00:41:04.680 --> 00:41:08.160
relatives of people with the
diagnosis, they often look

00:41:08.160 --> 00:41:12.100
like they have a kind of a
milder version of that.

00:41:12.100 --> 00:41:14.210
But they may have no problems
in their lives.

00:41:14.210 --> 00:41:16.490
They may be doing flourishingly
well in every

00:41:16.490 --> 00:41:18.240
regard that you could
think of.

00:41:18.240 --> 00:41:19.970
But they harbor some
of the same genes.

00:41:19.970 --> 00:41:22.190
To be a relative means
to share genes.

00:41:22.190 --> 00:41:23.620
And so that can make--

00:41:23.620 --> 00:41:25.610
there's something about that
happening here or in some

00:41:25.610 --> 00:41:27.070
subset of those individuals.

00:41:27.070 --> 00:41:29.170
Practically every study that's
done, if you take the

00:41:29.170 --> 00:41:32.250
relatives of people with a
diagnosis, there's some

00:41:32.250 --> 00:41:36.380
in-betweenness compared to
people picked in families

00:41:36.380 --> 00:41:37.630
without any history
of that disorder.

00:41:40.160 --> 00:41:41.400
But what matters is
the boundary.

00:41:41.400 --> 00:41:41.700
Right?

00:41:41.700 --> 00:41:44.040
I mean, this difference doesn't
matter if this person

00:41:44.040 --> 00:41:45.740
is doing well.

00:41:45.740 --> 00:41:47.840
This difference is associated
with something that really

00:41:47.840 --> 00:41:51.820
makes a big difference
in the person's life.

00:41:51.820 --> 00:41:54.710
The question about auditory
hallucinations and the deaf--

00:41:54.710 --> 00:41:55.530
this is kind of like that.

00:41:55.530 --> 00:41:56.810
But this is people
hearing people.

00:41:56.810 --> 00:41:59.500
But one of things you can
do with imaging is ask.

00:41:59.500 --> 00:42:02.130
Some patients with schizophrenia
have rapidly

00:42:02.130 --> 00:42:03.680
psyching auditory
hallucinations.

00:42:03.680 --> 00:42:03.980
Most don't.

00:42:03.980 --> 00:42:05.590
Most is every here and there.

00:42:05.590 --> 00:42:06.770
But some have it pretty often.

00:42:06.770 --> 00:42:09.720
So you can put them in a scanner
and when they hear a

00:42:09.720 --> 00:42:11.850
voice, they push a button.

00:42:11.850 --> 00:42:14.910
And you can ask, when they hear
a voice is their auditory

00:42:14.910 --> 00:42:17.520
cortex active?

00:42:17.520 --> 00:42:20.240
At the level of the brain is
it as if they were really

00:42:20.240 --> 00:42:21.350
hearing a voice?

00:42:21.350 --> 00:42:26.010
And here's the auditory cortex
active in the individuals at

00:42:26.010 --> 00:42:27.560
the moment they're
experiencing the

00:42:27.560 --> 00:42:28.990
hallucination.

00:42:28.990 --> 00:42:32.600
It's real to them because
somehow it's engaging the

00:42:32.600 --> 00:42:35.400
auditory cortex that really
hears the world.

00:42:35.400 --> 00:42:37.830
That's why it's so powerful.

00:42:37.830 --> 00:42:41.860
And it's somehow engaging the
very same tissue by which you

00:42:41.860 --> 00:42:45.300
really hear the world.

00:42:45.300 --> 00:42:46.150
How about treatment?

00:42:46.150 --> 00:42:49.810
So next session we'll
talk a lot about

00:42:49.810 --> 00:42:52.750
different kinds of treatment.

00:42:52.750 --> 00:42:54.820
Neuroleptics are the most
common treatment for

00:42:54.820 --> 00:42:55.440
schizophrenia.

00:42:55.440 --> 00:42:55.990
They block--

00:42:55.990 --> 00:42:56.900
I'll talk a bit about this--

00:42:56.900 --> 00:42:59.890
post-synaptic dopamine receptors.

00:42:59.890 --> 00:43:02.370
The drug is fully effective
within hours.

00:43:02.370 --> 00:43:06.220
The maximum clinical effect
takes weeks and then the

00:43:06.220 --> 00:43:08.670
effect remains after
treatment stops.

00:43:08.670 --> 00:43:11.510
A huge problem in schizophrenia
are side effects

00:43:11.510 --> 00:43:13.030
of these kinds of drugs.

00:43:13.030 --> 00:43:18.350
So early on, you induce a bit
of Parkinson's disease in

00:43:18.350 --> 00:43:20.570
patients who never had
Parkinson's disease with these

00:43:20.570 --> 00:43:21.350
typical drugs.

00:43:21.350 --> 00:43:23.160
Because atypical drugs, they
have their problems.

00:43:23.160 --> 00:43:24.450
I'll just focus on the
typical drugs.

00:43:24.450 --> 00:43:25.860
I'll tell you why in a minute.

00:43:25.860 --> 00:43:27.725
And then later on, this becomes
known as tardive

00:43:27.725 --> 00:43:30.160
dyskinesia in about
20% of patients.

00:43:30.160 --> 00:43:32.750
That's a lot of patients.

00:43:32.750 --> 00:43:35.140
You're producing, by the drug,
abnormal and involuntary

00:43:35.140 --> 00:43:37.360
movements-- smacking of lips,
chewing, and tongue

00:43:37.360 --> 00:43:38.835
protrusion.

00:43:38.835 --> 00:43:40.350
And there's some drugs
that don't do it.

00:43:40.350 --> 00:43:42.440
But they have other problems.

00:43:42.440 --> 00:43:45.890
And there is evidence that
behavioral therapy can be

00:43:45.890 --> 00:43:48.800
surprisingly useful
in schizophrenia.

00:43:48.800 --> 00:43:51.410
Most of us hardcore biologists
we thing that drugs

00:43:51.410 --> 00:43:52.070
got to be the deal.

00:43:52.070 --> 00:43:53.650
I think there's more evidence
than you would imagine that

00:43:53.650 --> 00:43:56.180
behavioral therapy or the
combination of the two can be

00:43:56.180 --> 00:43:57.990
very helpful for people.

00:43:57.990 --> 00:44:01.030
So you may know now--

00:44:01.030 --> 00:44:03.960
you wouldn't know this, I know
this because I am constantly

00:44:03.960 --> 00:44:05.980
in the fund raising business
as a researcher--

00:44:05.980 --> 00:44:09.720
drug companies have almost
stopped working on developing

00:44:09.720 --> 00:44:11.760
treatments for psychiatric
diseases.

00:44:11.760 --> 00:44:14.540
And they've almost stopped
because it's been so

00:44:14.540 --> 00:44:16.060
unsuccessful.

00:44:16.060 --> 00:44:18.530
The drugs that were found
were almost always by

00:44:18.530 --> 00:44:19.770
happenstance--

00:44:19.770 --> 00:44:22.260
drugs that were almost randomly
tried for various

00:44:22.260 --> 00:44:24.770
disorders or various
groups and worked.

00:44:24.770 --> 00:44:27.460
None of them are rationally
done in any biotechnology

00:44:27.460 --> 00:44:31.770
sense or molecular chemistry
design sense.

00:44:31.770 --> 00:44:34.820
Practically all of them are
happenstance applications of

00:44:34.820 --> 00:44:36.400
quasi-random drugs.

00:44:36.400 --> 00:44:39.460
And then people noticed
it helped individuals.

00:44:39.460 --> 00:44:41.850
And so in the last 28 years,
where there was much more

00:44:41.850 --> 00:44:46.250
rational development of drugs,
it's been spectacularly hard

00:44:46.250 --> 00:44:48.940
to develop new drugs for
psychiatric disorders.

00:44:48.940 --> 00:44:50.840
And so most pharmaceutical
companies have basically

00:44:50.840 --> 00:44:52.120
stopped in the last
couple years.

00:44:52.120 --> 00:44:54.220
They've just given up.

00:44:54.220 --> 00:44:57.380
We remain optimistic that
everybody thinks they'll come

00:44:57.380 --> 00:45:00.085
back into the picture when some
academics produce some

00:45:00.085 --> 00:45:01.490
things that look good.

00:45:01.490 --> 00:45:03.350
But it's turned out
to be really hard.

00:45:03.350 --> 00:45:05.800
And, furthermore, many of the
medications that are effective

00:45:05.800 --> 00:45:08.170
have all these side effects,
very undesirable

00:45:08.170 --> 00:45:09.920
side effects sometimes.

00:45:09.920 --> 00:45:12.840
At the same time, the fact that
these drugs affect the

00:45:12.840 --> 00:45:15.630
disorder sort of promoted
various theories.

00:45:15.630 --> 00:45:17.850
So once people noticed that
the anti-psychotic

00:45:17.850 --> 00:45:20.130
medications, medications that
diminish the psychosis of

00:45:20.130 --> 00:45:23.450
schizophrenia, act on the
dopamine system, that led to

00:45:23.450 --> 00:45:25.640
the dopamine theory
of schizophrenia.

00:45:25.640 --> 00:45:29.830
So you say, well if the drug is
pushing down dopamine and

00:45:29.830 --> 00:45:32.450
that's helping people be less
psychotic, then maybe what

00:45:32.450 --> 00:45:35.350
that real problem is that
there's too much dopamine

00:45:35.350 --> 00:45:36.820
flowing in the brain
of individuals with

00:45:36.820 --> 00:45:38.030
schizophrenia.

00:45:38.030 --> 00:45:40.010
And that got supported by
studies that if you give

00:45:40.010 --> 00:45:43.170
typical people overdoses of
amphetamine, you induce

00:45:43.170 --> 00:45:45.730
something that looks a bit, in
a typical person, like the

00:45:45.730 --> 00:45:48.490
paranoia of schizophrenia.

00:45:48.490 --> 00:45:50.720
And so let's talk about
this idea of drug

00:45:50.720 --> 00:45:52.410
action versus disease.

00:45:52.410 --> 00:45:55.400
So if you have a headache,
what do you take to help

00:45:55.400 --> 00:45:57.630
yourself with the headache?

00:45:57.630 --> 00:45:59.830
Ibuprofen or aspirin or
something like that?

00:45:59.830 --> 00:46:02.720
Does that mean the medical
problem was you didn't have

00:46:02.720 --> 00:46:05.210
enough aspirin in your blood?

00:46:05.210 --> 00:46:08.060
Were you "hypoasperinemia?"
No, right?

00:46:08.060 --> 00:46:10.840
The aspirin is doing something
else to counteract the

00:46:10.840 --> 00:46:12.160
headache, or the ibuprofen.

00:46:12.160 --> 00:46:15.800
It's not that you were
short on Tylenol.

00:46:15.800 --> 00:46:16.530
OK?

00:46:16.530 --> 00:46:18.570
But it treats the problem.

00:46:18.570 --> 00:46:22.040
So if a drug treats
schizophrenia by acting on the

00:46:22.040 --> 00:46:26.030
dopamine system, does that mean
dopamine was the culprit?

00:46:26.030 --> 00:46:29.670
And the answer is probably not
or it's hard to figure out.

00:46:29.670 --> 00:46:31.920
But the original assumption that
the way the drug works

00:46:31.920 --> 00:46:34.150
gives you a direct insight into
what the cause of the

00:46:34.150 --> 00:46:38.200
disease is, people have
pretty much dismissed.

00:46:38.200 --> 00:46:40.140
But what drew them to it, of
course, is still these

00:46:40.140 --> 00:46:40.880
anti-psychotics.

00:46:40.880 --> 00:46:43.460
The way they work is
they block the

00:46:43.460 --> 00:46:45.400
receptors that take dopamine.

00:46:45.400 --> 00:46:49.660
And, therefore, dopamine gets
catabolized here and is not

00:46:49.660 --> 00:46:51.190
used in neurotransmission.

00:46:51.190 --> 00:46:55.900
And, furthermore, amphetamine,
which produces a somewhat

00:46:55.900 --> 00:46:59.220
schizophrenia-like syndrome in
some healthy individuals, that

00:46:59.220 --> 00:47:00.880
accelerates the production
of dopamine.

00:47:00.880 --> 00:47:02.820
So that seemed to
favor the story.

00:47:02.820 --> 00:47:06.720
But, again, that's sort of not
taken very broadly now.

00:47:06.720 --> 00:47:09.990
Again, what favored the story
was the more powerfully a drug

00:47:09.990 --> 00:47:13.230
bound to dopamine receptors,
the less drug

00:47:13.230 --> 00:47:14.320
you had to give patients.

00:47:14.320 --> 00:47:15.590
All of that, you could
see, made people

00:47:15.590 --> 00:47:17.670
think, this is the story.

00:47:17.670 --> 00:47:20.160
And it may be that dopamine
is a part of the story.

00:47:20.160 --> 00:47:23.240
But everybody understands now
that just because a drug acts

00:47:23.240 --> 00:47:25.450
on a disease, does not mean it's
treating the disease in

00:47:25.450 --> 00:47:28.330
the most direct way.

00:47:28.330 --> 00:47:31.100
And now why do patients get
tardive dyskinesia?

00:47:31.100 --> 00:47:36.690
Why is it an inadvertent
consequence of treating

00:47:36.690 --> 00:47:38.880
schizophrenia, producing
a version

00:47:38.880 --> 00:47:40.410
of Parkinson's disease?

00:47:40.410 --> 00:47:42.920
It's because the drugs
are too nonspecific.

00:47:42.920 --> 00:47:45.590
So we know the ventral tegmental
area in the brain

00:47:45.590 --> 00:47:50.230
stem sends dopamine into the
basal ganglia and into the

00:47:50.230 --> 00:47:52.300
prefrontal cortex.

00:47:52.300 --> 00:47:54.680
Conceptually, what we understand
we're trying to

00:47:54.680 --> 00:47:58.430
achieve with schizophrenia is
something like diminishing

00:47:58.430 --> 00:48:00.690
something about this pathway.

00:48:00.690 --> 00:48:03.560
But the drug can't
just block this.

00:48:03.560 --> 00:48:06.340
It also affects the
basal ganglia.

00:48:06.340 --> 00:48:09.710
And what Parkinson's diseases
is is a shortage of dopamine

00:48:09.710 --> 00:48:10.500
in the basal ganglia.

00:48:10.500 --> 00:48:12.710
In the case of Parkinson's
disease, it's because of death

00:48:12.710 --> 00:48:14.460
of substantial nigral cells.

00:48:14.460 --> 00:48:17.580
But you're producing a
pharmacological version of

00:48:17.580 --> 00:48:22.430
Parkinson's disease in the
effort to treat schizophrenia.

00:48:22.430 --> 00:48:25.180
Not in all patients, not as
severe as Parkinson's disease,

00:48:25.180 --> 00:48:26.900
but a big side effect
in many patients.

00:48:26.900 --> 00:48:27.740
And there's other drugs.

00:48:27.740 --> 00:48:28.790
They have their problems.

00:48:28.790 --> 00:48:34.760
There's almost no drug that's
completely successful and pure

00:48:34.760 --> 00:48:39.400
in any treatment sense
for the patient.

00:48:39.400 --> 00:48:41.390
Despite that, there's been
a fantastic effect.

00:48:41.390 --> 00:48:43.790
We talked about that
when people were

00:48:43.790 --> 00:48:45.730
behaving very oddly--

00:48:45.730 --> 00:48:48.810
and certainly schizophrenia is
perhaps the scariest set of

00:48:48.810 --> 00:48:52.200
behaviors, if you have to pick
one disorder in that way--

00:48:52.200 --> 00:48:56.560
then once they began to have
drugs that diminished the

00:48:56.560 --> 00:49:00.910
unusual behavior, people were
let out of state and

00:49:00.910 --> 00:49:03.230
government hospitals where they
had been sort of secluded

00:49:03.230 --> 00:49:05.250
in many ways and not helped
in many ways.

00:49:05.250 --> 00:49:08.250
And people viewed this as
a tremendous success.

00:49:08.250 --> 00:49:10.450
And I think it is to let
people back into the

00:49:10.450 --> 00:49:13.510
community, interacting in a sort
of more typical way, as

00:49:13.510 --> 00:49:15.650
opposed to being segregated
in areas that were

00:49:15.650 --> 00:49:17.520
often not the best.

00:49:17.520 --> 00:49:19.650
But there was a fantastic
consequence, which is now

00:49:19.650 --> 00:49:21.970
these people, as you may know,
have no safety net.

00:49:21.970 --> 00:49:23.320
They're back in the community.

00:49:23.320 --> 00:49:25.440
And if they don't have people
who care for them or follow

00:49:25.440 --> 00:49:28.040
them, there are risks
for themselves.

00:49:28.040 --> 00:49:30.400
So it's great to give
a medication to

00:49:30.400 --> 00:49:31.100
let somebody out.

00:49:31.100 --> 00:49:32.470
Everybody agrees on that.

00:49:32.470 --> 00:49:34.920
But then if you don't have
a kind of a safety net of

00:49:34.920 --> 00:49:37.790
physicians and family and so
on, a person's out on their

00:49:37.790 --> 00:49:40.710
own, they stop taking their
medication, who's

00:49:40.710 --> 00:49:42.450
there to help them?

00:49:42.450 --> 00:49:45.010
So it's a societal challenge
on top of that.

00:49:45.010 --> 00:49:48.210
So next time I'm going to talk
about treatments for

00:49:48.210 --> 00:49:49.200
neuropsychiatric disorders.

00:49:49.200 --> 00:49:50.870
But for just one minute I'll
ask you, do you have any

00:49:50.870 --> 00:49:54.310
questions or thoughts about
this whole topic?

00:49:54.310 --> 00:49:55.708
Yeah?

00:49:55.708 --> 00:49:56.958
AUDIENCE: [INAUDIBLE]

00:50:03.612 --> 00:50:07.564
I read somewhere that 90% of
schizophrenics [INAUDIBLE]

00:50:11.022 --> 00:50:12.680
PROFESSOR: There's
a fantastic--

00:50:12.680 --> 00:50:15.790
the question was, why is there
such a fantastically high rate

00:50:15.790 --> 00:50:18.020
of smoking-- which there is-- in
patients with schizophrenia

00:50:18.020 --> 00:50:19.530
and bipolar?

00:50:19.530 --> 00:50:21.630
So people will use phrases like
they're self-medicating

00:50:21.630 --> 00:50:23.300
in some way.

00:50:23.300 --> 00:50:24.560
But I don't think there's--

00:50:24.560 --> 00:50:25.980
you could make up a little
bit of a story,

00:50:25.980 --> 00:50:28.330
but it is very striking.

00:50:28.330 --> 00:50:30.230
I don't know a deeper
story than that.

00:50:30.230 --> 00:50:31.080
There might be.

00:50:31.080 --> 00:50:32.025
But it's very striking.

00:50:32.025 --> 00:50:33.768
AUDIENCE: [INAUDIBLE]

00:50:33.768 --> 00:50:37.736
One girl said she had a
schizophrenic episode and

00:50:37.736 --> 00:50:40.712
started smoking afterwards
[INAUDIBLE]

00:50:40.712 --> 00:50:42.710
it made the voices go away.

00:50:42.710 --> 00:50:44.395
PROFESSOR: It made the
voices go away?

00:50:44.395 --> 00:50:45.645
Yeah.

00:50:47.330 --> 00:50:47.990
I don't know.

00:50:47.990 --> 00:50:48.860
I mean there's--

00:50:48.860 --> 00:50:50.140
But it's very--

00:50:50.140 --> 00:50:52.130
there's a phenomenal high
rate of smoking among

00:50:52.130 --> 00:50:54.090
patients like that.

00:50:54.090 --> 00:50:56.010
OK, thanks very much.