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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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00:00:56,860 --> 00:00:59,610
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

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from your book where there's
a guy named Ray.

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He has Tourette's syndrome.

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So we classified that as a
neurological disorder but has

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a sort of psychiatric pieces.

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You know Tourette's syndrome.

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If you don't know from your own
life some way or another,

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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

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syndrome do?

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00:10:01,120 --> 00:10:03,480
They have involuntary
physical tics.

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And part of what they have is
they, during those tics, they

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00:10:07,800 --> 00:10:13,110
curse in pretty horrific ways,
in an uncontrollable way.

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00:10:13,110 --> 00:10:15,640
So that's ideal for television
plot lines.

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It's unbelievably hard for the
children and adults who have

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00:10:18,700 --> 00:10:21,770
it because they're often
perceived as being scary and

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dangerous if they're not
in a controlled state.

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So here's a guy named Ray who
has tics every few seconds

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since age four.

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Imagine if you haven't been--

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maybe some of you have gone
through this or know somebody.

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It's very tough on children to
have that problem, tough on

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00:10:36,360 --> 00:10:37,840
adults but really tough
on children.

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By the time he's an adult,
he's a weekend drummer.

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00:10:40,330 --> 00:10:41,930
He loves to play ping-pong.

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00:10:41,930 --> 00:10:44,570
But he's not doing too well
in terms of jobs.

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He loses his jobs
all the time.

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And his home life is
pretty miserable.

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He has a pretty miserable life
at work and at home.

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He tries Haldol which is a
drug that can help with

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Tourette's.

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And what happens to him?

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Is he instantly cured
of his tics and the

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00:11:00,310 --> 00:11:03,090
happiest person around?

239
00:11:03,090 --> 00:11:06,840
Have any of you glanced
at this?

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00:11:06,840 --> 00:11:07,310
Yeah?

241
00:11:07,310 --> 00:11:08,768
AUDIENCE: Life seemed
to slow down.

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00:11:08,768 --> 00:11:10,712
And he keeps trying to
do things he used

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00:11:10,712 --> 00:11:11,198
to do with his tics.

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00:11:11,198 --> 00:11:14,114
And he hurts himself,
because his eyes--

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00:11:14,114 --> 00:11:15,520
PROFESSOR: Yeah, because
it's slowing his--

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00:11:15,520 --> 00:11:16,420
he feels slowed down.

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00:11:16,420 --> 00:11:16,920
Exactly.

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00:11:16,920 --> 00:11:19,220
So he comes back with a black
eye and a broken nose.

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00:11:19,220 --> 00:11:21,480
So now, in a controlled,
voluntary way he

250
00:11:21,480 --> 00:11:23,490
curses at the doctor.

251
00:11:23,490 --> 00:11:25,520
And he says, like just trying
to go through a revolving

252
00:11:25,520 --> 00:11:29,200
door, his timing is so off
that he injures himself

253
00:11:29,200 --> 00:11:32,550
because the drug has changed,
in some sense, who he is.

254
00:11:32,550 --> 00:11:33,410
And he feels that.

255
00:11:33,410 --> 00:11:35,140
He's not himself anymore.

256
00:11:37,820 --> 00:11:41,210
He stays on the drug
for three months.

257
00:11:41,210 --> 00:11:43,280
It starts to work.

258
00:11:43,280 --> 00:11:45,545
Over the next nine years
he has a steady jobs.

259
00:11:45,545 --> 00:11:47,390
His familial relations
improve.

260
00:11:47,390 --> 00:11:49,440
He's successfully treated
by sort of

261
00:11:49,440 --> 00:11:51,010
every objective measure--

262
00:11:51,010 --> 00:11:54,170
happiness at home with your
family, holding a job, the

263
00:11:54,170 --> 00:11:56,160
sort of two practical things.

264
00:11:56,160 --> 00:11:58,810
But he likes to live
a life as two Rays.

265
00:11:58,810 --> 00:12:01,420
On the weekends, he likes to go
off his medication and be

266
00:12:01,420 --> 00:12:03,670
himself and be the fast drummer
and ping-pong player

267
00:12:03,670 --> 00:12:06,000
that he enjoyed for
his early life.

268
00:12:06,000 --> 00:12:08,380
And then he'll take the
medication and be the sober,

269
00:12:08,380 --> 00:12:11,800
slow, somewhat sedated
individual who is valued at

270
00:12:11,800 --> 00:12:13,710
the workplace and that can
work things out with this

271
00:12:13,710 --> 00:12:16,910
family more easily.

272
00:12:16,910 --> 00:12:18,640
It's always this interesting
thing about how you're

273
00:12:18,640 --> 00:12:20,820
changing people in order
to help them.

274
00:12:20,820 --> 00:12:24,040
And then, what's that line
between changing them to fit

275
00:12:24,040 --> 00:12:26,140
in versus helping them?

276
00:12:26,140 --> 00:12:27,130
So what is abnormal?

277
00:12:27,130 --> 00:12:29,680
And we mean in a very
statistical sense here, just

278
00:12:29,680 --> 00:12:31,050
being at the tail end
of distributions.

279
00:12:33,990 --> 00:12:37,680
Some things we value being
abnormal, at one end of the

280
00:12:37,680 --> 00:12:40,400
distribution in terms
of success in life.

281
00:12:40,400 --> 00:12:41,340
So what's a mental disorder?

282
00:12:41,340 --> 00:12:43,890
It's a clinically significant
behavioral or psychological

283
00:12:43,890 --> 00:12:46,620
syndrome or pattern that occurs
in a person and that is

284
00:12:46,620 --> 00:12:51,320
associated with present distress
or disability or with

285
00:12:51,320 --> 00:12:53,070
significantly increased risk
of suffering death, pain,

286
00:12:53,070 --> 00:12:54,550
disability, or important
loss of freedom.

287
00:12:54,550 --> 00:12:56,940
So when I talk with
psychiatrists-- and I

288
00:12:56,940 --> 00:12:58,800
collaborate a lot with
them on research--

289
00:12:58,800 --> 00:13:01,910
they emphasize, again, the
functional consequence.

290
00:13:01,910 --> 00:13:05,230
Can you lead a happy
personal life?

291
00:13:05,230 --> 00:13:09,150
Can you lead a reasonably
successful professional life?

292
00:13:09,150 --> 00:13:10,690
And that's almost the
most important

293
00:13:10,690 --> 00:13:13,400
thing beyond anything.

294
00:13:13,400 --> 00:13:16,590
And there's amazing stories
that make you think about

295
00:13:16,590 --> 00:13:21,290
sources of apparent madness
or insanity.

296
00:13:21,290 --> 00:13:26,970
And a powerful story for me is
the story of Semmelweis.

297
00:13:26,970 --> 00:13:32,150
So he noticed, as a physician
in 1840's, that the rate of

298
00:13:32,150 --> 00:13:36,320
death of childhood fever in a
ward served by physicians was

299
00:13:36,320 --> 00:13:39,370
four times as high as mothers in
a ward in the same hospital

300
00:13:39,370 --> 00:13:41,090
served by midwives.

301
00:13:41,090 --> 00:13:43,840
At that time practically every
physician was a male.

302
00:13:43,840 --> 00:13:46,270
And every midwife
was a female.

303
00:13:46,270 --> 00:13:48,300
But you were four times
more likely to die.

304
00:13:48,300 --> 00:13:52,176
That's a big increase in his
death if you were in a ward

305
00:13:52,176 --> 00:13:55,500
that physicians served
compared to midwives.

306
00:13:55,500 --> 00:13:57,830
So he wondered what
that was about.

307
00:13:57,830 --> 00:13:59,790
And he tended to know,
furthermore, that the deaths

308
00:13:59,790 --> 00:14:03,090
tended to occur in women
serially who were in one bed

309
00:14:03,090 --> 00:14:03,700
next to the other.

310
00:14:03,700 --> 00:14:06,370
There were physical
clusters of these.

311
00:14:06,370 --> 00:14:08,770
And so he began to think, well,
for example, if the

312
00:14:08,770 --> 00:14:10,940
priest comes to give the last
rites to this person, does

313
00:14:10,940 --> 00:14:14,780
that psychologically discourage
the next person?

314
00:14:14,780 --> 00:14:19,120
And he also found out that
didn't seem to tell the story.

315
00:14:19,120 --> 00:14:20,930
And then he asked, was
the same doctor

316
00:14:20,930 --> 00:14:22,500
going from bed to bed?

317
00:14:22,500 --> 00:14:23,910
And the answer was yes.

318
00:14:23,910 --> 00:14:24,720
It makes sense, right?

319
00:14:24,720 --> 00:14:28,646
Bed to bed, the same doctors
going down the line of women.

320
00:14:28,646 --> 00:14:31,350
And what he began to notice is
that the physicians we're

321
00:14:31,350 --> 00:14:33,800
reluctant to wash their hands.

322
00:14:33,800 --> 00:14:35,660
Now this sounds ridiculous.

323
00:14:35,660 --> 00:14:38,270
But this is 1840 medicine.

324
00:14:38,270 --> 00:14:41,100
And when he asked them why they
didn't wash their hands,

325
00:14:41,100 --> 00:14:43,090
which we would now consider
pretty fundamental in a

326
00:14:43,090 --> 00:14:44,570
medical environment.

327
00:14:44,570 --> 00:14:47,510
The basic response was
that it was unmanly.

328
00:14:47,510 --> 00:14:49,530
Like, men didn't wash
their hands.

329
00:14:49,530 --> 00:14:50,040
I'm a doctor.

330
00:14:50,040 --> 00:14:50,380
I'm a man.

331
00:14:50,380 --> 00:14:51,130
I don't wash my hands.

332
00:14:51,130 --> 00:14:53,720
I'll come back to this
in a couple minutes.

333
00:14:53,720 --> 00:14:55,700
So he asked them to wash their
hands in a solution of

334
00:14:55,700 --> 00:14:57,040
chlorine and lime.

335
00:14:57,040 --> 00:15:01,570
The deaths fell from 12% to
about 1% in 15 months.

336
00:15:01,570 --> 00:15:04,360
All right, many lives were saved
because the physicians

337
00:15:04,360 --> 00:15:08,110
simply washed their hands and
did not carry infections from

338
00:15:08,110 --> 00:15:14,760
one person to another down the
row of child-bearing women.

339
00:15:14,760 --> 00:15:15,510
1848--

340
00:15:15,510 --> 00:15:17,640
there's a revolution
in Austria.

341
00:15:17,640 --> 00:15:19,460
He's fired from his job.

342
00:15:19,460 --> 00:15:20,920
The doctors--

343
00:15:20,920 --> 00:15:22,860
you would think this would be
better world-- but the doctors

344
00:15:22,860 --> 00:15:24,710
immediately are happy
they no longer have

345
00:15:24,710 --> 00:15:26,020
to wash their hands.

346
00:15:26,020 --> 00:15:28,760
And the death rate goes
right back up.

347
00:15:28,760 --> 00:15:31,595
Joseph Lister in 1880 figured
out the formula of Listerine.

348
00:15:31,595 --> 00:15:33,290
But Lister--

349
00:15:33,290 --> 00:15:36,740
what was going on in terms of
cleanliness and sanitation.

350
00:15:36,740 --> 00:15:41,015
Semmelweis in Austria
becomes crazy.

351
00:15:41,015 --> 00:15:44,300
He runs around to people in the
street, telling them to

352
00:15:44,300 --> 00:15:46,800
wash their hands and
avoid physicians.

353
00:15:46,800 --> 00:15:50,566
And he dies in a mental
institution in 1865.

354
00:15:50,566 --> 00:15:52,530
And imagine if you were
walking here.

355
00:15:52,530 --> 00:15:54,710
And sometimes when you do walk
on the street, you run into

356
00:15:54,710 --> 00:15:56,280
people with psychiatric
difficulties.

357
00:15:56,280 --> 00:15:57,980
And it can be a bit scary.

358
00:15:57,980 --> 00:16:02,600
Imagine somebody runs up to you
and tells you, God sakes,

359
00:16:02,600 --> 00:16:05,760
avoid physicians and please
wash your hands.

360
00:16:05,760 --> 00:16:07,190
Most of us would shrink
back a little bit.

361
00:16:07,190 --> 00:16:09,270
It would be unusually slightly
scary, right?

362
00:16:09,270 --> 00:16:12,290
But is he-- who's the
crazy person, right?

363
00:16:12,290 --> 00:16:14,430
And he's tragically feeling
that if he could just tell

364
00:16:14,430 --> 00:16:17,570
doctors to wash their hands, he
would save lives that day

365
00:16:17,570 --> 00:16:18,970
and into the future.

366
00:16:18,970 --> 00:16:23,040
So but more recently there's
a compelling story for

367
00:16:23,040 --> 00:16:23,990
checklists.

368
00:16:23,990 --> 00:16:25,760
I don't know if any of you
have seen this book.

369
00:16:25,760 --> 00:16:28,750
So in an emergency room-- you
think, OK, that's 1840.

370
00:16:28,750 --> 00:16:30,660
But now we're modern-day USA.

371
00:16:30,660 --> 00:16:33,020
We know what we're doing and
doctors do and other

372
00:16:33,020 --> 00:16:34,220
professionals wash
their hands.

373
00:16:34,220 --> 00:16:37,620
More recently there's a best
seller, couple years ago about

374
00:16:37,620 --> 00:16:38,970
checklists.

375
00:16:38,970 --> 00:16:41,700
So this is what's done
in emergency rooms.

376
00:16:41,700 --> 00:16:43,890
And you may know that there's an
unfortunately high rate of

377
00:16:43,890 --> 00:16:46,550
errors in hospitals, even
among highly skilled

378
00:16:46,550 --> 00:16:49,370
physicians in the best of
academic hospitals.

379
00:16:49,370 --> 00:16:51,870
There's just miscommunications
between doctors and nurses,

380
00:16:51,870 --> 00:16:53,160
changes of shifts, and so on.

381
00:16:53,160 --> 00:16:54,620
Mistakes happen.

382
00:16:54,620 --> 00:16:58,790
And they began to use, as an
experiment, a small checklist,

383
00:16:58,790 --> 00:16:59,580
like five items.

384
00:16:59,580 --> 00:17:02,550
Did you do the following five
things about the catheter or

385
00:17:02,550 --> 00:17:04,560
replacing needles or so on?

386
00:17:04,560 --> 00:17:07,410
And almost instantly, there
was opposition from the

387
00:17:07,410 --> 00:17:07,970
physicians.

388
00:17:07,970 --> 00:17:10,020
They said, we're doctors.

389
00:17:10,020 --> 00:17:12,030
And some of this was at Johns
Hopkins which is, as you know,

390
00:17:12,030 --> 00:17:13,130
a famous academic place.

391
00:17:13,130 --> 00:17:14,950
But I think it would apply
at every hospital.

392
00:17:14,950 --> 00:17:16,730
We're doctors-- now men
and women doctors.

393
00:17:16,730 --> 00:17:17,880
OK?

394
00:17:17,880 --> 00:17:20,089
We don't need a checklist.

395
00:17:20,089 --> 00:17:20,869
I went to college.

396
00:17:20,869 --> 00:17:21,690
I went to medical school.

397
00:17:21,690 --> 00:17:22,490
I've been through
my residency.

398
00:17:22,490 --> 00:17:24,319
I got my specialty
and my boards.

399
00:17:24,319 --> 00:17:26,069
I don't need a checklist.

400
00:17:26,069 --> 00:17:28,010
That's for the intern, right?

401
00:17:28,010 --> 00:17:29,440
So they really opposed it.

402
00:17:29,440 --> 00:17:33,400
But they got almost instantly
far better results of safety.

403
00:17:33,400 --> 00:17:35,750
And including saving lives
almost instantly from the

404
00:17:35,750 --> 00:17:38,070
checklists.

405
00:17:38,070 --> 00:17:39,270
But the physicians still
don't like it

406
00:17:39,270 --> 00:17:40,670
because it seems childish.

407
00:17:40,670 --> 00:17:45,370
So even to this day, it's a
bit of a challenge to get

408
00:17:45,370 --> 00:17:47,590
professionals with pride to do
certain things that go against

409
00:17:47,590 --> 00:17:50,870
the grain, even if it helps
people's health.

410
00:17:50,870 --> 00:17:53,230
So, again, we talked about that
some people think that

411
00:17:53,230 --> 00:17:56,390
mental illness is nothing but
labeling that which we find

412
00:17:56,390 --> 00:17:59,560
unpleasant or difficult,
non-conforming, or deviant.

413
00:17:59,560 --> 00:18:01,200
On the other hand, there's
two things.

414
00:18:01,200 --> 00:18:03,510
One is-- again, so many
hands were up.

415
00:18:03,510 --> 00:18:06,440
I think if you're around it, you
know that for many, many

416
00:18:06,440 --> 00:18:10,270
psychiatric diagnoses there's
a lot of misery involved for

417
00:18:10,270 --> 00:18:12,130
the patient, for the family.

418
00:18:12,130 --> 00:18:14,390
It's not just a conceptual
argument.

419
00:18:14,390 --> 00:18:16,730
And then for many diseases,
like for schizophrenia for

420
00:18:16,730 --> 00:18:19,810
example, in very different
cultures around the world the

421
00:18:19,810 --> 00:18:23,190
rates are strikingly
similar around 1%.

422
00:18:23,190 --> 00:18:25,510
We'll talk about disorders like
autism and ADHD where the

423
00:18:25,510 --> 00:18:26,360
numbers have gone up.

424
00:18:26,360 --> 00:18:28,870
But in schizophrenia, for as
long as people have roughly

425
00:18:28,870 --> 00:18:31,200
had a definition, around
the world is roughly

426
00:18:31,200 --> 00:18:32,740
1%, which is a lot--

427
00:18:32,740 --> 00:18:38,090
1 out of 100 for a very, very
severe, life-altering disease.

428
00:18:38,090 --> 00:18:42,420
So the challenges of diagnosis
are huge because no brain

429
00:18:42,420 --> 00:18:45,540
disorder for all these
neuropsychiatric disorders

430
00:18:45,540 --> 00:18:48,995
that affect so many people can
be spotted by a blood test or

431
00:18:48,995 --> 00:18:49,810
a brain image.

432
00:18:49,810 --> 00:18:51,090
None, zero to this day.

433
00:18:51,090 --> 00:18:53,700
Everybody's working on
it for many years.

434
00:18:53,700 --> 00:18:55,210
And that corner may turn.

435
00:18:55,210 --> 00:18:56,330
Or a genetic test--

436
00:18:56,330 --> 00:18:57,490
none.

437
00:18:57,490 --> 00:19:00,830
So everything is a discussion
between the physician and the

438
00:19:00,830 --> 00:19:02,490
patient and the family.

439
00:19:02,490 --> 00:19:04,550
Everything's a discussion
like that.

440
00:19:04,550 --> 00:19:06,470
You can use your common sense
and do a good job.

441
00:19:06,470 --> 00:19:07,130
But there's risks.

442
00:19:07,130 --> 00:19:09,460
So here's a famous study
that psychiatrists

443
00:19:09,460 --> 00:19:10,710
get really mad about.

444
00:19:10,710 --> 00:19:11,740
I'll tell you, OK?

445
00:19:11,740 --> 00:19:13,240
And you'll hear why
in a moment.

446
00:19:13,240 --> 00:19:15,870
So this is David Rosenhan, a
psychologist at Stanford.

447
00:19:15,870 --> 00:19:19,000
And what he did is he and his
graduate students became

448
00:19:19,000 --> 00:19:19,910
pseudopatients.

449
00:19:19,910 --> 00:19:23,530
They pretended to hear voices,
which is one of the signal

450
00:19:23,530 --> 00:19:25,510
symptoms of schizophrenia,
to hear

451
00:19:25,510 --> 00:19:28,130
voices telling you things.

452
00:19:28,130 --> 00:19:31,020
And of course if you go to an
emergency room and say you're

453
00:19:31,020 --> 00:19:34,650
hearing voices telling you to
do things, you get admitted.

454
00:19:34,650 --> 00:19:37,140
You get a psych consult.

455
00:19:37,140 --> 00:19:39,020
And then what they did is once
they were admitted into a

456
00:19:39,020 --> 00:19:42,730
psychiatry ward, they just
became themselves again.

457
00:19:42,730 --> 00:19:43,620
OK?

458
00:19:43,620 --> 00:19:47,740
But now they had the label that
they had a behavior at

459
00:19:47,740 --> 00:19:50,530
the check-in at the moment of
admission that look like

460
00:19:50,530 --> 00:19:51,980
schizophrenia.

461
00:19:51,980 --> 00:19:54,560
Seven of eight of these people
were diagnosed as

462
00:19:54,560 --> 00:19:55,780
schizophrenia by the
physicians and

463
00:19:55,780 --> 00:19:57,020
nurses who saw them.

464
00:19:57,020 --> 00:20:00,840
And it took them anywhere from
three weeks to two months to

465
00:20:00,840 --> 00:20:03,250
be released.

466
00:20:03,250 --> 00:20:05,520
And every behavior they did--

467
00:20:05,520 --> 00:20:07,680
like taking notes because
they were doing it for

468
00:20:07,680 --> 00:20:09,070
the research paper--

469
00:20:09,070 --> 00:20:12,760
they were frequently interpreted
as another sign of

470
00:20:12,760 --> 00:20:17,970
their disorder like abnormal
writing behavior.

471
00:20:17,970 --> 00:20:19,380
And if they got a little bit
better they would say

472
00:20:19,380 --> 00:20:21,360
schizophrenia but now in
remission because, you

473
00:20:21,360 --> 00:20:25,280
understand, once you have that
perspective on somebody then

474
00:20:25,280 --> 00:20:28,660
every behavior can be
interpreted as a momentary

475
00:20:28,660 --> 00:20:30,470
abatement or, if you're sitting
there scribbling

476
00:20:30,470 --> 00:20:33,770
something, unusual
writing behavior.

477
00:20:33,770 --> 00:20:35,980
So one pseudopatient described
that he had a close

478
00:20:35,980 --> 00:20:38,750
relationship with his mother but
was rather remote from his

479
00:20:38,750 --> 00:20:40,440
father during early childhood.

480
00:20:40,440 --> 00:20:42,890
During adolescence and beyond,
his father became a close

481
00:20:42,890 --> 00:20:45,660
friend while his relationship
cooled with his mother.

482
00:20:45,660 --> 00:20:48,860
OK, so that happens, right?

483
00:20:48,860 --> 00:20:50,660
His present relationship
with his wife was

484
00:20:50,660 --> 00:20:52,170
characteristically
close and warm.

485
00:20:52,170 --> 00:20:54,520
Apart from occasional
angry exchanges,

486
00:20:54,520 --> 00:20:55,770
friction was minimal.

487
00:20:55,770 --> 00:20:57,820
The children had rarely
been spanked.

488
00:20:57,820 --> 00:20:58,860
This is what he told them.

489
00:20:58,860 --> 00:20:59,890
This is the truth.

490
00:20:59,890 --> 00:21:01,670
Nothing's remarkable in
this story, right?

491
00:21:01,670 --> 00:21:02,360
OK.

492
00:21:02,360 --> 00:21:06,840
But because you're a health
professional who's now trying

493
00:21:06,840 --> 00:21:10,960
to figure out why did this
person hear voices, the notes

494
00:21:10,960 --> 00:21:14,560
were this white 39-year-old male
manifests a long history

495
00:21:14,560 --> 00:21:17,730
of considerable ambivalence and
close relationships which

496
00:21:17,730 --> 00:21:19,660
began in early childhood.

497
00:21:19,660 --> 00:21:22,130
A warm relationship with his
mother cools during his

498
00:21:22,130 --> 00:21:22,760
adolescence.

499
00:21:22,760 --> 00:21:24,880
A distant relationship to his
father is described as

500
00:21:24,880 --> 00:21:26,960
becoming very intense.

501
00:21:26,960 --> 00:21:29,720
Affective stability is absent.

502
00:21:29,720 --> 00:21:31,960
His attempts to control
emotionality with his wife and

503
00:21:31,960 --> 00:21:34,800
children are punctuated by angry
outbursts and, in the

504
00:21:34,800 --> 00:21:37,060
case of children, spankings.

505
00:21:37,060 --> 00:21:38,250
I mean, this is human.

506
00:21:38,250 --> 00:21:38,820
This is not--

507
00:21:38,820 --> 00:21:39,390
OK?

508
00:21:39,390 --> 00:21:42,620
Because once you have a take
on somebody, you keep

509
00:21:42,620 --> 00:21:43,970
connecting the dots.

510
00:21:43,970 --> 00:21:47,370
And while he says that he has
several good friends, one

511
00:21:47,370 --> 00:21:49,820
senses considerable ambivalence
embedded in those

512
00:21:49,820 --> 00:21:51,090
relationships also.

513
00:21:51,090 --> 00:21:52,500
OK, you understand that
the interpret--

514
00:21:52,500 --> 00:21:54,530
and you could say, but this
is just the problem of

515
00:21:54,530 --> 00:21:55,740
psychiatric diagnoses--

516
00:21:55,740 --> 00:21:59,960
all discussion and
interpretation.

517
00:21:59,960 --> 00:22:01,700
Finally, they were remitted.

518
00:22:01,700 --> 00:22:05,780
Patient resumes writing
behavior, oral fixation.

519
00:22:05,780 --> 00:22:07,330
It's a little too good
to be almost true.

520
00:22:07,330 --> 00:22:09,540
But there's some stories where
other patients were skeptical.

521
00:22:09,540 --> 00:22:11,460
One patient said quote,
"You're not crazy.

522
00:22:11,460 --> 00:22:13,030
You're a journalist
or professor--

523
00:22:13,030 --> 00:22:15,010
referring to the continual
note-taking.

524
00:22:15,010 --> 00:22:17,740
You're checking up on the
hospital." As if the freed-up

525
00:22:17,740 --> 00:22:18,270
up patients.

526
00:22:18,270 --> 00:22:21,580
Now this is a little bit of a
fable because this makes a

527
00:22:21,580 --> 00:22:23,830
psychiatric disorder sound like
we have a better sense of

528
00:22:23,830 --> 00:22:24,800
reality on the world.

529
00:22:24,800 --> 00:22:27,180
And I don't think anybody thinks
that in a deep way.

530
00:22:27,180 --> 00:22:30,030
But it just shows you how
far off the health

531
00:22:30,030 --> 00:22:31,140
professionals were.

532
00:22:31,140 --> 00:22:33,590
So you tell this story to
psychiatrists, and they get

533
00:22:33,590 --> 00:22:35,030
really mad at you.

534
00:22:35,030 --> 00:22:36,600
I mean, it's a true story.

535
00:22:36,600 --> 00:22:39,470
It shows you the difficulty
of diagnosis.

536
00:22:39,470 --> 00:22:42,010
The psychiatrists I talk with
say, well, they could fake any

537
00:22:42,010 --> 00:22:45,310
disease they wanted to and go
pretty far because if you know

538
00:22:45,310 --> 00:22:47,380
the medical symptoms and you
go and tell doctor those

539
00:22:47,380 --> 00:22:50,280
things, a non-psychiatric
disease, you could get pretty

540
00:22:50,280 --> 00:22:51,900
far in terms of treatment
before they figure out

541
00:22:51,900 --> 00:22:54,350
something's not there, if
you know what to say.

542
00:22:54,350 --> 00:22:56,190
So they just think it's
nothing specific about

543
00:22:56,190 --> 00:22:58,190
psychiatry.

544
00:22:58,190 --> 00:22:59,620
But, in any case, diagnosis--

545
00:22:59,620 --> 00:23:03,230
so what are the criteria for
diagnostic categories?

546
00:23:03,230 --> 00:23:06,180
Signs are what the examiner
sees in symptoms, what the

547
00:23:06,180 --> 00:23:07,460
patient says.

548
00:23:07,460 --> 00:23:10,320
And a syndrome is a cluster
of signs and symptoms.

549
00:23:10,320 --> 00:23:12,540
Everyone neuropsychiatric
psychiatric disorder is

550
00:23:12,540 --> 00:23:14,860
basically a syndrome.

551
00:23:14,860 --> 00:23:17,670
It's a cluster of things that
tend to go together.

552
00:23:17,670 --> 00:23:20,330
But individual patient,
individual patient, individual

553
00:23:20,330 --> 00:23:24,830
patient, shows a different
picture than other people.

554
00:23:24,830 --> 00:23:27,400
They want diagnosis that can
be relatively reliably

555
00:23:27,400 --> 00:23:29,420
assessed, consistently
assessed.

556
00:23:29,420 --> 00:23:31,490
Some sense that there's
some validity to this.

557
00:23:31,490 --> 00:23:34,130
But all of this is sort of
thinking things through.

558
00:23:34,130 --> 00:23:36,160
And then finally all these
thoughts are organized by

559
00:23:36,160 --> 00:23:39,000
experts meeting in hotel rooms
around the country in

560
00:23:39,000 --> 00:23:40,080
conferences.

561
00:23:40,080 --> 00:23:42,590
And they produce a book called
the Diagnostic and Statistical

562
00:23:42,590 --> 00:23:44,910
Manual of the American
Psychiatric Association--

563
00:23:44,910 --> 00:23:46,430
DSM-IV.

564
00:23:46,430 --> 00:23:50,850
DSM-V is about to come
out in a little bit.

565
00:23:50,850 --> 00:23:52,560
This is the official
list of diagnoses.

566
00:23:52,560 --> 00:23:55,390
These are the lists that all
doctors use, school systems

567
00:23:55,390 --> 00:23:57,130
use, health insurers use.

568
00:23:57,130 --> 00:23:59,510
You have to meet the
criteria in this

569
00:23:59,510 --> 00:24:01,350
book to get a diagnosis.

570
00:24:01,350 --> 00:24:02,680
It looks like that.

571
00:24:02,680 --> 00:24:05,670
People like to point out that
if you pile up the original

572
00:24:05,670 --> 00:24:10,180
DSMs with each version, the
lists get bigger and bigger.

573
00:24:10,180 --> 00:24:15,900
All of these lists are debated
in various ways.

574
00:24:15,900 --> 00:24:19,530
Let me give you a sense of
a couple of the ones.

575
00:24:19,530 --> 00:24:21,830
And you can see the
ambivalence and

576
00:24:21,830 --> 00:24:23,630
the dangers of this.

577
00:24:23,630 --> 00:24:28,080
So psychiatrists in the Soviet
Union, before the Soviet Union

578
00:24:28,080 --> 00:24:31,830
fell, were thrown out of the
worldwide psychiatric

579
00:24:31,830 --> 00:24:34,620
associations because they
would regularly diagnose

580
00:24:34,620 --> 00:24:40,550
protesters of the Soviet Union
as being crazy and had to be

581
00:24:40,550 --> 00:24:43,130
put into mental institutions
and given anti-psychotic

582
00:24:43,130 --> 00:24:46,140
medications because only a crazy
person would fail to

583
00:24:46,140 --> 00:24:49,800
recognize the correctness of
Marxist principles in the

584
00:24:49,800 --> 00:24:53,140
Soviet Union and the
incorrectness of all other

585
00:24:53,140 --> 00:24:54,220
competing systems.

586
00:24:54,220 --> 00:24:54,750
All right?

587
00:24:54,750 --> 00:24:57,120
Now that's what we consider to
be politically abusive, in the

588
00:24:57,120 --> 00:24:59,000
worst sense.

589
00:24:59,000 --> 00:25:01,130
I think some of that is thought
to go on a bit in

590
00:25:01,130 --> 00:25:03,190
China still and other
countries.

591
00:25:03,190 --> 00:25:05,770
But it was manifest in
the Soviet Union.

592
00:25:05,770 --> 00:25:08,390
So that we can throw
out as really bad.

593
00:25:08,390 --> 00:25:11,000
But it just shows you that the
dominant powers in a culture

594
00:25:11,000 --> 00:25:12,750
could make these decisions.

595
00:25:12,750 --> 00:25:16,540
About 20 years ago, if you were
a homosexual, you had a

596
00:25:16,540 --> 00:25:22,440
diagnosis in this book as
a psychiatric disorder.

597
00:25:22,440 --> 00:25:23,910
On a lighter side people--

598
00:25:23,910 --> 00:25:25,270
not always lighter
side, maybe--

599
00:25:25,270 --> 00:25:28,750
people would have debated
whether video game addiction

600
00:25:28,750 --> 00:25:30,630
should count as a
real addiction.

601
00:25:30,630 --> 00:25:31,600
People debate all the time.

602
00:25:31,600 --> 00:25:34,140
What is the borderline between
addictions that almost

603
00:25:34,140 --> 00:25:37,100
everybody agrees in terms of
alcoholism and drug dependency

604
00:25:37,100 --> 00:25:40,260
count as full-scale addictions
versus other things.

605
00:25:40,260 --> 00:25:43,160
What would it take for a person
not to leave the room

606
00:25:43,160 --> 00:25:47,920
ever playing video games to
count as an addiction?

607
00:25:47,920 --> 00:25:51,530
There's debates now in autism
spectrum disorders.

608
00:25:51,530 --> 00:25:53,580
They're about to eliminate
the separate

609
00:25:53,580 --> 00:25:56,770
listings of two diagnoses.

610
00:25:56,770 --> 00:26:00,390
One of them called Asperger's
which is sort of the milder

611
00:26:00,390 --> 00:26:02,530
form of autism, in general.

612
00:26:02,530 --> 00:26:04,670
They're about to eliminate
that distinction.

613
00:26:04,670 --> 00:26:06,110
Many patients and families with

614
00:26:06,110 --> 00:26:08,070
Asperger's don't like that.

615
00:26:08,070 --> 00:26:10,330
And also something called--
here's a bad label--

616
00:26:10,330 --> 00:26:15,410
PDD-NOS, pervasive developmental
disorder not

617
00:26:15,410 --> 00:26:16,460
otherwise specified.

618
00:26:16,460 --> 00:26:18,020
Imagine if you have a child
with difficulty.

619
00:26:18,020 --> 00:26:20,390
And the doctor tells you,
your child has pervasive

620
00:26:20,390 --> 00:26:23,370
developmental disorder not
otherwise specified.

621
00:26:23,370 --> 00:26:25,910
That's a child, basically,
who has two of the three

622
00:26:25,910 --> 00:26:30,330
components of a diagnosis
for autism.

623
00:26:30,330 --> 00:26:31,770
So why draw the line there?

624
00:26:31,770 --> 00:26:34,290
And so psychiatrist, I think,
reasonably are saying, we

625
00:26:34,290 --> 00:26:35,410
don't really understand
the lines.

626
00:26:35,410 --> 00:26:36,340
We're going to call
all of these

627
00:26:36,340 --> 00:26:39,120
autism spectrum disorders.

628
00:26:39,120 --> 00:26:41,050
But you could see these things
are shifting over time.

629
00:26:41,050 --> 00:26:43,920
These labels move as people
think about things.

630
00:26:43,920 --> 00:26:46,530
And there's no definitive
evidence one way or the other

631
00:26:46,530 --> 00:26:49,100
besides best attempts by
people to figure out

632
00:26:49,100 --> 00:26:49,640
what's going on.

633
00:26:49,640 --> 00:26:51,080
And not everybody agrees.

634
00:26:51,080 --> 00:26:51,660
Also--

635
00:26:51,660 --> 00:26:53,060
I'll talk about this
next time--

636
00:26:53,060 --> 00:26:56,290
when one DSM switched to
another, for example, the

637
00:26:56,290 --> 00:26:59,590
number of children in Germany
who qualified for ADHD

638
00:26:59,590 --> 00:27:03,430
diagnosis doubled overnight
because the diagnostic

639
00:27:03,430 --> 00:27:04,980
criteria changed.

640
00:27:04,980 --> 00:27:06,570
That doesn't mean that the--

641
00:27:06,570 --> 00:27:07,810
which is the better one.

642
00:27:07,810 --> 00:27:09,320
You couldn't even begin
to prove which

643
00:27:09,320 --> 00:27:10,580
is the better one--

644
00:27:10,580 --> 00:27:12,640
the original or the one
that had admitted more

645
00:27:12,640 --> 00:27:13,790
children into it.

646
00:27:13,790 --> 00:27:15,400
So these are tough calls.

647
00:27:15,400 --> 00:27:17,100
And you could say, well it's
all kind of a little bit

648
00:27:17,100 --> 00:27:18,110
arbitrary and a bit
subjective.

649
00:27:18,110 --> 00:27:19,680
And it's true.

650
00:27:19,680 --> 00:27:21,460
On the other hand, you've
got to help people.

651
00:27:21,460 --> 00:27:23,870
So why have these labels if
there's all kinds of issues?

652
00:27:23,870 --> 00:27:26,250
Well first, allocation
of resources.

653
00:27:26,250 --> 00:27:30,460
If a person usually needs such
a diagnostic label to get

654
00:27:30,460 --> 00:27:34,300
services at school, to get
medical services in hospitals,

655
00:27:34,300 --> 00:27:36,780
to have insurers support them,
and that's independent of the

656
00:27:36,780 --> 00:27:38,850
kind of medical service
you have.

657
00:27:38,850 --> 00:27:39,980
Right?

658
00:27:39,980 --> 00:27:43,840
Second, if you have a label
that's somewhat useful for--

659
00:27:43,840 --> 00:27:45,680
that helps you know what kind
of service is needed,

660
00:27:45,680 --> 00:27:49,090
different services are needed
for a child with ADHD versus

661
00:27:49,090 --> 00:27:51,200
an adult with depression or
an adult with obsessive

662
00:27:51,200 --> 00:27:52,330
compulsive disorder.

663
00:27:52,330 --> 00:27:53,330
Different things are needed.

664
00:27:53,330 --> 00:27:55,160
A label is needed to even
begin to figure out

665
00:27:55,160 --> 00:27:56,680
which way to go.

666
00:27:56,680 --> 00:27:58,490
And then people also want to
understand a little bit what

667
00:27:58,490 --> 00:28:00,720
can they predict about the
future course of that person--

668
00:28:00,720 --> 00:28:03,300
a little bit of treatment and
their fine, a lot of treatment

669
00:28:03,300 --> 00:28:04,970
and monitoring needed?

670
00:28:04,970 --> 00:28:06,200
You have to do something
practical.

671
00:28:06,200 --> 00:28:08,440
And the labels help you organize
around that with all

672
00:28:08,440 --> 00:28:10,970
the risks of these labels.

673
00:28:10,970 --> 00:28:14,055
So we're going to focus a little
bit on schizophrenia.

674
00:28:14,055 --> 00:28:15,430
And I'll describe
it a little bit.

675
00:28:15,430 --> 00:28:17,170
And then we'll see a film.

676
00:28:17,170 --> 00:28:20,120
So sometimes the word
schizophrenia is used in kind

677
00:28:20,120 --> 00:28:22,750
of a medically incorrect way
which is like multiple

678
00:28:22,750 --> 00:28:23,790
personality disorder.

679
00:28:23,790 --> 00:28:25,690
That's not what schizophrenia
is.

680
00:28:25,690 --> 00:28:28,000
It was described by Bleuler
as a splitting of mental

681
00:28:28,000 --> 00:28:30,000
functions; disintegration
of emotions,

682
00:28:30,000 --> 00:28:32,160
thoughts, and actions.

683
00:28:32,160 --> 00:28:36,820
About 1% worldwide, another 2%
to 3% have a partial version

684
00:28:36,820 --> 00:28:38,110
of schizophrenia.

685
00:28:38,110 --> 00:28:41,550
Practically for every disorder
there's patients

686
00:28:41,550 --> 00:28:42,450
who meet the disorder.

687
00:28:42,450 --> 00:28:44,900
And there's patients
who come close.

688
00:28:44,900 --> 00:28:47,400
And what that exact dividing
line should be and what the

689
00:28:47,400 --> 00:28:51,110
value of it is is constantly
struggled with.

690
00:28:51,110 --> 00:28:53,330
Similar around the world, a
slight tendency from birth in

691
00:28:53,330 --> 00:28:54,410
winter or spring--

692
00:28:54,410 --> 00:28:55,770
people don't know why
schizophrenia happens.

693
00:28:55,770 --> 00:28:58,580
It makes them think about a
virus as part of the story.

694
00:28:58,580 --> 00:29:00,270
Patients with schizophrenia
are defined as having

695
00:29:00,270 --> 00:29:02,740
psychosis, an alteration in
thoughts, perception, and

696
00:29:02,740 --> 00:29:03,870
consciousness.

697
00:29:03,870 --> 00:29:06,170
The thoughts are disconnected
and loose.

698
00:29:06,170 --> 00:29:08,160
They've unusual beliefs
or delusions, often of

699
00:29:08,160 --> 00:29:09,920
persecution.

700
00:29:09,920 --> 00:29:12,070
Somebody else is possessing
their thought.

701
00:29:12,070 --> 00:29:14,100
They can have abnormal
experiences in terms of

702
00:29:14,100 --> 00:29:18,990
auditory hallucinations, mood
disorders, motor alteration.

703
00:29:18,990 --> 00:29:21,720
You'll see in the movie, it was
a restless, purposeless

704
00:29:21,720 --> 00:29:23,480
overactivity.

705
00:29:23,480 --> 00:29:25,460
Can have impoverished
social function.

706
00:29:25,460 --> 00:29:28,165
For a while, people thought a
really important distinction

707
00:29:28,165 --> 00:29:31,070
of schizophrenia was between
what they called negative and

708
00:29:31,070 --> 00:29:32,940
positive symptoms.

709
00:29:32,940 --> 00:29:35,860
So the negative ones were they
did less of what a person

710
00:29:35,860 --> 00:29:36,840
typically does--

711
00:29:36,840 --> 00:29:40,610
poverty of speech, poor
attention, flat affect, lack

712
00:29:40,610 --> 00:29:42,540
of motivation.

713
00:29:42,540 --> 00:29:43,240
Sorry, that's negative.

714
00:29:43,240 --> 00:29:45,260
And the positive were active
things that people don't

715
00:29:45,260 --> 00:29:47,410
usually do-- delusions,
hallucinations, bizarre or

716
00:29:47,410 --> 00:29:49,220
disorganized behaviors.

717
00:29:49,220 --> 00:29:51,390
Biologically, it's been hard to
show that that's kind of a

718
00:29:51,390 --> 00:29:53,940
distinction that matters.

719
00:29:53,940 --> 00:29:57,380
And so what happens with
patients with schizophrenia,

720
00:29:57,380 --> 00:30:02,100
very mysteriously the clinical
onset in most cases is late

721
00:30:02,100 --> 00:30:03,640
adolescence and early
adulthood.

722
00:30:03,640 --> 00:30:06,360
And nobody understands this.

723
00:30:06,360 --> 00:30:11,110
So typically it's in your
18, 20, 22, 24.

724
00:30:11,110 --> 00:30:15,380
How is that such a psychiatric
disorder waits that long and

725
00:30:15,380 --> 00:30:18,410
not much longer in the vast
majority of cases?

726
00:30:18,410 --> 00:30:22,050
What biological thing is ticking
in a person that will

727
00:30:22,050 --> 00:30:24,850
lead to a psychotic break
with reality?

728
00:30:24,850 --> 00:30:27,280
A huge amount of research
now is to try to look at

729
00:30:27,280 --> 00:30:32,310
individuals who are in their
teens and step in and stop

730
00:30:32,310 --> 00:30:35,050
somebody before they have
a psychotic episode.

731
00:30:35,050 --> 00:30:37,890
The positive symptoms are most
evident in this acute

732
00:30:37,890 --> 00:30:38,960
schizophrenic episode.

733
00:30:38,960 --> 00:30:41,530
Negative symptoms often
predominate in the long run.

734
00:30:41,530 --> 00:30:44,440
Huge variability from one
person to the other.

735
00:30:44,440 --> 00:30:46,680
In terms of outcome, the
outcome often responds

736
00:30:46,680 --> 00:30:49,210
positively to anti-psychotic
drugs.

737
00:30:49,210 --> 00:30:52,030
It's estimated about a quarter
of patients make a pretty

738
00:30:52,030 --> 00:30:52,990
strong recovery.

739
00:30:52,990 --> 00:30:55,060
About a quarter remain
very disturbed.

740
00:30:55,060 --> 00:30:58,160
And about half are going
back and forth,

741
00:30:58,160 --> 00:30:59,520
fluctuating over the years.

742
00:30:59,520 --> 00:31:02,250
So a picture that people will
use is there's premorbid

743
00:31:02,250 --> 00:31:04,950
functioning, and then somewhere
in the late teens,

744
00:31:04,950 --> 00:31:08,650
early 20s some dramatically bad
thing happens, and then

745
00:31:08,650 --> 00:31:12,860
some sort of stable condition
with occasional relapses.

746
00:31:12,860 --> 00:31:15,330
And a lot has to do with the
challenge of individuals like

747
00:31:15,330 --> 00:31:18,490
this taking their medications,
partly being organized enough

748
00:31:18,490 --> 00:31:23,430
to take them, partly again
feeling like their real selves

749
00:31:23,430 --> 00:31:28,000
often is not what the
medicated self is.

750
00:31:28,000 --> 00:31:31,880
You may know the movie Beautiful
Mind with John Nash.

751
00:31:31,880 --> 00:31:36,780
And it's just an example how
psychiatric disorders

752
00:31:36,780 --> 00:31:40,680
challenge people of every
mental caliber.

753
00:31:40,680 --> 00:31:45,240
So he won the 1994 Nobel
Prize in Economics.

754
00:31:45,240 --> 00:31:46,470
And if you've seen the movie--

755
00:31:46,470 --> 00:31:48,080
although it's interesting if
you've seen the movie, also

756
00:31:48,080 --> 00:31:50,500
you could go up on YouTube and
see him talking about the

757
00:31:50,500 --> 00:31:55,310
movie because they sanitized him
somewhat to make him more

758
00:31:55,310 --> 00:32:00,340
popular with the movie-going
public because they made it a

759
00:32:00,340 --> 00:32:03,730
more charming disorder than
everybody says it was,

760
00:32:03,730 --> 00:32:05,690
including himself.

761
00:32:05,690 --> 00:32:09,270
But he had a terrific aptitude
for math, went to the Carnegie

762
00:32:09,270 --> 00:32:12,580
Mellon, Princeton for his Ph.D.,
famous for bargaining

763
00:32:12,580 --> 00:32:17,350
problem and non-cooperative
games theory, came to MIT in

764
00:32:17,350 --> 00:32:19,970
1951 as an instructor.

765
00:32:19,970 --> 00:32:22,185
And then, after doing his
fantastic work that won him

766
00:32:22,185 --> 00:32:26,130
the Nobel Prize, developed
acute schizophrenia.

767
00:32:26,130 --> 00:32:27,530
So why don't we watch
the movie.

768
00:32:27,530 --> 00:32:28,410
Tyler, can we do that?

769
00:32:28,410 --> 00:32:28,860
Let me do this.

770
00:32:28,860 --> 00:32:31,720
So here's a fairly
typical patient.

771
00:32:42,588 --> 00:32:44,070
Yeah?

772
00:32:44,070 --> 00:32:46,540
AUDIENCE: [INAUDIBLE]

773
00:32:46,540 --> 00:32:47,034
PROFESSOR: Sorry?

774
00:32:47,034 --> 00:32:48,284
AUDIENCE: [INAUDIBLE]

775
00:32:52,500 --> 00:32:53,985
PROFESSOR: I have no idea.

776
00:32:53,985 --> 00:32:56,770
Is there any different rate of
schizophrenia in people who--

777
00:32:56,770 --> 00:32:58,227
AUDIENCE: I was just wondering
about the voices, hearing

778
00:32:58,227 --> 00:32:59,100
voices in their head.

779
00:32:59,100 --> 00:33:01,530
But if you--

780
00:33:01,530 --> 00:33:02,716
PROFESSOR: That's a--

781
00:33:02,716 --> 00:33:03,670
that's a good--

782
00:33:03,670 --> 00:33:08,180
somebody who were deaf, would
they hear voices in their

783
00:33:08,180 --> 00:33:08,950
schizophrenia?

784
00:33:08,950 --> 00:33:10,890
AUDIENCE: [INAUDIBLE]

785
00:33:10,890 --> 00:33:11,820
PROFESSOR: It's a fascinating
question

786
00:33:11,820 --> 00:33:12,370
because I have no idea.

787
00:33:12,370 --> 00:33:15,760
I've never thought about that.

788
00:33:15,760 --> 00:33:16,455
It's rare.

789
00:33:16,455 --> 00:33:18,730
Its combination of the two
are moderately rare,

790
00:33:18,730 --> 00:33:19,690
just numbers wise.

791
00:33:19,690 --> 00:33:21,130
But that'd be an interesting
question.

792
00:33:21,130 --> 00:33:22,690
I don't know.

793
00:33:22,690 --> 00:33:23,120
Any other?

794
00:33:23,120 --> 00:33:26,580
I saw another hand, or no?

795
00:33:26,580 --> 00:33:29,010
OK.

796
00:33:29,010 --> 00:33:32,490
So we know one thing that
practically for every

797
00:33:32,490 --> 00:33:35,220
neuropsychiatric disorder,
there's strong familial

798
00:33:35,220 --> 00:33:38,200
evidence that there's a genetic
component to the

799
00:33:38,200 --> 00:33:40,930
disorder and a big one.

800
00:33:40,930 --> 00:33:42,310
So here are four--

801
00:33:42,310 --> 00:33:44,880
this is a very touching
picture, in a way.

802
00:33:44,880 --> 00:33:48,330
These are identical quadruplets,
four girls, who

803
00:33:48,330 --> 00:33:49,970
all grew up to have
schizophrenia.

804
00:33:53,420 --> 00:33:55,450
Not every identical
twin will do that.

805
00:33:55,450 --> 00:34:01,200
So if one twin has
schizophrenia, half the time

806
00:34:01,200 --> 00:34:04,660
the second twin will
have schizophrenia.

807
00:34:04,660 --> 00:34:07,380
If it's dizygotic, it's
still higher than 1%.

808
00:34:07,380 --> 00:34:09,310
But it gets down to 15%.

809
00:34:09,310 --> 00:34:12,790
But I think people have
rethought this because very

810
00:34:12,790 --> 00:34:18,290
often the sibling or the twin,
if you look a little bit more

811
00:34:18,290 --> 00:34:21,159
carefully, they won't meet
the diagnostic criteria.

812
00:34:21,159 --> 00:34:24,120
But they often have struggles
of some kind, as well.

813
00:34:24,120 --> 00:34:26,580
The lifetime probability in
a first degree relative

814
00:34:26,580 --> 00:34:28,560
is 10% versus 1%.

815
00:34:28,560 --> 00:34:31,659
If one parent is 13%,
two parents 50%.

816
00:34:31,659 --> 00:34:34,300
So all this is lots of
suggestions that there's a

817
00:34:34,300 --> 00:34:36,679
genetic basis.

818
00:34:36,679 --> 00:34:39,055
Concordance rates for
monozygotic twins, for

819
00:34:39,055 --> 00:34:41,360
identical twins, is almost
identical whether they're

820
00:34:41,360 --> 00:34:43,710
reared together or apart--
again, suggesting a very

821
00:34:43,710 --> 00:34:46,989
strong genetic basis.

822
00:34:46,989 --> 00:34:48,820
Being adopted away from
relatives does

823
00:34:48,820 --> 00:34:51,239
not reduce the risk.

824
00:34:51,239 --> 00:34:54,449
Having said that, if it's not
100% concordance, there's got

825
00:34:54,449 --> 00:34:55,969
to be something else going
on besides the

826
00:34:55,969 --> 00:34:58,860
simple genes at birth.

827
00:34:58,860 --> 00:35:01,450
It is higher in urban areas,
areas that we think have more

828
00:35:01,450 --> 00:35:03,390
stress in them.

829
00:35:03,390 --> 00:35:04,870
People have noticed
that often times

830
00:35:04,870 --> 00:35:06,520
when people move cultures--

831
00:35:06,520 --> 00:35:09,900
for example, African communities
in London were of

832
00:35:09,900 --> 00:35:11,690
recent immigres.

833
00:35:11,690 --> 00:35:14,350
They kind of seemed to notice a
higher rate, as well, as if

834
00:35:14,350 --> 00:35:17,200
a big cultural move can
put you at risk.

835
00:35:17,200 --> 00:35:20,020
And so everybody pretty much
agrees that there's what

836
00:35:20,020 --> 00:35:21,540
people would call
multifactorial

837
00:35:21,540 --> 00:35:23,360
polygenic-environmental
threshold model.

838
00:35:23,360 --> 00:35:25,480
That is, there's a lot of
different genes, plus

839
00:35:25,480 --> 00:35:27,850
environmental stressors that
come together in some way we

840
00:35:27,850 --> 00:35:29,100
don't understand.

841
00:35:31,340 --> 00:35:35,270
And you would think that with
the human genome decoded to a

842
00:35:35,270 --> 00:35:38,770
large extent and so on, that we
have some clarity on this.

843
00:35:38,770 --> 00:35:41,330
It's been-- you can
debate this.

844
00:35:41,330 --> 00:35:44,190
And certainly identifying the
genes that put you at risk for

845
00:35:44,190 --> 00:35:47,270
these disorders is a hugely
important topic.

846
00:35:47,270 --> 00:35:49,880
The progress in identifying
certain genes for any of these

847
00:35:49,880 --> 00:35:54,050
psychiatric disorders
has been horrible.

848
00:35:54,050 --> 00:35:56,390
Genes are identified one year
and the next five studies

849
00:35:56,390 --> 00:35:57,970
don't replicate it and so on.

850
00:35:57,970 --> 00:35:59,940
So people at the Broad Institute
across the street

851
00:35:59,940 --> 00:36:03,120
now say for them to believe that
a gene is associated with

852
00:36:03,120 --> 00:36:07,300
schizophrenia, they think you
have to have samples of 10,000

853
00:36:07,300 --> 00:36:11,230
patients with schizophrenia and
10,000 people without it.

854
00:36:11,230 --> 00:36:12,950
What does that mean?

855
00:36:12,950 --> 00:36:16,350
That means there's nothing
like a smoking gun gene--

856
00:36:16,350 --> 00:36:18,980
10,000 to have enough statistics
to support a

857
00:36:18,980 --> 00:36:19,940
difference.

858
00:36:19,940 --> 00:36:24,860
That means many, many of the
10,000 don't have that gene

859
00:36:24,860 --> 00:36:26,520
who have schizophrenia.

860
00:36:26,520 --> 00:36:29,500
If it were one gene, one
disorder you don't need 10,000

861
00:36:29,500 --> 00:36:30,750
people to get a statistic.

862
00:36:30,750 --> 00:36:32,750
You need five people.

863
00:36:32,750 --> 00:36:38,440
So it's been a shock to people
that there's been so slow

864
00:36:38,440 --> 00:36:40,940
progress, given that all the
things they can decode the

865
00:36:40,940 --> 00:36:44,240
genome, to find the genes
that are at the heart of

866
00:36:44,240 --> 00:36:45,520
psychiatric diseases.

867
00:36:45,520 --> 00:36:49,120
And that's true for practically
all of them.

868
00:36:49,120 --> 00:36:51,920
So there's something complex
about genes and environment

869
00:36:51,920 --> 00:36:54,390
and people that far exceeds
their understanding at the

870
00:36:54,390 --> 00:36:57,260
moment at every level.

871
00:36:57,260 --> 00:36:59,060
And so people could be modelled
like this because it

872
00:36:59,060 --> 00:36:59,920
makes us feel better.

873
00:36:59,920 --> 00:37:02,260
And there's something probably
right about it.

874
00:37:02,260 --> 00:37:04,850
There's an amount of stress in
your life that can come up

875
00:37:04,850 --> 00:37:08,640
from socioeconomic risk,
health problems, family

876
00:37:08,640 --> 00:37:09,740
situations.

877
00:37:09,740 --> 00:37:12,500
There's a predisposition that's
genetically based.

878
00:37:12,500 --> 00:37:16,770
And some combination of them
determines whether you

879
00:37:16,770 --> 00:37:19,910
manifest the disorder
or don't.

880
00:37:19,910 --> 00:37:22,970
So we said there's no definitive
biological marker

881
00:37:22,970 --> 00:37:26,260
for schizophrenia, as there
isn't for every other

882
00:37:26,260 --> 00:37:27,160
psychiatric disease.

883
00:37:27,160 --> 00:37:29,990
There's no blood test, no brain
test, no nothing that

884
00:37:29,990 --> 00:37:32,720
definitively tells you if a
person has a diagnosis.

885
00:37:32,720 --> 00:37:35,590
But people have been studying
things that are, on average,

886
00:37:35,590 --> 00:37:36,540
different in brains.

887
00:37:36,540 --> 00:37:40,110
And I'll show you some of the
most consistent findings about

888
00:37:40,110 --> 00:37:43,190
ventricles, about hippocampal
involvement, PET scans.

889
00:37:43,190 --> 00:37:44,120
I'll show you this.

890
00:37:44,120 --> 00:37:47,030
And I'll show you a few examples
in schizophrenia.

891
00:37:47,030 --> 00:37:49,540
So one thing people have
noticed is that if they

892
00:37:49,540 --> 00:37:52,360
compare-- these are
identical twins.

893
00:37:52,360 --> 00:37:54,910
And you can see the ventricle,
the fluid filled space, is

894
00:37:54,910 --> 00:37:56,360
somewhat larger in
the twin with the

895
00:37:56,360 --> 00:37:58,900
diagnosis than without.

896
00:37:58,900 --> 00:38:00,920
That's about the least
specific brain marker

897
00:38:00,920 --> 00:38:01,710
we could ever have.

898
00:38:01,710 --> 00:38:03,490
The ventricle just means
that there's tissue

899
00:38:03,490 --> 00:38:04,740
missing around it.

900
00:38:04,740 --> 00:38:05,360
OK?

901
00:38:05,360 --> 00:38:06,890
It's just this fluid-filled
space.

902
00:38:06,890 --> 00:38:08,200
There should be a
bit more tissue.

903
00:38:08,200 --> 00:38:09,830
It's very far from any specific

904
00:38:09,830 --> 00:38:10,970
biology of the disorder.

905
00:38:10,970 --> 00:38:14,800
And here's the actual twins
with their actual MRIs.

906
00:38:14,800 --> 00:38:16,780
So we don't think it's the
size of the ventricle.

907
00:38:16,780 --> 00:38:17,760
That makes no sense.

908
00:38:17,760 --> 00:38:20,690
But that somehow roughly
correlated over the brain

909
00:38:20,690 --> 00:38:22,700
basis of the disorder is.

910
00:38:22,700 --> 00:38:24,530
And then people have shown--
and these are relatively

911
00:38:24,530 --> 00:38:26,790
extreme examples, post-mortem
samples.

912
00:38:26,790 --> 00:38:29,510
Here's the hippocampus in
healthy individuals.

913
00:38:29,510 --> 00:38:32,870
Here you can see a somewhat
shrunken in patients with a

914
00:38:32,870 --> 00:38:36,750
diagnosis of schizophrenia.

915
00:38:36,750 --> 00:38:38,470
And if you look at those
pictures that are kind of

916
00:38:38,470 --> 00:38:40,490
picked, you could say,
well that's easy.

917
00:38:40,490 --> 00:38:43,480
Give me the MRI and I'll
tell you who has it.

918
00:38:43,480 --> 00:38:45,410
But statistically it doesn't
work that way at all.

919
00:38:45,410 --> 00:38:48,380
There's tremendous overlap in
the size of the hippocampus

920
00:38:48,380 --> 00:38:51,070
between people without a
diagnosis and people with

921
00:38:51,070 --> 00:38:51,690
schizophrenia.

922
00:38:51,690 --> 00:38:54,310
So it's a statistical thing.

923
00:38:54,310 --> 00:38:56,160
People have also noticed the
cellular organization

924
00:38:56,160 --> 00:39:00,830
sometimes looks somehow better
in the typical people than

925
00:39:00,830 --> 00:39:01,690
people with schizophrenia.

926
00:39:01,690 --> 00:39:04,500
Again, a suggestion about
a developmental history

927
00:39:04,500 --> 00:39:06,700
underlying this for
the risk but

928
00:39:06,700 --> 00:39:09,250
without any kind of certainty.

929
00:39:09,250 --> 00:39:12,970
When they've done studies
looking at resting scanning

930
00:39:12,970 --> 00:39:13,830
metabolism--

931
00:39:13,830 --> 00:39:15,250
you just laying there.

932
00:39:15,250 --> 00:39:16,160
This is a PET scan.

933
00:39:16,160 --> 00:39:19,010
It's just where is the
blood flowing.

934
00:39:19,010 --> 00:39:20,920
You can see that this
is a healthy person.

935
00:39:20,920 --> 00:39:23,930
A lot of our blood flows
as we sit there

936
00:39:23,930 --> 00:39:25,560
to the frontal cortex.

937
00:39:25,560 --> 00:39:28,210
And you can see it's kind of
diminished in schizophrenia.

938
00:39:28,210 --> 00:39:31,100
But, again, you cannot put
a patient in and say this

939
00:39:31,100 --> 00:39:33,670
patient has schizophrenia
because many patients will

940
00:39:33,670 --> 00:39:36,690
look like many controls.

941
00:39:36,690 --> 00:39:38,850
But the average can
look like this.

942
00:39:38,850 --> 00:39:42,830
Here's a task now of a
working memory task.

943
00:39:42,830 --> 00:39:45,220
So people see in the
easy condition,

944
00:39:45,220 --> 00:39:46,560
letters are running along.

945
00:39:46,560 --> 00:39:48,410
And every time there's an
X, they push a button.

946
00:39:48,410 --> 00:39:49,980
That's the easy condition.

947
00:39:49,980 --> 00:39:51,640
Here, letters are presented
rapidly.

948
00:39:51,640 --> 00:39:53,750
And every time the current
letter is identical to the one

949
00:39:53,750 --> 00:39:55,850
you saw two letters ago,
you push a button.

950
00:39:55,850 --> 00:40:00,980
So this is harder mental work,
harder working memory demands.

951
00:40:00,980 --> 00:40:04,860
And then here's what you
see in one data set.

952
00:40:04,860 --> 00:40:08,960
So as they're doing this task,
they turn on a lot of frontal

953
00:40:08,960 --> 00:40:10,550
cortex, working memory,
thinking.

954
00:40:10,550 --> 00:40:11,730
You're used to that.

955
00:40:11,730 --> 00:40:13,150
Here's controls--

956
00:40:13,150 --> 00:40:16,290
how much they turn it on,
the front of the brain

957
00:40:16,290 --> 00:40:17,750
viewed from the top.

958
00:40:17,750 --> 00:40:21,150
Here's relatives who don't
have the diagnosis.

959
00:40:21,150 --> 00:40:23,320
And here's patients who
do have the diagnosis.

960
00:40:23,320 --> 00:40:25,650
These are relatives
of these patients.

961
00:40:25,650 --> 00:40:26,600
And take a look at it.

962
00:40:26,600 --> 00:40:27,990
You can see they're growing.

963
00:40:27,990 --> 00:40:29,370
So this is this issue
of is more

964
00:40:29,370 --> 00:40:30,670
activation better or worse?

965
00:40:30,670 --> 00:40:31,880
Well it all depends.

966
00:40:31,880 --> 00:40:35,370
The way we interpret this is for
a typical person, here's

967
00:40:35,370 --> 00:40:39,800
how much they have to push the
pedal to accomplish that

968
00:40:39,800 --> 00:40:41,390
working memory task.

969
00:40:41,390 --> 00:40:43,520
If you're a patient, you
have to push it a lot

970
00:40:43,520 --> 00:40:45,220
more to do the task.

971
00:40:45,220 --> 00:40:48,190
And you still make
more mistakes.

972
00:40:48,190 --> 00:40:51,830
If you are a relative without a
diagnosis of schizophrenia,

973
00:40:51,830 --> 00:40:53,900
you're somewhere in between.

974
00:40:53,900 --> 00:40:57,040
And those relatives are
accurate as controls.

975
00:40:57,040 --> 00:40:59,400
But they perform somewhat
more slowly.

976
00:40:59,400 --> 00:41:00,920
This is a kind of interesting
thing.

977
00:41:00,920 --> 00:41:04,680
And practically every disorder,
if you take the

978
00:41:04,680 --> 00:41:08,160
relatives of people with the
diagnosis, they often look

979
00:41:08,160 --> 00:41:12,100
like they have a kind of a
milder version of that.

980
00:41:12,100 --> 00:41:14,210
But they may have no problems
in their lives.

981
00:41:14,210 --> 00:41:16,490
They may be doing flourishingly
well in every

982
00:41:16,490 --> 00:41:18,240
regard that you could
think of.

983
00:41:18,240 --> 00:41:19,970
But they harbor some
of the same genes.

984
00:41:19,970 --> 00:41:22,190
To be a relative means
to share genes.

985
00:41:22,190 --> 00:41:23,620
And so that can make--

986
00:41:23,620 --> 00:41:25,610
there's something about that
happening here or in some

987
00:41:25,610 --> 00:41:27,070
subset of those individuals.

988
00:41:27,070 --> 00:41:29,170
Practically every study that's
done, if you take the

989
00:41:29,170 --> 00:41:32,250
relatives of people with a
diagnosis, there's some

990
00:41:32,250 --> 00:41:36,380
in-betweenness compared to
people picked in families

991
00:41:36,380 --> 00:41:37,630
without any history
of that disorder.

992
00:41:40,160 --> 00:41:41,400
But what matters is
the boundary.

993
00:41:41,400 --> 00:41:41,700
Right?

994
00:41:41,700 --> 00:41:44,040
I mean, this difference doesn't
matter if this person

995
00:41:44,040 --> 00:41:45,740
is doing well.

996
00:41:45,740 --> 00:41:47,840
This difference is associated
with something that really

997
00:41:47,840 --> 00:41:51,820
makes a big difference
in the person's life.

998
00:41:51,820 --> 00:41:54,710
The question about auditory
hallucinations and the deaf--

999
00:41:54,710 --> 00:41:55,530
this is kind of like that.

1000
00:41:55,530 --> 00:41:56,810
But this is people
hearing people.

1001
00:41:56,810 --> 00:41:59,500
But one of things you can
do with imaging is ask.

1002
00:41:59,500 --> 00:42:02,130
Some patients with schizophrenia
have rapidly

1003
00:42:02,130 --> 00:42:03,680
psyching auditory
hallucinations.

1004
00:42:03,680 --> 00:42:03,980
Most don't.

1005
00:42:03,980 --> 00:42:05,590
Most is every here and there.

1006
00:42:05,590 --> 00:42:06,770
But some have it pretty often.

1007
00:42:06,770 --> 00:42:09,720
So you can put them in a scanner
and when they hear a

1008
00:42:09,720 --> 00:42:11,850
voice, they push a button.

1009
00:42:11,850 --> 00:42:14,910
And you can ask, when they hear
a voice is their auditory

1010
00:42:14,910 --> 00:42:17,520
cortex active?

1011
00:42:17,520 --> 00:42:20,240
At the level of the brain is
it as if they were really

1012
00:42:20,240 --> 00:42:21,350
hearing a voice?

1013
00:42:21,350 --> 00:42:26,010
And here's the auditory cortex
active in the individuals at

1014
00:42:26,010 --> 00:42:27,560
the moment they're
experiencing the

1015
00:42:27,560 --> 00:42:28,990
hallucination.

1016
00:42:28,990 --> 00:42:32,600
It's real to them because
somehow it's engaging the

1017
00:42:32,600 --> 00:42:35,400
auditory cortex that really
hears the world.

1018
00:42:35,400 --> 00:42:37,830
That's why it's so powerful.

1019
00:42:37,830 --> 00:42:41,860
And it's somehow engaging the
very same tissue by which you

1020
00:42:41,860 --> 00:42:45,300
really hear the world.

1021
00:42:45,300 --> 00:42:46,150
How about treatment?

1022
00:42:46,150 --> 00:42:49,810
So next session we'll
talk a lot about

1023
00:42:49,810 --> 00:42:52,750
different kinds of treatment.

1024
00:42:52,750 --> 00:42:54,820
Neuroleptics are the most
common treatment for

1025
00:42:54,820 --> 00:42:55,440
schizophrenia.

1026
00:42:55,440 --> 00:42:55,990
They block--

1027
00:42:55,990 --> 00:42:56,900
I'll talk a bit about this--

1028
00:42:56,900 --> 00:42:59,890
post-synaptic dopamine receptors.

1029
00:42:59,890 --> 00:43:02,370
The drug is fully effective
within hours.

1030
00:43:02,370 --> 00:43:06,220
The maximum clinical effect
takes weeks and then the

1031
00:43:06,220 --> 00:43:08,670
effect remains after
treatment stops.

1032
00:43:08,670 --> 00:43:11,510
A huge problem in schizophrenia
are side effects

1033
00:43:11,510 --> 00:43:13,030
of these kinds of drugs.

1034
00:43:13,030 --> 00:43:18,350
So early on, you induce a bit
of Parkinson's disease in

1035
00:43:18,350 --> 00:43:20,570
patients who never had
Parkinson's disease with these

1036
00:43:20,570 --> 00:43:21,350
typical drugs.

1037
00:43:21,350 --> 00:43:23,160
Because atypical drugs, they
have their problems.

1038
00:43:23,160 --> 00:43:24,450
I'll just focus on the
typical drugs.

1039
00:43:24,450 --> 00:43:25,860
I'll tell you why in a minute.

1040
00:43:25,860 --> 00:43:27,725
And then later on, this becomes
known as tardive

1041
00:43:27,725 --> 00:43:30,160
dyskinesia in about
20% of patients.

1042
00:43:30,160 --> 00:43:32,750
That's a lot of patients.

1043
00:43:32,750 --> 00:43:35,140
You're producing, by the drug,
abnormal and involuntary

1044
00:43:35,140 --> 00:43:37,360
movements-- smacking of lips,
chewing, and tongue

1045
00:43:37,360 --> 00:43:38,835
protrusion.

1046
00:43:38,835 --> 00:43:40,350
And there's some drugs
that don't do it.

1047
00:43:40,350 --> 00:43:42,440
But they have other problems.

1048
00:43:42,440 --> 00:43:45,890
And there is evidence that
behavioral therapy can be

1049
00:43:45,890 --> 00:43:48,800
surprisingly useful
in schizophrenia.

1050
00:43:48,800 --> 00:43:51,410
Most of us hardcore biologists
we thing that drugs

1051
00:43:51,410 --> 00:43:52,070
got to be the deal.

1052
00:43:52,070 --> 00:43:53,650
I think there's more evidence
than you would imagine that

1053
00:43:53,650 --> 00:43:56,180
behavioral therapy or the
combination of the two can be

1054
00:43:56,180 --> 00:43:57,990
very helpful for people.

1055
00:43:57,990 --> 00:44:01,030
So you may know now--

1056
00:44:01,030 --> 00:44:03,960
you wouldn't know this, I know
this because I am constantly

1057
00:44:03,960 --> 00:44:05,980
in the fund raising business
as a researcher--

1058
00:44:05,980 --> 00:44:09,720
drug companies have almost
stopped working on developing

1059
00:44:09,720 --> 00:44:11,760
treatments for psychiatric
diseases.

1060
00:44:11,760 --> 00:44:14,540
And they've almost stopped
because it's been so

1061
00:44:14,540 --> 00:44:16,060
unsuccessful.

1062
00:44:16,060 --> 00:44:18,530
The drugs that were found
were almost always by

1063
00:44:18,530 --> 00:44:19,770
happenstance--

1064
00:44:19,770 --> 00:44:22,260
drugs that were almost randomly
tried for various

1065
00:44:22,260 --> 00:44:24,770
disorders or various
groups and worked.

1066
00:44:24,770 --> 00:44:27,460
None of them are rationally
done in any biotechnology

1067
00:44:27,460 --> 00:44:31,770
sense or molecular chemistry
design sense.

1068
00:44:31,770 --> 00:44:34,820
Practically all of them are
happenstance applications of

1069
00:44:34,820 --> 00:44:36,400
quasi-random drugs.

1070
00:44:36,400 --> 00:44:39,460
And then people noticed
it helped individuals.

1071
00:44:39,460 --> 00:44:41,850
And so in the last 28 years,
where there was much more

1072
00:44:41,850 --> 00:44:46,250
rational development of drugs,
it's been spectacularly hard

1073
00:44:46,250 --> 00:44:48,940
to develop new drugs for
psychiatric disorders.

1074
00:44:48,940 --> 00:44:50,840
And so most pharmaceutical
companies have basically

1075
00:44:50,840 --> 00:44:52,120
stopped in the last
couple years.

1076
00:44:52,120 --> 00:44:54,220
They've just given up.

1077
00:44:54,220 --> 00:44:57,380
We remain optimistic that
everybody thinks they'll come

1078
00:44:57,380 --> 00:45:00,085
back into the picture when some
academics produce some

1079
00:45:00,085 --> 00:45:01,490
things that look good.

1080
00:45:01,490 --> 00:45:03,350
But it's turned out
to be really hard.

1081
00:45:03,350 --> 00:45:05,800
And, furthermore, many of the
medications that are effective

1082
00:45:05,800 --> 00:45:08,170
have all these side effects,
very undesirable

1083
00:45:08,170 --> 00:45:09,920
side effects sometimes.

1084
00:45:09,920 --> 00:45:12,840
At the same time, the fact that
these drugs affect the

1085
00:45:12,840 --> 00:45:15,630
disorder sort of promoted
various theories.

1086
00:45:15,630 --> 00:45:17,850
So once people noticed that
the anti-psychotic

1087
00:45:17,850 --> 00:45:20,130
medications, medications that
diminish the psychosis of

1088
00:45:20,130 --> 00:45:23,450
schizophrenia, act on the
dopamine system, that led to

1089
00:45:23,450 --> 00:45:25,640
the dopamine theory
of schizophrenia.

1090
00:45:25,640 --> 00:45:29,830
So you say, well if the drug is
pushing down dopamine and

1091
00:45:29,830 --> 00:45:32,450
that's helping people be less
psychotic, then maybe what

1092
00:45:32,450 --> 00:45:35,350
that real problem is that
there's too much dopamine

1093
00:45:35,350 --> 00:45:36,820
flowing in the brain
of individuals with

1094
00:45:36,820 --> 00:45:38,030
schizophrenia.

1095
00:45:38,030 --> 00:45:40,010
And that got supported by
studies that if you give

1096
00:45:40,010 --> 00:45:43,170
typical people overdoses of
amphetamine, you induce

1097
00:45:43,170 --> 00:45:45,730
something that looks a bit, in
a typical person, like the

1098
00:45:45,730 --> 00:45:48,490
paranoia of schizophrenia.

1099
00:45:48,490 --> 00:45:50,720
And so let's talk about
this idea of drug

1100
00:45:50,720 --> 00:45:52,410
action versus disease.

1101
00:45:52,410 --> 00:45:55,400
So if you have a headache,
what do you take to help

1102
00:45:55,400 --> 00:45:57,630
yourself with the headache?

1103
00:45:57,630 --> 00:45:59,830
Ibuprofen or aspirin or
something like that?

1104
00:45:59,830 --> 00:46:02,720
Does that mean the medical
problem was you didn't have

1105
00:46:02,720 --> 00:46:05,210
enough aspirin in your blood?

1106
00:46:05,210 --> 00:46:08,060
Were you "hypoasperinemia?"
No, right?

1107
00:46:08,060 --> 00:46:10,840
The aspirin is doing something
else to counteract the

1108
00:46:10,840 --> 00:46:12,160
headache, or the ibuprofen.

1109
00:46:12,160 --> 00:46:15,800
It's not that you were
short on Tylenol.

1110
00:46:15,800 --> 00:46:16,530
OK?

1111
00:46:16,530 --> 00:46:18,570
But it treats the problem.

1112
00:46:18,570 --> 00:46:22,040
So if a drug treats
schizophrenia by acting on the

1113
00:46:22,040 --> 00:46:26,030
dopamine system, does that mean
dopamine was the culprit?

1114
00:46:26,030 --> 00:46:29,670
And the answer is probably not
or it's hard to figure out.

1115
00:46:29,670 --> 00:46:31,920
But the original assumption that
the way the drug works

1116
00:46:31,920 --> 00:46:34,150
gives you a direct insight into
what the cause of the

1117
00:46:34,150 --> 00:46:38,200
disease is, people have
pretty much dismissed.

1118
00:46:38,200 --> 00:46:40,140
But what drew them to it, of
course, is still these

1119
00:46:40,140 --> 00:46:40,880
anti-psychotics.

1120
00:46:40,880 --> 00:46:43,460
The way they work is
they block the

1121
00:46:43,460 --> 00:46:45,400
receptors that take dopamine.

1122
00:46:45,400 --> 00:46:49,660
And, therefore, dopamine gets
catabolized here and is not

1123
00:46:49,660 --> 00:46:51,190
used in neurotransmission.

1124
00:46:51,190 --> 00:46:55,900
And, furthermore, amphetamine,
which produces a somewhat

1125
00:46:55,900 --> 00:46:59,220
schizophrenia-like syndrome in
some healthy individuals, that

1126
00:46:59,220 --> 00:47:00,880
accelerates the production
of dopamine.

1127
00:47:00,880 --> 00:47:02,820
So that seemed to
favor the story.

1128
00:47:02,820 --> 00:47:06,720
But, again, that's sort of not
taken very broadly now.

1129
00:47:06,720 --> 00:47:09,990
Again, what favored the story
was the more powerfully a drug

1130
00:47:09,990 --> 00:47:13,230
bound to dopamine receptors,
the less drug

1131
00:47:13,230 --> 00:47:14,320
you had to give patients.

1132
00:47:14,320 --> 00:47:15,590
All of that, you could
see, made people

1133
00:47:15,590 --> 00:47:17,670
think, this is the story.

1134
00:47:17,670 --> 00:47:20,160
And it may be that dopamine
is a part of the story.

1135
00:47:20,160 --> 00:47:23,240
But everybody understands now
that just because a drug acts

1136
00:47:23,240 --> 00:47:25,450
on a disease, does not mean it's
treating the disease in

1137
00:47:25,450 --> 00:47:28,330
the most direct way.

1138
00:47:28,330 --> 00:47:31,100
And now why do patients get
tardive dyskinesia?

1139
00:47:31,100 --> 00:47:36,690
Why is it an inadvertent
consequence of treating

1140
00:47:36,690 --> 00:47:38,880
schizophrenia, producing
a version

1141
00:47:38,880 --> 00:47:40,410
of Parkinson's disease?

1142
00:47:40,410 --> 00:47:42,920
It's because the drugs
are too nonspecific.

1143
00:47:42,920 --> 00:47:45,590
So we know the ventral tegmental
area in the brain

1144
00:47:45,590 --> 00:47:50,230
stem sends dopamine into the
basal ganglia and into the

1145
00:47:50,230 --> 00:47:52,300
prefrontal cortex.

1146
00:47:52,300 --> 00:47:54,680
Conceptually, what we understand
we're trying to

1147
00:47:54,680 --> 00:47:58,430
achieve with schizophrenia is
something like diminishing

1148
00:47:58,430 --> 00:48:00,690
something about this pathway.

1149
00:48:00,690 --> 00:48:03,560
But the drug can't
just block this.

1150
00:48:03,560 --> 00:48:06,340
It also affects the
basal ganglia.

1151
00:48:06,340 --> 00:48:09,710
And what Parkinson's diseases
is is a shortage of dopamine

1152
00:48:09,710 --> 00:48:10,500
in the basal ganglia.

1153
00:48:10,500 --> 00:48:12,710
In the case of Parkinson's
disease, it's because of death

1154
00:48:12,710 --> 00:48:14,460
of substantial nigral cells.

1155
00:48:14,460 --> 00:48:17,580
But you're producing a
pharmacological version of

1156
00:48:17,580 --> 00:48:22,430
Parkinson's disease in the
effort to treat schizophrenia.

1157
00:48:22,430 --> 00:48:25,180
Not in all patients, not as
severe as Parkinson's disease,

1158
00:48:25,180 --> 00:48:26,900
but a big side effect
in many patients.

1159
00:48:26,900 --> 00:48:27,740
And there's other drugs.

1160
00:48:27,740 --> 00:48:28,790
They have their problems.

1161
00:48:28,790 --> 00:48:34,760
There's almost no drug that's
completely successful and pure

1162
00:48:34,760 --> 00:48:39,400
in any treatment sense
for the patient.

1163
00:48:39,400 --> 00:48:41,390
Despite that, there's been
a fantastic effect.

1164
00:48:41,390 --> 00:48:43,790
We talked about that
when people were

1165
00:48:43,790 --> 00:48:45,730
behaving very oddly--

1166
00:48:45,730 --> 00:48:48,810
and certainly schizophrenia is
perhaps the scariest set of

1167
00:48:48,810 --> 00:48:52,200
behaviors, if you have to pick
one disorder in that way--

1168
00:48:52,200 --> 00:48:56,560
then once they began to have
drugs that diminished the

1169
00:48:56,560 --> 00:49:00,910
unusual behavior, people were
let out of state and

1170
00:49:00,910 --> 00:49:03,230
government hospitals where they
had been sort of secluded

1171
00:49:03,230 --> 00:49:05,250
in many ways and not helped
in many ways.

1172
00:49:05,250 --> 00:49:08,250
And people viewed this as
a tremendous success.

1173
00:49:08,250 --> 00:49:10,450
And I think it is to let
people back into the

1174
00:49:10,450 --> 00:49:13,510
community, interacting in a sort
of more typical way, as

1175
00:49:13,510 --> 00:49:15,650
opposed to being segregated
in areas that were

1176
00:49:15,650 --> 00:49:17,520
often not the best.

1177
00:49:17,520 --> 00:49:19,650
But there was a fantastic
consequence, which is now

1178
00:49:19,650 --> 00:49:21,970
these people, as you may know,
have no safety net.

1179
00:49:21,970 --> 00:49:23,320
They're back in the community.

1180
00:49:23,320 --> 00:49:25,440
And if they don't have people
who care for them or follow

1181
00:49:25,440 --> 00:49:28,040
them, there are risks
for themselves.

1182
00:49:28,040 --> 00:49:30,400
So it's great to give
a medication to

1183
00:49:30,400 --> 00:49:31,100
let somebody out.

1184
00:49:31,100 --> 00:49:32,470
Everybody agrees on that.

1185
00:49:32,470 --> 00:49:34,920
But then if you don't have
a kind of a safety net of

1186
00:49:34,920 --> 00:49:37,790
physicians and family and so
on, a person's out on their

1187
00:49:37,790 --> 00:49:40,710
own, they stop taking their
medication, who's

1188
00:49:40,710 --> 00:49:42,450
there to help them?

1189
00:49:42,450 --> 00:49:45,010
So it's a societal challenge
on top of that.

1190
00:49:45,010 --> 00:49:48,210
So next time I'm going to talk
about treatments for

1191
00:49:48,210 --> 00:49:49,200
neuropsychiatric disorders.

1192
00:49:49,200 --> 00:49:50,870
But for just one minute I'll
ask you, do you have any

1193
00:49:50,870 --> 00:49:54,310
questions or thoughts about
this whole topic?

1194
00:49:54,310 --> 00:49:55,708
Yeah?

1195
00:49:55,708 --> 00:49:56,958
AUDIENCE: [INAUDIBLE]

1196
00:50:03,612 --> 00:50:07,564
I read somewhere that 90% of
schizophrenics [INAUDIBLE]

1197
00:50:11,022 --> 00:50:12,680
PROFESSOR: There's
a fantastic--

1198
00:50:12,680 --> 00:50:15,790
the question was, why is there
such a fantastically high rate

1199
00:50:15,790 --> 00:50:18,020
of smoking-- which there is-- in
patients with schizophrenia

1200
00:50:18,020 --> 00:50:19,530
and bipolar?

1201
00:50:19,530 --> 00:50:21,630
So people will use phrases like
they're self-medicating

1202
00:50:21,630 --> 00:50:23,300
in some way.

1203
00:50:23,300 --> 00:50:24,560
But I don't think there's--

1204
00:50:24,560 --> 00:50:25,980
you could make up a little
bit of a story,

1205
00:50:25,980 --> 00:50:28,330
but it is very striking.

1206
00:50:28,330 --> 00:50:30,230
I don't know a deeper
story than that.

1207
00:50:30,230 --> 00:50:31,080
There might be.

1208
00:50:31,080 --> 00:50:32,025
But it's very striking.

1209
00:50:32,025 --> 00:50:33,768
AUDIENCE: [INAUDIBLE]

1210
00:50:33,768 --> 00:50:37,736
One girl said she had a
schizophrenic episode and

1211
00:50:37,736 --> 00:50:40,712
started smoking afterwards
[INAUDIBLE]

1212
00:50:40,712 --> 00:50:42,710
it made the voices go away.

1213
00:50:42,710 --> 00:50:44,395
PROFESSOR: It made the
voices go away?

1214
00:50:44,395 --> 00:50:45,645
Yeah.

1215
00:50:47,330 --> 00:50:47,990
I don't know.

1216
00:50:47,990 --> 00:50:48,860
I mean there's--

1217
00:50:48,860 --> 00:50:50,140
But it's very--

1218
00:50:50,140 --> 00:50:52,130
there's a phenomenal high
rate of smoking among

1219
00:50:52,130 --> 00:50:54,090
patients like that.

1220
00:50:54,090 --> 00:50:56,010
OK, thanks very much.