Mental Disorders as Brain Disorders: Thomas Insel at TEDxCaltech


Translator: Reiko Bovee
Reviewer: ANTONIO RODRÍGUEZ DE LA TORRE This is the first time I’ve ever
followed Pinky the Mouse. (Laughter) If nothing else should tell you
that science can be fun, science can be counter-intuitive,
science can blow your mind, and what I’m going to do
in the next few minutes is to tell you
that science can also save lives. So let’s start with some good news. And the good news has to do with
what we know based on biomedical research that actually has changed the outcomes
for many very serious diseases. Start with Leukemia,
acute lymphoblastic leukemia, ALL, the most common cancer of children. When I was a student,
the mortality rate was about 95%. Today, some 25, 30 years later,
we are talking about a mortality rate is reduced by 85%. Six thousand children each year who would have previously
died of this disease are cured. If you want the really big numbers, look at the numbers for heart disease. Heart disease used to be
the biggest killer particularly men in their 40s. Today we’ve seen a 63% reduction
in mortality from heart disease. Remarkably 1.1 million deaths
averted every year. AIDS, incredibly
has just been named in the past month a chronic disease, meaning that a 20 years old
who becomes infected with HIV is expected not to live weeks,
months or a couple of years, as we said only a decade ago, but is thought to live for decades, probably to die in his 60s or 70s
from other causes altogether. These are just remarkable,
remarkable changes, in the outlook of some
of the biggest killers. One in particular that
you probably wouldn’t know about, stroke, which has been,
along with heart disease, one of the biggest killers in the country
along with cancer, is a disease we know now
if you can get people into the hospital, into the emergency room
within three hours of the onset, some 30% of them will leave the hospital
without any disabilities whatsoever. Remarkable stories, good news stories,
all of which boil down to understanding something about the diseases
that has allowed us to detect early and intervene early. Early detection and early intervention. That’s the story for these successes
across the board. And it tells you how biomedical research can really change the picture
for millions and millions of people. Unfortunately the news is not all good. Let’s talk about one other story
which has to do with suicide. Now this is of course
not a disease per se. It’s a condition or a situation
that leads to mortality. Which you may not realize
is how prevalent it is today. There are 38,000 suicides each year
in the United States. That means one in about 15 minutes. The third most common cause of death
among people between ages of 15 and 25. It’s kind of an extraordinary story
when you realize that this is twice as common as homicide, and actually more common
as a source of death than traffic fatalities in this country. Now when we talk about suicide,
there is also a medical contribution here. Because 90% of suicides
are related to a mental illness, depression, bipolar disorder,
schizophrenia, anorexia, borderline personality, there’s a long list of disorders
that contribute, and as I mentioned before,
often early in life. And it’s not just the mortality
from these disorders. It’s also morbidity.
If you look at disability, here as measured
by the World Health Organization, something they called
“Disability Adjusted Life Years.” It’s kind of a metric
that nobody would think of except an economist. Except it’s one way
of trying to capture what is lost in terms of disability
from medical causes. And as you can see virtually 30%
of all disabilities from all medical causes can be attributed to mental disorders
or neuro psychiatric syndromes. You’re probably thinking
that doesn’t make any sense. I mean cancer seems far more serious. Heart disease seems far more serious. But you can see actually they’re
further down this list. That is because
we are talking about disability. What drives disability
for these disorders like schizophrenia and
bipolar disorder and depression? Why are they number one here? Probably there are three reasons. One is that they’re highly prevalent. About one in five people will suffer from one of these disorders
in the course of their life time. The second of course is that
for some people these become truly disabling. It’s about 4 to 5%, that’s one in 20, are truly disabled
by one of these illnesses. But what really drives these numbers, this high morbidity and
to some extent the high mortality, is the fact that
these start very early in life. Fifty percent will have onset
by age 14, 75% by age 24. A picture that is very different
from that what one would see if we are talking about cancer
or heart disease, diabetes, hypertension, most of the major illnesses
that we think about, as being sources
of mobility and mortality. These are indeed the chronic disorders
of young people. Now I started by telling you
that there are some good news stories. This is obviously not one of them. This is the part of what is, perhaps the most difficult since this is kind of confession for me. My job is to actually make sure that we make progress
on all of these disorders, because I work for the Federal Government. I actually work for you.
You pay my salary. Maybe at this point,
when you know what I do or maybe what I’ve failed to do,
you’ll think I probably ought to be fired. I could certainly understand that. But what I want to suggest, and the reason I am here is to tell you that I think we are about to be
in a very different world as we think about these illnesses. And that is, to some extent,
going to be dependent on the work you’ll hear about today. That’s going to be really exciting, technically truly transformative. But the point I want to make is that the most important transformation here
is a conceptual one. What I’ve been
talking to you about so far is mental disorders, diseases of the mind. That’s actually becoming a rather
unpopular term these days. And people feel that,
for whatever the reason, it’s politically better to use the term
“behavioral disorders”, and to talk about these
as disorders of behavior. Fair enough,
they are disorders of behavior and they are disorders of the mind. But what I want to suggest to you
is that both of those terms which have been in play
for a century or more, are actually now
impediments to progress. That what we need conceptually
to make a progress here is to rethink these disorders
as brain disorders. Now some of you are going to say, “Oh my goodness. Here we go again, We are going to hear about
biochemical imbalance. We are going to hear about drugs. We are going to hear about
some very simplistic notion, that will take our subjective experience
and turn it into molecules, or maybe into some sort of very flat
uni-dimensional understanding of what it is to have
depression or schizophrenia.” Over the course of the day you are going to hear
that when we talk about the brain it is anything but uni-dimensional,
or simplistic or reductionistic. It depends, of course, on what scale or what scope you think about. But this is an organ
of surreal complexity. And we are just beginning to understand, how to even study it, whether you are thinking about
a hundred billion neurons in the cortex or a hundred trillion synapses that make up all the connections. We have just begun to try to figure out how we take this very complex machine that does extraordinary kinds
of information processing and use our own minds
to understand the very complex brain that supports it,
that supports our own mind. It’s actually kind of cruel
trick of evolution that we simply don’t have a brain that seems to be wired well enough
to understand itself. But we are making progress,
and because of some of the technologies you hear about today, we are actually able to begin
to string this together. In a sense it actually makes you feel that when you are in a safe zone studying
behavior and cognition, something you can observe, that in a way feels
more simplistic and reductionistic than trying to engage this very complex
and mysterious organ that we are beginning
to try to understand. Now already in a case
of the brain disorders that I’ve been talking to you about, depression, obsessive compulsive disorder,
post traumatic stress disorder, we don’t have an in-depth understanding of how they are abnormally processed or what the brain is doing
in those illnesses. We’ve been able to already identify
some of the connectional differences. Some of the ways of which
the circuitry is different for people who have these disorders. We call this the “Human Connectome.” You can think about Connectome,
as the wiring diagram of the brain. You’ll hear more about it
in a few minutes. The important piece here is
that as you begin to look at people who have these disorders, the one in five of us
who struggle in some way, you’ll find that there’s
a lot of variation in the way the brain is wired
but there are some predictable patterns. Those patterns are risk factors for developing one of these disorders. It’s a little different than
the way we think about brain disorders like Huntington’s, Parkinson’s
or Alzheimer’s disease where you have a bombed out
part of your cortex. Here we are talking about traffic jams
or sometimes detours or sometimes problems with
just the way things are connected and the way the brain functions, you could if you want
compare this to, on the one hand,
a myocardial infarction – a heart attack where you have dead tissue in the heart versus arrhythmia where
the organ simply isn’t functioning because of the communication problems
within it. Either one would kill you, and in only one of them
will you find a major lesion. As we think about this, maybe it’s better to actually go a little deeper
into one particular disorder. That would be schizophrenia. I think that’s a good case
for helping to understand why thinking of this
as a brain disorder matters. Schizophrenia is a disorder
that generally comes on by in terms of the psychotic symptoms, which is the way we diagnose it, delusions, hallucination,
problems with thinking problems with attention, generally around age of 18 to 22, 23, 24. These are scans from Judie Rapoport
and her colleagues at the National Institute
of Mental Health, in which they studied children
with very early onset schizophrenia. And you can see already
in the top there are areas that are red, orange and yellow, there’s places with less gray matter. And as they follow them over 5 years comparing them
to age-match controls, you can see that, particularly in areas like the dorsal lateral prefrontal cortex or the superior temporal gyrus, there is a profound loss of gray matter. This is important. It’s important if you try to model this. You can think about normal development
as a loss of cortical mass, loss of cortical gray matter. What’s happening in schizophrenia is that you overshoot that mark and at some point
when you overshoot you cross a threshold,
and it’s that threshold where we say
this is a person who has this disease because they have the behavioral symptoms, of hallucinations and delusions. That’s something we can observe. But look at this closely. You can see that actually
they’ve crossed a different threshold. They crossed a brain threshold
much earlier. That perhaps not at the age 22 or 20 but even by age 15 or 16, you can begin to see that the trajectory
for development is quite different at the level of the brain
not at the level of behavior. Why does this matter? Well first because for brain disorders,
behavior is the last thing to change. We know that for Alzheimer’s,
Parkinson’s, for Huntington’s. There are changes in the brain
a decade or more before you see the first signs
of a behavioral change. The tools we have, and you’ll hear
much more about this in the course of the day, they are getting better every year, now allow us to detect
these brain changes much earlier, long before the symptoms emerge. But most importantly,
go back to where we started. The good news stories in medicine are early detection, early intervention. If we waited until the heart attack we would be sacrificing 1.1 million lives every year in this country
to heart disease. That is precisely what we do today. When we decide that everybody
with one of these brain disorders, brain circuit disorders,
has a behavioral disorder we wait until the behavior
becomes manifest. That’s not early detection.
That’s not early intervention. Now to be clear,
we are not quite ready to do this. We don’t have all the facts. We don’t actually even know
what the tools would be nor what to precisely look for
in every case. to be able to get there
before the behavior emerges as different. But this tells us how we need
to think about it and where we need to go. Are we going to be there soon? I think that this is something
that will happen over the course of the next few years but I’d like to finish with the quote about trying to predict
how this will happen, by somebody who’s thought a lot
about changes in concepts
and changes in technology. “We always overestimate the change
that will occur in the next two years and underestimate the change that will occur in the next ten.” Bill Gates. Thanks very much. (Applause)

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