THURSDAY, MARCH 6, 2003
Session 1: Pediatric Psychopharmacology
DR. HYMAN: Thank you very much for inviting
me. As you and I discussed, we want to have an overview of
some very difficult issues, such as how we set diagnostic boundaries
in psychiatry in general. There are even more difficulties,
as you know, in children where the science is less advanced.
Steven E. Hyman, MD, Provost of Harvard University;
Professor of Neurobiology, Harvard Medical School;
and former Director, US National Institutes of Mental Health
I prepared a Power Point presentation. This has become
a necessary crutch for all of us for about 30 or 35 minutes.
I can't possibly address all of the wide-ranging issues
that we need to think about in order to grapple with these
topics, but would be happy afterwards as we engage in discussion
to go very, very far from what's in the Power Point.
Also, I think to be maximally useful, I'm happy to be
interrupted during this Power Point discussion if something
is opaque, or alternatively if you already have thought about
an issue, and feel that time would be better spent elsewhere.
I note that I wear my intellectual biases on my sleeve.
If you can even judge by the back drop of my title slide,
you can see that there's a brain there, so we have a number
of different questions when it comes to the use of psychotropic
drugs in children. As the absolute medical groundwork, we
have to ask whether particular drugs, Methylphenidate, Prozac-like
drugs, anti-psychotic drugs are safe and effective. And we
have to ask it for different age groups, because brain development
means a fortiori that children are not simply small adults.
Secondly, we have to worry, effective for what? When we're
testing the utility of a drug, are we looking, as we most
often do, for diagnosable disorders, or are we thinking as
we do increasingly in general medicine about early intervention
or even prevention? We have to ask whether we treat risk
states for psychiatric disorders in the same way as we do
for heart disease. So, for example, I wonder if you had planned
to have an ethical panel on the early and widespread use of
the statin drugs to lower cholesterol. And if not, I think
it's not a question beneath contempt, why we consider
drugs to treat the diseases of the mind differently than we
treat drugs to prevent general medical disorders.
We have to think about unknown, of course it's a great
conundrum on how we would learn about long term unwanted drug
effects. We'll come back to this. And then we also have
to ask a question that is so often forgotten, which is how
does an untreated mental disorder, or even - and here I think
we get to some of the issues you're grappling with - milder
impairment affect the developing brain, and how does it affect
Unfortunately, we do not have adequate empirical data on
almost any of these outstanding questions. There's some
things we -- I just would like to assert. I have a few picture
slides afterwards, and I don't want to get into scientific
detail, but I think it's very important that we not fall
into the ordinary trap of thinking that drugs are about the
brain, and lived experience is about the mind, and they do
not mechanistically interact.
In fact, both psychotropic drugs and lived experience affect
behavior, both brain, physical substrate and behavior, both
short-term and long-term. And both psychotropic drugs and
lived experience alter the brain probably by remodeling of
synapses, which is something that I know that those of you
who are not scientists don't think about every day. This
is really just a picture to help me make a few points. This
is a picture. It's a drug experiment. It's from
Terry Robinson at the University of Michigan, and I just thought
it would be worth your seeing physically what I mean by this.
On the screen in front of you are two dendrites, the receptive
processes of nerve cells, and these are a kind of neuron aptly
named medium spiny neurons because they have dendritic spines.
And we think that the communicative connections of different
neurons make these connections or synapses on these spines.
And what you can see is after a certain drug treatment, just
comparing the left and the right, that the architecture of
these spines is different.
Now there's a lot we don't know. Are synaptic connections
really made? Is information processing really changed? Is
this rat thinking and behaving differently in a way that correlates
with these synaptic changes. But I think what's really
important to recognize, again just to grapple with this mind/body
distinction, is that even beginning 20 years ago, Bill Greenough,
a psychologist at the University of Illinois, began comparing
rats raised in the normal laboratory shoebox cage with rats
raised in what might be called a rat park, you know, with
interesting toys and interesting food, not just Purina Rat
Chow, but also chocolate chips and so forth. And when he
looked at dendritic complexity and cortical thickness, they
were really quite different in the rats raised in this enriched
versus the shoebox cage environment.
The point is that there is no fundamental mechanistic physical
difference using drugs to affect the brain and lived experience.
In fact, drugs act on mechanisms that are present for normal
lived experience in the brain. Now, of course, the potency
of the effects and precise effects will vary enormously, but
there is no categorical difference. I think that's really
quite important to recognize.
Now one of the things I understand you're grappling
with are the boundaries of psychiatric disorders, so if I
can switch from that assertion to the issue of psychiatric
diagnosis. This will be fast. I misspelled the title a bit,
but -- and we can come back to this. Psychiatric diagnosis
today, whether it's for ADHD or depression or anything,
is made based on operationalized criteria derived from symptoms
and signs. There are no objective laboratory tests for any
mental disorders that we normally think about them. There
are some appearing, so narcolepsy, which could be considered
a mental disorder, has been discovered to be related to defective
expression of a particular gene, the orexin gene or its receptor,
and there will be tests for this. But in general, we are
talking about the scoring of symptoms and signs by human observers.
In the DSM-IV, the current American Diagnostic Manual, reliability
is king, not validity. Now let me tell you what this is.
Reliability is the notion that two independent observers will
arrive at the same diagnosis. This is not a trivial feat.
Prior to the DSM-III, published in 1978, psychiatry had the
Tower of Babel problem-- different people could not understand
each other. People had idiosyncratic diagnostic criteria.
The putative prevalence of schizophrenia in the United States
was said to be twice what it was in Great Britain. None of
this was credible, and we needed shared diagnostic criteria
that would be simple enough, and good enough to permit two
observers to arrive at the same diagnosis.
This is not the same as validity. This is -- I have another
slide later which mentions this, but this is -- validity is
about picking out natural kinds, carving nature at the joints,
and the two are obviously related to each other but are not
the same thing.
Now the fact that the DSM has only tenuous claims to validity,
although not zero claim, really reflects the early stages
of the sciences of brain and behavior. And also, the difficulties
of the genetics of behavior. Now at the same time that we
have these difficulties, we still have a need to make treatment
decisions and to communicate with our patients, so we've
come up with what really has to be considered a provisional
diagnostic schema. The problem is that that diagnostic schema
has become reified in a way that isn't warranted by the
science, but is all too predictable.
Now I'm just going to show you two pictures again, because
to say that the science is difficult and that it's early
is just -- it's such an important point to make. And
to say that it's difficult and early doesn't mean
we won't ultimately understand the biological basis of
mental disorders. And again remember, the biological basis
means the integration of genetic experience and lived experience,
and other environmental factors integrated by the functioning
of the brain. So this is a recent paper from Judy Rappaport
and colleagues showing over time the loss of gray matter,
of cells in the cerebral cortex of children who have an early
onset of schizophrenia. And what you can see in these pseudocolor
scales -- where always in pseudocolor red is bad -- comparing
a normal adolescent with an individual with schizophrenia,
that there has been loss of gray matter, and here you can
actually, by scanning the same person at intervals, you can
look five years later and actually map the loss of gray matter.
I'm showing you this because the technology to map,
find differences, small differences with reliability in the
brain, even to parcelate different brain regions is really
a technology of the last years of the 20th Century,
and it's still under development. People like Thomas
Szaz, who were true enemies of psychiatric diagnosis, were
mistaking the difficulty and the earliness of the science
for its impossibility.
Now we don't have answers. We can't turn these
pictures of regression of gray matter in the cortex of children
with schizophrenia into clinical diagnostic criteria. Maybe
this will never be a criterion, and if it is, maybe it will
take a decade. The point is that we are really at the birth
of the kinds of neuroscience technologies, and as you'll
see, genetic technologies that can help us get some handle
on the underlying biology of mental disorders.
Okay. Let's turn to genetics, because this is also
very, very important in understanding the boundaries of what
are called psychiatric disorders. And here, the glass is
both half-empty and half-full. Family studies with appropriate
designs, meaning properly designed studies comparing monozygotic
and dizygotic twins, that is twins that share 100 percent
of their DNA versus twins that share about 50 percent of their
DNA. Studies that have been performed of children adopted
out of their biological families early in life and so forth
do not fully corroborate the current DSM-IV diagnosis, which
is to say these diagnoses, based on symptoms and signs, have
chosen certain symptoms and signs that experts felt could
be reliably scored, and have decided that this cluster equals
We can then go to experiments in nature, to genetics and
ask whether the symptom clusters co-segregate; that is, whether
they are transmitted as a group, as a single entity from generation
to generation. And what we find when we look very carefully
is that there are, you know, again not complete invalidation,
but not complete validation of the way we do things, that
symptoms and signs mix and match in a rather uncomfortably
loose way often.
Now there's also reassurance. Despite these problems,
despite the fact that for, for example, many families with
manic depressive illness, you'll find that they have psychotic
symptoms, delusions and hallucinations, and the delusions
and hallucinations are not passed down exactly together with
the mood disorder, for example. Even though we have situations
like that, there is reassurance. If our categories were arbitrary,
if they were completely fantastical chimeras, we wouldn't
see any significant passage of these traits from generation
to generation. They would not cohere. And in fact, what
family and genetic studies show us, is that the categories
we have, as problematic as they are, are picking out something
real, so let me make you ersatz geneticists just for a few
A useful if imperfect measure of heredity, because it doesn't
perfectly separate genes and environment, but it goes something
like this. The likelihood of expressing a trait if something
is genetic should increase as a person shares a higher percentage
of DNA with someone else who expresses that trait. That means
that if you share 100 percent of your DNA with somebody and
they have schizophrenia, you should have a higher likelihood
of having schizophrenia or ADHD, or depression, or diabetes
than if you share about 50 percent of DNA with somebody, if
they are your dizygotic twin, your sibling, your parent.
And there should be correspondingly less association with
second degree relatives.
And when we, using this crude but useful measure, when we
look at what are called recurrence risk ratios, what you can
see is, and let me explain this. And I think after this,
we're done with the most technical slides, but I do think
some detail, rather than bald assertion, is important here.
What you're seeing here, this recurrence risk ratio is
as follows. Your increased risk of having a, in this case
disorder, given that in the first column you have a sibling
with a disorder, and then in the second column you have an
identical twin with the disorder, where the ratio is your
increased risk over the population base rate. And the higher
the risk ratio given a, in this case a monozygotic twin or
a first degree relative with the disorder, the higher the
ratio, the more genetic the disorder. And this kind of information
is used by people using the tools of genetics, even to pick
what diseases they want to work on.
So let's look at schizophrenia. We've been talking
about it. The population base rate of schizophrenia is 1
percent. If you have an identical twin with schizophrenia,
you have about a 50-fold increased risk over the population,
so in this case about a 50 percent, 48 percent risk overall
of having schizophrenia. If you have an ordinary sibling,
on average you'll share about half of your DNA, you have
a 9-fold increased risk. So I want to compare this with Type
II or Adult Onset Diabetes, which is widely understood to
be a genetic disease, and you can see that genes have a lot
more to say about schizophrenia than they do about Type II
Diabetes. And even with our problematic classification of
ADHD, it has recurrence risk ratios that look very much like
Type II Diabetes. So again, these are not ridiculous chimeras,
as imperfect as they are. They are picking out something
that is transmitted as disease risk across generations.
Now some of you who remember genetics would say ah-ha, but
those ratios - I should actually go back - like 9 and 48 are
not what Gregor Mendel would have taught us; that is, if --
I don't want to get into the details, but rather say this,
and we can come back to it in discussion. What the studies
tell us overall is that genes play a substantial role in,
I've shown you only pathology on these slides, but also
in normal behavioral variation. And this entails another
whole set of debates, but I would like to forestall them with
the second bullet here, which is that behavioral variation,
including psychopathology, is genetically complex. That is,
when we say in common parlance that something is genetic,
what most people have is a deterministic notion that there
is a single gene for Attention Deficit Hyperactivity Disorder,
or schizophrenia, or Diabetes Mellitus, or criminal tendencies,
when in fact, what genetic complexity means is that, as we're
going to see, this idea, this simple idea is really of little
which is relevant to some rare single gene disorders like
Huntington's Disease or Cystic Fibrosis, is of little
relevance to behavior, and actually the most common human
Where it is currently thought that many different genes,
many different places in the genome or loci interact to produce
risk, and that they interact equally with, or in some ratio
with environmental factors, and chance. Chance is often forgotten
in this. You can't wire up a hundred trillion synapses
in the brain in a mechanistic and reliable way. There are
a lot of stochastic effects in this, and that these interactions
are non-linear. Genotypes help select the salience of environmental
experiences, and those affect gene expression, so these are
extremely complex interactions.
The other thing which is very important in thinking about
disease, something like depression, depression which affects
15 percent of the population, these are not likely to be deleterious
mutations in the genome, the truncation of an important protein,
something important not being made. Instead, these are more
likely to be just variants, that in some combinations are
neutral, in others are advantageous, and only in certain infelicitous
combinations and in interaction with environmental factors
and chance do they produce disease.
So let's just think about this again. There's some
evolutionary speculation, and it is speculation about, you
know, Diabetes Mellitus, that the thrifty genes, the metabolically
thrifty genes that would have helped you store fat before
the neolithic revolution are not a good thing to have in the
era of McDonald's. And these are not harmful mutations,
these are just particular variants that are interacting, and
give you a particular metabolic situation. And similarly,
for behavioral variants, including mental disorders.
Now, of course, certain combinations of these variants can
give you the risk of very severe illness. I mean, there's
no doubt that even if Autism is a group of variants, that
depending on which ones you get set you up for being somewhere
on a spectrum of being a little bit aloof, which might help
you to be a great mathematician, versus somebody who can't
communicate at all with other humans, that still doesn't
make these things mutations. It means that these -- again,
this is an interaction of genetic variants. And let me just
say again, we think this is right. I mean, there's a
lot of data that this is right, but this is -- we're right
here on the edge of genomics and genetics.
Okay. Now I just also want to point out for our later discussions,
that the boundaries of mental disorders are not the only disorders
that are going to be redefined once we understand better the
genetics and the genomics. So let me show you a picture of
a breast cancer that looked the same to pathologists. So how
does one make a diagnosis of a cancer? Well, a tumor is removed
by a surgeon, and still today in most cases, a pathologist
will put an acidic dye, and a basic dye on the tissue specimen,
a 19th Century technology. And the pathologist
is very learned in comparing patterns of -- seen under a microscope
with certain clinical outcomes. And the pathologist will
say this is a certain kind of lymphoma or breast cancer.
Well, here is a gene chip, and the investigators here basically
arrayed 5,000 different human genes. And they asked whether
a gene was on being expressed in a cell, or not on, not being
expressed in a cell. And then they asked the computer just
to array patterns of gene expression in 98 different breast
tumors which are arrayed on the left to see whether there
was any pattern of correlation between the likelihood of metastasis.
And indeed, with this gene chip you can see that what looked
for many years, eons, like one disease, was actually at least
two diseases. There are two different patterns of gene expression
here shown by red and green. Green is off, red is on, and
these are genes that might be very much involved in invasiveness
and metastasis and so on, but the point is that genomics and
genetics are redefining the boundaries of disease everywhere.
The difference between this and behavior, frankly, is again,
this is an objective test outside the body; whereas, in behavior,
despite the early Judy Rappaport picture of this brain of
the young person with schizophrenia that I showed you, we
are still lacking any objective tests that we can look at
outside of the behaving human being.
Well, just to bring this full circle, and to make sure we
don't get too focused on the genes, and I've already
said this, if genetic complexity were not enough, ultimately
it's not our genes but our brain that regulates our behavior.
And that while genes are very important, neural circuits are
shaped by gene environment interactions over a life time.
This is the idea of synaptic remodeling by lived experience.
Thus, behavioral traits reflect the interaction of multiple
genetic, environmental and stochastic factors.
Okay. So it's very complicated, but we shouldn't
despair. Our genetic studies to date, for example, show us
that we have some coherence. I'm getting pretty close
to the end of this. The other thing, and this makes your
job harder as you ponder the questions that you are, is that
depression, ADHD, autism, and many other conditions appear
to be quantitative or dimensional traits.
Now the current DSM actually says, you know, to have depression
you need to have five out of nine DSM-IV symptoms of depression,
and you have to have those symptoms every day for two weeks.
Well, that's really quite arbitrary. In fact, of course,
the boundaries between -- really getting the boundaries right
between normal and diseased phenotypes have enormous impact
on treatment decisions. And the truth is that even though
these are handled relatively arbitrarily in the DSM-IV, medicine
is very comfortable dealing with quantitative traits like
Basically, how did we decide that 120/80 is terrific, and
140/90 is a disease and warrants treatment? Well, we did
long-term follow-up studies, and it turned out that if you
had 140/90, there seems to be a bit of a discontinuity, actually,
and you have a clear increased risk of strokes and myocardial
infarctions. And whereas, the 5 out of 9 DSM-IV criteria
for major depression just felt right to a committee, they
haven't been exposed to that kind of empirical test, to
understand what is a risk state and so forth. The other thing
is that we understand that there is early, and transient,
and mild, and moderate, and severe hypertension. And again,
in the DSM we have no capacity to do that.
Okay. Now this is a problem, this issue of not having rational
diagnostic thresholds defining either risk states or actual
pathology, has -- does a disservice, especially to children.
It creates a lot of lack of clarity with respect to when one
intervenes in children, both in the over-treatment domain,
and in the under-treatment domain. In the DSM approach, you
know, you only achieve it if you have 5 of 9 DSM-IV criteria.
If that were applied to cardiology, we might limit our diagnoses
to angina and heart attacks, and not to early coronary disease
or even elevated cholesterol.
Okay. The complexity of mental disorders is humbling at
the levels of genetics, neurobiology and behavior. But then
again, many illnesses in general medicine are not so simple.
I showed you a cancer example. It's just true for all
common disorders that these are not unitary disorders, but
have very complex boundaries. The difference is again, that
in general medical disorders there are objective tests that
get you within the pathophysiologic family, and we have to
live with this. We can't tell people in distress to come
back when our science is more advanced. We have to do as
well as we can.
Okay. So now in the last five minutes, just to give us
a -- put this to work, so Attention Deficit Hyperactivity
Disorder, you already know this. I assumed you've discussed
these things. It's defined as age inappropriate inattention,
impulsivity and hyperactivity. It's critical that the
diagnosis requires symptoms and disability in multiple settings.
Ideally, the workup, therefore, involves looking at the child,
interviewing the child, and also the parent and the teacher.
If symptoms only occur in Mrs. Smith's classroom but not
at home or on the playground, that's not ADHD. It is
a clinical diagnosis. There is still no objective test.
Even with these diagnostic criteria, when they are well
applied by experts with a proper workup, they are associated,
it is a high risk state. It is associated with bad outcomes.
It's associated with academic and occupational under-achievement
compared with abilities otherwise measured. There is an increased
risk for substance abuse which, by the way, is decreased with
Ritalin treatment, even though Ritalin is abusable. And there
is an increased risk for arrest.
Anecdotes, you know, one takes with a big grain of salt,
but when I was NIMH Director, some of our ADHD research was
co-funded by the Justice Department, because there was such
an over-representation of kids with untreated ADHD who are
It is also associated with an increased risk of other disorders,
depression, anxiety and conduct disorder. It's the most
common behavioral disturbance that results in a clinical referral.
Thirty to 50 percent of kids who are referred clinically for
a psychiatric illness have this diagnosis. It has to start
before the age of 7. And as you already know, it runs in
families and it's likely that some of the risk is genetic.
Treatment has been very well studied. Stimulant drugs in
particular have been around for a time. We know that behavior
therapy is effective. We know that stimulant medication,
Methylphenidate is effective. We know that from the very
extensive MTA trial which was conducted in 1999 through the
NIMH, I have -- it was initiated before I arrived, so I don't
have a sense of ownership, that careful use of medication
is more effective than behavior therapy.
Behavior therapy is interesting. It doesn't generalize
across different contexts, so behavior therapy in school doesn't
necessarily generalize to home or playground. Behavior therapy
in the home doesn't generalize to school. Combining medications
and behavior therapy is cost effective only for children,
not uncommon, but only for children with co-occurring disorders;
that is, ADHD plus anxiety or ADHD plus depression.
We also know that community treatment of ADHD is not as
good as it should be; that is, there are lots of kids who
are on Ritalin but don't have good outcomes, their doses
are wrong, they don't know about side effects, they're
not being monitored. A certain number of children who are
said to have ADHD in our communities and are being treated
with stimulants also do not meet criteria for ADHD. Adrian
Angold in 2000 had a paper that suggested - he's at Duke
- that 50 percent of children carrying this diagnosis wouldn't
really meet standardized criteria.
There's enormous variability with some communities treating
it far less than the epidemiology suggests. The epidemiology
again -- so now you know how, you know, problematic these
criteria are, but if you apply them, and apply them rigorously,
the suggestion is that 3 to 5 percent of boys have ADHD, but
we see rates of treatment often close to zero among non-caucasian
minorities and some inner cities to the best documented.
There was a paper looking at several suburban Virginia counties
- it's apt that we're in Virginia - where 20 percent
of the boys in some counties were getting Ritalin, and anecdotally
in some schools, especially among middle class or upper middle
class caucasian males, 30 or 40 percent of the boys may be
on Ritalin. That's not rigorous, but even rigorous epidemiology
shows this disparity between a 3 to 5 percent incidence, and
There is also an unexplained increase in stimulants and
other psychotropic drug use. I know that the Julie Zito studies
have alarmed many people. I would caution you though, the
studies are very difficult to interpret since drug prescription
data is divorced from good diagnostic workup, so we just really
have no idea what's going on with these kids.
The bottom line, there's a mismatch between children
in need of treatment and children getting a diagnosis, both
under-treatment and over-treatment. We need better diagnostic
methods. We need to understand the best use of existing treatment
in all age groups, and we need better treatments. I'll
skip over where we need to do research. So to conclude, how
do we take this -- how do we think about these things? Why
did I give you the first 20 or 25 minutes on genes, and brain,
and behavior and the complexity of diagnosis?
Well, partly we have to remember that while we're worried
about the risks of drugs on the brain, you also have to remember
that for childhood mental disorders there may also be risks
of no treatment. You have to ask how easy is it to recover
from persistent problems, in well diagnosed kids with school,
and parents, and peers, especially if the symptoms persist.
There may be a downward spiral for depression, anxiety, ADHD
in which a kid has symptoms, aggregates with deviant peers,
gets in trouble with the law and so forth, and these may leave
their permanent traces on brain and behavior, and life trajectories.
We live in a world of diagnostic gray zones, as Dr. Kass
said right at the outset. And increasingly in medicine, we
have an ethic of prevention and early intervention. We're
told that the time to treat -- that Osteoporosis is actually
a pediatric disease that expresses itself in old age, you
know, you're building your bone density as a child. Is
there a moral difference between lowering cholesterol levels
and altering neurotransmitter levels? Why might it be okay
for everyone to be on a statin but not an SSRI stimulant or
modafinil so that we can stay awake and work all night?
In treatment there's always a balance between risks
and benefits, and the balance is influenced by severity of
symptoms and stage of illness. Difficulties related to children
with psychological symptoms. For most conditions -- see,
if we had this answer it would be easy, but we do not know
enough to project trajectories with or without treatment.
There is abundant evidence that appropriate treatment decisions,
however, are not currently being made with ADHD in particular.
We could also talk about depression, because of outside pressures
to treat coming from family, school, drug advertising and
so forth. Inadequately trained physicians. There are very
few child psychiatrists, and pediatric neurologists, and behavioral
pediatricians in our communities. Almost all prescribing
is done by family physicians who are working in earnest, but
don't have the training, and they don't have adequate
time or reimbursement for full work-ups and follow-up. A
full work-up to demonstrate ADHD would take several hours,
or would require talking to several people. And also, medications
are seen in many health plans as cheaper and easier than behavioral
And when we go beyond well-defined disorders and high risk
states toward early intervention and prevention, the balance
of medical risk side effects shifts. Right? It shifts against
treatment. There are unknown long term effects of drugs.
Now I've talked about unknown effects of going untreated,
but now there are unknown long term effects of drugs on a
child's symptomatic trajectory. Does giving drugs now
mean that a child might need drugs later that they might not
otherwise have needed? Well, we don't know.
There are symbolic messages to children about self-efficacy.
Behavioral control comes from a bottle. We have the problem
of anabolic steroids for the soul. Can we really separate
health and prevention issues from performance enhancement
issues? I think that's a very, very difficult line to
draw. And then there's the issue of social coercion or
unilateral disarmament. I find it working at the University
an anathema that all of our kids, well many of our kids feel
the need to get coaching for their SATs, and they get their
resumes spruced up, and one couldn't possibly be a serious
professional football player, I would imagine, without the
use of some performance enhancing drugs. And one might take
an ethical position, but taking that position puts one at
a competitive disadvantage. And in the case of ADHD in schools,
and maybe one day Prozac in the work place, there might be
a sense that you'll get the message that to do well, you
know, you shouldn't be the only one not being treated.
So let me end there. You can see that you have -- well,
actually as you know, you've gotten yourself into an area
of extraordinary difficulty because of the intrinsic complex
nature of psychiatric disorders, because the science of understanding
and diagnosis is young, because despite that, we've empirically
discovered treatments that have efficacy and a low side-effect
burden, because if I'm right and these disorders really
are the left-tail of a bell curve and not something discontinuous,
these effective treatments will work not only for those severely
effected, but those less severely effected, and those who
wouldn't even receive a diagnosis. And you're addressing
this at a time when we really don't understand fully how
sets of behavioral symptoms portend a certain trajectory for
children. Thank you.
CHAIRMAN KASS: Thank you very much for
a very clear, comprehensive presentation. The floor is open
for discussion. Elizabeth Blackburn.
PROF. BLACKBURN: With relation to your
table with the risk ratios, you gave some very precise numbers,
and then you talked about the degrees and the quantitative
aspects of diagnoses. And I was curious about those numbers,
did they come from the extreme very, you know, say 9 out of
9 symptoms for depression, for example, category?
DR. HYMAN: Yes.
PROF. BLACKBURN: Because I could see --
DR. HYMAN: What we did basically, and
it's interesting. The genesis of this slide was when
I was NIMH Director, and we were about to make an enormous
investment in genetics, we were working out -- that is, which
diseases warranted an early attack on the genetics given the
complexity as genomic approaches were maturing. And it was
quite clear that autism, schizophrenia, and manic depressive
illness, because of their very high risk recurrence ratios,
were apt targets for genetic studies, and actually other things
were a lower priority. And the way we went about it is basically
to do a search and find every credible well-designed, adequate
"N" study that had been done comparing identical twins, dizygotic
twins and siblings. Per force they were done in different
countries using different diagnostic criteria, and if we did
this in a more technical meeting and you saw error bars, you
would be somewhat alarmed, but in the end, I think there's
a general consensus that these numbers are not far off, representing
PROF. BLACKBURN: Yes. No, I take the
point about the relative contributions of heritability, but
I was curious, for example, bipolar, you know, 7-fold for
sibs, 60-fold risk ratio for monozygotics. But then if depression,
which is only part --
DR. HYMAN: Yeah.
PROF. BLACKBURN: I mean bipolar is only
part of that, 15 percent so clearly there must have been a
DR. HYMAN: Oh, bipolar --
PROF. BLACKBURN: -- how broadly you define
DR. HYMAN: I'm sorry. Okay. So depression,
when we -- so if you've ever had a manic episode you're
not in the unipolar depression category, you're in the
PROF. BLACKBURN: Yes, but from what you're
saying, since you took studies from multiple countries --
DR. HYMAN: Yes.
PROF. BLACKBURN: -- it must have been
a fairly broad set of criteria that were included then in
DR. HYMAN: Yes.
PROF. BLACKBURN: I was curious about whether
this represented, you know, as you say, the right hand side
of the bell curve for these diseases.
DR. HYMAN: Right.
PROF. BLACKBURN: It sounds from what you're
saying as though it's a fairly broad set of definitions.
DR. HYMAN: Yeah. I would have to -- I
mean, for autism it's not so broad. For major depression,
it is broad. We were dependent on the world's existing
literature, but I take your -- your point is -- if your point
is that the input data has certain infirmities, it certainly
PROF. BLACKBURN: No, I wasn't --
DR. HYMAN: Yeah.
PROF. BLACKBURN: I think the point is
well-taken, and I certainly think there's every reason
to think this. But I was just curious about how broadly
some of these things were defined. Were they looking at the
extreme ones where you could be very, very clear.
DR. HYMAN: I think, yes.
PROF. BLACKBURN: Or did they segue into
DR. HYMAN: So for autism, bipolar disorder
and schizophrenia, they're very, very clear. I think
for major depression there is no clarity.
PROF. BLACKBURN: Okay. Thank you very
CHAIRMAN KASS: Rebecca Dresser.
PROF. DRESSER: You were very balanced
and fair in your presentation, and I wondered if I could get
you to express a point of view on something that's relevant,
not just to this project on "Beyond Therapy", but
also another project we have, which is regulation.
You seem to say that in some situations that diagnostic
criteria are fairly defensible, but there's still this
problem of getting professionals to apply them stringently,
or even with reasonable rigor. And also, dealing with parental
demand, I suppose sometimes patient demand. I wondered if
you had any ideas on what might be done to address that problem?
DR. HYMAN: I have no problem expressing
a direct opinion on this topic. I think that in medicine
in general, in psychiatry in particular, and in pediatric
mental disorders most particularly, there is -- as early as
our criteria are, if they were well-used, and if children
were followed-up appropriately to ensure that the first diagnostic
hypotheses and treatment suggestions were optimal, it would
be a much better world.
I think the data suggests, as my slide listed, that most
prescriptions, as far as we can tell, for psychotropic drugs
are made by family physicians, well-meaning to be sure. I
do not want to bash family physicians. They are working at
an extreme disadvantage. They have been untrained. They
have no time. I mean, it's fine for me to say that you
should spend several hours on a diagnosis, and one of the
things you want to do is make sure not only that the child
is in trouble in the classroom with the teacher, but also
is being rejected by peers on the playground, so it's
fine for me to say that. The family physician is not trained
to know what questions to ask, very often has 11 minutes to
get from the beginning of the intervention to writing a scrip,
and would not be reimbursed to take the time after the visit
to make those phone calls.
As a result, and in combination with outside pressures that
exist in certain school systems, and through advertising,
I think that what we -- there is a yawning gap between what
we know, which is imperfect but good enough in a rough-and-ready
way and what we do.
I would also say that while I focused on diagnosis, I think
the follow-up issues are as or more problematic; that is,
if the medicine isn't working and has side effects, it
may or may not be stopped. Kids who really need it may not
be complying, and nobody notices, so I think there is an enormous
problem of medical practice.
Let me say one other thing about coercion, and let me give
you a thought experiment, because I think it's -- coercion
already carries with it negative connotations, you know, the
evil empire forcing a child to take the medication. We can
certainly imagine a situation. Why you don't risk a unilateral
disarmament situation, where you have a few symptoms, and
you're not performing so well, and all of your friends
are taking this drug, and their parents and the teachers are
happy consumers. That's not an ideal situation. I don't
think anyone could defend that.
On the other hand, there's a case where there's
25 kids in a classroom or 28, and one teacher, and there are
two kids who have symptoms of severe behavioral disorder,
who absorb almost all of the teacher's time. And any
of you who have children or have been in a classroom know
that this is a reality, and so the 23 kids don't really
get much of an education.
Now the issue here is that schools should never be making
diagnoses, and schools should never be saying, as has been
rumored, you know, get Johnny on Ritalin. That's absolutely
wrong. But for schools to demand that somebody be worked-up
or treated in a certain way so that everybody could learn
I think is a different issue. And I think when we think about
the roles of schools, you have to think not only about the
dark 1984ish scenario, but also about the second scenario,
and weigh those.
CHAIRMAN KASS: Do you want to follow-up,
PROF. DRESSER: This is rather provocative.
I was involved in a group of pediatricians addressing the
growth hormone question, and one idea which didn't really
go very far was that only pediatric endocrinologists should
be able to prescribe because of this desire to do a good work-up,
and keep the boundaries. Has anybody ever proposed something
like that in this area?
DR. HYMAN: It is absolutely infeasible.
The number of -- I mean, in most -- if you think of inner
cities or most of rural America, the number of trained pediatric
psychopharmacologists, behavioral neurologists, or behavioral
pediatricians tend towards zero, and so the burden of doing
this correctly must be on the family physician.
The pediatric growth hormone issue is, as you know, exactly
analysis. Short stature, but my child does have short stature.
He was going to be a center for an NBA team, you know, and
I'm drawing that line.
CHAIRMAN KASS: If I -- Rebecca when she
first started to ask about the -- whether you had some suggestions,
in fact, about the regulation of this practice, you've
gone and indicated why it is in need of such attention, but
in effect said this is a problem for professional practice.
And almost all of the pressures make it almost impossible
for it be done. Is that the best that we can do?
DR. HYMAN: I hope not. On the other hand,
regulation that flies in the face of reality is -- decreases
respect for regulation and fails.
CHAIRMAN KASS: Of course.
DR. HYMAN: You know, I would -- I have
long believed -- so I've told you I believe that family
doctors are going to carry the burden of most of this. I
think certainly that at least in certification requirements,
there has to be increased attention among family physicians
to pediatric psychopharmacology. I mean, if you look at the
numbers of young people receiving Ritalin or an SSRI, this
must make up a very substantial part of general pediatric
and family physicians practice, and I think some kind of training
I must say in my years of looking at the gap, as I call
it, between what we know and what we do, and physician behavior,
I've become not quite despondent about the power of education
by itself, and I think that some kind of accountability to
make sure that these -- that what is being taught is being
practiced in some way is very, very important. But that accountability,
if it just accrues to the physician who doesn't have time
or resources, and is not reimbursed, becomes very, very problematic,
so I think it has to be -- it really has to look at health
systems in some sense, and really look at the quality of the
overall work-ups that are being performed and reimbursed within
CHAIRMAN KASS: Dan Foster.
DR. FOSTER: You used the term that on
a "rough-and-ready" basis if the things that we
know were followed, we would be in a much better world, the
sense being that although there might not be a bright line
between disease and --
DR. HYMAN: There isn't.
DR. FOSTER: There isn't and so it's
DR. HYMAN: There is not, yes.
DR. FOSTER: At least there would be some
broad category of defense about prevention and so forth.
And you talked earlier a little bit about a curve that went
on into normality, where there might still be an enhancement
from excitatory drugs and so forth. I just wondered if you
-- I think I know what you would say about this, but merging
out of the issue of children with - as an example here - what
is your opinion about the enhancement virtues that kids in
college and so forth, you know, are using these drugs extensively
and so forth? Is that defensible or not defensible in your
DR. HYMAN: I really struggle enormously
with this. It really comes down -- I'm not going to give
you a crisp answer because I'm not done struggling. It
comes down to the anabolic steroids issue in some sense.
Athletics has decided that you are supposed to -- I mean,
even though we know that illicit and problematic use of drugs
continues in sports at all levels, tragically sometimes leading
to death, the sports community will assert that it wants human
beings to compete with each other in athletics, only based
on their bodies and the physical training that they undergo.
And that the use of drugs is just not to be part of an athletic
contest. And in some sense, if you -- that idea, which is
so -- always breached, or often breached, that idea which
is so attractive, really doesn't translate very easily
to life as it is truly lived. And here my impulses, my libertarian
impulses, and impulses as a physician begin to take over.
If somebody feels distressed and doesn't meet any criteria,
and finally a physician says well, I don't really know
what's going on with you, but let's try this thing.
It's marketed as an anti-depressant, but since everything
is really probably on a bell curve, you know, it doesn't
stop working if you don't have 5 out of 9 DSM-IV symptoms.
And the person has no side effects, or model tolerable side
effects, and really it relieves their distress, and they're
a better husband or wife, and they're functioning better
at work. It seems very difficult in America to say that they
can't feel better. I think it's actually impossible
to say that. But then that scenario shades into the dystopic
notion that but if everybody in the work place is -- if these
drugs get better and better, and everybody in the work place
is on these drugs, might we not have a coercive situation
where somebody who wanted to engage life without a psychopharmacologic
agent is now being in some sense forced to join the crowd,
which is the situation if you want to an interior lineman
in the NFL. You might have moral questions about anabolic
steroids, but you would be ill-advised if that's your
chosen career to avoid them, so I can't give you a crisp
I think it's really -- if you think about the case,
the first case I gave you -- I mean, I've given you extreme
cases, but in the first case it would be very hard to say
that somebody couldn't have the drug, and in the second
case one begins to really imagine some fairly nightmarish
scenarios. And I think finding -- if there is some way of
finding an appropriate middle ground, I imagine that's
what you are all engaged in, and I can't make it easy.
You might think my interim solution while I struggle is
not strong enough, but my interim solution is really that
physicians, because these are prescription drugs, physicians
really have to be a lot better. They can't say -- somebody
can't say I've read an ad for -- you know, I've
been shy all my life, and I read an ad on a side of a bus,
and I want you to prescribe X. I mean, the physician really
has to understand the person's symptoms, and treat a prescription
as an empirical trial, and not a birthright, and stop it if
it's not working, and weigh risks and benefits. And maybe
it doesn't make you happy as an answer, but we're
not even there, we're not nearly there.
CHAIRMAN KASS: Could I pursue this with
you unless, Dan, you want to follow-up? Are you okay? Yeah.
In the presentation, on the one hand at the very beginning,
you make clear your view that both lived experience and drugs
affect the brain.
DR. HYMAN: That's correct.
CHAIRMAN KASS: And that there is no fundamental
DR. HYMAN: At the level of the brain.
CHAIRMAN KASS: At the level of the brain.
DR. HYMAN: Right.
CHAIRMAN KASS: Yet toward the end when
you talked about the kinds of problems that might -- and among
the list of problems about the use of these drugs was the
concern that you would be sending symbolic messages about
self-efficacy to children.
DR. HYMAN: Uh-huh.
CHAIRMAN KASS: That somehow drugs were
a better way to deal with their difficulties.
DR. HYMAN: Uh-huh.
CHAIRMAN KASS: And then this question
about the anabolic steroids for the soul which we talked about.
DR. HYMAN: Right.
CHAIRMAN KASS: If you bracket the question
of social coercion that might come if you were dealing with
competitive situations, and simply talked about the fact
that look, we don't know whether there's a diagnosis
here. In fact, it's not clear this is a medical condition,
but there's some kind of self-discontent. And you've
already pointed out that in the absence of certain kinds of
treatment, the possible plasticity of the brain might, in
fact, be under-developed and not used.
CHAIRMAN KASS: Why wouldn't you say
that -- why don't these concerns sort of vanish, concerns
at the end if you begin to think about the thought at the
beginning; namely, that we could use pharmacological agents
to help lots of people feel somehow better about themselves,
in the wake of which feeling better, all kinds of other experiences
might go better. The brain might, in fact, develop and become
richer. Isn't this just sort of priggish concerns that
DR. HYMAN: Yes. No, no. No, no. Well,
I think that's why I began with athletics, where society
has made a decision that you're supposed to be competing
naked of pharmacology. And we haven't made that decision
when it comes to the rest of life. WE're uneasy. I mean,
we are generally uneasy. And the whole reason I struggle
is because I can't refute that final position that you
Let me also say at the beginning, there are also certain
kinds of experience that can have bad effects on life trajectory
presumably mediated by the brain, by long-term changes in
the brain. I mean, we're worried about pathologic gambling,
you know. That's a lived experience. That's not
a pharmacologic experience, and it can have very profound
effect on brain function. I was really just making the point
that we can't -- you shouldn't rest your deliberations
on the idea that there's something fundamentally categorically
different between drugs and experience and their effect on
the organism. There are other issues that we are struggling
with, which has to do with symbolism, with relative moral
weights, and of course, with medical side effects, risks and
CHAIRMAN KASS: But bracket the side effects.
DR. HYMAN: Yes. Right.
CHAIRMAN KASS: Why isn't, in a way,
the philosophical teaching about the brain sort of at odds
with the desire to privilege the symbolic meaning of do it
for yourself without drugs?
DR. HYMAN: Yes.
CHAIRMAN KASS: Bracketing your -- no one
is going to ban anything here.
DR. HYMAN: Right.
CHAIRMAN KASS: Bracket libertarian concerns.
DR. HYMAN: Right.
CHAIRMAN KASS: And just talk about the
kind of anthropological question, moral self-understanding.
DR. HYMAN: Well, I think that there is
a symbolic difference that we don't -- that we often don't
recognize that plays itself out, often in irrational ways
in other aspects of medical practice. For example, we are
quite well aware that most people will not control their cholesterol
with diet and exercise over the long run. And yet, every
medical textbook tells you to start with diet and exercise,
and force somebody to fail through this exercise in self-control
before you would prescribe a statin, even though the statins
are, you know, they're -- we can bracket side effects,
but they have side effects. And I think what we'r talking
about here is what kind of society -- I think what we're
engaged in is what kind of society we want to have, and whether
we, as a society, want to recognize as valid, unstigmatized,
and in no way diminishing of someone's humanity, that
they gain appropriate treatment even early, or preventive
treatment for identifiable high risk states, but that in general
as a society, we would like people to work with their own
native abilities, with their own struggles.
The alternative view is that if we can find medications
which will enhance our performance, lengthen our life, decrease
the stress, do we really think that Aldous Huxley was right
and we'll end up, you know, in some "Brave New World",
or is it more likely that we will end up in a happier, healthier
world where people can all function well? And I think we
don't know the answer to that, and what you and -- what
we are all here together struggling with is we're worrying
about the Huxley and dystopic, but it would be hard to say
that we should not be aiming for the more utopian version
of this. And in fact, if such drugs were to be developed,
no regulation in the world would keep them from general use.
CHAIRMAN KASS: Michael Sandel.
PROF. SANDEL: I'd like to continue
along Leon's lines. What he's been doing has been
-- you gave us a very balanced and elegant, and terrifically,
for me, informative overview of these issues, and you have
an instinct that's emerged in the discussion for which
you call the appropriate middle ground, but Leon, and now
I am trying to drag you into the fray that we've been
DR. HYMAN: Uh-huh.
PROF. SANDEL: Which is partly an ethical
and ideological fray, as it intersects with the medical and
scientific account that you've given.
DR. HYMAN: Absolutely right. I mean,
medical practices -- there are a lot of problems in medical
practice that have to be addressed, but we're talking
about something very separate from medical practice now.
PROF. SANDEL: Right.
DR. HYMAN: So you're not letting me
PROF. SANDEL: Okay. So if I could continue
along these lines. First, when you gave your general, your
opening account of the mind, calling into question the sharp
metaphysical mind/body distinction, both drugs and experience
have effects on the brain, to some ears, to some people listening
to this, see that finding, if it's true, as threatening
to something they believe about ethics and about freedom,
and about moral responsibility. I don't think that they're
correct in seeing this as a threat --
DR. HYMAN: Correct.
PROF. SANDEL: -- to proper understandings
of freedom and moral responsibility, but there's a powerful
philosophical tradition that supports their worry that this
would be a threat.
DR. HYMAN: Right. I agree.
PROF. SANDEL: But in any case, to come
closer to the surface of these ethical and ideological issues,
so you signalled -- those were fighting words your account,
your brief account about drugs and experience having effects
on the brain. And then you reinforced them, and you posed
as a question if statin, why not stimulants?
DR. HYMAN: Right.
PROF. SANDEL: What's in principle
the difference between the use of the two for prevention and
early intervention?Maybe we stigmatize the second more than
the first, but is that defensible in the light of this earlier
thing, so that gets closer. And then -- so to take one step
further along the lines of Leon's questions, go back to
the sports case. Now you dodged that by saying well, we as
a society have decided that we want sports athletes to play
just with their bodies and physical training.
DR. HYMAN: Right, but you could imagine
a different --
PROF. SANDEL: Well, first of all, it's
not clear that that's true sociologically, and even if
it were, it might be mistaken.
DR. HYMAN: Right. Right.
PROF. SANDEL: And one could raise questions
about improved running shoes, or graphite tennis racquets
and so on, which have nothing to do with bodies or with physical
training, but which are external in just the way that drugs
would be external.
DR. HYMAN: Uh-huh.
PROF. SANDEL: You don't object to
that, so at the level of sociology, it's not so clear
that we've accepted that. In the Sports Illustrated
expose of the use of steroids that they pointed out that players
now speak to each other in the language of "playing naked",
you're not going to play naked, are you?
DR. HYMAN: Yes. That was my unilateral
PROF. SANDEL: Right.
DR. HYMAN: Right.
PROF. SANDEL: But here's the issue.
Suppose we put aside questions of safety, we find something
that doesn't have bad side effects as steroids do.
DR. HYMAN: Uh-huh.
PROF. SANDEL: And we put aside the question
of fairness, that by making it available to everyone if they
want to, to use it let's say in sports, some drug that
will enhance performance, that doesn't pose medical risk,
and that's equally available on a voluntary basis to anyone
who wants to use it, so you remove the fairness.
Now you may say well, there's some people who want to
be play naked, they'll be effectively coerced, but if
it's safe, then it's no more coercion in that direction
than it would be in the other direction if you said people
who want to use it, can't use it.
DR. HYMAN: Right.
PROF. SANDEL: So it would be a draw.
So the coercion is gone, the fairness is gone, the safety
objection is gone -- something objectionable about enhancing
performance through a drug rather than through, let's
say, a more rigorous training or better genetic luck. That's
The second question is the parallel to that in the case
of Ritalin, in the case of stimulants. And here, there's
been a lot of discussion about over-treatment, and over-treatment
reflecting an ideology of the, you know, the diagnostic manual,
this ideological --
DR. HYMAN: Right.
PROF. SANDEL: It's led, or permitted
DR. HYMAN: And there's also under-treatment.
PROF. SANDEL: Well, but you --
DR. HYMAN: As are more problems --
PROF. SANDEL: Well, that's a different
emphasis you brought from the ones we've had in previous
discussions. You said well, we have to look at the risks
of not treating, we have to look at the incidence of under-treatment.
And if it's safe, and let's say even hypothetically
to isolate the issue, if it doesn't have adverse health
side effects, then the under-treatment would be worse than
DR. HYMAN: Uh-huh.
PROF. SANDEL: So the question then, the
first question is this -- the hypothetical in the sports case,
and the analogy in the Ritalin case. If we do away hypothetically
with the medical risk, is there anything objectionable to
letting any kid whose parents let's say agree to have
Ritalin to improve behavior or concentration on the SAT, provided
it's available to everyone, and assuming for the sake
of argument it weren't risky.
DR. HYMAN: So you'll force me to take
off my medical hat that makes me worry, and to address in
very naked terms where I would come down. I would say that
if there were drugs that could enhance performance, that were
perfectly safe, but I want to define safe on my terms.
The key for me is, and this is very unlike the soma of "Brave
New World", there must be no clouding of consciousness,
there must be no alteration of -- no artificial control of
overall moods, but rather -- in short, we don't want people
getting high all the time. I would include that in a risk.
It's very important for me to segregate, you know, artificial
elevation of moods and change in human judgments into the
category of side effects. But if we had drugs that were free
of that, I would think that it would be -- they would be acceptable.
I think that --
DR. GAZZANIGA: We do. That's Ritalin.
DR. HYMAN: Well, not quite Ritalin. I
mean, Ritalin is not -- well, let me come back to the second
point. The reason that you've found me so worried about
this in talking about the moral symbolism is I also believe
that it is better for humans -- we never want somebody to
have to struggle against difficulties with some rectifiable
disorder, defect or disability. We want to bring everybody
up to a certain normal level of function, with the understanding
that that's a very gray zone. But it's also important
-- I would argue that a society which -- if a society errs
in the direction of increased personal responsibility and
sense of moral agency, that's a better society than a
society which errs in the opposite direction. And that while
I said yes ultimately to your first question, the way you
set it up, the way that such drugs would be used, the way
Ritalin can be used, worries me because of the risk of undercutting
a broad societal sense of moral agency and responsibility.
I don't think that -- and the two positions are not
really fully congruent. Right? Because I know that one of
the risks of having risk-free performance enhancers is potentially
to undercut a set of moral agency and responsibility. And
yet, it is very hard for me to find a bright line where if
these things were truly risk-free, didn't make people
-- give people artificial emotions and impair their human
judgments, that I could say that we can't have. We will
have. What I'm saying is we have to learn to manage them,
and we have to learn to manage them in a way that minimizes
the loss of a sense of moral agency.
DR. FOSTER: I just want to interrupt for
a second to say, I'm not sure at all about the issue of
safety of Ritalin in young children. I mean, I'm not
sure that it's a safe drug anywhere, but particularly
I don't think that the neurological circuits and everything
are completely, you know, at 7 years of age you're not
worried about that. You remember that -- if you look at
something like alcohol and pregnancy, I mean four hours of
alcohol at 200 milligrams percent you've got a defective
DR. HYMAN: You know, Dr. Foster, I don't
want to cut you off, but time -- I'm going to have to
go exactly at 10:30.
DR. FOSTER: All right.
DR. HYMAN: Let me just say, if you actually
look at the data, imperfect as it is in any clinical trial,
the data would tell you that properly used by any criteria
that we have, Ritalin is a safe drug. Can it be misused?
Yes. Can it be abused? Yes. Do all drugs we have today
have side effects? Yes. But compared with almost actually
another drug we have that we use in psychopharmacology, oddly
the data that we have suggests that Ritalin is the safest.
Now you and I might argue about this, but I don't think
that's where these questions are going.
CHAIRMAN KASS: I have Gil, Paul, Bill.
You have how much time?
DR. HYMAN: I have to leave at 10:30, about
CHAIRMAN KASS: Okay. Well, let's
try to -- briefly then.
PROF. MEILAENDER: Yeah. I'm confused.
If I follow what you said to Leon, and then to Michael, it
would seem that you're not prepared to draw a line against
enhancing performance for perfectly normal people.
DR. HYMAN: Right.
PROF. MEILAENDER: Enhancing performance
so long as it doesn't have bad side effects, one of which
would be altering of moods.
DR. HYMAN: Artificial elevation.
PROF. MEILAENDER: Yes. So somehow a person
who just, you know, is not clinically depressed or anything,
but just goes through life a little discontented and would
like to be happier, has less claim to be helped than someone
who without help can get a 1400 SAT and would really like
to hit 1550. If I'm understanding your right, I just
don't see why anybody would draw that line.
DR. HYMAN: Would draw the line.
PROF. MEILAENDER: Yes. Why do you have
more sympathy for the person who wants to notch up the SAT
than the person who would like to be a little happier.
DR. HYMAN: I'm sorry. I don't
have more sympathy. I just --
PROF. MEILAENDER: Well, you're more
prepared to permit them to look with some --
DR. HYMAN: I must not have expressed myself
-- well, I just said I have much more sympathy with the sickest
person, and --
PROF. MEILAENDER: I'm not talking
about a sick person, just a person who'd like to be a
DR. HYMAN: What I'm saying is, I don't
find a rational way to draw the line to say that at some point
we can't -- I've been trying to take refuge in good
medical practice, and I've been not allowed to do that,
and ask whether in principle I would draw a line in which
somebody with no diagnosable illness - right - with no diagnosable
illness would not be allowed to take a medication. And what
I'm saying is that if you ask me naked of all my protections
about medical practice, follow-up, and this and that, I would
have to say I can't find that line right now, but that
I'm worried about the impact of that on the sense of moral
agency and personal responsibility.
CHAIRMAN KASS: Paul.
DR. McHUGH: I'm sorry you have to
leave, Steve, because we could go on for a long time talking
about your presentation, and how thorough it was. But I want
to come, if you would, just briefly to talk about the foundations
of your opinions here today as expressed. I know you have
other opinions, and they turn on this idea that we're
dealing with reality out there, and we have to make accounts
of reality. But, Steve, you know perfectly well that those
realities of our making, particularly from the psychiatric
side. And that DSM-III-R, IV, and IV-TR are based on a particular
approach to things that had a reason 25 years ago, to try
to get us to talk, but now has its own deep problems, very
DR. HYMAN: Right.
DR. McHUGH: Including the expansion of
psychiatric disorder so that it's now a huge, huge thing.
DR. HYMAN: Right.
DR. McHUGH: The belief in appropriate
treatments now being offered for various forms of conditions
that are placed in there, certain forms of PTSD, social phobia,
multiple personality disorder, and all of that rests upon
this idea that a top-down approach of checking off a checklist
is the right way to diagnosis. With your hope that ultimately
we'll find a validation of that from --
DR. HYMAN: A different set of --
DR. McHUGH: Yeah, entirely different.
Now since that reality is of our making, that's what makes
for the 11 minutes is all you, and that you can't teach
people appropriate approaches to psychiatry, I have two questions.
What are we going to do about getting a psychiatric approach
to diagnosis that approximates medicine? DSM-IV does not
approximate anything like medicine in ICD-9 and 10, as you
know that, so that's the first question.
And the second question is, do we understand development,
maturation and acculturation for it's psychosocial tasks
adequately, and its responsibilities for the development of
the child right now to be able -- for most children to be
able to intervene with medications? You said that drugs and
life experience do the same thing to the brain. And you know
I agree with that. They certainly change the synapses. But
we also know that both drugs and live experiences can do terrible
things in the process of building --
DR. HYMAN: Right.
DR. McHUGH: So question one, where are
you going with DSM-IV to DSM-V? Secondly, do we understand
anything to be able to satisfy the gentlemen on this side,
and ladies on this side, to say that we know how to build
a child sufficiently well to make the gains on your SAT scores
adequate to the things you lose in depriving them of the opportunity
to play more, to have different friends.
DR. HYMAN: Right. Okay. So this is --
right, these were not exactly yes or no questions.
DR. McHUGH: No.
DR. HYMAN: You know because you've
read my criticisms of current psychiatric diagnostic nomenclature,
that I find enormous problems, and again, in one minute, we
have a difference between trying to coalesce around and name
important conditions that we really see that people have,
like manic depressive illness or schizophrenia, versus the
exigencies of a profession that wants to be reimbursed for
its work and is forced by, you know, the reimbursement system
to give a lot of things names, and we know that there is a
lot of -- this is not theoretically neutral or apolitical,
but at the same time, I have a certain amount of sympathy
in my better moments given the -- the real difficulties of
doing better given the state of our science, so we have to
change, but I don't have any easy prescription for how
to change. And I'm very conservative about blowing up
an existing system. I'd like to fight its excesses.
You and I would both like to fights its excesses, but I don't
want to blow it up until I have something really that -- until
our genetics is farther along, our neuro imaging is farther
along, because we'll go back to Babel.
The other issue is exactly my problem, and Professor Sandel
here smoked me out, that I am living -- on the one hand I
can't find, you know, a bright line that if we really
had perfect drugs which didn't create, you know, the 1980
-- I'm sorry, the "Brave New World" scenario.
I could find a bright line to outlaw them, but at the same
time, my -- as I said my precise concern is the messages that
we deliver in terms of human self-efficacy and moral responsibility.
And if you can find a way to manage the reality that will
dawn on us, there is just no doubt that minimizes the undercutting
of a sense of human agency and moral responsibility, without
unfairly stigmatizing those who are truly in need of treatment.
You have my blessing and best wishes. Unfortunately, I have
to be off --
DR. McHUGH: If I could just reply to that
just to say that maybe the thing that we need is not more
neuroscience at some level and better psychiatry at some level,
both to develop a classification and to answer some of these
questions about what maturation itself is doing to individuals,
and that's where my problem.
CHAIRMAN KASS: Dr. Hyman has to return
to teach a class. It's heroic of him to have come on a
teaching day to spend time with us. Thank you enormously
for a wonderful session. We're adjourned for 15 minutes.
(The session then went off the record for a break.)
CHAIRMAN KASS: This is a session on the
topic of "Beyond Therapy: Ageless Bodies?" Before
we start into that, at least a couple of the people who had
their hands up when time ran out have spoken to me about a
possibility of at least putting into the record certain kinds
of questions or concern, not so much to interrogate Dr. Hyman,
who unfortunately had to leave, but if people would briefly
like to simply put into the discussion the questions or concerns
that they had, since that was a conversation that was just
about to take off, I think it would be appropriate if we allowed
room for that. I had on my list Bill May, and Bill Hurlbut,
and I don't know if there was anyone else in the queue.
Bill, do you want to add something?
DR. MAY: Well, I felt that Dr. Hyman talked
about the gap between what we know and what we do, which tends
to lead to too much over-treatment, and too much under-treatment.
But earlier he really talked about the gap in science really,
it's a young science we're talking about. And also,
there's a second gap between what we know now, and what
we would like to know to feel comfortable about what we do.
And both of those gaps seems to lead in the direction of saying
no regulations, no bans, but it makes you very dependent upon
a guardian class in the interval before you narrow the gap
between what we know now, and what we should know to feel
fully confident in what we do.
But what was quite depressing, it seemed to me, is you depend
upon the guardian class, but it turns out that our guardian
class doesn't have the timing, or the time or the training
to do what it ought to do in order to guard. So no regulations
given the gaps with which we live, real dependency upon the
clinicians, but we discover the clinicians are woefully under-trained
in operating in a system where they have no time, even if
they had the training, to do what needs to be done. Which
again leads bioethics out in the direction of systems, institutions
and structures, away from some of the issues that we've
CHAIRMAN KASS: Bill Hurlbut.
DR. HURLBUT: I was going to inquire of
Dr. Hyman whether he thinks that he would see ADHD in a hunter/gatherer
community, and in the same amount. And whether it really
is in some way an artifact of narrowing our definition of
normal, because it seems to me that -- well, if it were a
Mendelian trait, we'd define polymorphism as 1 percent
of the population. Here we have 3 to 5 percent. It seems
like well, 3 to 5 percent of the population could have some
kind of a deficit, but then the question becomes well, is
this just part of the spectrum of human variation in a positive
aspect of our society which should not necessarily be treated
or narrowed, but given a different educational process and
opportunity to develop in its own trajectory.
I think it's interesting that ADHD is kind of a derivative
diagnosis based on the educational system. Isn't that
where it's first picked up, as inability to sit at a little
desk, read little black symbols off of white pages, and not
playing out with the activity that normally accompanies childhood
for most of human history? What worries me about this is
it also goes deeper than that. I think the idea that this
is a genetic disease, which is -- certainly, there's a
strong corollary between monozygotic twins, but that doesn't
necessarily mean it's even genetic, of course, because
it's -- they share nine months in the womb. And there
are some people that believe that maternal stress during gestation
provokes this problem, and that even if it were correlated
through generations doesn't prove its genetic because
there are now evidences that stress itself is echoed generation
after generation. And what worries me in that is that when
you label something genetic, it's much easier to justify
the concept that it has a single unitive source as maybe a
missing enzyme or something like that, and then justify a
medical diagnosis and a pharmacologic intervention, so I think
those are worth saying.
And then just two final points. One is that I disagree
with the statement that was made, if I understood it right,
that there was no difference between treating somebody who
seems to fall below the norm and somebody above. I think
there's an intrinsic difference there, and one case you
might argue that it is more like therapy in the sense that
it's normalizing, that it's bringing somebody into
On the other hand, that's when you treat the left side
of the bell curve. But when you treat the right side of the
bell curve, it's intrinsically competitive because it's
moving you away from the norm into a realm of superior performance.
I mean, there's a lot more to be said about that, but
I think if you think of human community as the ground not
just of human strength in sociology, but also human meaning,
then there's an intrinsic difference between the treatment
of those two sides of the bell curve.
And finally, it seems to me that one of the fundamental
dangers in this simplistic notion of a genetic deficit is
that the reification of a very complex human phenomenon where
we tend to think of complicated human realities as treatable
by some kind of magic bullet, when in fact the closer you
get to meaningful human existence, the less easy it will be
to intervene, because human beings have evolved, or have been
created, however you want to see it, to be distanced from
determinism, and even simple molecular interventions. The
most meaningful human existence is somehow the comprehensive
willed self-governance of our humanizing activities. And
to the degree that we give over easily to notions that there
are simple deficit disorders, we have to be very cautious
about that because that's a very dangerous assumption
in a complicated species like our's.
That's not to say I don't believe there are disorders
like that, and I'm not saying this one isn't, but
it just strikes me as a very, very important point. And actually,
let me add one final point to that. Even if you say this
is directly related to say a genetic cause, there are historical
conditions that suggest that we need to be very, very careful
about what we think that cause is. An example of that would
be cleft palate and the relationship with mental retardation,
which was long assumed to be correlated. And then when it
got to the point where our medical treatments could go in
and do surgical interventions early enough, we realized that
that so-called genetic mental retardation was actually a byproduct
of the fact that the cleft palate was blocking the eustachian
tubes, causing earaches and otitis media, and muffling speech,
and therefore, causing the children to not be able to keep
up with their peers because they couldn't hear and understand
what was going on. So what looked like a genetic cause of
mental retardation, turned out to be just a secondary.
CHAIRMAN KASS: Okay. I think there are
people who are also in the midst of developing their own thoughts
in relation to Dr. Hyman's presentation. And Paul and
others, if you'd be so inclined, a couple of paragraphs
leading to some kind of question, we would welcome them at
the office, and we can send them on to him and see if we can
elicit from him some further elaboration on some of the things
of concern to us.
Let me turn to --
DR. FOSTER: Leon, let -- could I just
CHAIRMAN KASS: Please, Dan.
DR. FOSTER: I want to sort of give a reference
for the library that people might have here, because one of
the things we talked about in the last hour was the issue,
the moral issue of one struggling without the help of drugs
and so forth in mental illness, and maybe some of you have
seen it, but Leon Rosenberg, who happens to be a close friend
of mine, Leon Rosenberg has published his experience with
manic depressive illness. Leon was a Dean at Yale Medical
School for 10 years, and now works at Princeton, and Robby
probably knows him in molecular biology and so forth. He
published an article called "Brainsick", and it's
in Cerebrum, Vol. IV. I can't remember the pages,
last year. It's one of the most remarkable documents
that I have ever read, a confession about a struggle from
youth, ending up finally in a suicide attempt in which ultimately
then somebody who struggled against this for life, was a great
investigator, became the Dean of Yale, and all these things,
trying to fight this alone, and eventually succumbed and surrendered
to a suicide, requiring ultimately electroconvulsive therapy
and Lithium and so forth. It also is a familial, as he outlines,
it's a familial illness, and it simply emphasizes to me
the difference between a highly moral struggle to try to do
it by one's own in an illness which ultimately requires
medical therapy. And so it's heroic in one sense, and
in another sense it's a tragedy. I mean, not that he
didn't achieve everything, but he might have had a happier
life if he could have done that. So I simply wanted, if you
haven't seen it. It's a rather obscure journal, and
so -- but I thought it would be an interesting article to
put into the archives of the library that the Council is putting
CHAIRMAN KASS: Yeah. Thank you, Dan.
We'll find it and actually circulate it to members.
DR. FOSTER: Yeah. Leon Rosenberg is the
author. It's called "Brainsick" in Cerebrum.