In my institute at NIMH, we've been very interested in sort of scoping out the next
5 years and where we think the most important developments will need to be,
and clearly we're in this revolutionary period in genomics so there will be a lot of activity there.
Clearly there is a need to understand the link between the candidate genes that
are coming up and the biology of those genes.
As we step back and look at
the place we are at now and the place we want to be, the thing that has jumped up at
us most of all is that most mental disorders
start very early in life. That way they are a little different than most
neurological disorders that come
much, much later in life and most chronic medical illnesses that come on late in life.
But schizophrenia, autism, even mood disorders and most anxiety disorders
start early. 50% of people who are adults with
those illnesses will talk about onset by
age 14, at least 50% of those with mood and anxiety disorders
which were the prototypic adult mental illnesses,
50% of those have onset by age 14.
So these are really early onset.
What we've begun to understand is that we really know very little about
the interactions of genes and environment in brain development;
yes there are these very important transition times,
there are points that are probably so-called sensitive periods for experience,
whether it's the acquisition of language, the acquisition of social skills,
the acquisition of basic motor skills
and certainly we've known for a long time about the acquisition of vision and auditory
information and how they getting encoded.
What we have yet to do is for these much more complex, for instance social
information processing kinds of functions,
we haven't been able to really pin down
what are those critical periods and most importantly how are the
behavioral changes, that is these behavioral transitions,
how they associated with changes in brain systems and changes in
cellular properties within those systems
and changes in patterns of gene expressions within those cells?
That's where we're going.
It's doable; we can do this certainly within mice and probably within
flies and probably using a zebra fish for some properties, not for language but for some
things that were interested in.
But this is going to be the challenge of the next few years, because one of the
things we're likely to learn
is that there are these very narrow windows when the right gene has to be
turned on in the right place to get the long term
pattern that you need in terms of function.
There's a whole book to be written about this, and this is a place that I think we're just
beginning to get a handle.
So much of what we've been thinking about in terms of
development has been the either behavioral development
or neural development
and we haven't made that bridge; we haven't made in the right way.
Much of our neurodevelopmental research, that is neural biology,
has been a very early stage;
early stages of differentiation, early stages of migration,
a little bit about how circuits form and how the brain gets sculpted.
Most of the behavioral development research
has been, particularly in humans, at a very late stage. It's looking at such
things as the development of language for the development of visual processing.
What we need to do now is to bring these together and to begin to understand, in
both humans and nonhuman animals,
how do these behavioral changes, these behavioral transitions map onto
molecular cellular systems changes in the brain which is supporting them?