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?