Cracking the brain’s genetic code  pg. 3

It turns out that because of the complex genetics, it’s quite possible that in different populations we’ll see certain risk genes that we don’t see in other populations. So it’s going to take a while, but I have to say that I’m much more optimistic than I was 10 years ago.

Why are you more optimistic?

Coyle: Because we have the human genome pretty much mapped, our ability to find these risk genes has been very powerfully enhanced. Right now is going to be kind of the grunt work of identifying them. If we can use the Alzheimer’s story as sort of a template, I think that once one or two are identified in a specific disorder, we’ll get a handle on a pathway that could be quite revealing.

Scolnick: I think finding these risk genes was a literally impossible problem before the human genome was mapped. I think it was just too hard. The technology wasn’t there and the information to do the studies wasn’t there. I don’t think anyone ever would have found them.

What are some of the ethical issues that impede hypothesis-testing in the psychiatric clinic?

Scolnick: I don’t think they’re special to this field. Clinical research studies require clear informed consent forms, and protocols need to be evaluated in advance by institutional review boards. The special problem in studying brain or behavioral diseases is whether the patient is competent to understand the form and sign it or whether someone else representing the patient needs to do it. I think that’s the more unique part of this field.

Coyle: I would agree with that. I think a very special challenge would be autism, where the symptom onset is typically in the second year of life. There’s growing evidence from behavioral and educational intervention research that the earlier the intervention is brought to bear, the better the outcome. If we’re going to think about potential pharmacological interventions to treat autism, we’re going to be presented with special challenges about how do you do this in very young children.

The final thing I would say is that I don’t see these disorders as being easily parsed into disorders that simply respond to drugs and not to psychological interventions. I think what we’re finding more and more is that the combination of an appropriate psychological or psycho-educational intervention with the appropriate drug can result in much more robust responses.

Scolnick (to Coyle): Do you think that the system for conducting clinical trials in younger patients in the U.S. is optimally set up from an operational and training perspective, or do you think more attention or more training programs are needed?

Coyle: The National Institute of Mental Health funds a consortium of child and adolescent psychiatry clinical trial units, so that’s the good news. The bad news is that the clinician-scientist is an endangered species, and especially in the area of child and adolescent psychiatry, the number of individuals who are involved in research and have the knowledge and skill sets to do this research is really quite small. At the leading residency training programs, a significant portion of the M.D./Ph.D.s – about 20 percent – go into psychiatry. But that is not enough to carry the load. This is an area that really needs, I think, a sustained investment from NIH.

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