ADHD, DRD4, and brain development

Professor Philip Shaw discusses his team's research linking ADHD with a variant of the DRD4 gene, which is also associated with brain development.

We have been looking at one of the genetic variants in ADHD. It’s one of the dopamine receptors. It’s the D4 receptor. There are probably five types of receptors and this is the fourth one. There is a genetic variation in it and we’re particularly interested in the variant that is called the 7-repeat. People know that if you have this 7-repeat variation of the gene, your risk for having ADHD is increased, and this has been found in many studies. It has been replicated in many different countries, not always but most of the time. What we were looking at is, can we go a bit further and look at how this gene variation relates to clinical outcome and to brain development? So what we found in terms of clinical outcome I think surprised us a little bit. We found that if you had this risk variation of the gene, then you had a slightly better clinical outcome. And some other groups have found this, and some haven’t, so it’s certainly not a settled finding. Interestingly we also found that if you have this variation of the gene, that you have quite a distinct pattern of cortical or brain development – the cortex, the gray outer mantle of the brain. What you find is that, people who have this risk gene, they show, with time, a sort of normalization of the early problems they have with their cortex. This is particularly prominent in a part of the brain called the parietal cortex, which is kind of here, on the right side. So that was interesting because, in a previous study, we had found that normalization of this part of the brain, in general, is associated with having a good outcome of ADHD. So, it’s a good example of how you can link a gene variation with clinical outcome and then, in turn, link that with brain development.