Towards an integrative theory of the genetically mediated neural substrates of ADHD
06 / 2010 - 06 / 2014
Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder, affecting 3-7% of children. It is characterized by a persistent pattern of impulsiveness and inattention, with or without hyperactivity. Structural imaging studies have demonstrated regional brain changes, including (sub)cortical grey matter volume reductions in children with ADHD. Twin studies indicate that ADHD is highly heritable. However, genome-wide-association studies have failed to reliably identify genetic variants that explain even a small part of the genetic risk. Most likely, the combination of many genetic variants explains the vulnerability to ADHD. We propose a novel approach that utilizes functional genomic information to group genes into ?functional gene networks? (FGNs). We will subsequently test for the association of FGNs with ADHD symptoms and a clinical diagnosis of ADHD, in a large population-based cohort (n=3600) and a clinical cohort (N=300 cases). In addition, we will investigate how these FGNs relate to ADHD by conducting functional genetic experiments as well as brain imaging experiments. Large international replication cohorts are available. This project integrates expertise from child psychiatry, functional genomics and brain imaging. We propose to link functional gene networks to brain morphology, and directly relate any patterns observed to the morphological and clinical correlates of ADHD, aiming to formulate an integrative theory of the genetically mediated neural substrates of ADHD.