Over the past year several key findings have emerged. (1) In a recent longitudinal study we found that the disorder was characterized by anomalous development of cortical asymmetry (Shaw, Lalonde et al. 2009). In early childhood, the left orbitofrontal/prefrontal cortex and right parieto-occipital cortex were relatively thicker than their homologues, but with age this asymmetry reversed so that by early adulthood the well-known pattern of greater right prefrontal and left occipital cortical dimensions emerged. In children with ADHD, the prefrontal component of this changing cortical asymmetry was lost, but the posterior changing asymmetry remained largely intact. Given the role of the corpus callosum in interhemispheric integration, we thus hypothesized that there would be a disruption in the growth of the anterior portions of the corpus callosum, which connects prefrontal cortical regions. Conversely we predicted no significant difference from the trajectory of typical development for the posterior callosal regions. Using a semi-automated measure of 895 corpus callosum acquired prospectively on 210 children with ADHD and matched controls, we confirmed this hypothesis (Gilliam, Malek et al. Submitted). 2) In collaboration with colleagues at the Children's Hospital of Philadelphia we have been examining the role of Copy Number Variants (large scale deletions and duplications of DNA sequences) in the pathogenesis of ADHD. Within our cohort, several potentially interesting deletions within genes were found- including the gene identified in the pathogenesis of restless leg syndrome and genes in nicotinic receptors. This work is currently under review in the New England Journal of Medicine and we intend to expand on the initial findings (Elia, Glessner et al. Submitted). 3) A recurrent theme of our work is that recovery from ADHD is associated with a convergence towards the template of typical development. We found this held for several cortical regions (the right parietal cortex) and cerebellar regions (the posterior inferior lobules). We thus extended our work to examine hippocampal and amygdala developmental trajectories and their links with clinical outcome in ADHD. We found that hippocampal growth reflected clinical course: a progressive deviation away from typical trajectories was associated with clinical persistence. There was no link with clinical outcome and the patterns of amygdala growth (Shaw, Malek et al. Submitted).
| Shaw, Philip (2010) The shape of things to come in attention deficit hyperactivity disorder. Am J Psychiatry 167:363-5 |
| Shaw, Philip; Lalonde, Francois; Lepage, Claude et al. (2009) Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 66:888-96 |
| Shaw, Philip; Sharp, Wendy S; Morrison, Meaghan et al. (2009) Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder. Am J Psychiatry 166:58-63 |
| Shaw, P; Wallace, G L; Addington, A et al. (2009) Effects of the Val158Met catechol-O-methyltransferase polymorphism on cortical structure in children and adolescents. Mol Psychiatry 14:348-9 |
| Rapoport, Judith L (2009) Personal reflections on observational and experimental research approaches to childhood psychopathology. J Child Psychol Psychiatry 50:36-43 |
