For our initial sample, children with Attention-Deficit/Hyperactivity Disorder (ADHD) participated in double-blind placebo-controlled randomized trials of stimulants while undergoing anatomic imaging with magnetic resonance imaging (MRI). The children are now being followed, with yearly clinical and neuroanantomic assessments. Genetic studies are being conducted in tandem, allowing links to be made between genes, clinical outcome and brain development. Over the past year several key findings have emerged. (1) Adolescents treated with psychostimulants for ADHD showed a very similar pattern of cortical development compared to their peers who were untreated by psychostimulants. There were subtle differences in the development of the right motor strip, the left middle/inferior frontal gyrus;and the right parieto-occipital region, where there was more slower cortical thinning in the group who were treated;this more closely resembled the healthy control group trajectory (published in the American Journal of Psychiatry). 2) In collaboration with colleagues at the Childrens Hospital of Philadelphia we have been examining whether Copy Number Variants large scale deletions and supplications of DNA sequences- are found in ADHD. We have already identified several large scale deletions within genes controlling glutamatergic neurotransmission and are now relating these to clinical outcome and neuroanatomic data. This work is under review at Nature. 3) Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). In the first longitudinal study to examine the development of cortical asymmetry using longitudinal neuroanatomical data we found that in right-handed typically developing individuals, an increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age was balanced against a relative left-hemispheric increase in the occipital cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders. This work is published in the Archives of General Psychiatry.
| 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 |
