For our initial sample, children with Attention-Deficit/Hyperactivity Disorder (ADHD) participated in double-blind placebo-controlled randomized trails of stimulants while undergoing anatomic imaging with magnetic resonance imaging (MRI). The children are now being followed, with repeated clinical and neuroanantomic assessments every 2 years. 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) We demonstrated that cortical development in ADHD children is delayed by several years, as measured by the age of attaining peak cortical thickness. This delay was most prominent in prefrontal cortical regions implicated in the control of attention. This work was recently published in the Proceedings of the National Academy of Science. ? ? (2) ADHD children with good outcome have a different regional brain trajectory in the posterior parietal region and cerebellar hemispheres suggesting compensatory plasticity (work published in the Archives of General Psychiatry and the American Journal of Psychiatry). Additionally, unpublished analyses indicate that a good outcome subgroup is developmentally delayed while others with continued disorder have a different brain developmental pattern. A large sample is being gathered in order to follow more remitted and non-remitted adolescents to test this hypothesis. A sample of adult subjects is also being collected to test the hypothesis that """"""""good outcome"""""""" adults are able to use the parietal region to supplement frontal lobe hypofunction compared with adults with continuing disorder. ? ? (3) The most commonly implicated risk gene for ADHD (the 7-repeat form of the gene for the dopamine D4 receptor) is related to cortical thinning in childhood and good outcome during adolescence (published in the Archives of General Psychiatry. ? ? (4) 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 rapid cortical thinning in the group who were untreated.
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