Over the past year several key findings have emerged. (1) In a longitudinal analysis, a total of 193 typically developing children with 389 neuroanatomic magnetic resonance images and varying levels of symptoms of hyperactivity and impulsivity were contrasted with 197 children with ADHD with 337 imaging scans. The relationship between the rates of regional cortical thinning and severity of symptoms of hyperactivity/impulsivity was determined. We found that youth with higher levels of hyperactivity/impulsivity had a slower rate of cortical thinning, predominantly in prefrontal cortical regions, bilaterally in the middle frontal/premotor gyri, extending down the medial prefrontal wall to the anterior cingulate;the orbitofrontal cortex;and the right inferior frontal gyrus. For each increase of one point in the hyperactivity/impulsivity score, there was a decrease in the rate of regional cortical thinning of 0.0054 mm/year (SE=0.0019 mm/year). Children with ADHD had the slowest rate of cortical thinning. Slower cortical thinning during adolescence thus characterizes the presence of both the symptoms and syndrome of ADHD, providing neurobiological evidence for dimensionality of the disorder. 2) We aimed to contrast the patterns of connectivity across development between the trajectories of the cerebral cortex and deeper structures in attention-deficit/hyperactivity disorder with typical development. From 840 neuroanatomic resonance images acquired prospectively on 232 typically developing and 232 age and sex matched youth with ADHD, we defined the developmental trajectories of the cerebral cortex and the caudate, putamen, nucleus accumbens, hippocampus and amygdala. We determined the cortical vertices where developmental trajectories did not differ significantly from the trajectories of each deep structure and were aligned developmentally. There were many similarities in the connectivity patterns found in both ADHD and in typical development. In both groups the development trajectories of the caudate and dorsolateral prefrontal cortex were very similar. Likewise the trajectories of the putamen and premotor/motor cortex were aligned as were those of the nucleus accumbens and cingulate cortex. These links may represent the developmental homologues of partly segregated cortico-striatal loops which are pivotal in cognition. In both ADHD and typically development, the hippocampus and amygdala showed similar trajectories to each other and to the polar/medial temporal cortex, mirroring patterns of anatomical connectivity established prenatally. There were however some notable diagnostic differences, particularly the link found in ADHD but not in typical development between trajectories of the hippocampus and dorsolateral prefrontal cortex. Such links may reflect anomalous plasticity in hippocampo-prefrontal circuits which mediate cognitive functions disrupted in ADHD such as working memory. 3) A recurrent theme of our work is that recovery from ADHD is associated with a convergence towards the template of typical development. In previous work we examined outcome in adolescence (mean age 15 years, SD 3 years). We have just completed a major project to examine the adult outcomes of these same subjects (conducted at a mean age of 22, SD 4 years), using multimodal imaging along with clinical and neuropsychological assessments. We are currently using these data to test our hypothesis that recovery from ADHD is associated with a convergence towards the template of typical development, whereas persistent ADHD is associated with progressive deviation away from typical trajectories.

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U.S. National Institute of Mental Health
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Shaw, Philip (2010) The shape of things to come in attention deficit hyperactivity disorder. Am J Psychiatry 167:363-5
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
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