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Philip Shaw, MD; Jason Lerch, PhD; Deanna Greenstein, PhD; Wendy Sharp, MSW; Liv Clasen, PhD; Alan Evans, PhD; Jay Giedd, MD; F. Xavier Castellanos, MD; Judith Rapoport, MD

Arch Gen Psychiatry. 2006;63:540-549.

Context  Data from a previous prospective study of lobar volumes in children with attention-deficit/hyperactivity disorder (ADHD) are reexamined using a measure of cortical thickness.

Objective  To determine whether regional differences in cortical thickness or cortical changes across time characterize ADHD and predict or reflect its clinical outcome.

Design, Setting, and Participants  Longitudinal study of 163 children with ADHD (mean age at entry, 8.9 years) and 166 controls recruited mainly from a local community in Maryland. Participants were assessed with magnetic resonance imaging. Ninety-seven patients with ADHD (60%) had 2 or more images and baseline and follow-up clinical evaluations (mean follow-up, 5.7 years).

Main Outcome Measures  Cortical thickness across the cerebrum. Patients with ADHD were divided into better and worse outcome groups on the basis of a mean split in scores on the Children's Global Assessment Scale and persistence/remission of DSM-IV–defined ADHD.

Results  Children with ADHD had global thinning of the cortex (mean reduction, –0.09 mm; P=.02), most prominently in the medial and superior prefrontal and precentral regions. Children with worse clinical outcome had a thinner left medial prefrontal cortex at baseline than the better outcome group (–0.38 mm; P=.003) and controls (–0.25 mm; P=.002). Cortical thickness developmental trajectories did not differ significantly between the ADHD and control groups throughout except in the right parietal cortex, where trajectories converged. This normalization of cortical thickness occurred only in the better outcome group.

Conclusions  Children with ADHD show relative cortical thinning in regions important for attentional control. Children with a worse outcome have "fixed" thinning of the left medial prefrontal cortex, which may compromise the anterior attentional network and encumber clinical improvement. Right parietal cortex thickness normalization in patients with a better outcome may represent compensatory cortical change.

Author Affiliations: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md (Drs Shaw, Greenstein, Clasen, Giedd, and Rapoport and Ms Sharp); Montreal Neurological Institute, McGill University, Montreal, Quebec (Drs Lerch and Evans); and New York University Child Study Center, New York (Dr Castellanos).

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