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PSYCHOLOGY
Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation

P. Shaw^,, K. Eckstrand, W. Sharp, J. Blumenthal, J. P. Lerch, D. Greenstein, L. Clasen, A. Evans, J. Giedd, and J. L. Rapoport

Child Psychiatry Branch, National Institute of Mental Health, Room 3N202, Building 10, Center Drive, Bethesda, MD 20892; and Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2T5

Edited by Leslie G. Ungerleider, National Institutes of Health, Bethesda, MD, and approved October 5, 2007 (received for review August 17, 2007)

Abstract

There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test (1)² = 5,609, P < 1.0 x 10^–20). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.

cortical development | structural neuroimaging

Author contributions: P.S. and J.L.R. designed research; P.S., W.S., J.B., L.C., J.G., and J.L.R. performed research; K.E., J.B., J.P.L., and A.E. contributed new reagents/analytic tools; P.S., K.E., and D.G. analyzed data; and P.S. and J.L.R. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

To whom correspondence should be addressed. E-mail: shawp{at}mail.nih.gov

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This article has been cited by other articles in HighWire Press-hosted journals:

				Cortical Maturation in Children with ADHD Journal Watch Psychiatry, January 28, 2008; 2008(128): 3 - 3. [Full Text]

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				K. Rubia Neuro-anatomic evidence for the maturational delay hypothesis of ADHD PNAS, December 11, 2007; 104(50): 19663 - 19664. [Full Text] [PDF]

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