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F. Xavier Castellanos; Patti P. Lee; Wendy Sharp; et al.
JAMA. 2002;288(14):1740-1748 (doi:10.1001/jama.288.14.1740) http://jama.ama-assn.org/cgi/content/full/288/14/1740
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Pediatrics; Adolescent Medicine; Psychiatry; Attention Deficit Hyperactivity Disorder; Radiologic Imaging; Magnetic Resonance Imaging
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Related Articles published in the same issueAttention-Deficit/Hyperactivity Disorder
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Developmental Trajectories ofBrain Volume Abnormalities in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
F. Xavier Castellanos, MD Patti P. Lee, MD Wendy Sharp, MSW Neal O. Jeffries, PhD Deanna K. Greenstein, PhD Liv S. Clasen, PhD Jonathan D. Blumenthal, MA Regina S. James, MD Christen L. Ebens, BA James M. Walter, MA Alex Zijdenbos, PhD Alan C. Evans, PhD Jay N. Giedd, MD Judith L. Rapoport, MDTTENTION - DEFICIT / HYPER activity disorder (ADHD), the most common childhood psychiatric disorder, is thought to reflect subtle abnormalities in central nervous system functioning.1 For this reason, ADHD is being studied increasingly with a variety of brain imaging techniques throughout the life span. Magnetic resonance imaging (MRI) is particularly suitable for the study of pediatric patients,providing high-resolution images without ionizing radiation. Previous MRI neuroimaging studies, most with small samples, have reported smaller anatomic areas and/or volumes in patients with ADHD in regions of the cor-
Context Various anatomic brain abnormalities have been reported for attentiondeficit/hyperactivity disorder (ADHD), with varying methods, small samples, crosssectional designs, andwithout accounting for stimulant drug exposure. Objective To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. Design, Setting, and Participants Case-control study conducted from 19912001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescentswith ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. Main Outcome Measures Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of thebrain were compared in patients and controls. Results On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (−3.2%, adjusted F1,280 =8.30, P=.004) and in significantly smaller cerebellar volumes (−3.5%, adjusted F1,280 =12.29, P=.001).Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F2,288 =6.65; all pairwise comparisons Bonferroni corrected, −5.8%; P=.002) and cerebellar volumes (−6.2%, F2,288 =8.97, P .001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F2,288 =11.65) compared with controls (−10.7%,...