Regional brain volumes have been compared at initial MRI scans and their change over time in 152 medicated and previously unmedicated male and female patients (age range, 5-18 years) with attention-deficit/hyperactivity disorder (ADHD) and 139 age- and sex-matched healthy controls. In a case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, MD, total cerebrum, cerebellum, gray and white matter for the four major lobes, and caudate nucleus volumes were measured by automated methods. On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, amounting to a 3% decerease. Compared with controls, previously unmedicated ADHD children had significantly smaller total cerebral volumes, cerebellar volumes, and especially white matter volumes. In these unmedicated patients, white matter volumes were also smaller when compared with medicated ADHD children. Abnormal volumes persisted with age, except for caudate volumes which decreased in both patients and controls during adolescence. Male and female ADHD patients showed comparable abnormalities in regional brain volumes, and the changes correlated significantly with parent- and physician-rated severity of ADHD. It is concluded that brain volumetric and development changes related to genetic and/or early environmental factors in children with ADHD are fixed and nonprogressive through adolescence, and are unrelated to stimulant medication. 
COMMENT. It should be emphasized to parents that these quantitative MRI studies are only appropriate in research and not applicable to the diagnostic assessment and management of ADHD. The decreases in brain total and regional volumes in ADHD patients appear to reflect neurobiological insults or genetic factors that have influenced brain development early. The 3% disparity in brain volume stays constant through adolescence. In later childhood and adolescence, for the most part these decreases in brain volumes remain static and nonprogressive and are not influenced by medications or behavioral interventions. The previously emphasized frontal-striatal brain abnormality in ADHD is not confirmed in this study. Never medicated ADHD children have smaller white-matter volumes than those with ADHD who receive stimulants and compared to normal controls. These findings appear to further support arguments in favor of using medications for ADHD.