Developmental Trajectories of Brain Volume Abnormalities in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
2002
ContextVarious anatomic brain abnormalities have been reported for attention-deficit/hyperactivity
disorder (ADHD), with varying methods, small samples, cross-sectional designs,
and without accounting for stimulant drug exposure.ObjectiveTo 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 ParticipantsCase-control study conducted from 1991-2001 at the National Institute
of Mental Health, Bethesda, Md, of 152 children and adolescents with 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 MeasuresUsing 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 the brain were compared in patients
and controls.ResultsOn 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%, P<.001) and with medicated
children with ADHD (−8.9%, P<.001). Volumetric
abnormalities persisted with age in total and regional cerebral measures (P = .002) and in the cerebellum (P =
.003). Caudate nucleus volumes were initially abnormal for patients with ADHD
(P = .05), but diagnostic differences disappeared
as caudate volumes decreased for patients and controls during adolescence.
Results were comparable for male and female patients on all measures. Frontal
and temporal gray matter, caudate, and cerebellar volumes correlated significantly
with parent- and clinician-rated severity measures within the ADHD sample
(Pearson coefficients between −0.16 and −0.26; all P values were <.05).ConclusionsDevelopmental trajectories for all structures, except caudate, remain
roughly parallel for patients and controls during childhood and adolescence,
suggesting that genetic and/or early environmental influences on brain development
in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.
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