Nakao · The American journal of psychiatry 2011 · Voxel-based morphometry meta-analysis of case-control studies · n=14 studies (378 ADHD patients, 344 healthy controls)

Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication.

Cited 604 times in the scientific literature.

Level 3 - non-randomized controlled study

Meta-analysis of observational case-control neuroimaging studies

PubMed 21865529 · doi:10.1176/appi.ajp.2011.11020281 · record verified 2026-08-26

What was done

The authors conducted a meta-analysis of voxel-based morphometry studies comparing children and adults with ADHD to healthy comparison subjects using PubMed, ScienceDirect, Web of Knowledge, and Scopus (2001–2011). Coordinates of significant gray matter volume differences between groups were extracted. Metaregression analyses were used to assess the potential effects of age and the percentage of patients taking stimulant medication on regional gray matter volumes.

What was found

Fourteen data sets were included, comprising 378 patients with ADHD and 344 healthy comparison subjects. ADHD patients showed global reductions in gray matter volumes, robustly localized to the right lentiform nucleus and extending into the caudate nucleus. In metaregression, increasing age and higher percentage of patients taking stimulant medication were independently associated with more normal values in this region. Patients also showed slightly greater gray matter volumes in the left posterior cingulate cortex. No numerical effect sizes, test statistics, or confidence intervals were reported in the abstract.

Why it matters

This study pinpoints the basal ganglia (lentiform and caudate nuclei) as the primary site of structural gray matter alterations in ADHD across pediatric and adult cohorts. It also provides preliminary evidence that developmental maturation and stimulant treatment may be associated with structural normalization.

Limits

The underlying studies were cross-sectional case-control designs, preventing causal inferences regarding developmental trajectories or medication effects. Metaregression used study-level aggregated data rather than individual patient-level data. The abstract does not provide exact effect estimates, confidence intervals, or details on medication duration and dosage.

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