Gray Matter Volume Abnormalities in ADHD: Voxel-Based Meta-Analysis Exploring the Effects of Age and Stimulant Medication

Abstract

These findings confirm that the most prominent and replicable structural abnormalities in ADHD are in the basal ganglia. They furthermore suggest that ADHD patients may progressively catch up with their developmental delay with advancing age and that use of stimulant medication may be associated with normalization of structural abnormalities in ADHD, although longitudinal studies are needed to confirm both observations.

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“…13 Two of the VBM meta-analyses mentioned previously found that subcortical volume differences between patients with ADHD and controls were smaller when the patients had taken medication. 6,7 Further, increasing age was found to be associated with smaller brain volume differences 6,7 between participants with ADHD and controls, which is in line with the findings of studies reporting delayed brain maturation in participants with ADHD. 2,14 As previous MRI studies of ADHD included mostly children or adults, 5-7 the present study adds to the literature by focusing on adolescents and young adults.…”

“…28 However, findings in the prefrontal cortex have been inconsistent and are not supported by meta-analyses. [5][6][7] A possible contributing factor is the heterogeneity in age among studies, as development of the prefrontal cortex is late and protracted. 21 Subtyping of ADHD has been proposed based on dorsalfrontostriatal, orbitofrontal-striatal and fronto-cerebellar circuits involved in cognitive control, reward and motivation, and timing and building temporal expectations, respectively.…”

“…5 A more recent meta-analysis (202 children and adolescents and 176 adults with ADHD and 344 controls) confirmed the reduced localized subcortical grey matter findings in the right globus pallidus and putamen and also reported on a smaller right caudate nucleus, whereas larger local grey matter volume was found in the left posterior cingulate cortex. 6 The most recent study (175 children and adolescents and 145 adults with ADHD plus 288 controls) found reduced right globus pallidus and putamen volumes in children with ADHD, whereas the adult samples were characterized by anterior cingulate cortex volume reductions. 7 However, studies used to generate the meta -analyses showed strong heterogeneity among samples and methods; reliability analysis revealed inconsistency in findings in 50%-75% of the studies.…”

“…Three meta-analyses of VBM studies reporting on partly the same samples have investigated the most prominent volumetric differences between participants with ADHD and controls. [5][6][7] The first meta-analysis (114 children with ADHD and 143 controls) reported smaller grey matter volume in the right putamen and globus pallidus in children with ADHD than in controls. 5 A more recent meta-analysis (202 children and adolescents and 176 adults with ADHD and 344 controls) confirmed the reduced localized subcortical grey matter findings in the right globus pallidus and putamen and also reported on a smaller right caudate nucleus, whereas larger local grey matter volume was found in the left posterior cingulate cortex.…”

“…7 However, studies used to generate the meta -analyses showed strong heterogeneity among samples and methods; reliability analysis revealed inconsistency in findings in 50%-75% of the studies. 6 Given these limitations, investigating local volume differences within a single large sample has substantial added value over existing meta-analyses.…”