Developmental trajectories of the corpus callosum in attention-deficit/hyperactivity disorder

Abstract

Background: It was recently found that the development of typical patterns of prefrontal, but not posterior, cortical asymmetry is disrupted in right-handed youth with attention-deficit/hyperactivity disorder (ADHD). Using longitudinal data, we tested the hypothesis that there would be a congruent disruption in the growth of the anterior corpus callosum, which contains white matter tracts connecting prefrontal cortical regions.

Methods: Areas of five subregions of the corpus callosum were quantified using a semiautomated method from 828 neuroanatomic magnetic resonance scans acquired from 236 children and adolescents with ADHD (429 scans) and 230 typically developing youth (399 scans), most of whom had repeated neuroimaging. Growth rates of each diagnostic group were defined using mixed-model linear regression.

Results: Right-handed participants with ADHD showed a significantly higher rate of growth in the anterior-most region of the corpus callosum (estimated annual increase in area of .97%, SEM .12%) than their typically developing peers (annual increase in area of .32% SEM .13%; t = 3.64, p = .0003). No significant diagnostic differences in growth rates were found in any other regions in right-handed participants, and no significant diagnostic differences were found in non-right-handed participants.

Conclusions: As hypothesized, we found anomalous growth trajectories in the anterior corpus callosum in ADHD. This disrupted anterior callosal growth may reflect, or even drive, the previously reported disruption in the development of prefrontal cortex asymmetry. The finding documents the dynamic, age-dependent nature of callosal and congruent prefrontal cortical abnormalities characterizing ADHD.

Figure 1

Topography of the corpus callosum, as devised by Witelson (bottom panel) and modified by Hofer and Frahm (top panel).

Figure 2

Estimated growth rates in right handed, typically developing participants. Bar indicates mean percent change per year in area and lines indicate ± SE.

Figure 3

A. Estimated growth rates in right handed participants by diagnosis. Bars indicate estimated percent change per year in area. Lines indicate ± SE. B. Difference in annual percentage growth rates between right-handed participants with ADHD and typically developing controls. Bars indicate estimated percent change per year in area. Lines indicate ± SE.

Figure 4

Estimated area (in mm²) by age in right-handed ADHD and typically developing participants in each callosal subregion. Solid lines represent fitted growth curves, with dashed lines for 95% confidence intervals, estimated from linear mixed model regression.