Abstract
Attention-Deficit/Hyperactivity Disorder (ADHD) and intelligence (IQ) are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development.In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with below median IQ is associated more with a delay of cortical development.
Highlights
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with substantial heterogeneity in terms of its cognitive correlates, changes in brain development, and genetic influences [1,2,3,4]
Analyses of the developmental trajectories of cortical thickness in above median and below median IQ subgroups suggest that this may be related to small but widespread reductions in cortical thickness that are difficult to detect in isolation but appear to be relatively stable over development
These findings suggest that differences in gray matter in children with ADHD and above median IQ may be more distributed throughout the brain and more developmentally stable than for children with ADHD and below median IQ
Summary
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with substantial heterogeneity in terms of its cognitive correlates, changes in brain development, and genetic influences [1,2,3,4]. Due to this heterogeneity, it has proven difficult to detect the etiological cascades that lead to symptoms of the disorder. Twin studies have shown that the relationship between ADHD and IQ is almost entirely explained by shared genetic factors [8,9]. This does not appear to be merely an epiphenomenon of the relationship between ADHD and established cognitive endophenotypes, such as cognitive control, as the genetic factors affecting IQ are disparate from those influencing other cognitive endophenotypes in ADHD [7,10,11]
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