White Matter Microstructure in Subjects With Attention-Deficit/Hyperactivity Disorder and Their Siblings

Abstract

Objective Previous voxel-based and regions-of-interest (ROI)-based diffusion tensor imaging (DTI) studies have found above-normal mean diffusivity (MD) and below-normal fractional anisotropy (FA) in subjects with attention-deficit/hyperactivity disorder (ADHD). However, findings remain mixed and few studies have examined the contribution of ADHD familial liability to white matter microstructure. Method We used refined DTI tractography methods to examine MD, FA, axial diffusivity (AD) and radial diffusivity (RD) of the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major, forceps minor, superior longitudinal fasciculus and uncinate fasciculus in children and adolescents with ADHD (n = 56), unaffected siblings of ADHD probands (n = 31) and healthy controls (n = 17). Results Subjects with ADHD showed significantly higher MD than controls in the anterior thalamic radiation, forceps minor, and superior longitudinal fasciculus. Unaffected siblings of subjects with ADHD displayed similar differences in MD as subjects with ADHD. While none of the tested tracts showed a significant effect of FA, the tracts with elevated MD likewise displayed elevated AD in both subjects with ADHD and unaffected siblings. Differences in RD between subjects with ADHD, unaffected siblings and controls were not as widespread as differences in MD and AD. Conclusion Our findings suggest that disruptions in white matter microstructure occur in several large white matter pathways in association with ADHD and indicate a familial liability for the disorder. Furthermore, MD may reflect these abnormalities more sensitively than FA.

The Relation Between ADHD and Cognitive Profiles of Children with NF1

“…In regard to weaknesses on tasks measuring attentional control, working memory, and cognitive processing and response speed, the NF1 IQ profile is in keeping with research on other developmental disabilities, showing a consistent susceptibility to disruption in attention, working memory, and cognitive efficiency functions (Oliveras-Rentas et al 2011;Mayes and Calhoun 2006). These types of neuropsychological deficits are linked to disruptions in white matter tracts, which are particularly vulnerable due to their protracted developmental trajectory (e.g., Barnea-Goraly et al 2005) and are commonly seen in developmental disabilities including NF1, ADHD, and autism spectrum disorders (ASD) (e.g., Lawrence et al 2013;Weinstein et al 2011;Cutting et al 2002). From this perspective, the IQ profile seen in children with NF1 reflects similar vulnerabilities as those observed in other developmental disabilities, such as ADHD and ASD.…”

Altered white matter tract property related to impaired focused attention, sustained attention, cognitive impulsivity and vigilance in attention-deficit/hyperactivity disorder

“…[31][32][33] Despite the lack of change of the cingulum bundle property in individuals with ADHD reported in our prior investigation 23 and in another study 32 with a much larger independent sample and a different DSI tractography approach from our earlier investigation, current studies support decreased diffusion anisotropy of the cingulum bundle in youths with ADHD.…”

Attention Deficit Hyperactivity Disorder

“…Casey et al (2007 showed that disruption in fronto-striatal fiber tracts of subjects with ADHD was correlated with lower performance on a go/no go task, suggesting atypical fronto-striatal circuitry affects cognitive control in children with ADHD. Importantly, some of these findings are strengthened by work showing their heritability (Casey et al 2007;Lawrence et al 2013). In a sibling study by Lawrence et al (2013), individuals with ADHD and their unaffected siblings show similar differences in white matter microstructure, compared to controls, in the anterior thalamic radiation, forceps minor, and superior longitudinal fasciculus.…”