Abstract
Widespread disparities in white matter (WM) microstructure and organization have been found in adolescents with attention-deficit/hyperactivity disorder (ADHD); however, little is known about the role sex plays in these differences. The present diffusion tensor imaging (DTI) study performed whole-brain, tract-based, voxel-wise, and region of interest (ROI) analyses to investigate WM microstructure differences between ADHD and healthy control (HC) adolescents to examine the impact of sex on measures of fractional anisotropy (FA). Eighteen adolescents with ADHD and 24 HC were included in this study. All participants received a 64-direction DTI scan on a 3 Tesla Siemens scanner. FSL's TBSS was used to perform whole-brain, tract-based, voxel-wise analyses. Tracts demonstrating significant sex-by-diagnosis interactions were further evaluated using univariate analyses performed on mean FA data that were extracted from ROIs using the Johns Hopkins University WM tractography atlas. TBSS analyses between diagnostic groups revealed significantly increased FA in HC relative to ADHD in the bilateral superior longitudinal fasciculus (SLF), forceps major, left cingulum, and bilateral callosal regions. In addition, both TBSS and separate ROI analyses revealed significant sex-by-diagnosis interactions for the corticospinal tract (CST), inferior longitudinal fasciculus (ILF) and SLF. In the HC group, FA was increased in males relative to females for all analyses. In WM regions demonstrating a significant sex-by-diagnosis, FA was increased in females relative to males in the ADHD group. Our findings suggest that WM microstructure in several major WM tracts differs between males and females with ADHD. These differences in WM microstructure may account for some of the differences in ADHD subtypes and comorbidities seen between the sexes. Additional studies in ADHD, examining sex differences in phenotypic expression, treatment response and brain network trajectories are warranted.
Highlights
Attention deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed chronic neurodevelopmental disorders in children and adolescents with recent reports citing prevalence rates of up to 10% for United States (US) (Bloom et al, 2013) and non-US populations (Faraone et al, 2003)
All five clusters indicated a significant sex-by-diagnosis interaction (p ≤ 0.001) with increased fractional anisotropy (FA) in males relative to females in the healthy controls (HC) group, while FA was increased in females relative to males in the attention-deficit/hyperactivity disorder (ADHD) group
In all instances where significant main effects of a sex-by-diagnosis interaction were found, FA was increased in males relative to females in the HC group, whereas in the ADHD group, FA was increased in females relative to males
Summary
Attention deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed chronic neurodevelopmental disorders in children and adolescents with recent reports citing prevalence rates of up to 10% for United States (US) (Bloom et al, 2013) and non-US populations (Faraone et al, 2003). Recent US health statistics report that male youths are three times more likely to be diagnosed with ADHD than females (Bloom et al, 2013); these differences in sex-related rates tend to converge in adult ADHD (Faraone et al, 2000) further supporting disparate clinical courses and neuropathologies between the sexes (Nussbaum, 2012). Castellanos et al (2002) reported a decrease in overall WM volume in ADHD when compared to HC
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