Sex differences in white matter integrity in youths with attention-deficit/hyperactivity disorder: a pilot study

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.

Research Review: Diffusion tensor imaging studies of attention‐deficit/hyperactivity disorder: meta‐analyses and reflections on head motion

“…Details of included studies are provided in Table 1. Twelve studies with 13 datasets, including a total of 557 individuals with ADHD and 568 TD participants, were included in the meta-analysis of TBSS studies (Adisetiyo et al, 2014;Chuang, Wu, Huang, Weng, & Yang, 2013;Cooper, Thapar, & Jones, 2015;Cortese et al, 2013;De Luis-Garcia et al, 2015;King, Yurgelun-Todd, Stoeckel, Dimuzio, & Lopez-Larson, 2015;Nagel et al, 2011;O'conaill et al, 2015;Onnink et al, 2015;Silk, Vance, Rinehart, Bradshaw, & Cunnington, 2009;Van Ewijk et al, 2014;Yoncheva et al, 2016). Since one of two datasets in Cortese et al, recruited individuals with a current ADHD diagnosis, the study was included in the analysis (Cortese et al, 2013).…”

Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury

“…Notably, children born preterm often exhibit hyperactivity and limited inhibition (Hutchinson et al 2013, Wilson-Ching et al 2013, Anderson 2014, Murray et al 2014). Widespread disparities in white matter microstructure and organization have been found in adolescents with ADHD (King et al 2015). Little is known about the role of sex (King, Yurgelun-Todd et al 2015), or recently discovered novel molecular mediators of attention, such as stress-inducible phosphoprotein 1 (STIP1) (Beraldo et al 2015, King, Yurgelun-Todd et al 2015) and serotonin deficiency (Banerjee and Nandagopal 2015, Whitney et al 2016), in the elaboration of attention deficits and concomitant DTI abnormalities over time.…”

“…Widespread disparities in white matter microstructure and organization have been found in adolescents with ADHD (King et al 2015). Little is known about the role of sex (King, Yurgelun-Todd et al 2015), or recently discovered novel molecular mediators of attention, such as stress-inducible phosphoprotein 1 (STIP1) (Beraldo et al 2015, King, Yurgelun-Todd et al 2015) and serotonin deficiency (Banerjee and Nandagopal 2015, Whitney et al 2016), in the elaboration of attention deficits and concomitant DTI abnormalities over time. Here resources did not allow sufficient DTI analyses to investigate the impact of sex on microstructural abnormalities after injury, and in response to EPO treatment.…”

Structural and functional neuroimaging in attention‐deficit/hyperactivity disorder

“…58 Regarding sex, because of the higher prevalence of ADHD in males (male to female approximate prevalence ratio of 2:1), 1 females are usually underrepresented in studies, which hinders the study of the effects of sex on brain alterations in ADHD. While some studies have shown differences between ADHD in males and females in terms of brain volume (corpus callosum, caudate, anterior cingulate cortex), 4,59,60 working memory and inhibition related activity, 34,61 and white matter microstructure, 62 pointing to distinct neurobiological deficits underlying ADHD in both sexes, other structural and functional studies have failed to demonstrate an effect of sex. 9,10,63 Some studies have investigated the effect of symptom presentation and comorbidities (especially oppositional defiant disorder and conduct disorder) 8,10,64,65 in order to determine disorder specific abnormalities, but more studies are required to elicit clear-cut conclusions.…”