Anomalous subcortical morphology in boys, but not girls, with ADHD compared to typically developing controls and correlates with emotion dysregulation

Abstract

There has been limited investigation of volume and shape difference in subcortical structures in children with ADHD and a paucity of examination of the influence of sex on these findings. The objective of this study was to examine morphology (volume and shape) of subcortical structures and their association with emotion dysregulation (ED) in girls and boys with ADHD as compared to their typically-developing (TD) counterparts. Participants included 218 children ages 8-12 years old with and without DSM-IV ADHD. Structural magnetic resonance images were obtained, and shape analyses were conducted using large deformation diffeomorphic metric mapping (LDDMM). Compared to TD boys, boys with ADHD showed reduced volumes in the bilateral globus pallidus and amygdala. There were no volumetric differences in any structure between ADHD and TD girls. Shape analysis revealed localized compressions within the globus pallidus, putamen and amygdala in ADHD boys relative to TD boys, as well as significant correlations between increased ED and unique subregion expansion in right globus pallidus, putamen, and right amygdala. Our findings suggest a sexually dimorphic pattern of differences in subcortical structures in children with ADHD compared to TD children, and a possible neurobiological mechanism by which boys with ADHD demonstrate increased difficulties with ED.

Reduced subcortical volumes among preschool-age girls and boys with ADHD

“…Based on previous findings of ADHD-related sex differences in basal ganglia volumes (Qiu et al, 2009; Seymour et al, 2017), we compared the magnitude of diagnostic group differences separately among girls and boys for each of the subcortical structures despite the absence of a diagnostic group × sex × ROI interaction, F (3, 81) = 1.4, p = 0.242, d = 0.26. Among boys, although volume was generally reduced across all subcortical structures, there were no significant diagnostic group differences ( ps > 0.05), with medium effect sizes observed across all subcortical structures, ( ds ranging from 0.43 − 0.53), suggesting insufficient power to detect these effects.…”

“…In particular, a recently published study from our research group identified sex-differences in subcortical morphology (volume and shape) among school-age children (8–12 years) with and without ADHD (Seymour et al, 2017). In this older sample, boys with ADHD showed reduced volumes and localized compression in the globus pallidus and putamen, but not the caudate or thalamus, compared to TD boys, whereas no diagnostic group differences were observed in girls with ADHD compared to TD girls.…”

“…Interpretation of results focused on effects involving diagnostic group as this is our primary interest. We also explored ADHD-related sex differences given our previous findings of reduced basal ganglia volumes in boys, but not girls, with ADHD compared to same-sex TD peers (Qiu et al, 2009; Seymour et al, 2017). Cohen's d is reported as a measure of effect size for diagnostic group differences (absolute value) in volume such that d = 0.2, 0.5, and 0.8 are considered small, medium, and large effects, respectively (Cohen, 1988).…”

“…Specifically, Raznahan et al (2014) suggest that the estimated peak volume of the globus pallidus is earlier in males (age 7.7) than females (age 9.5) whereas the estimated peak volume of the striatum and thalamus is earlier in girls (ages 12 and 13.8, respectively) than boys (ages 14.7 and 17.4, respectively). Of the neuroimaging studies that included a greater proportion of females with ADHD allowing for examination of sex differences, some have reported that diagnosis-by-sex interactions in basal ganglia structures did not emerge (Castellanos et al, 2002; Hoogman et al, 2017; Villemonteix et al, 2015; Yang et al, 2008), although other studies suggested that diagnostic differences in basal ganglia morphology are specific to boys (Qiu et al, 2009; Seymour et al, 2017) or (for studies including girls only) not observed in girls (Castellanos et al, 2001). These inconsistent findings may be partially due to the age range of samples in these studies and or methodological differences, such as diagnostic methods, screening for comorbidities, image acquisition, processing, and statistical modeling, and, importantly, differences in the proportion and length of medication treatment for ADHD that have been shown to affect subcortical morphology (Sobel et al, 2010).…”

“…In addition, we have used an automated subcortical segmentation procedure that has shown to be superior to other segmentation algorithms, such as those implemented in Freesurfer (Tang et al, 2015). Given previous findings of sex differences in anomalous basal ganglia morphology among children with ADHD (Qiu et al, 2009; Seymour et al, 2017), we specifically compared subcortical volumes among girls and boys with ADHD to same-sex TD children. We hypothesized that preschool children with ADHD would show reduced subcortical volumes compared to age- and sex-matched TD preschoolers, but (in contrast to findings in school-aged children) the patterns of greater relative anomaly among boys with ADHD would be attenuated in pre-schoolers, given the earlier patterns of brain development in girls (Giedd and Rapoport, 2010; Giedd et al, 2015; Raznahan et al, 2014; Shaw et al, 2008).…”