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

Seymour, Karen E.; Tang, Xiaoying; Crocetti, Deana; Mostofsky, Stewart H.; Miller, Michael I.; Rosch, Keri S.

doi:10.1016/j.pscychresns.2017.01.002

Cited by 44 publications

(50 citation statements)

References 65 publications

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Methodsmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Rosch

Crocetti

Hirabayashi

et al. 2018

Psychiatry Research: Neuroimaging

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Anomalous brain structure and function are implicated in children with attention-deficit/hyperactivity disorder (ADHD). Most neuroimaging research, however, has examined school-aged children, despite the typical onset of symptoms in early childhood. This study compared the volumes of subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) among preschoolers with ADHD and typically developing (TD) children. High resolution T1-weighted 3D MPRAGE images covering the whole brain were acquired on a 3T scanner and subcortical volumes were automatically extracted. Analyses were conducted in a total of 87 medicationnaïve preschoolers, ages 4–5 years (47 with ADHD, 40 controls; 63% boys). ADHD was diagnosed using modified DSM-IV criteria based on review of developmental history, structured psychiatric interview and caregiver ratings. Compared to typically developing children, subcortical volumes were reduced among preschoolers with ADHD, with largest reductions in the caudate, globus pallidus, and thalamus. Among girls (but not boys) with ADHD, putamen and thalamus volumes were associated with ADHD symptom severity. The observed patterns of subcortical differences in preschoolers with ADHD (larger reductions in girls), contrasted with differences observed among school-aged children, (larger reductions in boys) suggests that children with ADHD show sexual dimorphism in neuroanatomical development that parallels early trajectory of symptom onset and attenuation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Rosch

Crocetti

Hirabayashi

et al. 2018

Psychiatry Research: Neuroimaging

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Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder

Vetter

Backhausen

Buse

et al. 2019

Human Brain Mapping

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About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD-only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ-including 36 boys with ADHDonly, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms.No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD. K E Y W O R D SADHD, adolescence, conduct disorder, FreeSurfer, oppositional defiant disorder, structural morphology, structural MRI † Shared senior-authorship.

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Attention‐deficit/hyperactivity disorder and white matter microstructure: The importance of dimensional analyses and sex differences

et al. 2022

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Background Attention‐deficit/hyperactive disorder (ADHD) has substantial heterogeneity in clinical presentation. A potentially important clue may be variation in brain microstructure. Using fractional anisotropy (FA), previous studies have produced equivocal results in relation to ADHD. This may be due to insufficient consideration of possible sex differences and ADHD's multi‐componential nature. Methods Using whole‐brain analyses, we investigated the association between FA and both ADHD diagnosis and ADHD symptom domains in a well‐characterized, ADHD (n = 234; 32% female youth) and non‐ADHD (n = 177; 52% female youth), case‐control cohort (ages 7–12). Sex‐specific effects were tested. Results No ADHD group differences were found using categorical assessment of ADHD without consideration of moderators. However, dimensional analyses found total symptoms were associated with higher FA in the superior corona radiata. Further, inattention symptoms were associated with higher FA in the corpus callosum and ansa lenticularis, and lower FA in the superior longitudinal fasciculus (SLF), after controlling for overlap with hyperactivity‐impulsivity. Hyperactivity‐impulsivity symptoms were associated with higher FA in the SLF, and lower FA in the superior cerebellar peduncles, after control for overlap with inattention. Meanwhile, both categorical and dimensional analyses revealed ADHD‐by‐sex interactions (voxel‐wise p < .01). Girls with ADHD had higher FA, but boys with ADHD had lower FA (or no effect), compared to their same‐sex peers, in the bilateral anterior corona radiata. Further, higher ADHD symptom severity was associated with higher FA in girls, but lower FA in boys, in the anterior and posterior corona radiata and cerebral peduncles. Conclusions ADHD symptom domains appear to be differentially related to white matter microstructure, highlighting the multi‐componential nature of the disorder. Further, sex differences will be crucial to consider in future studies characterizing ADHD‐related differences in white matter microstructure.

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

Cited by 44 publications

References 65 publications

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

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

Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder

Attention‐deficit/hyperactivity disorder and white matter microstructure: The importance of dimensional analyses and sex differences

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