Structural Brain Alterations and Their Association with Cognitive Function and Symptoms in Attention-Deficit/Hyperactivity Disorder Families

Abstract

<jats:title>Abstract</jats:title><jats:p>Gray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 – 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a case/control difference with sub-clinical cases being intermediate between cases and controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to cases, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity.</jats:p>

Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

“…Recently, we leveraged structural magnetic resonance imaging (sMRI) data from reasonable large adult and adolescent samples to study brain alterations underlying persistent ADHD symptoms and cognitive impairments using consistent analytical approaches. We identified that GMV of the superior/middle/inferior frontal regions was consistently associated with working memory performance, and cerebellum GMV was consistently related to inattention symptoms in both adults and adolescents with ADHD [22,28,36]. Our findings emphasize that not only the symptom and impaired cognitive functions but also the underlying neurological alterations persist from childhood to adulthood in individuals with ADHD.…”

“…Converging evidence from anatomical studies suggest that children/adolescents with ADHD have global gray matter volume (GMV) reductions [11][12][13][14][15] and regional GMV reductions in the basal ganglia [12,[16][17][18], the frontal lobe [13,[18][19][20], the anterior cingulate cortex [21], and the cerebellum [11,14,18,22]. Adults with ADHD also showed reduced total (cortical) GMV [23][24][25], reduced GMV in the frontal lobe [23,[25][26][27][28], caudate nucleus [29,30], and cingulate cortices [16,25,27,31], but the reduction is less conclusive as the recent ENIGMA-ADHD studies revealed no significant ADHD versus control differences for adults [32,33].…”