Neural mechanisms underlying irritability in children with and without attention-deficit/hyperactivity disorder (ADHD) and their associations with impairment

<span style="font-weight: 400;">Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by inattention, hyperactivity, and impulsivity, and it has been linked to increased emotion dysregulation and irritability. However, research examining the relationships between irritability, brain network organization, and impairment in children with ADHD and typically developing (TD) children is lacking. To examine these relationships using </span><em><span style="font-weight: 400;">t</span></em><span style="font-weight: 400;">-tests, analyses of covariance, and hierarchical regressions, the parents of 72 children (50 children with ADHD and 22 TD children) completed surveys targeting irritability levels and global impairment. Children completed an fMRI scan in order to examine graph metrics&mdash;within-module degree (WD) and participation coefficient (PC)&mdash;of a previously constructed irritability network. Children with ADHD demonstrated significantly higher parent-reported irritability (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;"> = .001) and impairment (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;"> &lt; .001) than their TD peers. No significant differences were observed in the WD or PC of the irritability network between groups, and graph metrics failed to predict impairment levels. We did find that ADHD was a significant predictor of behaviorally reported impairment (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;"> &lt; .001) and that irritability predicted this impairment above and beyond ADHD&nbsp; (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;"> &lt; .001). Our results suggest that understanding irritability may be critical for improving daily functioning in youth.&nbsp;</span>