Characterizing the Neural Correlates of Response Inhibition and Error Processing in Children With Symptoms of Irritability and/or Attention-Deficit/Hyperactivity Disorder in the ABCD Study®.

Ka Shu Lee,Ellen Leibenluft,Jiajun Luo,Wan-Ling Tseng,Jingyuan Xiao,Zeyan Liew

doi:10.3389/fpsyt.2022.803891

Abstract

Attention-deficit/hyperactivity disorder (ADHD), characterized by symptoms of inattention and/or hyperactivity and impulsivity, is a neurodevelopmental disorder associated with executive dysfunctions, including response inhibition and error processing. Research has documented a common co-occurrence between ADHD and pediatric irritability. The latter is more characterized by affective symptoms, specifically frequent temper outbursts and low frustration tolerance relative to typically developing peers. Shared and non-shared neural correlates of youths with varied profiles of ADHD and irritability symptoms during childhood remain largely unknown. This study first classified a large sample of youths in the Adolescent Brain Cognitive Development (ABCD) study at baseline into distinct phenotypic groups based on ADHD and irritability symptoms (N = 11,748), and then examined shared and non-shared neural correlates of response inhibition and error processing during the Stop Signal Task in a subset of sample with quality neuroimaging data (N = 5,948). Latent class analysis (LCA) revealed four phenotypic groups, i.e., high ADHD with co-occurring irritability symptoms (n = 787, 6.7%), moderate ADHD with low irritability symptoms (n = 901, 7.7%), high irritability with no ADHD symptoms (n = 279, 2.4%), and typically developing peers with low ADHD and low irritability symptoms (n = 9,781, 83.3%). Latent variable modeling revealed group differences in the neural coactivation network supporting response inhibition in the fronto-parietal regions, but limited differences in error processing across frontal and posterior regions. These neural differences were marked by decreased coactivation in the irritability only group relative to youths with ADHD and co-occurring irritability symptoms and typically developing peers during response inhibition. Together, this study provided initial evidence for differential neural mechanisms of response inhibition associated with ADHD, irritability, and their co-occurrence. Precision medicine attending to individual differences in ADHD and irritability symptoms and the underlying mechanisms are warranted when treating affected children and families.

Highlights

Attention-deficit/hyperactivity disorder (ADHD), characterized by symptoms of inattention and/or hyperactivity and impulsivity, is a common neurodevelopmental disorder in youths [1]
A fourclass solution was identified as the best fitting solution, Akaike Information Criterion (AIC) = 56111.24, Bayesian Information Criteria (BIC) = 56782.04, adjusted BIC (ABIC) = 56492.85, entropy =0.97, VLMR LRT p
To provide a more concrete overview of the differences in symptom profiles, Figure 2B presents a descriptive summary of the ADHD and irritability symptoms based on item-level symptom counts on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) in each LCA group

Summary

Introduction

Attention-deficit/hyperactivity disorder (ADHD), characterized by symptoms of inattention and/or hyperactivity and impulsivity, is a common neurodevelopmental disorder in youths [1]. Irritability, the frequent manifestation of temper outbursts and low frustration tolerance compared to peers [2, 3], is common in child psychiatry. Youths with disruptive mood dysregulation disorder (DMDD), for which severe irritability and temper outbursts are hallmark symptoms, show high rates of co-occurring ADHD [6]. Irritability symptoms in ADHD can be impairing and difficult to manage because temper outbursts and extreme frustration exacerbate maladaptive behavior with peers and caregivers and increase the risk of developing aggressive behaviors [5, 7], anxiety, and depression [8]. Despite the high prevalence of co-occurring ADHD and irritability, which is associated with greater impairment in social functioning and mental health than either alone, the underlying mechanisms of this co-occurrence remain unclear [9]. The goal of this study was to use data-driven latent modeling approaches to identify dissociable neural correlates of ADHD, irritability, and their co-occurrence during the Stop Signal Task (SST), a well-validated cognitive control task [10–12]

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