Elucidating distinct and common fMRI-complexity patterns in pre-adolescent children with Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, and Obsessive-Compulsive Disorder diagnoses.

Abstract

Importance: The pathophysiology of ADHD is complicated by high rates of psychiatric comorbidities, thus delineating unique versus shared functional brain perturbations is critical in elucidating illness pathophysiology.

Objective: To investigate resting-state fMRI (rsfMRI)-complexity alterations among children with ADHD, oppositional defiant disorder (ODD), and obsessive-compulsive disorder (OCD), respectively, and comorbid ADHD, ODD, and OCD, within the cool and hot executive function (EF) networks.

Design: We leveraged baseline data (wave 0) from the Adolescent Brain and Cognitive Development (ABCD) Study.

Setting: The data was collected between September 2016 and September 2019 from 21 sites in the USA.

Participants: Children who singularly met all DSM-5 behavioral criteria for ADHD (N = 61), ODD (N = 38), and OCD (N = 48), respectively, were extracted, alongside children with comorbid ADHD, ODD, OCD, and/or other psychiatric diagnoses (N = 833). A control sample of age-, sex-, and developmentally-matched children was also extracted (N = 269).

Main outcomes and measures: Voxel-wise sample entropy (SampEn) was computed using the LOFT Complexity Toolbox. Mean SampEn within all regions of the EF networks was calculated for each participant and hierarchical models with Generalized Estimating Equations compared SampEn of comorbid-free and comorbid ADHD, ODD, and OCD within the EF networks.

Results: SampEn was reduced in comorbid-free ADHD and ODD in overlapping regions of both EF networks, including the bilateral superior frontal gyrus, anterior/posterior cingulate gyrus, and bilateral caudate (Wald statistic = 5.682 to 10.798, p < 0.05 & BH corrected), with ADHD additionally affected in the right inferior/middle frontal gyrus and bilateral frontal orbital cortex (Wald statistic = 7.231 to 9.420, p < 0.05 & BH corrected). Among comorbid presentations, the additional presence of ADHD symptomatology was associated with significantly lower SampEn in every region of interest (z = -3.973 to -2.235, p < 0.05 & BH corrected).

Conclusions and relevance: ADHD and ODD shared common impairments underlying the EF networks in the comorbid-free presentations, with ADHD showing more widespread complexity reduction. When ADHD co-occurred with other psychiatric disorders, the reduction in SampEn extended beyond the regions affected in comorbid-free ADHD, indicating that comorbidities amplify neural complexity deficits.