Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention–deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6—12 years) with rigorously–established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter–individual differences in clinician–based dimensional measures of autism and ADHD symptoms and whole–brain low motion intrinsic functional connectivity (iFC). Additionally, we explored their linked gene expression patterns in silico. Whole–brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes: the middle frontal gyrus of the frontoparietal network and posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD symptoms. Results from segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC interactions for autism symptom severity across diagnoses. No statistically significant brain–behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to: (i) have greater rate of variance in autism and ADHD, and (ii) be involved in neuron projection, suggesting shared genetic mechanisms for this specific brain–clinical phenotype. Overall, these findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically–defined phenomena to shared presentations at the macroscale circuit– and genomic–levels among children with diagnoses of autism and ADHD.

Drs. Lord and Bishop receive royalties for the sale of diagnostic instruments they have co–authored (ADOS–2 and/or SCQ); profits generated from any of their own research or clinical activities are donated to charity. Dr. Di Martino is coauthor of the Italian version of the Social Responsiveness Scale – child version distributed in Italy by Organizzazioni Speciali, Italy. All other co authors report no financial interests or potential conflicts of interest.

This work was partially funded by NIH R01MH105506 and R01MH115363 to ADM, R01MH091864 and R01MH120482 to MPM; the Korean Ministry of Science and ICT of the National Research Foundation RS-2023-00265410 to SHK, as well as generous gifts to the Child Mind Institute from the Dr. John and Consuela Phelan (to ADM), and from the Phyllis Green and Randolph Cowen Foundation (to MPM).

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The study was approved by and conducted in compliance with the Institutional Review Boards of the NYU Langone Health and Advarra Inc.

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