Cortical Thickness and Curvature in Autism and ADHD: A Mega-Analysis

Existing evidence suggests cortical morphometric alterations occur in people with autism and ADHD. However, these findings remain tentative due to small sample sizes, heterogeneous imaging pipelines, varied statistical approaches, and limited harmonization across acquisition sites. Few studies have applied standardized processing to large, clinically enriched datasets or addressed site-related batch effects.

We leveraged six large-scale brain imaging datasets (n = 9,647; male=5,835; female=3,812; ages 5-64 years), including 1,533 individuals with ADHD, 1,080 with autism spectrum disorder, and 7,034 matched controls. All imaging data were processed using the validated ABCD-HCP pipeline, with cortical parcellation into 360 regions based on the Human Connectome Project (HCP) atlas, and ComBat harmonization was applied to account for variability across 67 acquisition sites. Group-level differences in cortical thickness and sulcal curvature were examined with ANCOVAs, controlling for covariates and using Bonferroni correction for multiple comparisons.

Our analyses revealed distinct neuroanatomical signatures for both autism and ADHD. Individuals with autism exhibited regionally thinner cortex and curvature alterations particularly in the Cingulo-Opercular network. In contrast, individuals with ADHD displayed regionally thicker cortex, particularly in the default mode and somatomotor networks, alongside curvature differences. Control participants showed intermediate patterns, suggesting that autism and ADHD may represent diverging extremes of cortical maturation.

Cortical thickness and curvature emerge as potential biomarkers that can advance understanding of neurodevelopmental conditions and disentangle heterogeneity across diagnostic groups. These findings highlight the value of harmonized, large-scale, standardized analyses for resolving inconsistencies in the literature.