Brain-Charting Autism and Attention-Deficit/Hyperactivity Disorder Reveals Distinct and Overlapping Neurobiology

Background: Autism and attention-deficit/hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together and sex differences are often overlooked. Population modeling, often referred to as normative modeling, provides a unified framework for studying age-specific and sex-specific divergences in brain development. Methods: Here, we used population modeling and a large, multisite neuroimaging dataset (N = 4255 after quality control) to characterize cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of more than 75,000 individuals. We also examined sex and age differences and relationship with autistic traits and explored the co-occurrence of autism and ADHD. Results: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume that was localized to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness but lower cortical volume and surface area across much of the cortex. The co-occurring autism+ADHD group showed a unique pattern of widespread increases in cortical thickness and certain decreases in surface area. We also found that sex modulated the neuroanatomy of autism but not ADHD, and there was an age-by-diagnosis interaction for ADHD only. Conclusions: These results indicate distinct cortical differences in autism and ADHD that are differentially affected by age and sex as well as potentially unique patterns related to their co-occurrence.