Autism and ADHD May Share a Hidden Brain-Gene Signature

Researchers have found that the severity of autism symptoms, rather than the diagnosis itself, is linked to patterns of brain connectivity associated with genes connected to autism and ADHD.

A study published in Molecular Psychiatry suggests that the biology underlying autism and ADHD does not fit neatly into current diagnostic categories. Although clinicians have long recognized that autism and ADHD frequently occur together, scientists have struggled to pinpoint the shared mechanisms behind that overlap.

Researchers from the Child Mind Institute and collaborating centers found that the intensity of autism symptoms, rather than whether a child carries a diagnosis of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD), is linked to specific patterns of brain connectivity and gene activity. The results add to a growing shift in psychiatry toward understanding neurodevelopmental conditions along dimensions of traits and biology, rather than as strictly separate disorders.

Symptom severity reveals shared biology

The research team, led by Adriana Di Martino, MD, Founding Director of the Autism Center at the Child Mind Institute and Senior Research Scientist, analyzed resting-state functional MRI scans from 166 verbal children between the ages of 6 and 12 who had been diagnosed with autism or ADHD (without autism). Resting-state imaging allows scientists to measure how different brain regions communicate while a person is not engaged in a specific task, offering insight into underlying network organization.

Children with more pronounced autism symptoms showed stronger connectivity between regions in the frontoparietal (FP) and default-mode (DM) networks. These networks play central roles in executive functioning, attention, and social cognition. In typical development, connectivity between these networks tends to decrease over time as the brain becomes more specialized. The heightened connectivity observed in children with greater symptom severity suggests differences in how these networks mature.

Importantly, this pattern appeared across the full group of children, regardless of whether they were formally diagnosed with ASD or ADHD. The connectivity differences also aligned with maps of gene expression in the brain, particularly genes involved in neural development that have previously been linked to both conditions. This overlap points to biological pathways that may cut across diagnostic labels.

“We see in the clinic that some children with ADHD share symptoms qualitatively similar to those observed in autism, even if they do not fully meet the diagnostic criteria for ASD,” says Dr. Adriana Di Martino. “By focusing on shared brain–gene expression patterns linked to autism symptoms across both ASD and ADHD, we can point towards a shared biological basis of these clinical observations. Our findings provide a more nuanced, dimensional understanding of neurodevelopmental conditions.”

Imaging and gene maps converge

The researchers were able to find this overlap between patterns of connectivity and gene expression by using a novel integrative approach that combines state-of the-art neuroimaging with in silico spatial transcriptomic analysis — a computational method that maps the connectivity patterns observed in participants against existing databases of where genes are expressed in the brain. This approach may be useful for future development of biomarkers associated with these neurodevelopmental conditions.

• Children diagnosed with ASD who show more severe autism traits display brain connectivity patterns that are also seen in a subset of children with ADHD who do not have a formal autism diagnosis.
• The observed differences in brain connectivity corresponded with regions where genes involved in neural development are active.
• The results indicate that overlapping behavioral features in autism and ADHD may stem from shared genetic influences.
• Processes that guide the maturation of large-scale brain networks appear to play an important role in the emergence of autistic traits in children with ASD, as well as in some children diagnosed with ADHD.
• The findings reinforce the value of combining dimensional approaches, which focus on symptom severity, with traditional diagnostic categories when studying neurodevelopmental conditions.
• This research lays the groundwork for identifying biological markers relevant to both autism and ADHD and for developing models that better predict vulnerability to more severe autism symptoms.

Implications for Clinical Practice and Research

The findings suggest that focusing on specific symptom dimensions and their biological correlates may lead to more precise recognition and treatment approaches tailored to individual neural profiles.

The results support a growing movement in psychiatry toward dimensional, transdiagnostic, and data-driven models of mental health. This approach has also been championed by the Child Mind Institute through its Healthy Brain Network, a landmark initiative that enables families to receive no-cost diagnostic assessments — and provides researchers with neuroimaging and phenotypic data from thousands of children.

Reference: “Connectome-based symptom mapping and in silico related gene expression in children with autism and/or attention-deficit/hyperactivity disorder” by Patricia Segura, Marco Pagani, Somer L. Bishop, Phoebe Thomson, Stan Colcombe, Ting Xu, Zekiel Z. Factor, Emily C. Hector, So Hyun Kim, Michael V. Lombardo, Alessandro Gozzi, Xavier F. Castellanos, Catherine Lord, Michael P. Milham and Adriana Di Martino, 23 October 2025, Molecular Psychiatry.
DOI: 10.1038/s41380-025-03205-8

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.

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