New study finds novel link between shared brain-gene patterns and autism symptom severity in children with autism and ADHD

(Press-News.org) NEW YORK, NY (November 2025) A new study published in Molecular Psychiatry reveals that the biological underpinnings of autism and ADHD may transcend traditional diagnostic boundaries. While there is increasing appreciation that ADHD and autism often co-occur, the underlying shared biological features have remained largely unknown. Researchers from the Child Mind Institute and collaborating institutions discovered that autism symptom severity, rather than diagnostic classification, corresponds to distinct patterns of brain connectivity and related gene expression in children diagnosed with either autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD). This finding supports an evolving clinical and research landscape that aims to better define the roots of neurodevelopmental co-occurrences.

The study, led by Adriana Di Martino, MD, Founding Director of the Autism Center at the Child Mind Institute and Senior Research Scientist, examined brain connectivity using resting-state functional MRI in 166 verbal children aged 6–12 diagnosed with autism or ADHD (without autism).

The team discovered that more severe autism symptoms were associated with increased connectivity between nodes of the frontoparietal (FP) and default-mode (DM) networks, which are known to be essential for social cognition and executive functions. In typical development, this connectivity decreases with maturation to support functional specialization, so these findings point to a locus of atypical maturation in children with more severe autistic symptoms. This pattern was observed across all children, regardless of their diagnostic classification, and overlapped with expression maps of genes — particularly those involved in neural development — previously implicated in both autism and ADHD.

“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.”

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.

Key findings include:

Autism symptom severity is associated with similar patterns of brain connectivity in children with a diagnosis of ASD, and at least a subset of those with ADHD who do not present with a clear diagnosis of autism Connectivity differences aligned with brain expression of genes involved in neural development  The study findings that shared clinical presentations are linked to shared genetic mechanisms between autism and ADHD  Mechanisms involved in functional network maturation may play a significant role in the development of autistic symptoms in children diagnosed with ASD, and at least a subset of those diagnosed with ADHD Findings support the importance of both dimensional and categorical models of neurodevelopmental conditions  This study will shape future research for biomarkers associated with both conditions, as well as models of vulnerability for autism symptom severity 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. 

Access the study:
“Connectome-based symptom mapping and in silico related gene expression in children with autism and/or attention-deficit/hyperactivity disorder” is available open access in Molecular Psychiatry:
https://www.nature.com/articles/s41380-025-03205-8

About the Child Mind Institute
The Child Mind Institute is an independent nonprofit organization dedicated to transforming the lives of children and families struggling with mental health and learning disorders. Through cutting-edge research, evidence-based clinical care, and public education, the Child Mind Institute builds open science platforms and digital tools to accelerate discovery and improve youth mental health worldwide. Learn more at childmind.org.

Additional Resources:
Child Mind Institute Autism Center: https://childmind.org/science/fundamental-neuroscience/autism-center/
Interview requests with Dr. Di Martino: Contact media office

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