Observational study finds autism symptom severity linked to brain connectivity patterns — Evidence Review
Published in Molecular Psychiatry, by researchers from Child Mind Institute
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Table of Contents
A new study finds that the severity of autism symptoms, rather than the diagnostic label of autism or ADHD, is linked to shared patterns of brain connectivity and gene expression. Related studies generally support the idea that neurodevelopmental disorders overlap in brain network features, though they also highlight unique and distinct patterns across conditions, as discussed by the original study source.
- Several studies report that autism and ADHD each display both hyper- and hypoconnectivity in brain networks, supporting the new study's emphasis on symptom severity and dimensional traits rather than categorical diagnoses 1 3 4 5.
- Genetic and neuroimaging evidence indicates shared biological pathways and overlapping neural signatures in neurodevelopmental disorders, consistent with the observed brain–gene expression patterns that cross diagnostic boundaries 7 11 13 14.
- However, systematic reviews and comparative studies also underscore that, despite some overlap, ASD and ADHD can have distinct neural correlates, reinforcing the importance of considering both shared and disorder-specific mechanisms 3 15.
Study Overview and Key Findings
Understanding the biological underpinnings of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is of growing importance, given the frequent co-occurrence of these conditions and the limitations of current diagnostic categories. The new study, led by researchers at the Child Mind Institute, addresses this by examining whether symptom dimensions—specifically the severity of autism traits—are more closely tied to patterns of brain connectivity and gene expression than categorical diagnoses. This approach reflects a broader shift in psychiatry towards dimensional and transdiagnostic models that may offer more precise insights into neurodevelopmental disorders.
| Property | Value |
|---|---|
| Study Year | 2025 |
| Organization | Child Mind Institute |
| Journal Name | Molecular Psychiatry |
| Authors | 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, Adriana Di Martino |
| Population | Children with autism or ADHD |
| Sample Size | n=166 |
| Methods | Observational Study |
| Outcome | Patterns of brain connectivity and gene activity |
| Results | Severity of autism symptoms linked to brain connectivity patterns |
Literature Review: Related Studies
To place these findings in context, we searched the Consensus database, which contains over 200 million research papers. The following search queries were used to identify relevant literature:
- autism ADHD brain connectivity patterns
- severity autism symptoms brain mechanisms
- neurodevelopmental disorders shared brain features
Below is a summary of key topics and findings from the literature:
| Topic | Key Findings |
|---|---|
| Do autism and ADHD share brain connectivity patterns, or are they distinct? | - Both ASD and ADHD display atypical connectivity, with varying patterns of hypo- and hyperconnectivity, but studies have also found distinct connectivity profiles in each disorder 1 3 4 5 15. - Some studies suggest greater overlap in brain network disruptions among co-occurring cases, but most evidence points to more distinct than shared neural correlates 3 15. |
| How does symptom severity relate to brain network organization in neurodevelopmental disorders? | - Greater autism symptom severity is associated with stronger connectivity between specific brain networks, such as between sensory networks or between the frontoparietal and default mode networks 1 4 5 10. - Individualized alterations in functional connectivity correlate with behavioral symptoms, and symptom dimensions often map onto neural network differences across diagnostic boundaries 1 4 5 9 10. |
| What genetic and molecular mechanisms underlie shared or distinct neurodevelopmental disorder features? | - Overlapping genetic risk factors and shared gene expression patterns are found across ASD, ADHD, and other neurodevelopmental disorders, supporting a continuum model 7 11 13 14. - Specific gene sets (e.g., those related to neural development, excitatory/inhibitory balance) correlate with both brain structure and symptom profiles, reinforcing the link between genetics, brain networks, and behavioral traits 6 7 8 14. |
| Are transdiagnostic and dimensional approaches to neurodevelopmental disorders supported by evidence? | - Studies increasingly support dimensional models, showing that brain and genetic markers often align with symptom dimensions rather than strict diagnostic categories 1 5 7 11 13. - Transdiagnostic gradients of neural and genetic alterations exist across neurodevelopmental and psychiatric disorders, suggesting that shared biological processes may underlie a spectrum of conditions 11 13. |
Do autism and ADHD share brain connectivity patterns, or are they distinct?
The literature indicates that while ASD and ADHD can show overlapping patterns of altered brain connectivity, especially in cases of co-occurrence, there are also distinct neural signatures associated with each disorder. The new study's finding that symptom severity, rather than diagnosis, best predicts connectivity patterns aligns with research documenting both shared and distinct network disruptions.
- Both ASD and ADHD show altered connectivity involving rich-club networks, default mode, and frontoparietal systems, but these alterations may manifest differently across disorders 3 4 5 15.
- Distinct patterns of hypo- and hyperconnectivity are reported in ASD and ADHD, often depending on the specific brain networks examined and the developmental stage 1 3 4 5.
- Systematic reviews caution that, despite common comorbidity, most neural features are more distinct than shared 15.
- The current study adds that dimensional symptom severity may explain overlapping network disruptions better than categorical diagnoses 1 5 15.
How does symptom severity relate to brain network organization in neurodevelopmental disorders?
Several studies support a close relationship between the intensity of autism symptoms and specific patterns of brain connectivity. Greater symptom severity often correlates with stronger or more atypical functional connectivity, especially in networks involved in social cognition, sensory processing, and executive function.
- Individual differences in connectivity patterns are strongly linked with behavioral symptom severity in ASD 1 4 5 10.
- Hyperconnectivity between sensory and motor networks is associated with greater autism symptoms in young children 10.
- Dimensional approaches reveal that connectivity alterations cut across diagnostic boundaries and relate to symptom dimensions 1 5 9.
- The new study's focus on symptom severity, rather than diagnosis, echoes the movement toward dimensional models in neurodevelopmental research 1 5 10.
What genetic and molecular mechanisms underlie shared or distinct neurodevelopmental disorder features?
Multiple studies highlight overlapping genetic risk and molecular pathways across neurodevelopmental disorders, providing biological support for the observed overlap in brain network disruptions. However, distinct gene expression profiles and molecular signaling mechanisms also contribute to the heterogeneity between and within conditions.
- Shared gene expression patterns and risk variants are found in ASD, ADHD, and related disorders, supporting a continuum of neurodevelopmental impairment 7 11 13 14.
- Specific gene sets involved in excitatory/inhibitory balance, neural development, and synaptic function correlate with both brain structure and clinical symptoms 6 7 8 14.
- Rare mutations in certain gene families (e.g., HNRNP) contribute to overlapping neurodevelopmental phenotypes 14.
- The new study's integration of spatial transcriptomic analysis aligns with these findings, linking gene expression maps to brain connectivity and behavioral traits 7 13 14.
Are transdiagnostic and dimensional approaches to neurodevelopmental disorders supported by evidence?
Emerging research increasingly favors dimensional and transdiagnostic models over categorical diagnostic approaches, as neural and genetic markers often relate more closely to symptom dimensions than strict disorder boundaries. The new study's results contribute to this evolving paradigm.
- Dimensional mapping of symptoms and brain connectivity provides a better fit for observed biological variation than strict diagnostic categories 1 5 7 11.
- Large-scale studies reveal transdiagnostic gradients of brain structure and function changes across multiple neurodevelopmental and psychiatric disorders 11 13.
- Overlapping and distinct connectivity and gene expression patterns suggest a spectrum model with shared and unique features 7 11 13.
- The present study's approach is consistent with this growing body of evidence, reinforcing the value of dimensional analysis in understanding neurodevelopmental conditions 1 5 7 11.
Future Research Questions
While this study advances understanding of shared neurobiological pathways in autism and ADHD by linking symptom severity to brain–gene signatures, several questions remain. Future research is required to clarify the developmental trajectories of these networks, the generalizability of findings to broader populations, and the potential for individualized interventions based on biological markers.
| Research Question | Relevance |
|---|---|
| How do brain connectivity patterns linked to autism symptom severity change over development? | Understanding developmental changes is critical for targeted early interventions, as connectivity patterns and symptom expression may evolve with age 4 5 10. |
| Can biological markers of shared brain-gene signatures predict clinical outcomes in autism and ADHD? | Identifying reliable biomarkers could improve diagnosis and personalized treatment strategies for children with neurodevelopmental disorders 5 7. |
| What are the distinct and shared genetic pathways in children with co-occurring autism and ADHD? | Clarifying which genetic mechanisms are unique versus shared will enhance understanding of comorbidity and may inform intervention strategies 7 13 14. |
| How do dimensional approaches to diagnosis and treatment compare to traditional categorical diagnoses in neurodevelopmental disorders? | Evidence is growing for dimensional models, but direct comparisons with standard diagnostic practices are needed to determine clinical utility 1 5 7 11 13. |
| What is the role of environmental and epigenetic factors in modulating brain-gene signatures across autism and ADHD? | Environmental and epigenetic influences may interact with genetic and neural mechanisms, affecting symptom expression and treatment responses 6 8. |