Autism and ADHD: When Symptoms Meet in The Brain

Autism and ADHD often present overlapping symptoms. This study analyzed 166 children diagnosed with autism or ADHD to investigate whether this overlap has a biological basis. The results showed that autistic symptoms, but not ADHD symptoms, are related to functional connectivity between specific brain regions. Furthermore, the genes associated with this connectivity are also linked to both conditions, suggesting a shared genetic basis.

In recent years, researchers have begun to look at neuropsychiatric conditions differently. Previously, studies compared people with and without diagnoses. Now, there is greater interest in understanding symptoms dimensionally, that is, observing how they manifest in different degrees, even among different diagnoses.

This type of approach is especially useful when discussing autism and ADHD. Although considered distinct diagnoses, there is much overlap between them. Many children with autism exhibit ADHD symptoms, and many children with ADHD exhibit autistic characteristics.

Clinical studies show that this combination is quite common: among children with autism, between 28% and 80% also exhibit symptoms of ADHD. Similarly, up to one-third of children with ADHD exhibit traits of the autism spectrum.

This overlap makes diagnosis more difficult and can hinder treatment, as each individual presents a unique profile. Therefore, many specialists advocate a transdiagnostic approach, which analyzes symptoms instead of relying solely on rigid diagnostic categories.

In the field of genetics, there is increasing evidence that autism and ADHD share hereditary factors. These two conditions often appear in the same family and show moderate genetic correlations.

Researchers believe that many genes involved in both conditions have not yet been discovered. However, the genes already identified are related to brain development, communication between neurons, and regulation of neuronal activity.

Despite these findings, it is still unclear whether these genes share similar patterns of expression in the brain, especially in regions linked to behavior and social communication, areas frequently associated with autism and ADHD.

From a neuroimaging perspective, there is evidence that both ADHD and autism are linked to differences in functional brain connectivity. This connectivity can be studied using resting-state functional magnetic resonance imaging (fMRI), which allows us to observe how different brain regions communicate with each other when the person is not performing a specific task.

Until now, few studies have directly examined the relationship between brain connectivity and dimensional symptoms of both diagnoses within the same group of participants.

Existing results are mixed: some studies have found no clear association, while others have suggested that brain connectivity may be related to symptom severity, but still without completely separating what is linked to autism or ADHD.

Based on this context, the study described aimed to investigate how individual differences in autism and ADHD symptoms relate to functional brain connectivity and specific genetic patterns. Participants included 166 children aged 6 to 12 years, all with a strict diagnosis of autism or ADHD, but without intellectual disability. All underwent the same clinical tests, parent interviews, and imaging exams.

The results showed a clear association between the severity of autistic symptoms and connectivity between two brain regions: the middle frontal gyrus (involved in executive functions) and the posterior cingulate cortex (part of the default mode network, associated with internal thinking and self-awareness).

The greater the connectivity between these regions, the more intense the autistic symptoms, regardless of the presence of ADHD symptoms. This suggests that this brain connection may be a specific transdiagnostic marker related to autism. On the other hand, no significant associations were found between ADHD symptoms and brain connectivity in this study.

Further research showed that the genes associated with the observed connectivity patterns were the same ones already linked to autism and ADHD in previous studies, especially genes involved in neuronal projections and brain development. This reinforces the hypothesis that there is a shared biological basis between some symptoms of the two conditions.

Overall, the results highlight the importance of analyzing symptoms as continuous dimensions and not just as separate diagnostic categories. This approach can help to better understand the shared biological mechanisms, improve future diagnoses, and support more personalized interventions.

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Connectome-based symptom mapping and in silico related gene expression in children with autism and/or attention-deficit/hyperactivity disorder

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 

Molecular Psychiatry. 23 October 2025

https://doi.org/10.1038/s41380-025-03205-8

Abstract:

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in N = 166 verbal children (6–12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in low motion whole-brain intrinsic functional connectivity (iFC) and dimensional measures of autism and ADHD symptoms indexed by clinician-based observation and parent interview, respectively. Additionally, we explored their linked gene expression patterns in silico. Whole-brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes primarily on the left hemisphere: the middle frontal gyrus of the frontoparietal network and the posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD ratings. Results from secondary segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC for autism symptom severity across diagnoses. No statistically significant brain-behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to: (i) have greater rate of variance in autism and ADHD, and (ii) be involved in neuron projections, suggesting shared genetic mechanisms for this specific brain-clinical phenotype. These findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically-defined and observation-based phenomena to shared presentations at the macroscale circuit- and genomic-levels across diagnoses.