Molecular Autism
Molecular Autism
RESEARCH
The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings
The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings
Abstract
Background Autism spectrum disorders are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of autism is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder. This study aimed to one investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to two link these variances to putative genomic underpinnings.
Methods We examined differences in cortical thickness and surface area and their genomic associations in a sample of five hundred thirty-three individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an autism spectrum disorder-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings.
Results In addition to significant main effects for autism spectrum disorder and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant autism spectrum disorder-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of cortical thickness and surface area, respectively. Moreover, individuals with autism spectrum disorder plus ADHD differed in cortical thickness to those without. Both main effects and the interaction were enriched for autism spectrum disorder-but not for ADHD-related genes.
Limitations Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N equals twenty-five individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-five rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting.
Conclusion Thus, our findings suggest that the neuroanatomy of autism is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression.