Brain morphology network profiles in male and female youth with autism

Neuroimaging studies based on altered functional and structural connectivity have contributed to better characterizing males and females with Autism Spectrum Disorder (ASD), advancing our understanding of the male prevalence in diagnosis. However, much less is known about how brain networks are altered from a morphological perspective, and whether these alterations help explain sex-related characteristics in ASD. Here, we used structural MRI from a sex- and diagnosis-balanced sample of 337 young individuals (8 to 18 years) from the Autism Center of Excellence to elucidate sex-related alterations in morphology-based connectivity, calculated as the similarity between region-wise multivariate morphological signatures. Although no diagnosis-by-sex interaction network profile was found, within-sex analysis demonstrated that in males, ASD had significantly increased morphology-based connectivity involving the fusiform gyrus, medial orbitofrontal, entorhinal, and parahippocampal cortices. This network profile was linked to a core social-communication trait within the autistic group. Females with ASD exhibited a network profile notably comprising increased morphology-based connectivity in the entorhinal cortex, followed by the inferior parietal lobule and lateral occipital cortex; yet it lacked association with core autistic traits. These within-sex profiles had minimal overlap with networks from normative sex differences. Together, these findings offer new insights into the neurobiology of males and females with autism.