title: The connectomes of males and females with autism spectrum disorder have significantly different white matter connectivity densities.
abstract: Autism spectrum disorder (ASD) encompasses a set of neurodevelopmental conditions whose striking sex-related disparity (with an estimated male-to-female ratio of 4:1) remains unknown. Here we use magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) to identify the brain structure correlates of the sex-by-ASD diagnosis interaction in a carefully selected cohort of 110 ASD patients (55 females) and 83 typically-developing (TD) subjects (40 females). The interaction was found to be predicated primarily upon white matter connectivity density innervating, bilaterally, the lateral aspect of the temporal lobe, the temporo-parieto-occipital junction and the medial parietal lobe. By contrast, regional gray matter (GM) thickness and volume are not found to modulate this interaction significantly. When interpreted in the context of previous studies, our findings add considerable weight to three long-standing hypotheses according to which the sex disparity of ASD incidence is (A) due to WM connectivity rather than to GM differences, (B) modulated to a large extent by temporoparietal connectivity, and (C) accompanied by brain function differences driven by these effects. Our results contribute substantially to the task of unraveling the biological mechanisms giving rise to the sex disparity in ASD incidence, whose clinical implications are significant.
authors.affiliation: Laboratory of Neuro Imaging, USC Mark &Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles CA 90032 USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Irimia
authors.affiliation: Laboratory of Neuro Imaging, USC Mark &Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles CA 90032 USA.
authors.forename: Carinna M
authors.initials: CM
authors.lastname: Torgerson
authors.affiliation: Laboratory of Neuro Imaging, USC Mark &Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles CA 90032 USA.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Jacokes
authors.affiliation: Laboratory of Neuro Imaging, USC Mark &Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles CA 90032 USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Van Horn
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging*; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D002648:Child; D063132:Connectome; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D059906:Neuroimaging; D009929:Organ Size; D012727:Sex Characteristics; D066127:White Matter / Q000000981:diagnostic imaging*