Towards robust and replicable sex differences in the intrinsic brain function of autism

Medientyp: E-Artikel
Titel: Towards robust and replicable sex differences in the intrinsic brain function of autism
Beteiligte: Floris, Dorothea L.; Filho, José O. A.; Lai, Meng-Chuan; Giavasis, Steve; Oldehinkel, Marianne; Mennes, Maarten; Charman, Tony; Tillmann, Julian; Dumas, Guillaume; Ecker, Christine; Dell’Acqua, Flavio; Banaschewski, Tobias; Moessnang, Carolin; Baron-Cohen, Simon; Durston, Sarah; Loth, Eva; Murphy, Declan G. M.; Buitelaar, Jan K.; Beckmann, Christian F.; Milham, Michael P.; Di Martino, Adriana
Erschienen: Springer Science and Business Media LLC, 2021
Erschienen in: Molecular Autism
Sprache: Englisch
DOI: 10.1186/s13229-021-00415-z
ISSN: 2040-2392
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7–18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level <jats:italic>P</jats:italic> < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples—EU-AIMS LEAP.</jats:p> </jats:sec><jats:sec> <jats:title>Limitations</jats:title> <jats:p>Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.</jats:p> </jats:sec>
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