%0 Journal Article %T The Link Between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression %+ Universität Zürich [Zürich] = University of Zurich (UZH) %+ Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre, 6525 EN Nijmegen. %+ Wellcome Trust Centre for Integrative Neuroimaging (WIN - FMRIB) %+ University of Cambridge [UK] (CAM) %+ Autism Research Centre [Cambridge, Royaume-Uni] %+ University of Trento [Trento] %+ Institute of Psychiatry, Psychology & Neuroscience, King's College London %+ Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)) %+ Donders Institute for Brain, Cognition and Behaviour %+ Radboud University Medical Center [Nijmegen] %+ Donders Center for Cognitive Neuroimaging %+ Monash University [Melbourne] %+ King‘s College London %+ Roche Pharma Research and Early Development [Basel] (pRED) %+ University Hospital Mannheim | Universitätsmedizin Mannheim %+ Heidelberg University %+ University Medical Center [Utrecht] %+ Curtin University [Perth] %+ Sackler Institute of Translational Neurodevelopment [London] %A Floris, Dorothea %A Peng, Han %A Warrier, Varun %A Lombardo, Michael %A Pretzsch, Charlotte %A Moreau, Clara %A Tsompanidis, Alex %A Gong, Weikang %A Mennes, Maarten %A Llera, Alberto %A van Rooij, Daan %A Oldehinkel, Marianne %A Forde, Natalie %A Charman, Tony %A Tillmann, Julian %A Banaschewski, Tobias %A Moessnang, Carolin %A Durston, Sarah %A Holt, Rosemary %A Ecker, Christine %A Dell’acqua, Flavio %A Loth, Eva %A Bourgeron, Thomas %A Murphy, Declan G.M. %A Marquand, Andre %A Lai, Meng-Chuan %A Buitelaar, Jan %A Baron-Cohen, Simon %A Beckmann, Christian %< avec comité de lecture %@ 0002-953X %J The American Journal of Psychiatry %I American Psychiatric Publishing %V 180 %N 1 %P 50-64 %8 2023-01-01 %D 2023 %R 10.1176/appi.ajp.20220194 %M 36415971 %K Autism Spectrum Disorder %K Brain Imaging Techniques %K Gender Differences %K Machine Learning %K Neuroanatomy %K Neurodevelopmental Disorders %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X Objective: The male preponderance in prevalence of autism is among the most pronounced sex ratios across neurodevelopmental conditions. The authors sought to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression.Methods: Using a novel deep learning framework trained to predict biological sex based on T1-weighted structural brain images, the authors compared sex prediction model performance across neurotypical and autistic males and females. Multiple large-scale data sets comprising T1-weighted MRI data were employed at four stages of the analysis pipeline: 1) pretraining, with the UK Biobank sample (>10,000 individuals); 2) transfer learning and validation, with the ABIDE data sets (1,412 individuals, 5-56 years of age); 3) test and discovery, with the EU-AIMS/AIMS-2-TRIALS LEAP data set (681 individuals, 6-30 years of age); and 4) specificity, with the NeuroIMAGE and ADHD200 data sets (887 individuals, 7-26 years of age).Results: Across both ABIDE and LEAP, features positively predictive of neurotypical males were on average significantly more predictive of autistic males (ABIDE: Cohen's d=0.48; LEAP: Cohen's d=1.34). Features positively predictive of neurotypical females were on average significantly less predictive of autistic females (ABIDE: Cohen's d=1.25; LEAP: Cohen's d=1.29). These differences in sex prediction accuracy in autism were not observed in individuals with ADHD. In autistic females, the male-shifted neurophenotype was further associated with poorer social sensitivity and emotional face processing while also associated with gene expression patterns of midgestational cell types.Conclusions: The results demonstrate an increased resemblance in both autistic male and female individuals' neuroanatomy with male-characteristic patterns associated with typically sex-differential social cognitive features and related gene expression patterns. The findings hold promise for future research aimed at refining the quest for biological mechanisms underpinning the etiology of autism. %G English %L pasteur-04069542 %U https://pasteur.hal.science/pasteur-04069542 %~ PASTEUR %~ CNRS %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SCIENCES %~ HUM-GEN-COGN-FUN %~ PASTEUR_UMR3571