| Title: | The Link Between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression |
| Journal: | American Journal of Psychiatry |
| Published: | 23 Nov 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36415971/ |
| DOI: | https://doi.org/10.1176/appi.ajp.20220194 |
| URL: | https://www.repository.cam.ac.uk/handle/1810/361632 |
| Citations: | 17 (15 in last 2 years) as of 8 Aug 2024 |
Publication 10718
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Abstract
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.</p>
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).</p>
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.</p>
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.</p>
9 Keywords
- Autism Spectrum Disorder
- Autistic Disorder
- Brain
- Cognition
- Female
- Gene Expression
- Humans
- Male
- Neuroanatomy
31 Authors
- Dorothea L. Floris
- Han Peng
- Varun Warrier
- Michael V. Lombardo
- Charlotte M. Pretzsch
- Clara Moreau
- Alex Tsompanidis
- Weikang Gong
- Maarten Mennes
- Alberto Llera
- Daan van Rooij
- Marianne Oldehinkel
- Natalie J. Forde
- Tony Charman
- Julian Tillmann
- Tobias Banaschewski
- Carolin Moessnang
- Sarah Durston
- Rosemary J. Holt
- Christine Ecker
- Flavio Dell'Acqua
- Eva Loth
- Thomas Bourgeron
- Declan G.M. Murphy
- Andre F. Marquand
- Meng-Chuan Lai
- Jan K. Buitelaar
- Simon Baron-Cohen
- Christian F. Beckmann
- the APEX Group
- the EU-AIMS LEAP Group
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