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The Link Between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression.
- Source :
-
The American journal of psychiatry [Am J Psychiatry] 2023 Jan 01; Vol. 180 (1), pp. 50-64. Date of Electronic Publication: 2022 Nov 23. - Publication Year :
- 2023
-
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.<br />Methods: Using a novel deep learning framework trained to predict biological sex based on T <subscript>1</subscript> -weighted structural brain images, the authors compared sex prediction model performance across neurotypical and autistic males and females. Multiple large-scale data sets comprising T <subscript>1</subscript> -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).<br />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.<br />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.
Details
- Language :
- English
- ISSN :
- 1535-7228
- Volume :
- 180
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The American journal of psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 36415971
- Full Text :
- https://doi.org/10.1176/appi.ajp.20220194