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Sex differences in cortical volume and gyrification in autism

BACKGROUND: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate...

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Autores principales: Schaer, Marie, Kochalka, John, Padmanabhan, Aarthi, Supekar, Kaustubh, Menon, Vinod
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491212/
https://www.ncbi.nlm.nih.gov/pubmed/26146534
http://dx.doi.org/10.1186/s13229-015-0035-y
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author Schaer, Marie
Kochalka, John
Padmanabhan, Aarthi
Supekar, Kaustubh
Menon, Vinod
author_facet Schaer, Marie
Kochalka, John
Padmanabhan, Aarthi
Supekar, Kaustubh
Menon, Vinod
author_sort Schaer, Marie
collection PubMed
description BACKGROUND: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females. METHODS: We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD. RESULTS: We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples. CONCLUSIONS: Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-015-0035-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-44912122015-07-05 Sex differences in cortical volume and gyrification in autism Schaer, Marie Kochalka, John Padmanabhan, Aarthi Supekar, Kaustubh Menon, Vinod Mol Autism Research BACKGROUND: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females. METHODS: We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD. RESULTS: We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples. CONCLUSIONS: Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-015-0035-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-07-04 /pmc/articles/PMC4491212/ /pubmed/26146534 http://dx.doi.org/10.1186/s13229-015-0035-y Text en © Schaer et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Schaer, Marie
Kochalka, John
Padmanabhan, Aarthi
Supekar, Kaustubh
Menon, Vinod
Sex differences in cortical volume and gyrification in autism
title Sex differences in cortical volume and gyrification in autism
title_full Sex differences in cortical volume and gyrification in autism
title_fullStr Sex differences in cortical volume and gyrification in autism
title_full_unstemmed Sex differences in cortical volume and gyrification in autism
title_short Sex differences in cortical volume and gyrification in autism
title_sort sex differences in cortical volume and gyrification in autism
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491212/
https://www.ncbi.nlm.nih.gov/pubmed/26146534
http://dx.doi.org/10.1186/s13229-015-0035-y
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