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Biological sex affects the neurobiology of autism

In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assum...

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Autores principales: Lai, Meng-Chuan, Lombardo, Michael V., Suckling, John, Ruigrok, Amber N. V., Chakrabarti, Bhismadev, Ecker, Christine, Deoni, Sean C. L., Craig, Michael C., Murphy, Declan G. M., Bullmore, Edward T., Baron-Cohen, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754459/
https://www.ncbi.nlm.nih.gov/pubmed/23935125
http://dx.doi.org/10.1093/brain/awt216
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author Lai, Meng-Chuan
Lombardo, Michael V.
Suckling, John
Ruigrok, Amber N. V.
Chakrabarti, Bhismadev
Ecker, Christine
Deoni, Sean C. L.
Craig, Michael C.
Murphy, Declan G. M.
Bullmore, Edward T.
Baron-Cohen, Simon
author_facet Lai, Meng-Chuan
Lombardo, Michael V.
Suckling, John
Ruigrok, Amber N. V.
Chakrabarti, Bhismadev
Ecker, Christine
Deoni, Sean C. L.
Craig, Michael C.
Murphy, Declan G. M.
Bullmore, Edward T.
Baron-Cohen, Simon
author_sort Lai, Meng-Chuan
collection PubMed
description In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the ‘extreme male brain’ theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P < 0.001) overlapped with areas that were sexually dimorphic in neurotypical controls, in both grey and white matter, suggesting neural ‘masculinization’. This was not seen in males with autism. How differences in neuroanatomy relate to the similarities in cognition between males and females with autism remains to be understood. Future research should stratify by biological sex to reduce heterogeneity and to provide greater insight into the neurobiology of autism.
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spelling pubmed-37544592013-08-27 Biological sex affects the neurobiology of autism Lai, Meng-Chuan Lombardo, Michael V. Suckling, John Ruigrok, Amber N. V. Chakrabarti, Bhismadev Ecker, Christine Deoni, Sean C. L. Craig, Michael C. Murphy, Declan G. M. Bullmore, Edward T. Baron-Cohen, Simon Brain Original Articles In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the ‘extreme male brain’ theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P < 0.001) overlapped with areas that were sexually dimorphic in neurotypical controls, in both grey and white matter, suggesting neural ‘masculinization’. This was not seen in males with autism. How differences in neuroanatomy relate to the similarities in cognition between males and females with autism remains to be understood. Future research should stratify by biological sex to reduce heterogeneity and to provide greater insight into the neurobiology of autism. Oxford University Press 2013-09 2013-08-09 /pmc/articles/PMC3754459/ /pubmed/23935125 http://dx.doi.org/10.1093/brain/awt216 Text en © The Author 2013. Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Lai, Meng-Chuan
Lombardo, Michael V.
Suckling, John
Ruigrok, Amber N. V.
Chakrabarti, Bhismadev
Ecker, Christine
Deoni, Sean C. L.
Craig, Michael C.
Murphy, Declan G. M.
Bullmore, Edward T.
Baron-Cohen, Simon
Biological sex affects the neurobiology of autism
title Biological sex affects the neurobiology of autism
title_full Biological sex affects the neurobiology of autism
title_fullStr Biological sex affects the neurobiology of autism
title_full_unstemmed Biological sex affects the neurobiology of autism
title_short Biological sex affects the neurobiology of autism
title_sort biological sex affects the neurobiology of autism
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754459/
https://www.ncbi.nlm.nih.gov/pubmed/23935125
http://dx.doi.org/10.1093/brain/awt216
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