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Mol Autism. 2015 Jun 5;6:33. doi: 10.1186/s13229-015-0024-1. eCollection 2015.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Mottron L#1,2,3,4, Duret P#1,2,3,4,5, Mueller S6,7,8, Moore RD4,9,10, Forgeot d'Arc B1,2,3,4, Jacquemont S4,11,12, Xiong L#3,4.

Author information

Centre d'excellence en Troubles envahissants du dévelopement de l'Université de Montréal (CETEDUM), Montréal, Canada.
Hôpital Rivière-des-Prairies, Département de Psychiatrie, Montréal, Canada.
Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal, Québec, Canada.
Department of Psychiatry, University of Montreal, Québec, Canada.
Département de Biologie, École Normale Supérieure de Lyon, Lyon, CEDEX 07 France.
Institute of Clinical Radiology, University Hospitals, Munich, Germany.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129 USA.
Harvard University, Center for Brain Science, Cambridge, MA 02138 USA.
Department of Health Sciences, University of Montreal, Montreal, Canada.
College of Applied Health Sciences, University of Illinois, Urbana-Champaign, USA.
Centre de recherche, Centre Hospitalier Universitaire Sainte Justine, Montréal, Canada.
Service of Medical Genetics, University Hospital of Lausanne, University of Lausanne, Lausanne, 1011 Switzerland.
Contributed equally


Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.


Autism spectrum; Enhanced perceptual functioning; Male bias; Perceptual associative cortex; Regional plasticity; Sex ratio; Sexual dimorphism; Synaptic plasticity

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