Abstract
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.
Highlights
Boys have a 4 to 7 higher-fold risk of developing autism than girls [1]
We searched for a possible link between enhanced perceptual functioning and the biased sex ratio in autism
We examined studies investigating sex differences in the brain transcriptome, brain imaging data, brain plasticity following trauma or disease in nonautistic individuals, and the association of these differences with comparable common features of autism spectrum (AS)
Summary
Boys have a 4 to 7 higher-fold risk of developing autism than girls [1], (for a review see [2]). Many genes involved in autism are related to synaptic plasticity, and some show sexually-dimorphic expression.Deleterious and DN CNV/ SNV are more frequent in autistic females than males.
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