Sex differences in autism have received a lot of attention from researchers over the years. Why are boys 3-4 times more likely to be diagnosed with autism than girls? CDN and MRC Centre for Neurodevelopmental Disorders researchers Laura Andrea and Albert Basson discuss the implications in their review in Nature Neuroscience of a recent study that offers some insight.

Over the last few years, several human genetic studies have shown that faced with the same highly-penetrant, autism-associated mutations, females show more resilience to their effects than males. One theory posits that neuronal activation in specific brain regions may be different between females and males. Using mouse models carrying autism-linked mutations, a new study has made progress towards understanding the neuronal and developmental basis of sex differences so apparent in the prevalence of autism.

The model carries a mutation strongly associated with autism in Chd8, a gene which encodes a protein that can modulate gene expression by altering chromatin structure. Behavioural analysis of the model showed that nearly all the sex differences in behaviour occurred in the presence of a social or sensory stressor. The researchers, using c-Fos protein levels as a marker for neuronal activation, saw markedly increased activity in the hippocampus and the prefrontal and sensory cortices in male pups. By contrast, the females showed reduced activity under baseline conditions which became ‘normalised’ following the stressor.

The differences in baseline, or control, conditions are thought to underlie the behavioural differences between the males and females in the study and indicate how the effects of an autism-associated mutation can differ between the sexes.