A new French study may shed more light on why autism spectrum disorder (ASD) affects males around four times more than females. The researchers found that exposure to androgens (male hormones) during early fetal brain development alters certain genes linked to autism.
The findings, published in the journal Biological Psychiatry, may point to a predisposition in males, rather than a protective effect in females.
By studying male human cells, researchers at the University of Strasbourg identified key genes that are both regulated by testosterone and also contribute to the risk for autism. The findings offer vital insights into how male hormones may be linked to the increased male susceptibility to ASD.
Male fetuses produce androgens during critical stages of brain development when cells are dividing and developing into neurons. The study found that androgens increase the spread of cells and prevent them from death, which could predispose boys to ASD by contributing to the excessive brain growth that occurs in people with ASD during the first years of life.
“Understanding the mechanisms for the male preponderance for autism is like pulling on a lose thread. It could help to ‘unravel’ important mechanisms contributing to autism risk,” said Dr. John Krystal, editor of Biological Psychiatry. Identifying the role of androgens in the risk for ASD could be important for prevention or the development of potential treatments.
For the study, co-senior authors Jean-Louis Mandel, M.D., Ph.D., and Amélie Piton, Ph.D., and colleagues used human pluripotent neural stems cells to model the cells that generate neurons during brain development.
Treatment with the testosterone metabolite DHT resulted in subtle changes in the expression of about 200 genes, several of which have previously been linked to ASD. Some of the genes that were most affected by DHT treatment included NRCAM, which has been linked to the brain abnormalities and symptoms in ASD, and FAM107A, which is increased in people with ASD. FAM107A also appeared to play a role in the ability of androgen to increase cell numbers in the study.
“These effects of male hormones may therefore contribute to the increased sensitivity of the male brain to develop ASD when also exposed to other genetic or environmental factors,” said Piton, suggesting that the biological explanation for the gender imbalance in ASD points to a predisposition in males, rather than a protective effect in females.
In addition to providing a clue into the gender imbalance in ASD, Piton said the list of genes altered by androgens in the study might be useful to identify new genes that might be involved in ASD or in other diseases that tend to occur more often in males.
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