Why do there seem to be fewer autistic women?

In February 1998, the English doctor Andrew Wakefield published a study in the prestigious journal The Lancet claiming that the triple viral vaccine was associated with autism. The outcry was immense. That same year, several experts countered that they had found no sign of this link. But the damage was already done: worldwide, distrust of vaccines grew, and many parents stopped vaccinating their children, which, as expected, led to several outbreaks of rubella, measles, and mumps. It wasn't until an investigation by the Sunday Times revealed in 2004 that Wakefield had simply invented the data for his article that public opinion began to change.

Despite everything, the ripple effect of the deception still resonates thirty years later, aided by powerful ignoramuses like the US Secretary of Health, Robert F. Kennedy Jr., who continues to promote the idea that immunization can cause autism even though there is no scientific evidence to prove it. The anti-vaccine movement will continue to use Wakefield's lies for their campaigns, even though it is clear that getting vaccinated does not increase the risk.

The truth is that the origin of this neurodivergence is not entirely clear. It is known to have a strong hereditary component (several areas of the genome have already been identified as associated with autism), but genetics cannot explain everything, so it is suspected that factors related to the environment could also be involved. For example, epidemiological studies suggest that the risk of autism increases with exposure to certain toxic substances during pregnancy, and an association with the gut microbiota has even been found. But until the mechanisms involved are defined, it is difficult to know what role all these elements really play.

If environmental factors that may have some influence are ever identified, it will be possible to know if they have anything to do with the significant increase in autism diagnoses seen lately, but, in the meantime, experts believe that the most likely explanation for this increase is that more tests are being done now than before and, furthermore, the definition of what we call autism has been broadened.

Sex bias

Another of the unanswered questions about the diagnosis of autism is why it is much more frequent in one sex than the other, in a proportion of three or four men for every woman. One of the prevalent hypotheses is that this difference is not really such, but that the problem is the difficulty of diagnosing it in women, both because the tests were originally designed from observations focused mainly on the male population, and because women would be more skilled at masking the symptoms of divergence in order to achieve better social integration.

But perhaps this does not fully explain this substantial difference, which is observed in all cultures and has been constant over several decades. According to a study recently published in the journal Nature genetics by Maya Talukdar and David C. Page, from the Whitehead Institute and MIT, an additional reason could be that women would be more protected against autism thanks to the second X chromosome.

Since the pioneering studies in epigenetics in the sixties of the last century, it was thought that one of the two X chromosomes that women have in all their cells was always "turned off" to avoid an "overdose" of the genes it contains: one active copy of these genes would be enough for the organism to function correctly, as evidenced by the fact that men only have one X chromosome. But in recent decades we have been accumulating evidence that shows that the second X chromosome is not completely silenced, because some of its genes would indeed be active.

According to Talukdar and Page, it would be this extra burden that would lead to a lower risk of neurodivergence, and perhaps also of other conditions and diseases with a hereditary component (such as hypertrophic cardiomyopathy, trisomies of chromosomes 13 and 18, ADHD, or clubfoot, all more frequent in men). The hypothesis they propose is that the X chromosome would hold the key to inactivating mutations that appear on other chromosomes and can lead to various disorders and conditions. This would explain why women diagnosed with autism accumulate more mutations in genes associated with the condition than men: more would be needed for them to take effect, thanks to this protective mechanism.

If this is confirmed, it would reinforce the idea that, beyond the sociocultural reasons that complicate diagnosis, there would also be a biological reason that would justify the sex bias seen in autism spectrum disorder. Furthermore, it would emphasize the genetic causes of neurodivergence. Be that as it may, more studies will still be needed to answer the question posed in the title.