Male/Female Sex Ratios and Neurodiversity Revisited (2/2)

Male/Female Sex Ratios and Neurodiversity Revisited (2/2)

One of the problems with this line of thinking is that similar ratios have been reported in other developmental disorders. Attention deficit hyperactivity disorder, dyslexia, intellectual disabilities, and stuttering are among those. The social problems of autism do not exist in these conditions and it would be a lot harder to hide them; a dyslexic either has difficulty reading or doesn’t, a stutterer either talks fluently or doesn’t.

However, though it’s possible that clinicians have missed some cases due to bias, there’s also an alternative explanation that females may have some sort of protective effect against autism. These may be hormonal, i.e. estrogen and a lack of testosterone in females and vice-versa with males.

Females also have two X chromosomes and males only have one. There are a variety of forms of autism which are X linked such as fragile X. The female’s spare copy of the X chromosome may protect her from this effect, but she still might be able to pass it on to her son. This could in part account for the higher ratio of autistic men to autistic women. However, the number of X linked cases which usually result in intellectual disability would probably be too limited to account for all of the varieties of autism that would account for the higher ratio in men.

It is also possible that differences in the way male and female brains are structured may give them some sort of protection against autism. Because of this females may need to have a higher level of genetic mutations than males in order to acquire autism.

Elise Robinson of Harvard university has given indirect evidence of this in one study. She compared a group of opposite sexed fraternal twins with autistic traits and found that when comparing boys and girls who were ranked in the top 10th percentile in these traits, the girls were more likely to have an autistic sibling than the boys. This provides indirect evidence that a greater amount of genetic loading may be required in girls to become autistic than in boys.

There were other researchers who failed to replicate Robinson’s findings. Robinson used a very large sample of twins from two national databases. It’s possible that the differences in sample size was the reason for lack of replication.

Robinson’s work only gives indirect evidence of a greater genetic load in females being necessary to become autistic. Work done by Sebastien Jacquemont and others gives more direct evidence. They found three times as many deleterious mutations in female autistics as in males. This was also the case when they controlled for cognitive abilities of the sexes, suggesting that this was not because of females more severely affected. They also found higher levels of these mutations in the mothers of the children than the fathers. This data suggests that females have some sort of protective effect, making them less vulnerable to autism.
Donna Werling and colleagues did a study in which they compared gene expression in male and female brains. Also in autistic post-mortem tissue versus controls matched for age. They found that the genes expressed more commonly in the male brains were also expressed more commonly that in autistic versus the non-autistics. They also studied the brains to see if genes associated with autism were differently distributed in male and female brains. They found this not to be the case. However, they found that genes that are indirectly associated with autism are expressed differently in the male brain versus the female brain, suggesting that females require a higher genetic load in order to get autism.

There are multiple other studies that have provided evidence of some sort of female protective effect, suggesting that even if some female cases are missed it would not profoundly affect the differential sex ratio.

Neurodiversity proponents have often spoken for people on the spectrum, saying ‘we don’t want to be cured’ or we don’t want this or we don’t want that, a phenomenon blogger Harold Doherty refers to as ‘the royal we’.

If those who advocate the neurodiversity mantra speak for all or most autistics, such as Alex Plank claiming that most autistics don’t want to be cured, we should assume that these individuals are very similar to a representative person with autism.

They are not similar, however. One of the most striking dissimilarities is that so many of them are females. Upon a sampling of the internet and autism conferences, it would seem there are far more many females than males. Even if the ability to assess autism in women improved and this came up with a 2:1 ratio of men to women, it would not come close to the neurodiversity sampling. There are probably at least a greater than 2:1 ratio of neurodiversity females to males. These are also the most high functioning cases with many of their numbers being college professors and lawyers.

One has to wonder why so many of them didn’t slip through the cracks. If autism is more difficult to assess in women because it is more subtle, then how did so many extremely mild cases come to the fore? One possibility is multiple doctor shopping Another is self-diagnosis. As seen from a previous post, it would appear that the autistic self advocacy network may encourage self-diagnosis through their statements such as “who identifies” on the autism spectrum.

This has been problematic as neurodiversity has been very effective in getting their message across and claiming that they represent the interests of the majority of autistic people. This is in spite of the fact that gender-wise and functioning-wise they are so dissimilar.

One of the main problems with this is that they would encourage accommodations and services over scientific research. Perhaps there is a reason that the skewed sex ratio in autism has been studied so much and genetic studies trying to show a protective effect have been so common. Though there is fairly strong empirical (though maybe not conclusive) evidence to suggest that females have some sort of protective effect from autism, the reason for this female over male advantage in not getting autism has not been found. If it could be found, the implications could be astonishing. If we could find out what causes this protective effect, it could lead to prevention and treatment. If there was some way the protective effect could be exploited in a male fetus, it could well prevent him from becoming autistic. It might also lead to a possible causation and *gasp* even a cure. This is so ironic that people so unrepresentative of autistic people can attempt to speak for most on the spectrum when research based on the skewed ratio could at some point in time make a real difference.

Katharina Dworzynski et al How Different Are Girls and Boys Above
and Below the Diagnostic Threshold for Autism Spectrum Disorders? Journal of the American Academy of Child and Adolescent Psychiatry Volume 51, Issue 8, August 2012, Pages 788–797

Werling et al Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. Nat. Commun. 7, 10717 (2016)

Jacquemont et al A Higher mutational Burden in Females Supports a “female protective model” in neurodevelopmental disorders The American Journal of Human Genetics 415-426

Robinson et al. Examining and interpreting the female protective effect against autistic behavior Proceedings of the national academy of science March 26, 2013 vol 110 no 13

http://autismgadfly.blogspot.co.uk/2016/10/malefemale-sex-ratios-and.html

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