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News

Brains of women with autism may sport male features

by  /  23 February 2017
Deep brains: The thickness of a number of brain areas distinguishes women with autism from those without the condition.

The brains of some women with autism more closely resemble those of typical men than those of typical women, according to a study published 8 February in JAMA Psychiatry1.

Using brain imaging, the researchers mapped the brains of typical men and women along a spectrum. Nearly 80 percent of the brains of women with autism fall at the male end of this spectrum, they found.

“We’re not saying that women with autism have male brains, but if you look at some aspects of brain anatomy, they have regions and features that look more like a male than a female brain,” says lead researcher Christine Ecker, professor of child and adolescent psychiatry at Goethe University in Frankfurt, Germany.

Autism is more prevalent in men than in women, with the ratio of those diagnosed at five to one. One theory holds that this is because women are somehow protected from autism. The new findings mesh with this theory. However, the brain differences in women with autism may also be a consequence of the condition.

The study also jibes with the ‘extreme male brain’ theory of autism. This theory posits that autism features are an extension of stereotypically male traits, such as the tendency to look at things systematically rather than empathetically.

The results diverge from that theory in one important respect, however: Men who have especially ‘male’ brains, according to the brain imaging findings, do not have an increased incidence of autism.

Machine learning:

Ecker and her team used magnetic resonance imaging to measure the thickness of the cerebral cortex, which coordinates higher-order cognitive functions. Previous studies have suggested that the cortex is thinner in people with autism than in people without the condition.

The researchers scanned the brains of 51 men and 47 women without autism, measuring the thickness of roughly 320,000 locations of the cortex. They then used a computer algorithm to ferret out a combination of regions for which differences in cortical thickness are most likely to differentiate men from women.

The algorithm, which involves machine learning, found a pattern of thickness that typifies a female brain, and assigned it a score of 0; it assigned a score of 1 to a pattern that is most predictive of a male brain. The algorithm then scored the cortical thickness patterns of each brain in the study relative to these idealized ones.

The researchers found that the majority of typical women score between 0 and 0.5 on this scale, and the majority of typical men between 0.5 and 1. Many men and women have scores that fall between 0.4 to 0.6, however, suggesting that all brains fall along a spectrum ranging from especially male to especially female, Ecker says.

Ranking brains along a scale rather than placing them into a male or female category is “an advance in the right direction,” says Daphna Joel, professor of psychology and neuroscience at Tel Aviv University in Israel. But referring to a ‘male’ or ‘female’ brain is still problematic, she says.

Risk shift:

The researchers then used the same measure to categorize the brains of 49 men and 49 women with autism. They found that 39 of the women fall into the male range of the scale.

Women in the study who scored in the male range are three times as likely as those in the female range to have autism, the researchers found. By contrast, men who score in the female range are 1.2 times less likely to have autism than those who score in the male range.

However, men who score near 1 have a similar incidence of autism to those scoring closer to 0.5. This suggests that having an especially ‘male’ brain does not increase the risk of autism, Ecker says.

The study’s size is one of its biggest strengths, says Donna Werling, a postdoctoral associate in Stephan Sanders’ lab at the University of California, San Francisco, who was not involved in the study. “That degree of matching and recruitment to fill all four of those categories is something that I wish more researchers would do.”

Another strength of the study is that the researchers generated the scores based on typical participants and then applied them to people with autism. Studies often use the same participants to make and validate their prediction, which is problematic, says Kevin Pelphrey, director of the Autism and Neurodevelopmental Disorders Institute at George Washington University in Washington, D.C., who was not involved in the study.

“It’s a really cool application of [this approach], just a really nice elegant set of math,” he says.

It is unclear whether the atypical cortical thickness seen in women with autism contributes to or arises from their autism. It is also not known whether cortical thickness tracks with sex-related cognitive or behavioral features, Ecker says.

The researchers plan to repeat the study in younger participants. They are especially interested in how the brain changes during adolescence, as puberty hormones are known to affect many brain regions.


References:
  1. Ecker C. et al. JAMA Psychiatry Epub ahead of print (2017) PubMed
  • we are not male brains in women’s bodies. rather we are female but human beings foremost. We are not influenced by societal or cultural notions of having to have a strong female identity because that sense more neutral

  • Zoran Bekric

    How far into the male half of the scale did the female autistic brains go?

    The scale already has an overlap with both male and female brains found in the 0.4 – 0.6 range, so there’s no hard and fast division between the two. If the female autistics fell in the 0.5 to 0.6 range, then they would be in the male half, but part of the standard variation. If they fall in the 0.6 to 0.8, then it might be valid to talk about female autistics having more male-like brains.

    Some scattershot graphs showing the scores would be helpful. That way we could see how strong the clustering is in each half for males and female brains, as well as how far into the male half the female autistic scores go, what the highest score for a female autistic was, and where most of the female autistic scores cluster — low, mid, or high male range.

    An interesting study. I especially like the machine learning as a way of avoiding contamination from cultural biases and presumptions.

    • Jessica Wright

      Dear Zoran,
      There is a scatterplot that illustrates this nicely in the study in Figure 1. I’m not sure if you’re able to access the full text:
      https://www.ncbi.nlm.nih.gov/pubmed/28196230

      From the figure, the female brains with autism span the entire male range. The most ‘male’ brain is male, but the next two are actually female, lying very roughly around 0.9. By eyeballing the figure, I counted 9 female brains with autism between 0.8 and 1 and about 23 between 0.6 and 0.8. (Please consider these counts estimates!)

      Thanks so much for your careful reading of Spectrum!
      Best,
      Jessica

      • Zoran Bekric

        Dear Jessica,
        Thank you very much for the reply.

        Unfortunately I don’t seem to be able to access the article — or at least not the figures associated with it. However, based on your eyeball counts, it seems the more-male-like-brain effect is quite pronounced. Most interesting.

        I don’t know if you’re familiar with Christopher Badcock’s Imprinted Brain theory which posits that autism and schizophrenia are neurologically “opposite” conditions, but I’d be interested in knowing how the brains of male and female schizophrenics score on this scale. It occurs to me that it might be an edifying test of Badcock’s ideas.

    • Jeanne Pauli

      Who tells the machine when it is wrong so that it can “learn”?

  • Megan M

    80% of women with autism have brains that fall at the “male end” of the spectrum, right? What % of ALL women have brains that tend towards the “male end”? I am, frankly, a bit dubious about the whole concept of “male” and “female” brains to begin with–not that there are not differences, but that the similarities seem much more pronounced than the differences.
    Back in the 1980s, there was a similar discussion about “male” and “female” brains and mathematical ability. As scientists, I’m sure you can see where the problem with that generalization lies.

    • Jessica Wright

      Thanks for your careful reading of Spectrum! In answer to your first question, roughly 32% of typically developing women in the study have brains with cortical thickness in the male range. Also, the authors make a point that the study is not tying differences in this one structural measure to any cognitive features or behavior.

  • Jeanne Pauli

    Many have found, as Leo Kanner first reported, a larger-than-normal head size as feature of autism. Did you measure head size in this study of brain thickness? Wouldn’t typical females have a smaller head size than males?

    • Jeanne Pauli

      And isn’t it true that after 16 years the cortical thickness in a individual changes at a different rate in different areas of the brain. Seems like a lot of variables in this sturdy. Were these men and women progressing in say Alzheimer’s? It’s been shown that volume- and thickness-based measures generally perform similarly for separating clinically normal from AD populations, and in correlation with Braak neurofibrillary tangle stage at autopsy. Who’s to say what you are measuring!

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