CohortAutism research : official journal of the International Society for Autism Research2021

Testing the extreme male brain hypothesis: Is autism spectrum disorder associated with a more male-typical brain?

Liza van Eijk, Brendan P Zietsch

PMID 34008924

WHAT IT FOUND

Autistic individuals showed slightly more male-typical brain shapes than controls, but this difference disappeared once brain size was accounted for.

The apparent link between brain maleness and autism symptoms was driven by larger brain size, not shape.

Key findings

01Brain maleness scores were higher in the autism group than controls when not adjusting for brain size, but no difference remained after adjusting for brain size.

02Associations between brain maleness and autism symptoms did not survive correction for multiple testing once brain size was fully adjusted for.

03Brain size was slightly larger in individuals with autism compared to controls, a difference that persisted across a wide age range.

STILL TO COME

How it was doneWhat they found

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What it does not show

The clinical datasets included only high-functioning individuals with autism, so results may not apply to those with more severe support needs. There was a significant imbalance in sex, with far fewer female participants than male participants, limiting the reliability of findings for females. The measure of brain maleness was derived only from subcortical brain regions because cortical landmarks could not be accurately placed in these datasets. The study relies on mean group statistics, and there is large overlap in brain measures between individuals with autism and controls, meaning these findings do not identify distinct biological types.

Declared interests

The study was supported by grants from the National Institutes of Health (N.I.H.) and non-U.S. government sources. No commercial conflicts of interest were declared.

The easy way to misread this

Do not interpret the initial finding of 'more male-typical brains' in autism as evidence that autism is a masculinized brain condition. This study shows that the effect is driven by brain size differences, not brain shape, and disappears when size is accounted for.

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The study

Participants
2,060 analysed (1,112 ABIDE-I and 1,114 ABIDE-II initially, minus 166 removed for processing errors)
Certainty of evidence
Low

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    Liza van Eijk, Brendan P Zietsch Testing the extreme male brain hypothesis: Is autism spectrum disorder associated with a more male-typical brain? Autism research : official journal of the International Society for Autism Research. 2021.

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