Autism and the 'female camouflage effect'

Two papers provide some blogging fodder today. The first is from Agnieszka Rynkiewicz and colleagues [1] (open-access available here) who introduces a concept that many people with an interest in autism might have considered: a 'female camouflage effect' in autism. The second paper is by C Ellie Wilson and colleagues [2] and continues the idea that sex/gender differences present in autism might have some important implications for diagnostic evaluation.

Both these papers entertain the idea that although the history of autism has been very 'male-dominated' in light of the sex ratio for the label for example (see here), science and clinical practice is coming round to the idea that there may be important sex/gender differences in the presentation of core issues (see here) that might mean quite a few females have been 'over-looked' or 'under-identified' when it comes to autism. It's of increasing interest.

Rynkiewicz et al set about to present "an innovative computerized technique to objectively evaluate the non-verbal modality of communication (gestures) during two demonstration tasks of ADOS-2 (Autism Diagnostic Observation Schedule, Second Edition)." ADOS, by the way, is one of the gold-standard assessment instruments designed with autism in mind (see here). As part of their really interesting report on "automated coding of non-verbal mode of communication (gestures)" and computation of a "Gesture Index (GI)" they compared results from boys and girls ("high-functioning" as they describe them) and whether "females with autism had a higher GI compared to males with autism."

After data were crunched and the like, the authors concluded that: "High-functioning females with autism might present better on non-verbal (gestures) mode of communication than boys with autism." Further: "This may be because they are effective at camouflaging other diagnostic features." Potentially very important information indeed.

The second paper by Wilson et al continues the theme that sex/gender might have a part to play on the manifestation of autism and onwards diagnostic evaluation. With the aim of reporting "sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment", researchers found among other things that: "Males had significantly more repetitive behaviours/restricted interests than females." Onwards: "The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype."

Variation in the presentation of repetitive and/or restricted behaviours/interests by sex has been talked about in the peer-reviewed research before [3]. As part of a wider suggestion of a specific female phenotype of autism potentially emerging (see here) (being careful with those generalisations) I'd like to think that a greater awareness of such issues could notably enhance the whole diagnostic system especially for females. Indeed, one area that I think would substantially benefit from a little more inspection of a potential 'female camouflage effect' in autism is that of the 'diagnosis' (although not formally noted in standardised texts) of pathological demand avoidance (PDA). At least one person has talked about female autism and the overlap with PDA (see here) and I'm minded to suggest that they might be on to something rather important.

Oh, and since I'm on the topic of sex/gender and autism, I'm minded to bring in the paper by Katarzyna Chawarska and colleagues [4] talking about infant 'at-risk for autism' girls and social attention potentially pertinent to discussions on any female camouflage effect...

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[1] Rynkiewicz A. et al. An investigation of the 'female camouflage effect' in autism using a computerized ADOS-2 and a test of sex/gender differences. Mol Autism. 2016 Jan 21;7:10.

[2] Wilson CE. et al. Does sex influence the diagnostic evaluation of autism spectrum disorder in adults? Autism. 2016. Jan 22.

[3] Van Wijngaarden-Cremers PJ. et al. Gender and age differences in the core triad of impairments in autism spectrum disorders: a systematic review and meta-analysis. J Autism Dev Disord. 2014 Mar;44(3):627-35.

[4] Chawarska K. et al. Enhanced Social Attention in Female Infant Siblings at Risk for Autism. Journal of the American Academy of Child & Adolescent Psychiatry. 2015. Dec 17.

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Rynkiewicz, A., Schuller, B., Marchi, E., Piana, S., Camurri, A., Lassalle, A., & Baron-Cohen, S. (2016). An investigation of the ‘female camouflage effect’ in autism using a computerized ADOS-2 and a test of sex/gender differences Molecular Autism, 7 (1) DOI: 10.1186/s13229-016-0073-0




Wilson CE, Murphy CM, McAlonan G, Robertson DM, Spain D, Hayward H, Woodhouse E, Deeley PQ, Gillan N, Ohlsen JC, Zinkstok J, Stoencheva V, Faulkner J, Yildiran H, Bell V, Hammond N, Craig MC, & Murphy DG (2016). Does sex influence the diagnostic evaluation of autism spectrum disorder in adults? Autism : the international journal of research and practice PMID: 26802113

Early sex differences are not autism-specific

The title of this post mirrors the title of the paper published by Daniel Messinger and colleagues [1] (open-access available here) that reported on "younger sibling sex differences and proband sex differences on the odds of ASD [autism spectrum disorder] in a large sample of prospectively followed high-risk siblings."

Researchers found that alongside "a three-to-one male:female odds ratio in ASD recurrence... the emergence of ASD symptoms in high-risk siblings—both with and without eventual ASD outcomes—occurs in the context of naturally occurring sex-related variability." Further that their results cast "doubt on a female protective effect among high-risk ASD siblings."

Based on participant data derived from the Baby Siblings Research Consortium (BSRC) [2], a collaborative initiative focused on identifying the earliest signs and symptoms of autism, researchers assessed cognitive functioning and autism symptom severity in over 1800 infants, over 1200 of whom were categorised as 'high risk' insofar as being a "younger sibling of a proband with an ASD diagnosis." Of those 1241 high-risk siblings "252 had ASD outcomes" on the basis of a clinical best estimate diagnosis derived from the various data sources available for each participant.

Results: well, there were quite a few of them as previously discussed but I'm going to pick out a few highlights:

• "The male rate of ASD recurrence in the high-risk siblings was approximately 1 in 4 (26.7 %) while the female rate was 1 in 10 (10.3 %)." Further: "The overall—combined male and female—ASD recurrence rate of 19.5 % yielded an ASD outcome for approximately one in five high-risk siblings." This is an important addition to the previous research done on sibling recurrence rates (see here) bearing in mind the potential effect of variables such as reproductive stoppage and multiplex status.
• "Challenging accounts of greater female affectedness, there was no evidence that girls exhibited lower levels of cognitive functioning or higher levels of symptom severity than boys." The idea that there may be a female phenotype of autism has gained significant research traction in recent times (see here) partially based on the idea that it may take 'more genetic issues to trigger autism in girls than boys'. Alongside the idea that females may somehow possess greater protection against autism is the suggestion that autism when it does appear in females, may show differences in terms of severity perhaps as a function of that larger genetic load required. Messinger et al however, report that things might not be so simple.
• "Boys across all groups exhibited slower growth trajectories and lower levels of cognitive performance than girls in fine motor, visual reception, receptive and expressive language functioning." Harking back to some previous musings on the 'fragile male' (see here) Messinger et al showed small but notable difference across the sexes and across ages suggesting female superiority of somewhere between "1.06 to 3.3 months on age-equivalent scores" compared to males. That's not to say males did not develop - everyone developed - rather that girls seemed to develop skills at a faster rate.
• "With respect to the ASD symptom severity indices, males exhibited higher levels of repetitive behaviors than females, but there were no sex differences in social affect severity scores." This finding tallies with other research in this area (see here). The indication being that aspects such as stereotyped language, hand and finger mannerisms or complex mannerisms may be quite a bit more prevalent in 'boy autism' compared to 'girl autism'. More than that however, such repetitive behaviours might be more present in boys over girls (taking out the variable of autism diagnosis) "consistent with a male focus on regularity in the behavior of non-social objects and events." 'Boys and their toys' is a phrase that springs to mind.

The authors conclude that their results "suggest that male:female ASD differences are not ASD-specific but instead reflect more general sex differences reflected through a prism of autism-linked symptoms."

These are interesting results that gain some scientific traction as a function of the large participant numbers included for study and the prospective nature of the study initiative. The authors have made quite a bit of the fact that their results provide "no overall evidence of a female protective effect" in their high-risk siblings group but acknowledge the need for further investigations in this area specifically where female autism is present and how "female probands in multiplex families (two or more female siblings) [may] confer greater risk for ASD in successive offspring." I wonder if this might include some further thought on how sex differences in brain plasticity [3] might potentially be linked to autism?

Once again, autism reveals just how complicated a condition it is...

Music: The Slits - Typical Girls.

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[1] Messinger DS. et al. Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Mol Autism. 2015 Jun 4;6:32.

[2] Messinger D. et al. Beyond autism: a baby siblings research consortium study of high-risk children at three years of age. J Am Acad Child Adolesc Psychiatry. 2013 Mar;52(3):300-308.

[3] Mottron L. et al. Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism. Molecular Autism. 2015. 6; 33.

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Messinger DS, Young GS, Webb SJ, Ozonoff S, Bryson SE, Carter A, Carver L, Charman T, Chawarska K, Curtin S, Dobkins K, Hertz-Picciotto I, Hutman T, Iverson JM, Landa R, Nelson CA, Stone WL, Tager-Flusberg H, & Zwaigenbaum L (2015). Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Molecular autism, 6 PMID: 26045943