A conversation about sex and gender variability in autism with Dr. Meng-Chuan Lai

Article by Iciar Iturmendi Sabater

Graphic design by Michie (Xingyu) Wu

Autism diagnoses are three to four times more common in men than women. Women are diagnosed with autism later than men.  A growing number of concerns have been raised over ascertainment bias in autism. Does the male to female ratio in autism diagnosis truly range from 4:1 to 3:1? Or is it possible that a particular research focus on male samples has led to autism definitions solely drawn from the observation of autistic male characteristics?¹ 

Dr. Meng-Chuan Lai’s scientific work lies at the center of this debate. Dr. Lai is an associate professor at the University of Toronto’s Institute of Medical Science (IMS), and a psychiatrist and O’Brien Scholar at the Centre for Addiction and Mental Health and the Hospital for Sick Children. As a Clinician-Scientist, he studies sex and gender variability in individuals with neurodevelopmental conditions, especially autism.

A theory that may be associated with this ascertainment bias in autistic* women and explain sex and gender differences in prevalence rates is the “extreme male brain” hypothesis, proposed twenty years ago. It was derived from the observation that in the general population and at the group level, women are on-average better at understanding the world through a social or empathizing lens, whereas men are on-average better at grasping meaning from a more technical lens. Yet among the autistic population, autistic women match their male counterparts’ higher systemizing abilities compared to their empathizing abilities. Thus, the extreme male brain hypothesis states that autistic women may show a shift towards ‘male’ profiles in these specific cognitive and behavioural characteristics.²

Dr. Lai calls for careful interpretation of this hypothesis, “the extreme male brain hypothesis, when misunderstood and mistaken as a fact, has led to the stereotype that autistic women should look like autistic men. As a consequence, lots of autistic women who do not show characteristics close to stereotypical autistic men would be perceived as not autistic. This negative impact was not intended based on my understanding of the hypothesis.” For Dr. Lai, the hypothesis was formulated from a cognitive and behavioural lens and confined in the domains of “empathising” and “systemising,” but it does not necessarily extrapolate onto the origins and neurobiological mechanisms underlying autistic cognition and behaviour.

There are three main reasons why it is important to go beyond the extreme male brain hypothesis of autism and study of sex and gender influences in autism, which Dr. Lai refers to as the “ABCs”: A for Aetiology (origin), B for Biological heterogeneity, and C for Clinical practice and care. At each level, research on sex and gender variability may reveal new information about the nature of autism.³

Before diving into this explanation, Dr. Lai emphasizes that “future autism research should differentiate sex and gender, and account for diverse gender identities.”

First, studying sex and gender influences may point towards different sex- and gender related origins of autism. Population studies suggest that multiple genetic factors contribute to the development of autism, and that the genetic load required for autism to manifest is higher for female than male individuals. Beyond genetics, it is possible that male-specific factors make boys more prone to developing autism. For example, higher levels of prenatal sex steroid hormones relate to heightened autistic-like traits or autism diagnosis likelihood later in life.³ This link between sex-hormones and autistic characteristics could reinforce the idea that autism is indeed an extreme male brain condition. However, new research challenges the extreme male brain hypothesis by considering how biology and social factors relate to sex and gender differences in autism.³ 

The idea of heterogeneity posits that the biological and developmental factors that lead to autism vary from one individual to another. That is, the different developmental pathways lead to autism and the adaptation of autistic individuals, like many roads lead to Rome. While many research efforts currently aim to unveil the sex and gender neurobiology that may differentially underlie autistic characteristics, Dr. Lai pioneers research on social phenomena that may influence the manifestation of autistic features. Part of his work focuses on understanding so-called camouflaging behaviours used to manage the impression one causes on others with the aim to pass as ‘normal’. Dr. Lai’s research suggests that autistic women are more likely to camouflage their autistic characteristics (social and communication differences, restricted interests, and repetitive behaviours) than autistic men. This observation has led to the hypothesis that recognizing autism may be easier and come earlier in boys and men since girls and women invest greater efforts in going unnoticed as autistic.⁴ This would mean that autism is not necessarily more common in boys and men, but rather that it is harder to acknowledge in girls and women. Future research is required to clarify how these differences in camouflaging are driven by biological, cultural, and developmental factors.

As a psychiatrist, Dr. Lai became interested in understanding how differently people process and cope in social situations throughout his general psychiatric training early in his career. This takes us to the last level of importance in understanding sex and gender differences in autism: clinical practice and care. “My research ideas are not necessarily pre-defined, but more post-hoc: they come after learning from clinical encounters and lived experiences shared by many autistic people,” Dr. Lai shares. In recent years, the autistic community has emphasized the need to make research in autism participatory. Autistic individuals should be included in the design, implementation, and interpretation of findings. Dr. Lai suggests that “it is not just about learning directly from autistic individuals, but also from their caregivers.”

In this way, Dr. Lai’s work at the IMS reconciles understanding sex and gender variability in autism from an aetiological, biological, and clinical practice lens. To achieve this, he highlights the importance of interdisciplinary collaboration and participatory research, “true collaboration should involve a commitment and discussion from the earliest stages when studies are being conceptualised and designed, rather than just receiving input on the interpretation of findings later on.” 

The interdisciplinary and collaborative products of Dr. Lai’s research on sex and gender influences in autism may help gain a better understanding of this condition in the years to come.

* Identity-first language has been used throughout this article to fit evidence available on the language preferences of the autistic community.⁵

References:

1. Mo K, Sadoway T, Bonato S, Ameis SH, Anagnostou E, Lerch JP, et al. Sex/gender differences in the human autistic brains: A systematic review of 20 years of neuroimaging research. NeuroImage Clin. 2021; 32:102811.  
2. Baron-Cohen S. The extreme male brain theory of autism. Trends Cogn Sci. 2002;6(6):248–54.
3. Lai MC, Lombardo M V., Auyeung B, Chakrabarti B, Baron-Cohen S. Sex/Gender Differences and Autism: Setting the Scene for Future Research. J Am Acad Child Adolesc Psychiatry. 2015;54(1):11–24.
4. Lai M-C, Lombardo M V, Ruigrok AN, Chakrabarti B, Auyeung B, Szatmari P, et al. Quantifying and exploring camouflaging in men and women with autism. Autism . 2017; 21(6):690-702.
5. Kenny L, Hattersley C, Molins B, Buckley C, Povey C, Pellicano E. Which terms should be used to describe autism? Perspectives from the UK autism community. Autism 2016; 20(4): 442-62.