An intriguing observation in the epidemiology of autism is the marked sex bias in its prevalence, with a commonly reported ratio of five males to one female. Age of diagnosis also differs between males and females, being on average later in the latter. Despite the consistent documentation of such a difference, there is a surprisingly low amount of research on sex differences in ASD.

The first question that arises in regard to this sex bias in autism spectrum disorders (ASD) is if males are indeed more prone to developing autism, or if it is due to different behavioral characteristics (real or stereotyped) between females and males.

Differences in neuroanatomy

A different neuroanatomy of the disease in males and females has actually been proposed, with some neuroanatomical sex differences in adult ASD patients having been described.

It has also been reported that brain areas which typically differ between sexes in control individuals are atypical in females, but not males with autism, suggesting what has been dubbed as neural ‘masculinization’. There is actually a theory of autism, the ‘extreme male brain’ theory, which proposes that autism represents an amplification of certain aspects of typical sexual specificities in cognition, but it has been widely criticized for being heavily based on stereotypes. Also, these proposed neuroanatomical differences raise the question of how they can underlie similar cognitive outcomes in males and females with autism.

Indeed, a study examining sex differences in developmental functioning and early social communication in children with ASD did not find any significant effects of sex, suggesting a similar phenotype in males and females, at least early in development. Another study has shown that, although no sex differences in autistic symptoms could be found, females tended to be somewhat more functional, suggesting a sex difference in the adaptive behavior. Although this was an observation from diagnosed patients, one can wonder if functional adaptations in females may mask the development of autistic traits and thereby delay or even hinder their diagnosis. This could account, at least partially, to the reported sex differences in ASD prevalence.

Differences in diagnosis

Given similar patterns of autistic traits, males are more easily diagnosed with autism than females, who usually require more coexisting features to be diagnosed with ASD. It has been argued that this may reflect a gender-bias in the diagnosis of ASD due to stereotyped views of “typical female behavior”.

For example, a young boy lacking social skills will trigger suspicion more promptly that a young girl with the same behavioral patterns, who will more likely be regarded as “just being shy”. Nevertheless, it is possible that autistic traits do develop later in females due to yet unknown different pathophysiological mechanisms.

When trying to understand the neurobiological and genetic aspects of autism in males and females, it is important to determine if the behavioral criteria for autism are appropriate for both. It has therefore been proposed that the threshold for the level of autistic traits for an individual to be considered as having ASD should be sex/gender specific. But this is a challenging question since there are too many behavioral stereotypes associated with gender that hamper these definitions.

Therefore, the answer to this question is not straightforward. The fact that the higher prevalence of ASD in males has led to a preference for males when choosing participants for research studies does not make it easier. As a result, females with autism have been somewhat neglected, and have been assumed to have the same neurobiological mechanisms as males with autism, which may not be true and may have generated a male-biased understanding of autism.

References

Hiller RM, Young RL, & Weber N (2015). Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder. Autism : the international journal of research and practice PMID: 25717130

Lai MC, Lombardo MV, Auyeung B, Chakrabarti B, & Baron-Cohen S (2015). Sex/gender differences and autism: setting the scene for future research. Journal of the American Academy of Child and Adolescent Psychiatry, 54 (1), 11-24 PMID: 25524786

Lai MC, Lombardo MV, Suckling J, Ruigrok AN, Chakrabarti B, Ecker C, Deoni SC, Craig MC, Murphy DG, Bullmore ET, MRC AIMS Consortium, & Baron-Cohen S (2013). Biological sex affects the neurobiology of autism. Brain : a journal of neurology, 136 (Pt 9), 2799-815 PMID: 23935125

Mandic-Maravic V, Pejovic-Milovancevic M, Mitkovic-Voncina M, Kostic M, Aleksic-Hil O, Radosavljev-Kircanski J, Mincic T, & Lecic-Tosevski D (2015). Sex differences in autism spectrum disorders: does sex moderate the pathway from clinical symptoms to adaptive behavior? Scientific reports, 5 PMID: 25988942

Reinhardt VP, Wetherby AM, Schatschneider C, & Lord C (2015). Examination of sex differences in a large sample of young children with autism spectrum disorder and typical development. Journal of autism and developmental disorders, 45 (3), 697-706 PMID: 25189824

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