Catch Us If You Can: Why Girls are Underdiagnosed with Autism

In special education classrooms, you can find several differences from a typical one. These include additional teachers, materials with large text and more pictures, sensory-friendly toys, and often more boys enrolled than girls. This is certainly true for students with autism spectrum disorder (ASD), a common developmental disability that affects communication, social interaction, and behavior. Based on population data in the U.S., boys with autism outnumber girls nearly 4 to 1 [1]. Scientists don’t fully know why ASD occurs this way, but there are several reasons that could explain the divide. One reason is that there are biological factors that make male children more likely to have autism. However, biology is not the only thing that can influence the number of diagnoses in a population. There are also factors in our society that make it harder for autistic girls to be diagnosed with autism. Unfortunately, both reasons combine and ultimately leave girls underdiagnosed, which has negative consequences.

Biology

Firstly, terms like boys and girls really refer to gender. Gender is a concept based on social and cultural norms; it includes the expectations a person may have about how to act, look, and feel about themselves and is not limited to just men and women. When we talk about biological differences in the likelihood of having autism, we need to consider the sex of an individual, not their gender. Sex is a label assigned at birth based on a baby’s physical characteristics, and usually (but not always) corresponds to having either two X chromosomes (female) or one X and one Y chromosome (male). Biologists have discovered that females are less likely to have some diseases than males because they have two X chromosomes. When harmful mutations occur on the X chromosome, females are sometimes “protected” from developing a condition because they have a functioning backup copy on their second X chromosome. However, males have only one copy of the X chromosome, so the same mutation may result in more severe conditions. For example, Fragile X Syndrome is a developmental disability caused by a mutation in the X chromosome gene FMR1 that is linked to autism. Males with Fragile X Syndrome are more likely than females to have autism and more severe intellectual disability because they do not have a second X chromosome [2]. Additionally, scientists have found evidence that there may be other underlying sex differences in ASD. Even outside of the X chromosome, autistic females tend to have more ASD-linked genetic variations in their DNA than males, which suggests they may be able to “tolerate” a higher number of these variations before they reach a diagnosis [3,4]. There are physical differences between autistic males and females: males are more likely to have especially large heads and brains [5,6]. Sex hormones, like estrogen, play a role in brain signaling and function differently in males and females, and several studies link their activity to autism [7-10]. 

To fully understand sex differences in autism, research needs to improve. Many animal studies, especially in neuroscience, are conducted with only male animals [11]. It was originally thought that female animals were more difficult to study than males because of their hormonal changes - but this isn’t necessarily true [12]. Because of this sex bias in research, a lot of information is lost about how disorders develop and how they should be treated in females. Having more female-inclusive neuroscience research can help us identify and understand girls with ASD better [13].

Diagnostic Bias

Why else are there fewer autistic girls than boys? It’s now recognized that girls face barriers to getting diagnosed with ASD that boys do not [14]. Unlike other health conditions, ASD diagnosis isn’t based on a medical test, like a blood test, that has a clear, quantitative result. To diagnose children with ASD, doctors first consider a child’s developmental progress, like when or if they started talking or walking. Then specialists, like psychiatrists, check whether children have autistic traits by interviewing parents and observing how kids engage in play and communication [15,16]. This process is subjective, and doctors don’t always catch things right away. Parents and doctors may incorrectly assume that their daughters/patients do not have ASD simply because they know it is more common in boys. When girls are finally diagnosed with ASD, their average age at diagnosis is older than that of boys [17]. 

Autistic symptoms in girls can be different, which makes ASD difficult to recognize. Boys are more likely to show externalizing behaviors, such as hyperactivity, aggression, and repetitive behaviors, which are more noticeable and likely lead to an earlier diagnosis. On the other hand, girls are more likely to have internalizing behaviors, such as social withdrawal or anxiety, which are often overlooked or assumed to be another condition [18,19]. This may be a result of adults interacting with children in different ways depending on their gender, which influences how children are socialized. Socialization is a process that teaches us the norms, values, behaviors, and expectations of our social surroundings. The difference in socialization based on gender is rooted in stereotypes, and even adults with good intentions may do this subconsciously. Girls are often taught to behave in ways that cause them to compensate or “mask” their autism symptoms that are not taught to boys [20].

Why This Matters

The earlier a person is diagnosed with ASD, the sooner they can begin to receive specialized education plans, therapies, and even medication to support their needs. During early childhood, our brains are more plastic, meaning more open to change and learning, so early interventions for autistic children are especially important. If girls are diagnosed later, or misdiagnosed completely, then they lose access to needed services and support systems. To help catch (and help) more autistic girls, we must improve biological research, diagnostic tools, and societal expectations.

References:

1. Maenner, M.J. et al. (2023) Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020. MMWR Surveill Summ 72, 1-14. 10.15585/mmwr.ss7202a1

2. Hunter, J. et al. (2014) Epidemiology of fragile X syndrome: a systematic review and meta-analysis. Am J Med Genet A 164A, 1648-1658. 10.1002/ajmg.a.36511

3. Werling, D.M. and Geschwind, D.H. (2013) Sex differences in autism spectrum disorders. Curr Opin Neurol 26, 146-153. 10.1097/WCO.0b013e32835ee548

4. Zhang, Y. et al. (2020) Genetic evidence of gender difference in autism spectrum disorder supports the female-protective effect. Transl Psychiatry 10, 4. 10.1038/s41398-020-0699-8

5. Ben-Itzchak, E. et al. (2013) Specific neurological phenotypes in autism spectrum disorders are associated with sex representation. Autism Res 6, 596-604. 10.1002/aur.1319

6. Amaral, D.G. et al. (2017) In pursuit of neurophenotypes: The consequences of having autism and a big brain. Autism Res 10, 711-722. 10.1002/aur.1755

7. Hwang, W.J. et al. (2020) The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders. Int J Mol Sci 22. 10.3390/ijms22010373

8. Marrocco, J. and McEwen, B.S. (2016) Sex in the brain: hormones and sex differences. Dialogues Clin Neurosci 18, 373-383. 10.31887/DCNS.2016.18.4/jmarrocco

9. Crider, A. et al. (2014) Dysregulation of estrogen receptor beta (ERbeta), aromatase (CYP19A1), and ER co-activators in the middle frontal gyrus of autism spectrum disorder subjects. Mol Autism 5, 46. 10.1186/2040-2392-5-46

10. Willsey, H.R. et al. (2021) Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience. Neuron 109, 788-804.e788. 10.1016/j.neuron.2021.01.002

11. Beery, A.K. and Zucker, I. (2011) Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev 35, 565-572. 10.1016/j.neubiorev.2010.07.002

12. Becker, J.B. et al. (2016) Female rats are not more variable than male rats: a meta-analysis of neuroscience studies. Biol Sex Differ 7, 34. 10.1186/s13293-016-0087-5

13. Shansky, R.M. and Murphy, A.Z. (2021) Considering sex as a biological variable will require a global shift in science culture. Nat Neurosci 24, 457-464. 10.1038/s41593-021-00806-8

14. Lockwood Estrin, G. et al. (2021) Barriers to Autism Spectrum Disorder Diagnosis for Young Women and Girls: a Systematic Review. Rev J Autism Dev Disord 8, 454-470. 10.1007/s40489-020-00225-8

15. Lord, C. et al. (1994) Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24, 659-685. 10.1007/BF02172145

16. Lord, C. et al. (2012). Autism diagnostic observation schedule, second edition (ADOS-2) manual (Part II): Toddler module.  

17. Shattuck, P.T. et al. (2009) Timing of identification among children with an autism spectrum disorder: findings from a population-based surveillance study. J Am Acad Child Adolesc Psychiatry 48, 474-483. 10.1097/CHI.0b013e31819b3848

18. Mandy, W. et al. (2012) Sex differences in autism spectrum disorder: evidence from a large sample of children and adolescents. J Autism Dev Disord 42, 1304-1313. 10.1007/s10803-011-1356-0

19. May, T. et al. (2014) Does gender matter? A one year follow-up of autistic, attention and anxiety symptoms in high-functioning children with autism spectrum disorder. J Autism Dev Disord 44, 1077-1086. 10.1007/s10803-013-1964-y

20. Dean, M. et al. (2017) The art of camouflage: Gender differences in the social behaviors of girls and boys with autism spectrum disorder. Autism 21, 678-689. 10.1177/1362361316671845

Edited by Alexandra Fink