Research in Autism Spectrum Disorders 7 (2013) 675–679

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Research in Autism Spectrum Disorders

Opinion: Sex, gender and the diagnosis of autism—A biosocial

A R T I C L E I N F O A B S T R A C T

Article history: Autism Spectrum Disorders (ASD) are behaviorally defined neurodevelopmental
Received 7 February 2013 disorders. The best known yet less understood characteristic of autism is its unexplained
Received in revised form 19 February 2013 male preponderance. Using a biosocial perspective, the goal of this article is to draw
Accepted 22 February 2013 attention to the role of gender-based socialization practices and behavioral expectations
during the clinical evaluation. Together with gender-biased standardized instruments
Keywords: used to support the diagnosis of ASD, these factors may contribute to the higher
Gender prevalence of males with ASD. The assumption is that both biological sex and gender
Sex
identity contribute, in distinct ways, to the male preponderance. While sex is genetically
Diagnosis
defined, gender is a psycho-social construct expressed through specific behaviors
Instruments
Socialization
consistent with socio-cultural expectations based on individuals’ genetic sex. As such,
clinicians are influenced by the expected behaviors based on the prominent gender
socialization attribute. Concurrently, most standardized clinical instruments used for the
diagnosis of ASD do not include gendered-norms. The first question raised here pertains to
the role of a child’s biological sex and the effect of hormones, be it protective versus
increase vulnerability for ASD. The second question focuses on the function of gendered
socialization practices, especially in regard to externalizing and internalizing behaviors
and how these practices may bias the diagnosis and thus the sex ratio.
ß 2013 Elsevier Ltd. All rights reserved.

Barbara, Virginia, and Elaine were the three girls among 11 children whom Leo Kanner described in his seminal paper
published in 1943. Hans Asperger did not report any girls in his original 1944 paper. Today in the United States, 1 in 88
individuals will be diagnosed with an Autism Spectrum Disorder and 1 in 4 will be a boy. Seventy years later, this opinion
paper outlines different attempts to explain the lower ratio of girls diagnosed with autism–from the role of sex hormones
and genetic susceptibility to the biases inherent to clinical diagnosis.
Autism Spectrum Disorders – autism for short – are behaviorally defined neurodevelopmental disorders of mostly
polygenic etiologies influenced by environmental factors. The best known yet less understood characteristic of autism is
prominent, unexplained prevalence in males. From a biosocial perspective that encompasses early gender-based
socialization practices, I propose that this striking sex difference may be enhanced by clinical expectations and by the
gender-biased standardized instruments used to support the diagnosis.

* Correspondence address: Albert Einstein College of Medicine, Kennedy Center, room 807, 1300 Morris Park Avenue, Bronx, NY 10461, United States.
Tel.: +1 718 430 3713; fax: +1 212 787 9312.
E-mail address: [email protected].

1750-9467/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.rasd.2013.02.006
676 S. Goldman / Research in Autism Spectrum Disorders 7 (2013) 675–679

The hypothesis presented in this article rests on the assumption that both sex and gender contribute, but in distinct
ways, to the male preponderance in autism (Cheslack-Postava & Jordan-Young, 2012). With rarest of exceptions, sex is
dichotomous and genetically determined at conception. Biological sex is expressed in the individual’s sexual dimorphisms,
whereas gender emerges from early socialization processes. Whereas sex is biologically defined, gender is a psycho-social
construct expressed through specific behaviors consistent with socio-cultural expectations derived from individuals’
genetic sex. Unlike the sex ratio in clinically diagnosed autism which is established merely by determining the number of
males and females, scores on diagnostic instrument like the Autism Diagnostic Observation Schedule (ADOS) (Lord et al.,
1989) or the parent report on the Autism Diagnostic Interview-Revised (ADI-R) (Lord, Rutter, & Le Couteur, 1994), may be
influenced by the child’s expected behaviors in accordance with the prominent socialization gender attribute. So far the
only widely used screening instrument using a differential gender cutoff is the Social Responsiveness Scale (SRS)
(Constantino et al., 2003).
Let me raise the following two questions (1) what can be said about a child’s biological sex and its effect on autism, and (2)
how do universal, culture-specific gendered socialization practices affect the sex ratio in diagnosing autism? The first
question ought to be addressed in the larger context of autism being but one among many other developmental disorders,
such as dyslexia, Attention Deficit Hyperactivity Disorder (ADHD), or conduct disorders which affect more boys than girls.
The reasons for the male preponderance in these conditions remain unclear and, thus far, it is being explained by tantalizing,
but highly speculative mechanisms. Some studies suggest that boys are more vulnerable to a variety of prenatal insults (e.g.,
infection, malnutrition, stress) (Gardener et al., 2011) and, for uncertain reasons, might be more susceptible to genetic
mutations relevant to autism (Goin-Kochel, Abbacchi, & Constantino, 2007; Szatmari et al., 2012). Other studies suggest that
girls are more resilient to these prenatal potentially deleterious factors. A favored explanation for such a protective feature is
higher exposure to female sex hormones and to oxytocin at critical periods of fetal development (Carter, 2007; Yamasue,
Kuwabara, Kawakubo, & Kasai, 2009). Oxytocin (OT) is a sexually dimorphic neuropeptide associated with attachment,
affiliative, and maternal behaviors. OT is known to foster pro-social behaviors, including social recognition, social learning,
and reproductive behavior in both animals and humans (Feldman, Gordon, Influs, Gutbir, & Ebstein, 2013; Insel, 1997).
Furthermore, in rodents estrogens acting in the amygdala together with OT reduce social anxiety — frequently elevated in
autism — and foster higher levels of positive social interactions (Lee, Macbeth, Pagani, & Young, III, 2009; Ross & Young,
2009). In doing so these hormones — in animals — apparently oppose the influence of testosterone-dependent social arousal
and anxiety (Lukas & Neumann, 2012). Several clinical trials are on their way testing the effect of daily nasal spray of OT on
prosocial behaviors in ASD, however so far no results from longitudinal studies are available to assess the long term effects of
these treatments in children (Miller, 2013).
According to one hypothesis, the male preponderance in autism could be merely due to the fact that girls need a larger
genetic load to become symptomatic. Yet a recent large epidemiological study reports lack of evidence for genetic loading
among families with affected girls (Goin-Kochel et al., 2007). Clearly, there is no shortage of complex explanations to
envision how sex, primarily through its endocrine influences on the developing brain, may modulate the propensity to
develop a neuro-developmental disorder like autism (Bale et al., 2010; Connors et al., 2008; Marco, Macri, & Laviola, 2011).
Fetal testosterone (fT) plays a central role in human neurobehavioral sexual differentiation and in later social behavior
(Bergman, Glover, Sarkar, Abbott, & O’Connor, 2010; Constantinescu & Hines, 2012). Thus, elevated testosterone exposure
during critical periods of early development might be responsible for permanent behavioral changes. These influences have
been demonstrated primarily in individuals who experienced marked prenatal hormone abnormalities associated with
ambiguous genital development (e.g. congenital adrenal hyperplasia). Recently, Auyeung et al. examined the link between
autistic traits and fT levels measured in amniotic fluid during routine amniocentesis and suggested that the brain basis of
autistic traits may reflect individual differences in prenatal androgens and androgen-related genes (Auyeung, Taylor,
Hackett, & Baron-Cohen, 2010; Knickmeyer, Baron-Cohen, Auyeung, & Ashwin, 2008).
In regard to epidemiological studies, it is worth remembering that the male prevalence of 4:1 in autism (Fombonne,
2009), is highly modulated by cognitive function. For instance, as intellectual functioning, namely IQ, decreases, the
skewness of the sex ratio decreases to the extent that in severely cognitively impaired children with autism the sex ratio
approaches 1:1. In contrast, when IQ increases, skewness of the sex ratio increases as well, which is illustrated in the 8:1 sex
ratio in Asperger Syndrome, a form of autism with near-average to high intellectual function (Scott, Baron-Cohen, Bolton, &
Brayne, 2002).
Thus the relationship between IQ and sex ratio seems to be biologically based, but might a diagnosis of autism perhaps
also be related to the qualitative aspects of the clinical behaviorally based diagnosis? (Banach et al., 2009; McLennan,
Lord, & Schopler, 1993; Pilowsky, Yirmiya, Shulman, & Dover, 1998). Severe cognitive deficits may override and attenuate
other more subtle gendered behaviors and characteristics of communication that contribute to making a diagnosis of
autism (Kopp & Gillberg, 2011). Autism is not a disease like diabetes or Parkinson disease which is diagnosed on the basis
of well-recognized and validated biological criteria. Instead, autism is a developmentally defined syndrome characterized
by a set of behavioral symptoms, not on validated biomarkers (Walsh, Elsabbagh, Bolton, & Singh, 2011). Therefore to
arrive at the diagnosis of autism, clinicians rely on a series of observations, and scores on descriptive behavioral tests
based on the magnitude of departures from the expected norms at specific ages, often supplemented by parent
questionnaires.
What is the role of gender during this diagnosis? The process of socialization begins at birth and differs by sex. A
mother attends to her baby boy or girl’s emotions differently and her responses are molded by to the baby’s sex. Similar
 S. Goldman / Research in Autism Spectrum Disorders 7 (2013) 675–679 677

gender-based differences are observed toward the baby’s motor behaviors. The same scenario will take place in the case of a
child who only later will be diagnosed with autism, and the mother will naturally be influenced by the same psychological
and cultural beliefs when interacting with that child. Children with autism do not come into the world with an ‘‘autism
mark’’ on their forehead or with defining stigmata. Moreover, some children will not manifest clear symptoms until age 18
months or so when language deficits or highly routinized play become apparent. Thus, those children diagnosed in the
second year of life are raised like any other children from the day they were born, according to their sex. They are perceived as
girls or boys and are taught to play, talk, and interact in accordance with the particular gender-based rules of their families
(Condry & Condry, 1976). Therefore, despite their symptomatic social impairment, most verbal children with autism
presumably have sufficiently preserved sociability, especially in the language and play domains, to acquire many of the
gender markers to conform to the main sex-based behavioral expectations of their culture. On the other hand, in non-verbal,
severely cognitively impaired children with limited communication skills, the typical gender traits may be less noticeable
and thus boys and girls may be identified at a more comparable rate. At the other extreme, usual female higher verbal
communication skills and social empathy may help girls with high functioning autism to more easily camouflage their social
deficits. In turn, in boys the same social communication issues may readily be more salient and thus reinforce male
identification (Attwood, 2006; Lai et al., 2011). Another significant issue related to the effect of gender in autism is the later
identification of high functioning girls with autism possibly due to specific presentation of social and verbal abilities as well
as variations in the frequency of specific types of co-morbid disorders (Begeer et al., 2012). These factors may play a role in
the longer delay between parental concern and diagnosis in girls.
Biologic sex almost certainly bears the major responsibility for the male preponderance in autism, yet the issue of the
sensitivity of the clinical diagnostic instruments needs to be raised. Germane to this discussion is the fact that the majority
of the behavioral instruments used to diagnose autism have been standardized using male cohorts and very few studies
have tested their sensitivity for identifying girls with autism (Kopp & Gillberg, 2011; Rinehart, Cornish, & Tonge, 2011).
Also, the number of studies that examine common and sex-specific core symptoms of autism across age remain limited
(Kozlowski, Matson, & Rieske, 2012; Rivet & Matson, 2011; Sipes, Matson, Worley. J.A, & Kozlowski, 2011). Lastly, although
externalizing (e.g., aggressiveness, destructiveness) and internalizing behaviors (e.g., depression, anxiety) are known to be
differentially distributed across the sexes, diagnostic instruments remain mostly sensitive to the presentation of the
syndrome in males.

1. Conclusion

Clinical diagnosis is in the eyes of the beholder. Overall, girls are expected to be social, caring and empathic, therefore they
must show greater positive symptoms like externalizing behaviors (e.g., aggressiveness, hyperactivity, severe lack of
reciprocity) to be referred and diagnosed with autism (Bauminger, Solomon, & Rogers, 2010; Constantino & Charman, 2012;
Dworzynski, Ronald, Bolton, & Happe, 2012). Stronger examiner bias toward male expectations may inflate the prevalence of
autism in males, along with the fact that so far, the science of autism has been dominated by a male view of the disorder (e.g.,
test standardization, MRI samples, Baron-Cohen’s ‘‘extreme male theory’’ (Baron-Cohen, 2002)).
It is now undisputable that both male and female brain development requires interactions with the environment and
that these interactions shape the expression of behaviors, in particular language and communication (Hines, 2011). In turn,
continuous cross-talk between sex and gender contributes to differences in the autism phenotype and its variable outcome.
The potential effect of gendered social environment on the expression of symptoms may be quite different for a boy and a
girl with autism, to the point where, despite the same social deficit, a girl may be perceived as shy and a boy as
unresponsive. These gendered perceptions of symptoms may contribute to the diagnostic bias toward increased
identification of social psychopathology in boys (Giarelli et al., 2010; Lai et al., 2011; Worley & Matson, 2011). Furthermore,
socialization being an ongoing developmental process, the outcome of autism in terms of symptom severity and success of
remediation is no doubt influenced in part by hormonal changes during puberty, but also by reinforcement of behaviors
shaped by perceived gender.
As long as we have such imperfect understanding of the pathophysiology and etiologies of autism explanations for the
striking male preponderance, both the biological and psycho-social contributions to the imbalance need to be explored.
More studies should examine the expression of symptoms as a function of IQ and of both sex and gendered social factors in
autism and other developmental disorders (Rinehart et al., 2011). Cognitive functioning being negatively associated with
severity of autistic features, sex discrepancy in IQ in some studies may have obscured true differences in autistic symptoms
between boys and girls (Lai et al., 2012). As an example, it would be relevant to identify verbal and non-verbal gender
markers from ADOS videos and in unidentified gender written protocols or standardized testing reports, and to develop a
coding system to rate gender magnitude across IQ levels and autism severity. Together, basic scientists and clinicians ought
to design longitudinal studies using instruments standardized for each sex to test the hypothesis that girls are less likely to
be diagnosed with autism but when they are, girls are often more severely affected or may display a distinctive
presentation.

Conflict of interest

None declared.
678 S. Goldman / Research in Autism Spectrum Disorders 7 (2013) 675–679

Acknowledgements

This article is based on an invited talk to the Research Forum on Sex and Gender Differences in Cognition and
Neurobiology on behalf of the Institute for Women’s Health and Leadership at Drexel University, October 27th 2011,
Philadelphia.
The author wishes to thank Isabelle Rapin, from Albert Einstein College of Medicine for her support and stimulating
conversation around this topic. The author is supported by the Einstein/Montefiore Autism Center and a grant from the
Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (NIH)
under Award Number P30HD071593.

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