cells. Relevant to this hypothesis is the observation that mothers of children with ASC show an aberrant immune response to their child’s lymphocytes [33].
Müllerian Inhibiting Substance
MIS is another hormone produced by the testes. In the developing embryo it causes regression of the Müllerian ducts (which in females develop into the fallopian tube, uterus, and upper portion of the vagina). MIS has been observed to support the survival and differentiation of embryonic motor neurons in vitro [34], which raises the possibility that circulating MIS during embryonic development could play a role in sexual differentiation of the brain and the vulnerability to male-biased neurodevelopmental disorders.
Outstanding Issues: Sex Differences in Symptomatology
Due to the highly biased sex ratio, few studies have explicitly tested the possibility that the ASC phenotype is different in males than in females. The most consistent finding regarding this issue is that females with ASC have, on average, lower IQ scores compared to males with ASC. This finding has generally been interpreted as evidence that more severe brain damage is required to produce ASC in females due to their stronger genetic protection against the condition. There are very few in-depth studies of females with ASC who do not have a comorbid intellectual disability, and sex differences in phenotypes when controlling for IQ are inconsistent between studies. For example, some studies have suggested that females with ASC show worse communication impairments than males, while others have reported the opposite. Higher rates of repetitive and stereotyped behaviors have been reported in young boys with ASC compared to girls, but the majority of studies have found no differences in the core clinical symptoms [35]. It has been suggested that the ASC phenotype in females is sufficiently distinct that it presents as a different condition, such as anorexia, which shares overlapping features with ASC such as empathizing deficits and rigid behavior.
References
1 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, APA, 1994.
2 Baron-Cohen S, Scott FJ, Allison C, Williams J, Bolton P, Matthews FE, Brayne C: Prevalence of autism-spectrum conditions: UK school-based population study. Br J Psychiatry 2009;194:500–509.
3 Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M: Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25:63–77.
4 Baron-Cohen S, Lombardo MV, Auyeung B, Ashwin E, Chakrabarti B, Knickmeyer R: Why are autism spectrum conditions more prevalent in males? PLoS Biol 2011;9:e1001081.
5 Frith U: Autism and Asperger’s Syndrome. Cambridge, Cambridge University Press, 1991.
6 Jolliffe T, Baron-Cohen S: Are people with autism or Asperger’s syndrome faster than normal on the Embedded Figures Task? J Child Psychol Psychiatry 1997;38:527–534.
7 Lawson J, Baron-Cohen S, Wheelwright S: Empathising and systemising in adults with and without Asperger syndrome. J Autism Dev Disord 2004;34:301–310.
8 O’Riordan M, Plaisted K, Driver J, Baron-Cohen S: Superior visual search in autism. J Exp Psychol Hum Percept Perform 2001;27:719–730.
9 Knickmeyer RC, Wheelwright S, Fane BA, Hines M, Baron-Cohen S: Autistic traits in people with congenital adrenal hyperplasia: a test of the fetal testosterone theory of autism. Horm Behav 2006;50:148–153.
10 Manning JT, Baron-Cohen S, Wheelwright S, Sanders G: The 2nd to 4th digit ratio and autism. Dev Med Child Neurol 2001;43:160–164.
11 Ingudomnukul E, Wheelwright S, Baron-Cohen S, Knickmeyer R: Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav 2007;51:597–604.
12 Knickmeyer RC, Hoekstra R, Wheelwright S, Baron-Cohen S: Age of menarche in females with autism spectrum conditions. Dev Med Child Neurol 2006;48:1007–1008.
13 Ruta L, Ingudomnukul E, Taylor K, Chakrabarti B, Baron-Cohen S: Increased serum androstenedione in adults with autism spectrum conditions. Psychoneuroendocrinology 2011;36:1154–1163.
14 Henningsson S, Jonsson L, Ljunggren E, Westberg L, Gillberg C, Rastam M, Anckarsater H, Nygren G, Landen M, Thuresson K, Betancur C, Leboyer M, Gillberg C, Eriksson E, Melke J: Possible association between the androgen receptor gene and autism spectrum disorder. Psychoneuroendocrinology 2009;34:752–761.
15 Schmidtova E, Kelemenova S, Celec P, Ficek A, Ostatnikova D: Polymorphisms in genes involved in testosterone metabolism in Slovak autistic boys. Endocrinologist 2010;20:245–249.
16 Chakrabarti B, Dudbridge F, Kent L, Wheelwright S, Hill-Cawthorne G, Allison C, Banerjee-Basu S, Baron-Cohen S: Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism Res 2009;2:157–177.
17 Sarachana T, Xu M, Wu R, Hu V: Sex hormones in autism: androgens and estrogens differentially and reciprocally regulate RORA, a novel candidate gene for autism. PLoS One 2011;6:e17116.
18 Kallai J, Csatho A, Kover F, Makany T, Nemes J, Horvath K, Kovacs N, Manning JT, Nadel L, Nagy F: MRI-assessed volume of left and right hippocampi in females correlates with the relative length of the second and fourth fingers (the 2D: 4D ratio). Psychiatry Res 2005;140:199–210.
19 Chura LR, Lombardo MV, Ashwin E, Auyeung B, Chakrabarti B, Bullmore ET, Baron-Cohen S: Organizational effects of fetal testosterone on human corpus callosum size and asymmetry. Psychoneuroendocrinology 2010;35:122–132.
20 Lombardo MV, Ashwin E, Auyeung B, Chakrabarti B, Taylor K, Hackett G, Bullmore ET, Baron-Cohen S: Fetal testosterone influences sexually dimorphic gray matter in the human brain. J Neurosci 2012;32:674–680.
21 Pfaff D, Rapin I, Goldman S: Male predominance in autism: neuroendocrine influences on arousal and social anxiety. Autism Res 2011;4:163–176.
