Sexual Differentiation and the Neuroendocrine Hypothesis of Autism
Version of Record online: 8 SEP 2011
Copyright © 2011 Wiley-Liss, Inc.
The Anatomical Record
Special Issue: Thematic Papers: New Concepts in Developing Brain Disorders—Autism
Volume 294, Issue 10, pages 1663–1670, October 2011
How to Cite
Aiello, T. P. and Whitaker-Azmitia, P. M. (2011), Sexual Differentiation and the Neuroendocrine Hypothesis of Autism. Anat Rec, 294: 1663–1670. doi: 10.1002/ar.21251
- Issue online: 17 SEP 2011
- Version of Record online: 8 SEP 2011
- Manuscript Accepted: 25 MAY 2010
- Manuscript Received: 9 FEB 2010
- sexual differentiation;
- extreme male
The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis—that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphic—the amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-β estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism. Anat Rec, 2011. © 2011 Wiley-Liss, Inc.