Sex Differences in Autism

Dr. Pelphrey and his daughter

The institute will adapt new methods to diagnose and treat different gender and age groups based on the latest research, with particular interest in understanding girls and boys with ASD as they transition through adolescence and into young adulthood. By improving understanding of ASD’s development for people at different life stages, these new tests will help clinicians more clearly understand the extent of neurodevelopmental disorders and how the brain responds and adapts throughout the development process.

Findings

  • Boys and men are diagnosed with autism spectrum disorder more frequently than girls and women, at rates of 3 or 4 to 1 (Halladay et al., 2015). The exact reason for this skewed ratio is currently unknown, but may include both sociocultural and biological factors. In the sociocultural domain, factors could include diagnostic bias in clinicians or differences in the early life experiences and training provided to girls versus boys. In the realm of biology, theorized factors include elements of male risk (e.g., fetal testosterone) and/or female resilience.
  • Genetic studies have discovered that girls with ASD tend, on average, to exhibit larger, more frequent, and more severe genetic mutations (Jacquemont et al., 2014) than boys with ASD. This suggests that boys require fewer genetic "hits" to express ASD, which in turn provides support for the idea that a biologically-based "Female Protective Effect" is at work among girls and women (Robinson et al., 2013). However, the nature of this effect is still unknown.
  • As part of an NIH-funded Autism Centers of Excellence (ACE) Network, the Autism and Neurodevelopmental Disorders Institute has received a grant to study the origins of the Female Protective Effect, identify other sex differences in ASD brain development, and translate these findings into practical interventions to improve the quality of life for people with ASD. By better understanding the experience and manifestation of ASD in women and girls, clinicians will be able to serve their needs more effectively and prevent misdiagnosis. 

Literature

Halladay AK, Bishop S, Constantino JN, Daniels AM, Koenig K, Palmer K, Messinger D, Pelphrey K, Sanders SJ, Singer AT, Taylor JL, Szatmari P (2015) Sex and gender differences in autism spectrum disorder: Summarizing evidence gaps and identifying emerging areas of priority. Mol Autism.

Hu VW, Sarachana T, Sherrard RM, Kocher KM (2015) Investigation of sex differences in the expression of RORA and its transcriptional targets in the brain as a potential contributor to the sex bias in autism. Mol Autism.

Jacquemont S, Coe BP, Hersch M, Duyzend MH, Krumm N, Bergmann S, Beckmann JS, Rosenfeld JA, Eichler EE (2014) A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders. Am J Hum Genet.

Robinson EB, Lichtenstein P, Anckarsater H, Happe F, Ronald A (2013) Examining and interpreting the female protective effect against autistic behavior. Proc Natl Acad Sci.