title: Behavioral and cognitive characteristics of females and males with autism in the Simons Simplex Collection.
abstract: OBJECTIVE
  To examine differences in behavioral symptoms and cognitive functioning between males and females with autism spectrum disorder (ASD).
  
  
  METHODS
  We analyzed data from 2,418 probands with autism (304 females and 2,114 males) included in the Simons Simplex Collection. Sex differences were evaluated across measures of autism symptoms, cognitive and motor functioning, adaptive behavior, and associated behavior problems. Measurement bias was examined using latent variable models of symptoms. Unadjusted and propensity-adjusted analyses were computed to ensure that sex differences were not due to unbalanced sampling. Moderator and mediator analyses evaluated whether sex differences were modified by clinical characteristics or were driven by cognitive ability.
  
  
  RESULTS
  Females with ASD had greater social communication impairment, lower levels of restricted interests, lower cognitive ability, weaker adaptive skills, and greater externalizing problems relative to males. Symptom differences could not be accounted for by measurement differences, indicating that diagnostic instruments captured autism similarly in males and females. IQ reductions mediated greater social impairment and reduced adaptive behavior in females with ASD, but did not mediate reductions in restricted interests or increases in irritability.
  
  
  CONCLUSIONS
  A specific female ASD phenotype is emerging that cannot be accounted for by differential symptom measurement. The present data suggest that the relatively low proportion of high-functioning females may reflect the effect of protective biological factors or may be due to under-identification. Additional carefully accrued samples are needed to confirm the present pattern and to evaluate whether observed sex ratios in high-functioning cases are reduced if female-specific indicators of restricted interests are included.
authors.affiliation: Center for Pediatric Behavioral Health and Center for Autism, Cleveland Clinic. Electronic address: fraziet2@ccf.org.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Frazier
authors.affiliation: McMaster University and Offord Centre for Child Studies.
authors.forename: Stelios
authors.initials: S
authors.lastname: Georgiades
authors.affiliation: Center for Autism and the Developing Brain, Weill Cornell Medical College.
authors.forename: Somer L
authors.initials: SL
authors.lastname: Bishop
authors.affiliation: Stanford University.
authors.forename: Antonio Y
authors.initials: AY
authors.lastname: Hardan
mesh_terms: D000293:Adolescent; D001526:Behavioral Symptoms / Q000503:physiopathology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000145:classification / Q000503:physiopathology*; D002675:Child, Preschool; D003072:Cognition Disorders / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D012042:Registries; D012737:Sex Factors; D012919:Social Behavior
keywords: autism spectrum disorder (ASD); behavior problems; cognitive; females; restricted interests