Neural Phenotypes of Females with Autism Spectrum Disorder

Investigator: Fumiko Hoeft, MD, PhD
Sponsor: University of California Davis

Location(s): United States


Although autism spectrum disorder (ASD) is more prevalent in males, the disorder still affects 1 in 252 females, which is a higher prevalence rate than many other childhood disorders such as type 1 diabetes, leukemia, and other childhood cancers. Yet, we know very little about brain abnormalities in females with ASD and how they might be different from males with ASD. Identifying brain regions that are abnormal in ASD is a critical step towards understanding the underlying etiologies and mechanisms of the disorder and ultimately developing treatments.

Autism spectrum disorder (ASD) affects 1 in 88 children in the United States, but the disorder is much more common in boys than in girls. The prevalence of ASD in boys is 5 times higher than in girls, with a rate of 1 in 54 for boys and 1 in 252 for girls. Although this disparate sex ratio is among the most highly replicated findings in studies of ASD, sex differences in ASD remain poorly understood. The neuropathology of ASD in females is understudied because ASD samples recruited for research studies typically reflect the strong male bias of the disorder. The goal of this study is to evaluate a large, sex-balanced cohort of preschool-aged children with ASD in order to elucidate the neural phenotypes of females with ASD and to identify sex-differences in the neuropathology of ASD. Children will be enrolled at the time of diagnosis (2-3 years of age) and followed longitudinally for two years. Imaging will be carried out at study enrolment and then at two additional annual time points and behavioral testing will be conducted twice, in conjunction with the first and third MRI time points Imaging will include structural, diffusion-weighted and resting state functional connectivity in order to accomplish the following aims: 1) to evaluate sex differences in the neural systems that underlie core deficits in ASD 2) to investigate sex differences in brain growth trajectories in these neural systems and 3) to identify associations between distinct neural phenotypic subgroups and etiologic factors or behavioral outcomes. A comprehensive understanding of the female phenotype of ASD is a pressing and timely topic, as indicated by national efforts to direct research towards this topic. This program of research responds to the Interagency Autism Coordinating Committee (IACC) strategic plan to evaluate females with ASD as well as the mission of the NIH Office of Research on Women's Health to strengthen and enhance research related to diseases, disorders and conditions that affect females.