A Data-Driven Approach in an Unbiased Sample Reveals Equivalent Sex Ratio of Autism Spectrum Disorder-Associated Impairment in Early Childhood

Catherine A Burrows; Rebecca L Grzadzinski; Kevin Donovan; Isabella C Stallworthy; Joshua Rutsohn; Tanya St John; Natasha Marrus; Julia Parish-Morris; Leigh MacIntyre; Jacqueline Hampton; Juhi Pandey; Mark D Shen; Kelly N Botteron; Annette M Estes; Stephen R Dager; Heather C Hazlett; John R Pruett Jr; Robert T Schultz; Lonnie Zwaigenbaum; Kinh N Truong; Joseph Piven; Jed T Elison; IBIS Network

doi:10.1016/j.biopsych.2022.05.027

A Data-Driven Approach in an Unbiased Sample Reveals Equivalent Sex Ratio of Autism Spectrum Disorder-Associated Impairment in Early Childhood

Biol Psychiatry. 2022 Oct 15;92(8):654-662. doi: 10.1016/j.biopsych.2022.05.027. Epub 2022 Jun 7.

Authors

Catherine A Burrows¹, Rebecca L Grzadzinski², Kevin Donovan³, Isabella C Stallworthy⁴, Joshua Rutsohn⁵, Tanya St John⁶, Natasha Marrus⁷, Julia Parish-Morris⁸, Leigh MacIntyre⁹, Jacqueline Hampton⁷, Juhi Pandey⁸, Mark D Shen¹⁰, Kelly N Botteron¹¹, Annette M Estes¹², Stephen R Dager¹³, Heather C Hazlett², John R Pruett Jr⁷, Robert T Schultz⁸, Lonnie Zwaigenbaum¹⁴, Kinh N Truong⁵, Joseph Piven², Jed T Elison¹⁵; IBIS Network

Affiliations

¹ Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota. Electronic address: cburrows@umn.edu.
² Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
³ Department of Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.
⁴ Institute of Child Development, College of Education and Human Development, University of Minnesota, Minneapolis, Minnesota.
⁵ Department of Biostatistics, Gillings School of Global PubLic Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
⁶ UW Autism Center, Center on Human Development & Disability, University of Washington, Seattle, Washington.
⁷ Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
⁸ Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
⁹ McGill Centre for Integrative Neuroscience, Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.
¹⁰ Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; UNC Neuroscience Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
¹¹ Department of Radiology, University of Washington Medical Center, Seattle, Washington; Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
¹² UW Autism Center, Center on Human Development & Disability, University of Washington, Seattle, Washington; Department of Speech & Hearing Sciences, University of Washington, Seattle, Washington.
¹³ Department of Radiology, University of Washington Medical Center, Seattle, Washington.
¹⁴ Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Alberta, Canada.
¹⁵ Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota; Institute of Child Development, College of Education and Human Development, University of Minnesota, Minneapolis, Minnesota.

Abstract

Background: Sex differences in the prevalence of neurodevelopmental disorders are particularly evident in autism spectrum disorder (ASD). Heterogeneous symptom presentation and the potential of measurement bias hinder early ASD detection in females and may contribute to discrepant prevalence estimates. We examined trajectories of social communication (SC) and restricted and repetitive behaviors (RRBs) in a sample of infant siblings of children with ASD, adjusting for age- and sex-based measurement bias. We hypothesized that leveraging a prospective elevated familial likelihood sample, deriving data-driven behavioral constructs, and accounting for measurement bias would reveal less discrepant sex ratios than are typically seen in ASD.

Methods: We conducted direct assessments of ASD symptoms at 6 to 9, 12 to 15, 24, and 36 to 60 months of age (total n_observations = 1254) with infant siblings of children with ASD (n = 377) and a lower ASD-familial-likelihood comparison group (n = 168; n_observations = 527). We established measurement invariance across age and sex for separate models of SC and RRB. We then conducted latent class growth mixture modeling with the longitudinal data and evaluated for sex differences in trajectory membership.

Results: We identified 2 latent classes in the SC and RRB models with equal sex ratios in the high-concern cluster for both SC and RRB. Sex differences were also observed in the SC high-concern cluster, indicating that girls classified as having elevated social concerns demonstrated milder symptoms than boys in this group.

Conclusions: This novel approach for characterizing ASD symptom progression highlights the utility of assessing and adjusting for sex-related measurement bias and identifying sex-specific patterns of symptom emergence.

Keywords: Autism spectrum disorder; Measurement invariance; Mixture modeling; Restricted and repetitive behaviors; Sex differences; Social communication.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autism Spectrum Disorder* / diagnosis
Autism Spectrum Disorder* / epidemiology
Child
Child, Preschool
Female
Humans
Infant
Male
Prospective Studies
Sex Characteristics
Sex Ratio
Siblings

Abstract

Publication types

MeSH terms

Grants and funding