Large-scale examination of early-age sex differences in neurotypical toddlers and those with autism spectrum disorder or other developmental conditions.

Journal: Nature human behaviour
Published Date: May 26, 2025

Abstract

Autism spectrum disorder (ASD) is clinically heterogeneous, with ongoing debates about phenotypic differences between boys and girls. Understanding these differences, particularly at the age of first symptom onset, is critical for advancing early detection, uncovering aetiological mechanisms and improving interventions. Leveraging the Get SET Early programme, we analysed a cohort of 2,618 toddlers (mean age: ~27 months) through cross-sectional, longitudinal and clustering analyses, performed using statistical and machine learning approaches, to assess sex differences in groups with ASD, developmental delay and typical development across standardized and experimental measures, including eye tracking. The results revealed no significant sex differences in toddlers with ASD across 17 of 18 measures, including symptom severity based on the Autism Diagnostic Observation Schedule, receptive and expressive language based on the Mullen Scales of Early Learning and social attention based on the GeoPref eye-tracking test. In contrast, girls with typical development outperformed boys on several measures. Subtyping analyses stratifying toddlers into low, medium and high clusters similarly showed virtually no sex differences in ASD. Overall, our findings suggest that phenotypic sex differences are minimal or non-existent in those with ASD at the time of first symptom onset.

Authors

  • Sanaz Nazari
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Sara Ramos Cabo
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Srinivasa Nalabolu
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Cynthia Carter Barnes
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Charlene Andreason
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Javad Zahiri
    Department of Neuroscience, University of California San Diego, La Jolla, CA, USA. jzahiri@health.ucsd.edu.
  • Ahtziry Esquivel
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Steven J Arias
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Andrea Grzybowski
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Michael V Lombardo
    4Department of Psychology, University of Cyprus, 2109 Aglantzia, Nicosia, Cyprus.
  • Linda Lopez
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
  • Eric Courchesne
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA. ecourchesne@health.ucsd.edu.
  • Karen Pierce
    Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA. kpierce@health.ucsd.edu.

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