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

Sanaz Nazari, Sara Ramos Cabo, Srinivasa Nalabolu, Cynthia Carter Barnes, Charlene Andreason, Javad Zahiri, Ahtziry Esquivel, Steven J. Arias, Andrea Grzybowski, Michael V. Lombardo, Linda Lopez, Eric Courchesne () and Karen Pierce ()
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Sanaz Nazari: University of California, San Diego
Sara Ramos Cabo: University of California, San Diego
Srinivasa Nalabolu: University of California, San Diego
Cynthia Carter Barnes: University of California, San Diego
Charlene Andreason: University of California, San Diego
Javad Zahiri: University of California, San Diego
Ahtziry Esquivel: University of California, San Diego
Steven J. Arias: University of California, San Diego
Andrea Grzybowski: University of California, San Diego
Michael V. Lombardo: Istituto Italiano di Tecnologia
Linda Lopez: University of California, San Diego
Eric Courchesne: University of California, San Diego
Karen Pierce: University of California, San Diego

Nature Human Behaviour, 2025, vol. 9, issue 8, 1697-1709

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41562-025-02132-6

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