Nazari Sanaz, Ramos Cabo Sara, Nalabolu Srinivasa, Carter Barnes Cynthia, Andreason Charlene, Zahiri Javad, Esquivel Ahtziry, Arias Steven J, Grzybowski Andrea, Lombardo Michael V, Lopez Linda, Courchesne Eric, Pierce Karen
Department of Neurosciences and Autism Center of Excellence, University of California, San Diego, La Jolla, CA, USA.
Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy.
Nat Hum Behav. 2025 May 26. doi: 10.1038/s41562-025-02132-6.
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.
自闭症谱系障碍(ASD)在临床上具有异质性,关于男孩和女孩之间的表型差异一直存在争论。了解这些差异,尤其是在首次出现症状的年龄时的差异,对于推进早期检测、揭示病因机制和改善干预措施至关重要。利用“尽早准备”(Get SET Early)项目,我们通过横断面、纵向和聚类分析,运用统计和机器学习方法,对2618名幼儿(平均年龄:约27个月)进行了分析,以评估自闭症谱系障碍组、发育迟缓组和正常发育组在标准化和实验性测量(包括眼动追踪)方面的性别差异。结果显示,在18项测量中的17项上,自闭症谱系障碍幼儿没有显著的性别差异,这些测量包括基于《自闭症诊断观察量表》的症状严重程度、基于《穆伦早期学习量表》的接受性和表达性语言以及基于GeoPref眼动追踪测试的社会注意力。相比之下,正常发育的女孩在几项测量上表现优于男孩。将幼儿分为低、中、高聚类的亚型分析同样表明,自闭症谱系障碍中几乎不存在性别差异。总体而言,我们的研究结果表明,在首次出现症状时,自闭症谱系障碍患者的表型性别差异很小或不存在。