The effect of sex on sleep EEG in typical and altered neurodevelopment

Abstract

Sleep electroencephalography (EEG) patterns exhibit complex variations influenced by multiple factors, including sex. While sex effects in sleep neurophysiology are relatively well described in adults, evidence in pediatric populations is more limited, particularly in the context of neurodevelopmental disorders (NDDs). Here, we analyzed a large pediatric clinical dataset to examine sex differences in whole-night sleep EEG among children without NDDs (N=1523, 2.5-17.5 years) and those with autism spectrum disorder (ASD, N=196), attention deficit hyperactivity disorder (ADHD, N=523), and intellectual disabilities (IntDis, N=167). Medical record analysis revealed limited sex differences in the prevalence of sleep disorders. Using the open-source package Luna, we extracted a broad range of sleep EEG features (435 in total) and found that 25% of all tested metrics showed significant sex differences in the non-NDD sample with the majority replicated in an independent population-based pediatric cohort. Non-NDD boys exhibited more fragmented sleep compared to girls, but this pattern was not observed among children with NDDs. In contrast, fast spindle density was lower in boys regardless of NDD diagnosis, which may contribute to males increased susceptibility to developing NDDs. No sex differences were observed in EEG-based brain age predictions. Several sleep EEG metrics showed nominal group-by-sex interactions with ASD and ADHD girls displaying more pronounced alterations, pointing to a varying degree of sleep disturbance. Overall, our findings demonstrate that many sleep EEG features exhibit significant sex differences during childhood, but these differences may be distinct in NDD populations. The sex-specific sleep alterations in NDDs underscore the importance of including both sexes in future research.