Demographic, genetic, neuroimaging, and behavioral correlates of short social responsiveness scale in a large pediatric cohort

The Social Responsiveness Scale (SRS) is an established tool for screening autism. An increasing number of studies have utilized the SRS in the general population as an outcome measure to gain insight into the etiology of autism spectrum disorder (ASD). However, SRS scores have not been well characterized in large pediatric cohorts, particularly in relation to their demographic, genetic, neuroimaging, and comorbidity profiles, or how these patterns compare to those observed in clinically diagnosed ASD. This study included 9788 non-ASD children and 182 autistic children aged 9-11 years from the Adolescent Brain Cognitive Development Study. Generalized linear mixed-effect models were applied to evaluate the associations of short social responsiveness scale (SSRS) with a spectrum of demographic, genetic, neuroimaging, and behavioral characteristics. We estimated the heritability of SSRS using a subsample of twin and sibling data. Our finding revealed that children with higher SSRS exhibited a higher male-to-female ratio. SSRS had a high heritability of 0.52 (95% CI, 0.45-0.63), and higher SSRS scores were correlated with increased polygenic risk for ASD (P < 0.001). Neuroimaging analyses identified both overlapping and unique neurobiological underpinnings, with sex-specific variations in structural and functional connectivity similar to those observed in ASD. Higher SSRS scores were linked to lower fluid intelligence, more behavioral problems, more sleep problems, and more psychotic-like symptoms. These findings highlight both the overlap and distinction between patterns reflected in SSRS scores and those observed in clinical ASD, highlighting the need for caution when interpreting findings only utilizing SRS as the outcome for autistic-like trait.