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Cross-Domain Behavioral Fingerprints in ASD

Fernandez, A.

2026-05-26 neuroscience
10.64898/2026.05.25.727621 bioRxiv
Show abstract

The behavioral features of autism spectrum disorders (ASD) span multiple domains, yet the relationships among them remain incompletely characterized. Using phenotypic data from the Simons Foundation Powering Autism Research (SPARK), the largest autism cohort to date (N = 197,187), we characterized associations among motor (DCDQ), repetitive behavior (RBS-R), social-communication (SCQ), and psychopathology (CBCL) measures. Broad positive correlations were observed across all domain pairs, with the strongest effects for RBS-R sensory and obsessive/repetitive features. Covariate-adjusted {surd}{Delta}R2 analyses, controlling for age, sex, and nonverbal IQ, revealed heterogeneous but structured association profiles, with the largest unique contributions observed for CBCL thought problems, social problems, and internalizing outcomes. Principal component analysis (PCA) confirmed that these dimensions dominated a shared covariance structure. Split-half replication and out-of-sample ridge regression both demonstrated strong reproducibility of these profiles. Adjustment for anxiety/depressive symptoms attenuated many associations, particularly those involving sensory and repetitive predictors, though substantial cross-domain structure remained, revealing a reproducible behavioral fingerprint linking motor, sensory-repetitive, social-communicative, and cognitive dimensions in ASD, one that is internally consistent across analytic approaches and only partially explained by co-occurring anxiety and depression.

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