0789 Sleep Spindle Density is Associated with Core Symptom Severity in Autism Spectrum Disorder

Abstract

Abstract Introduction Converging evidence suggests that dysregulation of thalamocortical interactions, mediated by the thalamic reticular nucleus (TRN), contributes to the expression of autism spectrum disorder (ASD). Risk genes for ASD have been found to affect the TRN early in development. Two hallmarks of NREM sleep –slow oscillations (SO) and sleep spindles– reflect TRN function and distinct thalamic/thalamocortical circuits. While studies demonstrate disrupted sleep quality that correlates with symptoms in children with ASD, studies of spindles in ASD have produced inconsistent findings. It is yet unclear if and how spindle properties are associated with ASD symptoms. Herein, based on studies implicating TRN-mediated thalamocortical dysregulation in ASD, we hypothesized that 1) sleep spindles are reduced in ASD; 2) spindle abnormalities correlate with worse clinical symptoms and cognition. Methods Forty participants with ASD (32 males, age: 11.8 ± 3.2; range 6-15) and 46 typically developing (TD) controls (32 males, age: 11.2 ± 2.3; range 6-15) participated in the study. All participants underwent ambulatory overnight polysomnography (PSG) for sleep assessment after systematic desensitization. The Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) were used to assess core behavioral symptoms. Results Spindle density was significantly lower in ASD compared to TD participants (ASD: 2.5 ± 2.0; TD: 3.0 ± 2.1; d= 0.45, p=0.01). In the ASD group, less spindle density was associated with more severe behavioral symptoms, as measured by the total ADOS score (R2=0.15, p=0.01) and the three main subscales of the ADI-R (reciprocal social interaction: R2=0.22, p=0.002; communication and language: R2=0.19, p=0.003; and restricted and repetitive, stereotyped interests and behaviors: R2=0.14, p=0.01). Conclusion Alterations in the maturational trajectory of spindles are related to the core symptoms of ASD individuals. The results have the potential to identify novel biomarkers that index distinct aspects of ASD pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. The study may contribute to producing novel evidence to elucidate the bidirectional relationship between sleep and ASD. Support (if any) Simons Foundation Autism Research Initiative grant (177986).