Vagal Tone As a Predictor of Separation Anxiety in Preschoolers at Elevated Risk for ASD

Background: Separation anxiety disorder (SAD) affects about 4% of typically-developing (TD) children. However, rates of SAD are twice as high for children with autism spectrum disorder (ASD). While traditional screening and diagnostic measures help define behavioral expressions of SAD, physiological indices may serve as valuable biomarkers given subtle signs and limited verbal skills that could preclude accurate recognition of early features. Vagal tone indexes parasympathetic/vagal regulation and atypical vagal tone has been tied to anxiety in TD children and adults. It is unclear if children with ASD have atypical vagal tone because their ASD symptoms interact with anxiety symptoms in a complex manner.

Objectives: The current study aims to characterize differences in vagal tone in groups at high risk for SAD, including children with fragile X syndrome (FXS) and younger siblings of children diagnosed with ASD (ASIBs), compared to TD peers. The study also aims to determine if ASD symptom severity correlates with vagal tone during a socially stressful task and if vagal tone predicts SAD in the high-risk groups.

Methods: Participants included TD males (CA=52.41 months; n=17), ASIBs (CA=60.12 months; n=19) and children with FXS (CA=60.53 months; n=21). Vagal tone was measured during a maternal separation task. Respiratory sinus arrhythmia (RSA), an index of vagal tone, was measured during baseline, maternal separation, and recovery periods. RSA in each period and RSA reactivity between periods was computed. The Spence Children’s Anxiety Scale (Spence & Rapee, 1999) was used as a measure of parent-reported SAD. The Autism Diagnostic Observation Schedule – Second Edition (ADOS-2; Lord, Rutter, DiLavore, & Risi, 2001) was used to measure ASD symptom severity.

Results: One-way ANOVAs indicated that groups did not differ on Spence SAD subscale scores, F(2,52)=0.303, p=.740 or on baseline RSA, F(2,56)=1.028, p=.364. However, children with FXS exhibited lower RSA than ASIBs during the separation period F(2,56)=3.823, p=.028 and lower RSA than both ASIB and TD groups during the recovery periods, F(2,56)=3.743, p=.030. Regression analyses indicated ASD severity did not predict RSA in any groups; however, RSA reactivity from baseline to separation periods predicted SAD for ASIBs R²=.505, F(1,9)=9.188, p=.014 and approached significance for the FXS group R²=.201, F(1,17)=4.288, p=.054.

Conclusions: Regulation of vagal tone during stressful situations serves an adaptive function; therefore, the FXS group’s lower vagal tone during separation and recovery provides evidence of physiological dysregulation. SAD has been shown to exacerbate impairments in children with ASD; therefore, analyzing how biological measurements of SAD correspond with behavioral features in high-risk groups is essential to understanding the expression of SAD in these groups. Severity of ASD does not appear to influence vagal tone, suggesting vagal tone in high-risk groups may be influenced by other factors. However, vagal reactivity did predict SAD symptoms in the ASIB group and marginally in the FXS group, indicating vagal tone may serve as a biomarker of SAD in at-risk populations.