Arousal Dysregulation in Children with Autism Spectrum Disorder
Objectives: The purpose of this study was to investigate the relationship between anxiety, biomarkers of arousal dysregulation and sleep parameters in ASD versus typically-developing controls (TDC). We hypothesize that individuals with ASD and anxiety as compared to individuals with ASD without anxiety and TDC will have: (1) greater rate of insomnia, defined as difficulty falling and maintaining sleep with daytime impairment, and a sleep latency of greater than 30 minutes as measured by actigraphy; (2) greater sleep latency, decreased sleep efficiency; (3) higher levels of urine catecholamines; (4) lower Respiratory Sinus Arrhythmia score.
Methods: Setting: Home and center visit at the Center for Autism Research (CAR) at the CHOP. Anxiety diagnosis was made with Anxiety Disorders Interview Schedule. Sleep parameters included CSHQ and 7 nights of actigraphy. Biomarkers of arousal dysregulation included urine catecholamine diurnal samples. Respiratory Sinus Arrhythmia (RSA) was obtained using a BioHarness ECG system taking a clean 5-minute interval from a 30-minute session at the CAR lab.
Results: Sample = 57 ASD, 15 TDC, ages 6-18.
47% of ASD subjects had anxiety. 53% of ASD subjects had insomnia. Our sample had a significant relationship between anxiety and insomnia (Χ2<.0001): 88.9% of children with ASD and anxiety also had insomnia, while insomnia was present in only 20% children with ASD without anxiety. In order to identify the relationship between a phenotype of arousal dysregulation and biomarkers, we separated the cohort into two groups: Group A including children with ASD without anxiety and no insomnia (n=24), and Group B including children with ASD, anxiety and insomnia (n=24).
ASD cohort had longer sleep latency than TDCs (30.5 min vs. 19.8 min, p=.025). Group A sleep latency was 19.7 min, and Group B sleep latency was 40.1 min (p=.001).
Group B had a higher CSHQ score than Group A (p=.082), specifically sleep anxiety (p=.072) and daytime sleepiness (p=.039). Group B sleep onset delay and sleep anxiety scores were greater than TDC (p=.065, p=.026).
Total sample mean evening urine epinephrine level was 9.39 μg/g creatinine, with Group A 7.57 μg/g creatinine, Group B 12.43 μg/g creatinine, and TDC 7.62 μg/g creatinine. Reference epinephrine level for children aged 10-15 years is 8 μg/g creatinine (Pussard). Urine epinephrine levels were greater in Group B than in TDCs and Group A (p=.1628).
Group B had lower RSA than Group A (6.1 vs. 6.9, p=.035).
Conclusions: A potential link between insomnia and anxiety in children with ASD was found. Sleep latency differed significantly between TDC and ASD, with Group B having the longest sleep latency. Increased epinephrine in evening urine and lower RSA support a hypothesis of an arousal dysregulation phenotype in children with ASD.