The Impact of Anxiety and Attention-Deficit/Hyperactivity Symptoms on the Pupillary Light Reflex Among Children with ASD: Results from the ABC-CT Interim Analysis

Background: Pupillary light reflex (PLR) is an involuntary response to a flash of light mediated by levels of norepinephrine and acetylcholine. Previous literature has found differences in PLR in children with autism spectrum disorder (ASD) compared to typically-developing (TD) individuals (Daluwatte et al., 2013). However, limited research has explored the impact of common co-occuring symptomology, such as anxiety or hyperactivity and attention difficulties, on the PLR in children with ASD. These symptoms may impact the PLR, as the locus-coeruleus and associated norepinephrine activity (LC-NE) are implicated in both attentional control and anxiety (Redmond & Huang, 1979).

Objectives: To examine PLR among children with and without ASD in relation to anxiety and hyperactive symptomology.

Methods: PLR were collected across five sites from 126 children with ASD between 6-11 (mean age=8.7, mean IQ=96.7) and 58 TD children (mean age=8.9, mean IQ=115). Participants were shown white flashes of light during a passive eye-tracking task using a SR EyeLink 1000+. Stimuli consisted of a central fixation point on a black background that flashed white for 75 milliseconds. The flash onset occurred randomly between 1,600 and 2,400 milliseconds during the 6-second stimulus. Participants completed 16 trials with video clips interspersed between trials. The Autism Diagnostic Observation Schedule, Second Edition (ADOS-II) was used for clinical characterization. Caregivers completed the Child and Adolescent Symptom Inventory, Fifth Edition (CASI-5). Correlations and multiple regressions were used to determine associations between ADOS calibrated severity scores (CSS), anxiety and hyperactivity symptoms (CASI-5 General Anxiety and Hyperactivity subscales T-scores), and relative pupil constriction (RPC) and constriction velocity (CV) in the PLR.

Results: Anxiety scores were significantly higher in the ASD group (M=66.9, SD=14.8) than in the TD group (M=47.2, SD=6.3)[t(181)=-9.8, p<.01)]. Hyperactivity scores were also significantly higher in the ASD group (M=14.1, SD=1.3) compared to the TD group (M=7.1, SD=.96)[t(181)=-11.2, p<.01)]. Within the ASD group, when controlling for CSS, anxiety symptoms significantly predicted RPC (β=.22, p=.02). Hyperactivity also significantly predicted RPC when controlling for CSS in this group (β=.18, p=.04). The overall models were statistically significant for both anxiety and hyperactivity, F(2,122)=4.79, p=.01 (R²=.07); F(2,122)=3.94, p=.02 (R²=.06). Individuals with ASD who met anxiety symptom cutoff on the CASI-5 (>60) showed a significant negative correlation between anxiety symptomology and CV (r=-.43, p<.01). These relationships were not found in the TD group.

Conclusions: Overall, ASD, anxiety, and hyperactive symptomology predicted unique variance in pupillary dynamics; however, collinearity between anxiety and hyperactivity scores precluded dissociation between these constructs and their relation to the PLR. Ongoing analyses including multiple time points will help to elucidate these relationships. Neither relationship was found in the TD group, though elevated levels of anxiety and hyperactivity were exclusionary, yielding a restricted range. These findings suggest PLR in individuals with ASD may index anxiety and hyperactivity and associated neurological mechanisms, such as LC-NE activity. Ongoing analyses will include the effects of medication impacting adrenergic and cholinergic function in the sample. Future directions include utilizing PLR as a potential biomarker to target treatment for different clinical presentations among those with ASD.