Pupil and salivary indicators of autonomic dysfunction in autism spectrum disorder

Abstract

Dysregulated tonic pupil size has been reported in autism spectrum disorder (ASD). Among the possible sources of this dysregulation are disruptions in the feedback loop between norepinephrine (NE) and hypothalamic systems. In the current study, we examined afternoon levels of salivary alpha-amylase (sAA, a putative correlate of NE) and cortisol (used to assess stress-based responses) in two independent samples of children with ASD. We found a larger pupil size and lower sAA levels in ASD, compared to typical and clinical age-matched controls. This was substantiated at the individual level, as sAA levels were strongly correlated with tonic pupil size. Relatively little diurnal variation in sAA taken in the home environment in the ASD group was also observed, while typical controls showed a significant linear increase throughout the day. Results are discussed in terms of potential early biomarkers and the elucidation of underlying neural dysfunction in ASD.

Figure 1

Study 1, average observed mean tonic pupil size from both testing days for the Autism Spectrum Disorder (ASD), Down syndrome (DS), and Typically-developing (TD) groups, presented in the bar graph. Observed mean pupil size and standard error for each individual subject, organized by group, presented in the scatterplot; the ASD group is separated by Autistic Disorder (AD) and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). **p < .025

Figure 2

Study 1 mean afternoon laboratory concentrations of salivary alpha-amylase (sAA) and cortisol for the Autism Spectrum Disorder (ASD), Down syndrome (DS), and Typically-developing (TD) groups, presented in the bar graph. Mean concentrations and standard errors for each individual subject, organized by group, are presented in the scatterplot; the ASD group is separated by Autistic Disorder (AD) and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). The means are presented as the pre-transformed concentrations of afternoon laboratory sAA and cortisol, but it was the square root and logarithm transformations that were used in the respective analyses to adjust for positive skew and variability. ** p < .025; * p < .05.

Figure 3

Study 1, scatterplot of tonic pupil size to afternoon laboratory salivary concentrations of alpha-amylase (sAA) for the Autism Spectrum Disorder (ASD), Down Syndrome (DS), and Typically-developing (TD) groups.

Figure 4

Bar graph for Study 2 displaying the average observed mean tonic pupil size for the Autism Spectrum Disorder (ASD) and Typically-developing (TD) groups; observed mean tonic pupil size and standard error for each individual subject is organized by group and presented in the scatterplot. The ASD group is separated by Autistic Disorder (AD) and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). ***p < .001

Figure 5

Study 2 mean afternoon laboratory concentrations of salivary alpha-amylase (sAA) and cortisol for the Autism Spectrum Disorder (ASD) and Typically-developing (TD) groups, presented in the bar graph. Mean afternoon salivary concentrations and standard error for each individual subject is organized by group and presented in the scatterplot. The ASD group is separated by Autistic Disorder (AD) and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). The means are presented as the pre-transformed concentrations of afternoon sAA and cortisol, but it was the square root and logarithm transformations that were used in the respective analyses to adjust for positive skew and variability. *** p < .001.

Figure 6

Study 2 observed means of diurnal variations in salivary concentrations of alpha-amylase (sAA) for the Autism Spectrum Disorder (ASD) and Typically-developing (TD) groups. The means are presented as the pre-transformed concentrations of sAA, but it was the square root transformations that were used in the respective analyses to adjust for positive skew and variability. *p < .05.