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.

Terbutaline impairs the development of peripheral noradrenergic projections: Potential implications for autism spectrum disorders and pharmacotherapy of preterm labor

“…In the current study, we evaluated the effects of terbutaline (β 2 -agonist) on development of cardiac and hepatic noradrenergic innervation in contrast to the effects of isoproterenol (β 1 - and β 2 -agonist) and methoxamine (α 1 -agonist) during different developmental periods. We found evidence that β 2 -adrenoceptor stimulation during a critical developmental period leads to deficiencies in peripheral sympathetic noradrenergic innervation, providing a link to observations of autonomic dysfunction reported in ASD (Anderson et al, 2012; Fan et al, 2009; Witter et al, 2009). …”

“…Our earlier work detailed adverse effects of terbutaline on expression of postsynaptic adrenergic and cholinergic receptors in these same target tissues (Auman et al, 2001a, b; Slotkin et al, 2005), properties that would amplify presynaptic defects; and indeed, we identified parallel changes in both cardiac and hepatic function in response to sympathetic and parasympathetic stimuli (Auman et al, 2001a; Hou and Slotkin, 1989; Navarro et al, 1991; Slotkin et al, 2005). The present results are therefore relevant for outcomes of inappropriate terbutaline use in preterm labor, specifically pointing to the need to examine whether exposed children show autonomic dysfunction, as well as providing a contributory component to autonomic manifestations in ASD (Anderson et al, 2012; Fan et al, 2009; Hirstein et al, 2001; Witter et al, 2009). …”

“…Prolonged prenatal terbutaline exposure increases the risk of ASD, especially in association with β 2 -adrenoceptor polymorphisms that enhance responsiveness (Cheslack-Postava et al, 2007; Connors, 2008; Connors et al, 2005; Witter et al, 2009), and some of our morphological findings for cerebellar development parallel those in ASD (Rhodes et al, 2004; Vargas et al, 2004; Zerrate et al, 2007). ASD is also associated with autonomic dysfunction (Anderson et al, 2012; Fan et al, 2009; Witter et al, 2009) and there is a subset of ASD patients who show specific defects in sympathetic activation (Hirstein et al, 2001). The present work shows that terbutaline exposure during the relevant developmental period for its use in preterm labor, impairs development of peripheral sympathetic projections, with the same sex selectivity found for the incidence of ASD (male > female).…”

The Mechanisms Underlying the ASD Advantage in Visual Search

“…For instance, 8-month-olds will show greater pupil dilation when presented with impossible events (Jackson & Sirois, 2009). Pupil responses in ASD and TD groups have been investigated by Anderson, Colombo and their colleagues (Anderson, Colombo, & Shaddy, 2006; Anderson & Colombo, 2009; Anderson, Colombo & Unruh, 2012). They found that tonic pupil size is significantly elevated in children with ASD.…”

Pupillary Motility: Bringing Neuroscience to the Psychiatry Clinic of the Future

“…A specific, often non-verbal group that may benefit from insights and use of pupillometry are individuals with Autism Spectrum Disorders (ASD). Indeed, recent years have observed features such as increased pupil diameter along with other indicators of autonomic dysfunction in autism spectrum disorders [80]. The pupil has also been associated with key features of autism such as empathy in adults [81] and children as young as two years old [82], and has specifically been shown to be decreased in response to social reward in autistic children [83] and positive information in Asperger’s disorder [84].…”