A Mechanistic Link between Olfaction and Autism Spectrum Disorder

Abstract

SummaryInternal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors [1]. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD) [2–4]. However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication [5], remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence [6–12]. To test the failed IAM theory in olfaction, we precisely measured the non-verbal non-task-dependent sniff response concurrent with pleasant and unpleasant odors in 36 children—18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff response within 305 ms of odor onset, ASD children had a profoundly altered sniff response, sniffing equally regardless of odor valance. This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = −0.75, p < 0.001), specifically with social (r = −0.72, p < 0.001), but not motor (r < −0.38, p > 0.18), impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD and directly linking an impaired IAM with impaired social abilities.

ASD Validity

“…Small and Pelphrey (2015) proposed, BInnate olfactory behaviors may provide a link between early emerging sensory motor behaviors and the social deficits that characterize ASD( p. R675). Rozenkrantz et al (2015) reported that longer time sniffing an unpleasant odor was 81 % accurate in differentiating children with ASD from typically developing children, and Rozenkrantz et al (2015) and Small and Pelphrey (2015) suggested that a sniff test could serve as an effective single biomarker for ASD.…”

Autism Spectrum Disorder: Sniffing Out a New Biomarker

“…Ideally, such measures will not rely upon emerging linguistic abilities or complex social behaviors. In a recent study in Current Biology, Rozenkrantz and colleagues [3] now describe a possible marker, based on link between olfaction and ASD.…”

“…Moreover, this could be achieved independently from language function and thus provide a valid measure at the earliest stages of development. It is this idea that is cleverly exploited by Rozenkrantz and colleagues [3].…”

“…Children with ASD exhibit deficits in the perception, understanding and regulation of emotion. Clinical impressions suggest that problems with emotion regulation in ASD can A typically developing two-year old girl wearing the custom made set-up of Rozenkrantz and colleagues [3], with which pleasant and unpleasant odors were presented to the children (red line) while their nasal airflow was monitored (green line). (Photo: Ofer Perl.)…”

“…Despite this, the underlying neurobiological mechanisms have yet to be explored. The measure developed by Rozenkrantz and colleagues [3] promises to provide a nonverbal assessment that will enable testing of an innate form of emotion regulation in even the youngest, most intellectually delayed, minimally verbal children with ASD.…”