Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

Abstract

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin’s dose–response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Looking to the Future of Nasal Drug Delivery–an Interview With Per Gisle Djupesland

“…Another of our papers was also published recently, where we studied 16 autistic patients and delivered the same drug with our device [16]. Although this was a small crossover study with 16 patients, and we used only one single dose, we saw changes in some of the end points, which is very encouraging.…”

Low-dose intranasal oxytocin delivered with Breath Powered device modulates pupil diameter and amygdala activity: a randomized controlled pupillometry and fMRI study

“…There is some human evidence that intranasal oxytocin administration increases central concentrations of oxytocin [39], however, it is unknown if this increase is due to direct nose-to-brain transport or through delivery across the blood brain barrier (BBB) via peripherally circulating blood. We have previously shown that an 8IU dose of oxytocin modulates social cognition [40] and amygdala activity, and that IV oxytocin administration (despite eliciting similar peripheral concentrations) does not elicit effects, which is consistent with nose-to-brain transport of oxytocin with intranasal administration [31,41]. However, the dose-and route-response effects on pupil activity, and its relationship with brain activity, are uncertain.…”

Empathy modulates the temporal structure of social attention

“…in response to reward [39]). Findings like these may question the sensitivity of methods that rely on much briefer stimulus exposures, such as visual probe paradigms [40][41][42] in detecting differences between groups that vary in empathic traits. There is widespread enthusiasm for the idea that electrophysiological methods with high temporal resolution may further clarify the temporal brain dynamics of empathy [43,44] and distinguish between competing explanatory models.…”