Oral, similar to intranasal, administration of oxytocin decreases top-down social attention

Abstract

The neuropeptide oxytocin (OXT) can modulate social cognition by facilitating attention towards social cues and may be a potential therapeutic intervention for social attention impairment in disorders such as autism. Intranasal administration of OXT is widely used to examine its functional effects in both adults and children. However, we have recently shown that administration orally as a lingual spray also modulates neural responses to emotional faces and is potentially better tolerated for therapeutic use. Here, we therefore examined if 24IU OXT administered orally is also effective in facilitating social attention. In a randomized, placebo-controlled, pharmacological study we used a validated emotional anti-saccade eye-tracking paradigm to explore effects of oral OXT on bottom-up and top-down attention processing in 80 healthy male subjects. Our findings showed in terms of top-down attention, oral OXT increased both errors and response latencies for all social stimuli (angry, fearful, happy, sad and neutral emotion faces) but not non-social stimuli (oval shape) in the anti-saccade condition. Comparison with our previous intranasal OXT study using the same task paradigm revealed both routes have a similar effect on increasing anti-saccade errors. However, compared with intranasal OXT, oral OXT significantly decreased error rates for social stimuli in the pro-saccade condition, indicative of increased bottom-up attention processing. Additionally, OXT administration both either route produced an anxiolytic effect evidenced by reduced state anxiety scores. Together, these findings suggest that orally administered OXT has a similar effect on top-down social attention control and anxiety as intranasal administration but more potently influences bottom-up control.

Oro-mucosal administration of oxytocin using medicated lollipops alters social attention, similar to intranasal and lingual routes: Implications for therapeutic use

“…In this paradigm, effects on volitional top-down attention are evidenced by errors and saccade latencies when subjects are required to look away from stimuli (anti-saccades) or on automatic bottom up attention when subjects are required to look toward stimuli (pro-saccades). The weaker effects of OXT on non-social top-down attention observed in previous studies (Xu et al, 2019;Zhuang et al, 2021Zhuang et al, , 2022 might have been due to greater complexity of faces compared to simple oval shapes. We therefore adapted the paradigm to include images of houses inside the oval shapes which are classically used as controls for face images (Arkush et al, 2013;Oruc et al, 2018).…”

“…A large number of studies in humans have demonstrated that intranasal OXT enhances attention toward social relative to non-social stimuli and salient cues such as eye-gaze in both healthy (Eckstein et al, 2019;Xu et al, 2019) and autistic individuals (Andari et al, 2016;Le et al, 2022). Our previous finding that lingually administered OXT has similar effects on modulating top-down attention to social and non-social cues as intranasal administration in an anti-saccade attentional task (Zhuang et al, 2022), suggests that an oral administration route for OXT might be used therapeutically. An intranasal administration route is potentially problematic therapeutically, especially for chronic treatment, since a number of factors can influence dosing efficiency, including application technique, size of the nasal cavity and nasal congestion.…”

“…In humans, we have recently reported that OXT administered via lingual spray can enhance brain reward responses and arousal in response to emotional faces more effectively than following intranasal administration and effects were associated with increases in blood concentrations (Kou et al, 2021). Effects of OXT on social attention and reducing state anxiety are also equivalent following intranasal or lingual routes of administration (Zhuang et al, 2022). Additionally, early studies in autistic adults have reported that intravenous oxytocin improved social cognition and repetitive behaviors (Hollander et al, 2003(Hollander et al, , 2007.…”

“…To allow comparison with previous intranasal (Xu et al, 2019) and lingual spray (Zhuang et al, 2022) OXT administration studies, the current oral OXT administration study also used an adapted version of the emotional anti-saccade paradigm to examine its effects in modulating top-down and bottom-up social and non-social attentional processing. In this paradigm, effects on volitional top-down attention are evidenced by errors and saccade latencies when subjects are required to look away from stimuli (anti-saccades) or on automatic bottom up attention when subjects are required to look toward stimuli (pro-saccades).…”

Effects of exogenous oxytocin administration on non-social executive function in humans: A preregistered systematic review and meta-analysis protocol

“…Also, experimental designs can affect statistical power of analyses. (2) Oxytocin administration route: Previous studies have shown mixed results of how oxytocin administration route affects cognitive/behavioral effects in social processing (Kou et al, 2021;Zhuang et al, 2022). (3) Non-social executive function measured as a primary vs. secondary outcome in individual studies: Whether non-social executive function was of main interest in individual studies might yield discrepant results.…”