Intranasal vasopressin like oxytocin increases social attention by influencing top-down control, but additionally enhances bottom-up control

Zhuang, Qian; Zheng, Xiaoxiao; Becker, Benjamin; Wei, Lei; Xu, Xiaoling; Kendrick, Keith M.

doi:10.1016/j.psyneuen.2021.105412

Cited by 24 publications

(19 citation statements)

References 65 publications

(86 reference statements)

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“…The effects of oral administration of OXT on top-down social attention processing are similar to those we have previously reported after intranasal administration of vasopressin (Zhuang et al, 2021). This suggests that both peptides have facilitatory effects on social attention and that both may act to enhance the salience of social stimuli as has been proposed…”

Section: Discussionsupporting

confidence: 87%

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

Zhuang

Zheng

Yao

et al. 2021

Preprint

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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.

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Section: Discussionsupporting

confidence: 87%

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

Zhuang

Zheng

Yao

et al. 2021

Preprint

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“…An adapted version of the anti-saccade paradigm from our previous studies was used (Xu et al, 2019;Zhuang et al, 2021Zhuang et al, , 2022, with a total of 576 trials in 14 blocks. The first two blocks presented non-social stimuli (one anti-saccade and one prosaccade block with 48 trials per block).…”

Section: Anti-saccade Paradigmmentioning

confidence: 99%

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

Li²,

Zhuang³

et al. 2022

Front. Neurosci.

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A key functional effect of intranasal administration of the neuropeptide oxytocin is on top-down control of social attention. However, an oro-mucosal administration route may be better tolerated for chronic therapeutic use and evidence suggests that some functional effects of oxytocin can be mediated via peripheral routes. The current study investigated if oxytocin administered orally using medicated lollipops can both increase blood oxytocin concentrations and influence social attention and state anxiety. In a randomized, double-blind, clinical trial adult male participants received oral oxytocin (24IU) or placebo 30-min before completing a well-established anti-saccade paradigm which can assess treatment effects on both top-down and bottom-up attention. Oxytocin administration modulated top-down social attentional processing by increasing anti-saccade error rates on both social and non-social stimuli although it only increased response latencies for social cues. Anti-saccade errors were also positively associated with the proportionate increase in plasma oxytocin concentrations. A comparison analysis showed that oral oxytocin administration increased blood concentrations to a similar degree as given by lingual spray, although less than when given intranasally. Importantly, attentional and anxiolytic effects of oxytocin in the anti-saccade task were similar across intranasal, lingual, and oral administration routes. These findings demonstrate that oral administration of oxytocin, similar to via intranasal and lingual routes, can modulate top-down social attention and state anxiety and support its potential for therapeutic use. They also provide further evidence that functional effects of exogenously administered oxytocin can be mediated indirectly either by crossing the blood brain barrier or producing receptor mediated vagal stimulation, as opposed to via direct entry into the brain.

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“…In one published autism trial, chronic intranasal arginine vasopressin (AVP) was found to positively impact social responsiveness in children with ASD [64]. Intranasal AVP has also been cited for its analgesic effects [65][66][67] and its role in social attention and facial-recognition eye-tracking in healthy adults [68]. Desmopressin, a synthetic form of vasopressin, was initially designed as an oral drug for peripheral disorders to be used instead of brain-behavior treatments; intranasal Desmopressin is currently available as a treatment for hemophilia (clotting promoter; brand name: Stimate manufactured by Ferring GmbH (Kiel, Germany) for CSL Behring LLC (King of Prussia, PA, USA) and nocturnal polyuria (antidiuretic; brand name: Noctiva, manufactured by Renaissance Lakewood LLC (Lakewood, NJ, USA) for Serenity Pharmaceutics LLC (Milford, PA, USA).…”

Section: Discussionmentioning

confidence: 99%

Utility of Downstream Biomarkers to Assess and Optimize Intranasal Delivery of Oxytocin

DuBois¹,

Tseng²,

Francis³

et al. 2022

Pharmaceutics

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Oxytocin (OT), a mammalian neurohormone associated with social cognition and behavior, can be administered in its synthetic form intranasally (IN) and impact brain chemistry and behavior. IN-OT shows potential as a noninvasive intervention for disorders characterized by social challenges, e.g., autism spectrum disorder (ASD) and anorexia nervosa (AN). To evaluate IN-OT’s efficacy, we must quantify OT uptake, availability, and clearance; thus, we assessed OT levels in urine (uOT) before and after participants (26 ASD, 7 AN, and 7 healthy controls) received 40 IU IN-OT or placebo across two sessions using double-blind, placebo-controlled crossover designs. We also measured uOT and plasma (pOT) levels in a subset of participants to compare the two sampling methods. We found significantly higher uOT and pOT following intranasal delivery of active compound versus placebo, but analyses yielded larger effect sizes and more clearly differentiated pre–post-OT levels for uOT than pOT. Further, we applied a two-step cluster (TSC), blinded backward-chaining approach to determine whether active/placebo groups could be identified by uOT and pOT change alone; uOT levels may serve as an accessible and accurate systemic biomarker for OT dose–response. Future studies will explore whether uOT levels correlate directly with behavioral targets to improve dosing for therapeutic goals.

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Intranasal vasopressin like oxytocin increases social attention by influencing top-down control, but additionally enhances bottom-up control

Cited by 24 publications

References 65 publications

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

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

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

Utility of Downstream Biomarkers to Assess and Optimize Intranasal Delivery of Oxytocin

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