Oral Administration of Oxytocin, Like Intranasal Administration, Decreases Top-Down Social Attention

Abstract

Background: The neuropeptide oxytocin (OXT) modulates social cognition by increasing attention to social cues and may have therapeutic potential for impaired social attention in conditions such as autism spectrum disorder. Intranasal administration of OXT is widely used to examine the drug's functional effects in both adults and children and is assumed to enter the brain directly via this route. However, OXT can also influence brain function through increased blood concentrations, and we have recently shown that orally (lingual) administered OXT also modulates neural responses to emotional faces and may be better tolerated for therapeutic use. Here, we examine whether 24 IU OXT administered orally can facilitate social attention.

Methods: In a randomized, placebo-controlled pharmacologic study, we used a validated emotional antisaccade eye-tracking paradigm to explore the effects of oral OXT on bottom-up and top-down attention processing in 80 healthy male participants.

Results: Our findings showed that in terms of top-down attention, oral OXT increased errors for both social (angry, fearful, happy, sad, and neutral emotion faces) and nonsocial stimuli (oval shapes) in the antisaccade condition but increased response latencies only in the social condition. It also significantly reduced post-task state anxiety, but this reduction was not correlated with task performance. A comparison with our previous intranasal OXT study using the same task revealed that both routes have a similar effect on increasing antisaccade errors and response latencies and on reducing state anxiety.

Conclusions: Overall, our findings suggest that oral administration of OXT produces similar effects on top-down social attention control and anxiety to intranasal administration and may therefore have therapeutic utility.

Keywords: Intranasal oxytocin; antisaccade task; face emotion; oral oxytocin; social attention.

Figure 1.

Consolidated Standards of Reporting Trials flow chart.

Figure 2.

The timing set for experimental procedure (in minutes) and the emotional antisaccade task, including the social-emotional stimuli, were presented (from a Chinese face expression database) (Ma et al., 2022). Abbreviations: PANAS, Positive and Negative Affect Schedule; SAI-TAI, State-Trail Anxiety Inventory.

Figure 3.

Oral oxytocin’s (OT’s) effect on error rates and latencies. (a) Oral OT increased error rates for both social and nonsocial stimuli (b) but only increased latencies for social stimuli (c) across all emotional faces (effect sizes: angry, Cohen d = 0.62; sad, Cohen d = 0.52; fearful, Cohen d = 0.72; happy, Cohen d = 0.64; neutral, Cohen d = 0.54) but not shapes in the antisaccade task. * and ** denote significant post hoc treatment effects at P_Bonferroni < .05 and P_Bonferroni < .01, respectively.

Figure 4.

State anxiety scores measured at before and after task in oral the placebo (PLC) and oxytocin (OXT) groups. Abbreviation: n.s., nonsignificant. ** denotes significant difference at P < .01.

Figure 5.

The comparison between intranasal and oral oxytocin’s (OT’s) effect on social attention processing. OT via different routes produced a similar effect on antisaccade errors (a) and latencies (b). Abbreviations: IN, intranasal; n.s., nonsignificant; PLC, placebo. * and ** denote significant post hoc comparisons for the main treatment effect at P_Bonferroni < .05 and P_Bonferroni < .01 respectively.