Acute oxytocin improves memory and gaze following in male but not female nursery-reared infant macaques

Abstract

Rationale Exogenous oxytocin administration is widely reported to improve social cognition in human and nonhuman primate adults. Risk factors of impaired social cognition, however, emerge in infancy. Early interventions—when plasticity is greatest—are critical to reverse negative outcomes. Objective We tested the hypothesis that oxytocin may exert similar positive effects on infant social cognition, as in adults. To test this idea, we assessed the effectiveness of acute, aerosolized oxytocin on two foundational social cognitive skills: working memory (i.e., ability to briefly hold and process information) and social gaze (i.e., tracking the direction of others’ gaze) in one-month-old nursery-reared macaque monkeys (Macaca mulatta). We did not predict sex differences, but we included sex as a factor in our analyses to test whether our effects would be generalizable across both males and females. Results In a double-blind, placebo-controlled design, we found that females were more socially skilled at baseline compared to males, and that oxytocin improved working memory and gaze following, but only in males. Conclusions These sex differences, while unexpected, may be due to interactions with gonadal steroids and may be relevant to sexually dimorphic disorders of social cognition, such as male-biased autism spectrum disorder, for which oxytocin has been proposed as a potential treatment. In sum, we report the first evidence that oxytocin may influence primate infant cognitive abilities. Moreover, these behavioral effects appear sexually dimorphic, highlighting the importance of considering sex differences. Oxytocin effects observed in one sex may not be generalizable to the other sex.

Bridging the gap between rodents and humans: The role of non‐human primates in oxytocin research

“…This finding suggests that: (i) OT increases interactive social behaviors; (ii) gaze-following, an interactive behavior elicited by videos, is unrelated to the time spent looking at the eyes; and (iii) looking at the eyes of static images may not be a good measure for the effect of OT on natural, interactive social behaviors. A similar finding was reported in infant rhesus monkeys but the increase in the frequency of gaze-following behaviors was observed only in males and not females (Simpson, Paukner, et al, 2017). It is possible that many of these socio-behavioral effects of OT are sex-specific.…”

Systematic review and meta‐analysis of reported adverse events of long‐term intranasal oxytocin treatment for autism spectrum disorder

“…In total, the search process yielded 80 unique studies. Based on the titles and abstracts, 68 studies were rejected . Based on full text review of the remaining 12 studies, five were rejected for being short‐term studies (less than a month), while one was rejected for not being a randomized controlled trial .…”

How the brain codes intimacy: The neurobiological substrates of romantic touch

“…It is noteworthy that our study revealed a more pronounced effect of OXT on NAcc activation to partner touch in female participants. Gender‐specific OXT effects have been found in various animal [Kelly and Goodson, ; Li et al, ; Simpson et al, ; Steinman et al, ; Young and Wang, ] and human [Ditzen et al, ; Feng et al, ; Hoge et al, ; Lischke et al, ; Scheele et al, ; Yao et al, ] studies. Specifically, intranasal OXT enhanced striatal responses to reciprocated cooperation in a Prisoner's Dilemma Game in men, but not in women [Rilling et al, ].…”