How Can Intranasal Oxytocin Research Be Trusted? A Systematic Review of the Interactive Effects of Intranasal Oxytocin on Psychosocial Outcomes

Abstract

<jats:p> Over the past two decades, research about the role of oxytocin (OT) in human behavior has grown exponentially. However, a unified theory of OT effects has yet to be developed. Relatedly, growing concerns about the robustness of conclusions drawn in the field have been raised. The current article contributes to this debate by reporting on and discussing key conclusions from a systematic review of published studies addressing the interactive effects of intranasal OT (IN-OT) administration on psychosocial outcomes in a healthy population. The review indicates that (a) tested interactive IN-OT effects were highly heterogeneous; (b) for most published interactions, no replication was attempted; (c) when attempted, replications were largely unsuccessful; (d) significance was unrelated to sample size; (e) statistical power was critically low and unrelated to the rate of significant results; and (f) research practices were characteristic of an exploratory approach. This concerning state of affairs makes it virtually impossible to tease apart true from false interactive IN-OT effects. We provide constructive directions on the basis of this observation and positive predictive value simulations for future research that should help extract true effects from noise and move the IN-OT field forward. </jats:p>

Neural correlates of mating system diversity: oxytocin and vasopressin receptor distributions in monogamous and non-monogamous Eulemur

“…In questioning the universality of these mechanisms across mammalian groups, our findings in this domain can also be considered within the broader context of psychological oxytocin research, which is similarly marked by interpretive challenges and heterogeneous findings (e.g. 74 ). We suggest that expanding the toolkits available to researchers, including broadening the animal models studied, will likely continue to reveal unexpected findings that require modification to existing theory (a point echoed by behavioral ecologists; e.g.…”

Oxytocin-Trust Link in Oxytocin-Sensitive Participants and Those Without Autistic Traits

“…The task timing of the trust game is supported by Spengler et al (2017), who reported that the oxytocin-induced inhibition of amygdala responses to fear was most effective in a time window between 45 and 70 min after administration of an oxytocin dose of 24 IU. As reviewed by Mierop et al (2020), however, adequate FIGURE 8 | Box plots of administration-induced increases in oxytocin concentration, stratified according to autism quotient (AQ) score. For each plot, the middle horizontal line denotes the median value; the box extends from the 25th to the 75th percentile values; the vertical lines extending from the box denote adjacent values (i.e., the most extreme values within 1.5 interquartile of the 25th and 75th percentile of each group); and the dots denote oxytocin concentration per investor.…”

“…The task timing of the trust game is supported by Spengler et al (2017) , who reported that the oxytocin-induced inhibition of amygdala responses to fear was most effective in a time window between 45 and 70 min after administration of an oxytocin dose of 24 IU. As reviewed by Mierop et al (2020) , however, adequate time windows following intranasal oxytocin administration are unclear. Further research is needed to advance our understanding of the task timing.…”

“… Leng and Ludwig (2016) reported that large concentrations of intranasal oxytocin are required to induce detectable behavioral effects, and questioned whether such could even be attained via the intranasal route. Mierop et al (2020) summarized these concerns as statistical and methodological problems. Further analysis is needed to understand the true effects of oxytocin on human behavior, and to move the intranasal oxytocin field forward.…”

No association between genetic variants in MAOA, OXTR, and AVPR1a and cooperative strategies

“…In particular, there are serious methodological concerns about the validity of several observations linking oxytocin with trust, which is one of the most studied associations in social neuroscience [59][60][61][62]. For instance, the association between exogenous intranasal oxytocin and higher levels of trust [54,63] and the correlation between trust and oxytocin plasma levels [64] has been poorly replicated [60,65]. Lack of robust results linking trust with OXTR has also been evidenced in candidate gene studies.…”