Divergent effects of oxytocin on “mind-reading” in healthy males

Abstract

The neuropeptide oxytocin (OT) has been associated with a broad range of human behaviors, particularly in the domain of social cognition, and is being discussed to play a role in a range of psychiatric disorders. Studies using the Reading The Mind In The Eyes Test (RMET) to investigate the role of OT in mental state recognition reported inconsistent outcomes. The present study applied a randomized, double-blind, cross-over design, and included measures of serum OT. Twenty healthy males received intranasal placebo or OT (24 IU) before performing the RMET. Frequentist and Bayesian analyses showed that contrary to previous studies (Domes et al., 2007; Radke & de Bruijn, 2015), individuals performed worse in the OT condition compared to the placebo condition (p = 0.023, Cohen’s d = 0.55, 95% confidence interval [CI] [0.08, 1.02], BF10 = 6.93). OT effects did not depend on item characteristics (difficulty, valence, intensity, sex) of the RMET. Furthermore, OT serum levels did not change after intranasal OT administration. Given that similar study designs lead to heterogeneous outcomes, our results highlight the complexity of OT effects and support evidence that OT might even interfere with social cognitive abilities. However, the Bayesian analysis approach shows that there is only moderate evidence that OT influences mind-reading, highlighting the need for larger-scale studies considering the discussed aspects that might have led to divergent study results.

Oxytocin—a social peptide? Deconstructing the evidence

“…However, authors have been reluctant to suggest that the outcome of Domes et al may be a false positive. Rather, Macchia et al proposed that ‘Given that similar study designs lead to heterogeneous outcomes, our results highlight the complexity of OT effects’ [ 59 , p. 112]. Radke & de Bruijn [ 60 ], in their attempt to replicate Domes et al, found that ‘Oxytocin did not affect mind-reading, neither in general nor when considering specific item characteristics’ (p. 75).…”

“…Other replications of Domes et al have had mixed outcomes [ 58 ]; recently, Macchia et al [ 59 ] reported that subjects performed worse after oxytocin than after placebo. However, authors have been reluctant to suggest that the outcome of Domes et al may be a false positive.…”

Intranasal Oxytocin Modulates Decision-Making Depending on Outcome Predictability—A Randomized Within-Subject Controlled Trial in Healthy Males

“…The present study was part of a larger project examining the effects of intranasally administered OT on different behavioral metrics in healthy males [ 34 ]. Due to the overall design of the project, participants of the present study had three randomized study visits (separated by at least 7 days), of which one was the experimental condition (active OT, see below for protocol of OT administration) and two were summarized as the control condition.…”

Oxytocin does not stand alone

“…However, accompanying this excitement are welljustified critiques. These include the following: (i) our understanding of how oxytocin modulates social cognition is lacking in methodological rigour [14][15][16][17]; (ii) the effects of oxytocin treatment can be highly context-dependent [18,19]; (iii) we are still building a mechanistic understanding for how oxytocin impacts social behaviours at the neurobiological level [9,[20][21][22][23][24]; (iv) developmental and life experience can drastically change the function of oxytocinergic systems [25][26][27]; and (v) we lack a single overarching theory to predict how oxytocin may modulate behaviour [28][29][30][31]. These critical examinations are fundamental for advancing our understanding of oxytocin, enabling the utilization of oxytocinergic mechanisms as a means to study the neurobiology of social behaviours [32,33] and as a curative tool to restore the deficits in social cognition observed across a variety of psychiatric disorders [34,35].…”

“…Indeed, the field is already successfully moving in the direction of examining oxytocin function under more naturalistic contexts and more holistically, aided by advancements in technology [ 46 , 47 ] and decades of critical introspection in the literature [ 14 , 15 , 17 , 48 ]. For example, recent research has identified supralinear enhancements of social gaze from combinatorial treatment of oxytocin and the opioid antagonist naloxone [ 49 ], demonstrating a mechanistic link between the oxytocinergic and opioidergic systems in the regulation of social attention.…”