Sex- and Context-dependent Effects of Oxytocin on Social Reward Processing

Abstract

We interact socially and form bonds with others because such experiences are rewarding. However, an insecure attachment style or social anxiety can reduce these rewarding effects. The neuropeptide oxytocin (OXT) may facilitate social interactions either by increasing their rewarding experience or by attenuating anxiety, although effects can be sex-and attachment-style dependent. In this study, 64 pairs of same-sex friends completed a social sharing paradigm in a double-blind, placebo-controlled, between-subject design with one friend inside an MRI scanner and the other in a remote behavioral testing room. In this way we could examine whether intranasal-OXT differentially modulated the emotional impact of social sharing and associated neural processing. Additionally, we investigated if OXT effects were modulated by sex and attachment style. Results showed that in women, but not men, OXT increased ratings for sharing stimuli with their friend but not with a stranger, particularly in the friend in the scanner. Corresponding neuroimaging results showed that OXT decreased both amygdala and insula activity as well as their functional connectivity in women when they shared with friends but had the opposite effect in men. On the other hand, OXT did not enhance responses in brain reward circuitry. In the PLC treated group amygdala responses in women when they shared pictures with their friend were positively associated with attachment anxiety and OXT uncoupled this. Our findings demonstrate that OXT facilitates the impact of sharing positive experiences with others in women, but not men, and that this is associated with differential effects on the amygdala and insula and their functional connections. Furthermore, OXT particularly reduced increased amygdala responses during sharing in individuals with higher attachment anxiety. Thus, OXT effects in this context may be due more to reduced anxiety when sharing with a friend than to enhanced social reward.

Oxytocinergic modulation of stress-associated amygdala-hippocampus pathways in humans is mediated by serotonergic mechanisms

“…First, only male subjects were enrolled due to previous studies showing marked sex-differences in the 5-HT synthesis (Nishizawa et al, 1997) and sex-differences in the effects of OXT in rodents and humans (Dumais and Veenema, 2016;Dumais et al, 2017;Ma et al, 2018;Xu et al, 2020;Lieberz et al, 2020). Future studies need to determine whether the observed effects generalize to women.…”