Oxytocin moderates the association between testosterone-cortisol ratio and trustworthiness: A randomized placebo-controlled study.

Oxytocin has been proposed to enhance feelings of trust, however, these findings have been difficult to replicate. Environmental or hormonal factors might influence this association. We studied whether oxytocin moderates the association between the testosterone-cortisol ratio, which is associated with risk taking behavior and aggression, and trustworthiness, while controlling for the general level of trust. A randomized double-blind placebo-controlled study with 53 healthy males was performed in which 32IU oxytocin (n = 27) or placebo (n = 26) was administered intranasally. Participants subsequently played the Trust Game in which they were allocated to the role of trustee. In the third phase of the Trust Game, we found a positive association between the testosterone-cortisol-ratio and the proportion of the amount that is returned to the investor (P=<0.01). However, administration of oxytocin reduced reciprocity in those with a high testosterone-cortisol ratio after reciprocity restoration (a significant interaction effect between administration of oxytocin and the testosterone-cortisol ratio in the third phase of the Trust Game, P = 0.015). The third phase of the Trust Game represents the restoration of reciprocity and trustworthiness, after this is violated in the second phase. Therefore, our data suggest that oxytocin might hinder the restoration of trustworthiness and diminish risk-taking behavior when trust is violated, especially in those who are hormonally prone to risk-taking behavior by a high testosterone-cortisol ratio.

Intranasal administration of oxytocin decreases task-related aggressive responses in healthy young males.

Aggression and distrust are often challenging problems in mental health treatment. Converging evidence reveals that oxytocin increases trust in social interactions and decreases fear of social betrayal. However, oxytocin has also been associated with protective behavior and, as such, might increase defensive aggressive reactions. In this randomized double-blind, placebo-controlled study, the effects of intranasal oxytocin (32IU) on task-related aggressive responses were measured using the Point Subtraction Aggression Paradigm (PSAP). Fifty-seven healthy males were enrolled and randomized to oxytocin (N = 30) or placebo (n = 27). Salivary oxytocin, cortisol and testosterone were measured serially prior to the intervention, and then before and after the PSAP, to evaluate the effects of oxytocin administration on hormonal functioning in relation to aggression. In addition, oxytocin was measured in urine collected directly after the experimental task, reflecting the 2 h period after oxytocin or placebo administration. The proportion of aggressive responses to the PSAP was significantly lower in participants receiving oxytocin versus placebo (ß= -0.46, P = 0.01). No significant effect of oxytocin was found regarding defensive reactions. Urinary oxytocin was negatively associated with the proportion of aggressive responses to the PSAP in both the oxytocin and the placebo group (ß= -0.02, P < 0.01), suggesting that higher levels of urinary oxytocin corresponded with reduced aggressive responding. Our results indicate that oxytocin administration reduces aggressive behavior in healthy young men. Moreover, increased endogenous urinary oxytocin is associated with less aggressive responding. Taken together, these findings suggest that oxytocin signaling has a causal influence on aggressive behavior.

Oxytocin, vasopressin and trust: Associations with aggressive behavior in healthy young males.

Oxytocin enhances trust during social interactions and reduces the tendency for social betrayal. Animal studies have revealed that oxytocin is also an important factor in the establishment and regulation of aggression, for which social interaction is a critical precondition. In humans, however, the effects of oxytocin appear more nuanced and influenced by social context and personality traits. Moreover, the pro-social effects of oxytocin are not mirrored by vasopressin, despite their high chemical similarity. Rather, vasopressin has been associated with an increase of aggressive responses. Therefore, we sought to investigate the association of oxytocin and vasopressin with trust and aggressive behavior. Overnight urinary oxytocin and vasopressin levels were obtained from 62 healthy males (age range: 18-26 years) to compare with trait measures of trust and aggressive behavior. We found a significant interaction of oxytocin and trust on aggression in which low trait measures of trust, in combination with low levels of oxytocin, were associated with a history of aggressive behavior. Notably, we found no significant associations for vasopressin. Although both oxytocin and vasopressin have been shown to be important in the emergence of violent behavior, our study suggests that oxytocin may be particularly modified by affiliative behaviors. These findings provide insights into the neuropsychological influences of oxytocin, and highlights the potential for clinical translation regarding the treatment of patients who exhibit recurrent aggressive behavior.