Neural signature underlying the effect of intranasal vasopressin on emotional responses to spontaneous social comparison

Vasopressin, a key molecular regulator of social behavior, is implicated in promoting self-protective responses to threats against physical safety and resources. However, its role in defending against self-view threats--common in social interactions and critical to well-being--remains unclear. This study investigates the neural mechanisms through which vasopressin modulates self-protective responses to spontaneous social comparison. In a double-blind, placebo-controlled neuroimaging experiment, participants rated their satisfaction with social evaluations and monetary outcomes assigned to a stranger, friend, or themselves. Compared to placebo, vasopressin selectively intensified contrastive emotional responses to social evaluations of the stranger, decreasing satisfaction with positive evaluations and increasing satisfaction with negative evaluations, relative to those of the self or friend. At the neural level, vasopressin reduced the distinctions between the stranger and the self/friend in the medial prefrontal cortex activity, multivariate response patterns, and functional connectivity with the temporoparietal junction and precuneus, with this effect being especially pronounced among socially dominant individuals. These converging neuroimaging findings support the hypothesis that vasopressin alters the neural representation of the stranger, shifting it from a socially irrelevant figure under placebo to a psychologically salient competitor, thereby triggering self-protective emotional processes. These findings elucidate novel neuropsychological mechanisms through which vasopressin amplifies emotional defense against social threats and offer insights into potential clinical applications for psychiatric conditions characterized by impaired self-protection.