Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans

Abstract

The neuropeptide oxytocin has played an essential role in the regulation of social behavior and attachment throughout mammalian evolution. Because recent studies in humans have shown that oxytocin administration reduces stress responses and increases prosocial behavior, we investigated whether a common single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (OXTR) might interact with stress-protective effects of social support. Salivary cortisol samples and subjective stress ratings were obtained from 194 healthy male participants before, during, and after a standardized psychosocial laboratory stress procedure. Participants were randomly assigned either to prepare alone or to receive social support from their female partner or close female friend while preparing for the stressful task. Differential stress responses between the genotype groups were observed depending on the presence or absence of social support. Only individuals with one or two copies of the G allele of rs53576 showed lower cortisol responses to stress after social support, compared with individuals with the same genotype receiving no social support. These results indicate that genetic variation of the oxytocin system modulates the effectiveness of positive social interaction as a protective buffer against a stressful experience.

Fig. 1.

Mean salivary cortisol levels before, during (shaded area), and after acute social stress in individuals receiving social support or no social support. Error bars represent SEM. Inset: Bar graph of area under the response curves (AUC), representing aggregated hormone levels through the six measurement points.

Fig. 2.

Mean levels of subjective stress before, during (shaded area), and after acute social stress in individuals receiving social support or no social support. Error bars are SEM.

Fig. 3.

(A) Sequence of events and timeline of the study protocol. (B) Layout of stress room, depicting six participants (P) and two evaluators (E). VAS, visual analog scale.