Several studies have demonstrated links between oxytocin and socio-emotional information processing. Regarding the frequently studied single nucleotide polymorphism (SNP) rs53576 and the less studied, functional polymorphism rs2268498 of the oxytocin receptor (OXTR) gene, previous research suggested that their variants might be associated with different proficiency in the processing of social information. Differences between the genotype variants are not restricted to non-verbal stimulus processing but have also been reported in the verbal domain. Moreover, there is evidence that oxytocin expression influences empathic communication and language development during childhood, indicating that language-based theory-of-mind abilities may be affected by interindividual differences in OXTR genotypes as well. The present study therefore investigates whether two prominent SNPs of the OXTR gene (rs53576 GG vs. A+; rs2268498 TT vs. C+) also play a role in the affective evaluation of verbal stimuli varying in emotional valence and in self-other reference. Participants (N = 149 Caucasian participants, 104 females; A+: n = 80, GG: n = 69; C+: n = 98, TT: n = 51) were presented a series of written, self-, other-, and unreferenced words of positive, negative, and neutral valence and asked to affectively evaluate each word pair as positive, negative, or neutral by button press. In line with previous research, reaction times and accuracy (number of valence-congruent responses) showed a self-positivity bias (i.e., preferential processing of self-related positive words), which, however, was unaffected by participants\' genotype. Regarding affective evaluation of neutral words (interpretation bias), A+ carriers displayed a weaker positive interpretation bias compared to GG carriers in the other- and unreferenced stimulus categories. C+ carriers showed a weaker positive interpretation bias than TT carriers in the self-reference condition and in the other-reference condition. These effects were independent from participants\' gender. The present results suggest that the OXTR genotype and hence participants\' genetic oxytocin sensitivity may cause an interpretation bias in the spontaneous appraisal of neutral words.

Accumulating evidence suggests that stressful life events are associated with increased risk for aggressive behavior in adolescents; however, aggressive reactions to life stressors exhibit large individual differences. The present study sought to examine whether the interaction between a single nucleotide polymorphism (SNP [rs53576]) within the oxytocin receptor gene (OXTR) and stressful life events is related to aggression in Chinese Han adolescents.
A total of 197 Chinese Han adolescents (14-17 years of age) were included in this study. Aggression was assessed using the 12-item short version of Buss and Perry Aggression Questionnaire. Stressful life events during the past 12 months were assessed using the Adolescent Self-Rating Life Events Checklist. Genomic DNA was extracted from saliva and buccal cells from each individual.
Multivariate analysis of variance yielded a significant interaction between OXTR rs53576 SNP and life stress (F = 2.449, p = 0.043, partial η2 = 0.051) and of sex × SNP × life stress (F = 3.144, p = 0.016, partial η2 = 0.064). High life stress during the past 12 months was associated with high levels of physical aggression and hostility in OXTR rs53576 homozygous AA adolescents but not in G-carrier adolescents. In boys, homozygous AA individuals in the high life stress group reported significantly higher levels of physical aggression than participants in the other three groups; the interaction, however, was not significant in girls.
This study, which analyzed a specific gene-environment interaction, demonstrated that AA OXTR rs53576 homozygosity may correlate with higher levels of aggression under high life stress conditions with a sample of healthy Chinese Han adolescents. These findings promote the etiological understanding of adolescent aggression, highlighting the complex effect of stressful life events on aggression, and adding evidence supporting the relationship between the oxytocin system and aggressive behavior in adolescents.

Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner\'s Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment.