Genetic and epigenetic regulatory mechanisms of the oxytocin receptor gene (OXTR) and the (clinical) implications for social behavior.

Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles.

Neurobiobehavioral responses to virtual social rejection in females-exploring the influence of oxytocin.

In recent years, especially adolescents and young adults interact frequently via social media and digital communication. Mimicking an online communication platform where participants could initiate short conversations with two computerized interlocutors, the Verbal Interaction Social Threat Task (VISTTA) was used to induce feelings of social rejection. Motivational and physiological reactions were investigated in 43 healthy young women undergoing functional magnetic resonance imaging (fMRI), of which 22 received 24 international units (IU) intranasal oxytocin and 21 received placebo. Replicating previous findings, social rejection entailed a lower willingness to cooperate with the two peers. Increased activation in the anterior cingulate cortex and bilateral insula/inferior frontal gyrus was observed when receiving negative feedback from others, and in the precuneus when subsequently rating one's willingness to cooperate with them in the future. Oxytocin did not seem to alter responses to social rejection. The current findings provide validation of the VISTTA for examining consequences of rejection in a virtual social interaction that bears a strong resemblance to online communication platforms.

The Verbal Interaction Social Threat Task: A New Paradigm Investigating the Effects of Social Rejection in Men and Women.

In recent years, digital communication and social media have taken an indispensable role in human society. Social interactions are no longer bound to real-life encounters, but more often happen from behind a screen. Mimicking an online communication platform, we developed a new, fMRI compatible, social threat paradigm to investigate sex differences in reactions to social rejection. During the Verbal Interaction Social Threat Task (VISTTA), participants initiate 30 short conversations by selecting one of four predefined opening sentences. Two computerized interlocutors respond to the opening sentence mostly with negative comments and rejections toward the participant, which should induce social-evaluative threat. Physiological and subjective responses were measured, before, during, and after the VISTTA in 61 (29 male and 32 female) first year students who received either mostly negative (n = 31; threat group) or neutral comments (n = 30; control group). Two-level behavioral validation included social threat-induced mood changes in participants, and interlocutor evaluation. The latter consisted of multiple variables such as "willingness to cooperate" after every conversation, an overall fairness evaluation of interlocutors, and evaluations per reaction indicating how positive or negative it was received. We acquired additional physiological measures including cortisol assays via saliva samples, heart rate, and blood pressure. Confirming our hypotheses, peer rejection and exclusion during the VISTTA led to less willingness to cooperate and lower fairness evaluation of interlocutors. It also induced feelings of anger and surprise and lower happiness in the social-threat group. Women showed overall higher emotion ratings compared to men. Contrary to our a priori hypothesis, the VISTTA did not induce cortisol and heart rate increases. However, the stable cortisol response in women in the threat group does not follow the circadian decline and might reflect an endocrinological response. The decline in cortisol response in men in both the threat and control group could indicate faster habituation to the VISTTA. Taken together, these findings indicate effects of social-evaluative threat on a behavioral level, and more moderate effects on the emotional and physiological level. Sex differences in affective and cortisol responses may indicate that women are more susceptible for the social-evaluative threat than men. With a realistic implementation of verbal, interactive, and social components, the VISTTA is designed as an fMRI paradigm that can be applied to elucidate the neural representation of social-evaluative threat.