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.

Blunted insula activation reflects increased risk and reward seeking as an interaction of testosterone administration and the MAOA polymorphism.

Testosterone, a male sex hormone, has been suggested to partly explain mixed findings in males and females when investigating behavioral tendencies associated with the MAOA polymorphism. Prior studies indicated that the MAOA polymorphism represents a vulnerability factor for financial risk-taking and harm avoidance and that testosterone increases human risk-taking. We therefore assumed an interactive influence of the MAOA polymorphism and testosterone application on decision making and corresponding neural correlates in a risk and reward context. Stratified for the MAOA polymorphism (S =short, L =long), 103 healthy males were assigned to a placebo or testosterone group (double blind, randomized) receiving a topical gel containing 50 mg testosterone. During a functional MRI scan, the participants performed a sequential decision making task. Our results indicate that testosterone and the MAOA polymorphism jointly influence sequential decision making. The MAOA-S variant was associated with less automatic harm avoidance as reflected in response times on safe decisions. Moreover, after testosterone administration, MAOA-S carriers were more risk-taking. Overall activity in the anterior cingulate cortex, anterior insula and inferior frontal gyrus increased with growing risk for losses. In the anterior insula, testosterone administration mitigated this effect solely in MAOA-S carriers. This might be a reflection of an improved coping during risk-reward conflicts subsequently modulating risky decision making. While the molecular basis is not well defined so far, our results support the assumption of testosterone as a modulatory factor for previously reported sex differences of behavioral associations with the MAOA-S variant. Hum Brain Mapp 38:4574-4593, 2017. © 2017 Wiley Periodicals, Inc.

Exogenous testosterone decreases men's personal distance in a social threat context.

BACKGROUND: Testosterone can motivate human approach and avoidance behavior. Specifically, the conscious recognition of and implicit reaction to angry facial expressions is influenced by testosterone. The study tested whether exogenous testosterone modulates the personal distance (PD) humans prefer in a social threat context. METHODS: 82 healthy male participants underwent either transdermal testosterone (testosterone group) or placebo application (placebo group). Each participant performed a computerized stop-distance task before (T1) and 3.5h after (T2) treatment, during which they indicated how closely they would approach a human, animal or virtual character with varying emotional expression. RESULTS: Men's PD towards humans and animals varied as a function of their emotional expression. In the testosterone group, a pre-post comparison indicated that the administration of 50mg testosterone was associated with a small but significant reduction of men's PD towards aggressive individuals. Men in the placebo group did not change the initially chosen PD after placebo application independent of the condition. However comparing the testosterone and placebo group after testosterone administration did not reveal significant differences. While the behavioral effect was small and only observed as within-group effect it was repeatedly and selectively shown for men's PD choices towards an angry woman, angry man and angry dog in the testosterone group. In line with the literature, our findings in young men support the influential role of exogenous testosterone on male's approach behavior during social confrontations.

When opportunity meets motivation: Neural engagement during social approach is linked to high approach motivation.

Social rewards are processed by the same dopaminergic-mediated brain networks as non-social rewards, suggesting a common representation of subjective value. Individual differences in personality and motivation influence the reinforcing value of social incentives, but it remains open whether the pursuit of social incentives is analogously supported by the neural reward system when positive social stimuli are connected to approach behavior. To test for a modulation of neural activation by approach motivation, individuals with high and low approach motivation (BAS) completed implicit and explicit social approach-avoidance paradigms during fMRI. High approach motivation was associated with faster implicit approach reactions as well as a trend for higher approach ratings, indicating increased approach tendencies. Implicit and explicit positive social approach was accompanied by stronger recruitment of the nucleus accumbens, middle cingulate cortex, and (pre-)cuneus for individuals with high compared to low approach motivation. These results support and extend prior research on social reward processing, self-other distinctions and affective judgments by linking approach motivation to the engagement of reward-related circuits during motivational reactions to social incentives. This interplay between motivational preferences and motivational contexts might underlie the rewarding experience during social interactions.

The impact of emotional faces on social motivation in schizophrenia.

Impairments in emotion recognition and psychosocial functioning are a robust phenomenon in schizophrenia and may affect motivational behavior, particularly during socio-emotional interactions. To characterize potential deficits and their interplay, we assessed social motivation covering various facets, such as implicit and explicit approach-avoidance tendencies to facial expressions, in 27 patients with schizophrenia (SZP) and 27 matched healthy controls (HC). Moreover, emotion recognition abilities as well as self-reported behavioral activation and inhibition were evaluated. Compared to HC, SZP exhibited less pronounced approach-avoidance ratings to happy and angry expressions along with prolonged reactions during automatic approach-avoidance. Although deficits in emotion recognition were replicated, these were not associated with alterations in social motivation. Together with additional connections between psychopathology and several approach-avoidance processes, these results identify motivational impairments in SZP and suggest a complex relationship between different aspects of social motivation. In the context of specialized interventions aimed at improving social cognitive abilities in SZP, the link between such dynamic measures, motivational profiles and functional outcomes warrants further investigations, which can provide important leverage points for treatment. Crucially, our findings present first insights into the assessment and identification of target features of social motivation.

Acting on anger: social anxiety modulates approach-avoidance tendencies after oxytocin administration.

Oxytocin attenuates responses to stress and threat (e.g., by fostering social approach in animals), but direct investigations of whether the hormone also facilitates approach-related social behaviors in humans are lacking. To assess approach-avoidance tendencies, we had participants respond to images of happy and angry faces with direct or averted gaze by either pulling a joystick toward themselves (approach) or pushing it away from themselves (avoidance). When given a placebo, participants' action tendencies were typical, with happy faces eliciting approach responses and angry faces eliciting avoidance responses. However, 24 IU of oxytocin moderated these tendencies, with the inclination to approach angry faces with direct gaze being negatively related to social anxiety. The results demonstrate that oxytocin facilitates approach in humans in response to social threat, which verifies its anxiolytic potential. Moreover, they underscore the moderating role of dispositional factors reported in endocrine research and their therapeutic implications.

Hypersociability in the behavioral phenotype of 17q21.31 microdeletion syndrome.

The 17q21.31 microdeletion syndrome with its characteristic features including developmental delay, moderate intellectual disability, facial dysmorphisms, and anomalies of the brain and multiple organ systems was recently described. As to its behavioral profile, scarce data from clinical observations have suggested a remarkably amiable, friendly disposition, to some extent comparable to that observed in Angelman and Williams syndromes. The present study focuses on the various aspects of neurocognitive functioning, particularly social cognition, in patients with 17q21.31 microdeletion syndrome. Neuropsychological assessment was performed in three out of the four known Dutch patients with a genetically proven 17q21.31 microdeletion syndrome. Apart from developmental age, cognition and social-emotional functioning was extensively assessed. In addition, data of three intellectually disabled physically healthy reference subjects, recruited from a small outpatient sample, were included. The general cognitive profile of all subjects was in accordance with their lowered intellectual capacities, albeit that in patients with the 17q21.31 microdeletion, a relatively strong memory for social-contextual information was found. Basic emotion perception was intact, but patients with the 17q21.31 microdeletion syndrome showed less social fear and more approaching behavior. Interestingly, alexithymic traits, that is marked difficulties in the recognition and expression of emotions, were more prevalent in reference subjects. Despite the methodological limitations characteristic for research in people with intellectual disabilities, with a neuropsychological assessment strategy, in three patients with 17q21.31 microdeletion syndrome, preliminary evidence for hypersocial behavior with a high level of frustration tolerance was found that may be implicated in its behavioral phenotype.

Mistakes that affect others: an fMRI study on processing of own errors in a social context.

In social contexts, errors have a special significance and often bear consequences for others. Thinking about others and drawing social inferences in interpersonal games engages the mentalizing system. We used neuroimaging to investigate the differences in brain activations between errors that affect only agents themselves and errors that additionally influence the payoffs of interaction partners. Activation in posterior medial frontal cortex (pMFC) and bilateral insula was increased for all errors, whereas errors that implied consequences for others specifically activated medial prefrontal cortex (mPFC), an important part of the mentalizing system. The results demonstrate that performance monitoring in social contexts involves additional processes and brain structures compared with individual performance monitoring where errors only have consequences for the person committing them. Taking into account how one's behavior may affect others is particularly crucial for adapting behavior in interpersonal interactions and joint action.

Neuropsychobiological Fingerprints of Chronic Fatigue in Sarcoidosis.

BACKGROUND: Chronic fatigue is a prominent symptom in many sarcoidosis patients, affecting quality of life and interfering with treatment. This study investigated neuropsychobiological mechanisms and markers of chronic fatigue in sarcoidosis. METHODS: Thirty patients with a histological diagnosis of sarcoidosis were included. The Multidimensional Fatigue Inventory was used to define patients with and without chronic fatigue. All patients were then characterised using several depression, quality of life questionnaires, and executive functioning. Cognitive functioning and underlying neural correlates were assessed using an n-back task measuring working memory and (sustained) attention during functional magnetic resonance imaging. Sarcoidosis disease activity was determined using lung function, laboratory parameters, and exercise capacity. RESULTS: Nineteen patients had chronic fatigue and 11 did not; both groups had similar demographic and disease activity characteristics. Chronic fatigue patients showed more symptoms of depression and anxiety, and lower quality of life. During the n-back task, chronic fatigue was associated with a smaller increase in brain activation with increasing task difficulty versus the group without fatigue, especially in the angular gyrus. CONCLUSION: Inadequate adjustment of brain activation with increasing demands appears to be a potential neurobiological marker of chronic fatigue in sarcoidosis patients. The angular gyrus, which plays an important role in the working memory system, was the major area in which fatigue patients showed smaller increase of brain activation compared to those without fatigue. These findings might be relevant for a deeper understanding of chronic fatigue mechanisms in sarcoidosis and future clinical treatment of this disabling syndrome. TRIAL REGISTRATION: ClinicalTrials.gov, Trial registration number: NCT04178239Date of registration: November 26, 2019, retrospectively registeredURL: https://clinicaltrials.gov/ct2/show/NCT04178239.

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.

A Short Empathy Paradigm to Assess Empathic Deficits in Schizophrenia.

Empathy is important for successful social interaction and maintaining relationships. Several studies detected impairments in empathic abilities in schizophrenia, with some even indicating a broader deficit in several components, including emotion recognition, perspective taking, and affective responsiveness. The aim of our study was to validate a short version of the previous empathy paradigm as a reliable and easily applicable method to assess empathic deficits in patients with schizophrenia potentially within clinical routine. To do so, we applied the short version to 30 patients (14 females) diagnosed with schizophrenia meeting the DSM-5 criteria and 30 well matched healthy controls (14 females). The data analysis indicates a significant empathic deficit in patients due to worse performance in all three domains. We managed to replicate most of the findings of our previous study. In contrary to the previous study, significant correlations between performance in the empathy tasks and psychopathology occurred: the severity of negative symptoms was negatively associated with performance in the emotion recognition task and the affective responsiveness task. Gender did not significantly affect performance in the empathy tasks. Regarding the results, our short empathy paradigm appears to be a valid method in assessing empathic impairments in schizophrenia that may be useful in clinical routine.

The Association Between Vulnerable/Grandiose Narcissism and Emotion Regulation.

Narcissism has been widely discussed in the context of career success and leadership. Besides several adaptive traits, narcissism has been characterized by difficulties in emotion regulation. However, despite its essential role in mental health, there is little research on emotion regulation processes in narcissism. Specifically, the investigation of not only the habitual use of specific regulation strategies but also the actual ability to regulate is needed due to diverging implications for treatment approaches. Thereby it is important to differentiate between vulnerable and grandiose narcissism as these two phenotypes might be related differently to regulation deficits. The aim of this study was to examine the association between grandiose and vulnerable narcissism and emotion regulation in healthy individuals (30f/30m) focusing on the strategy reappraisal. Additionally, potential sex effects have been explored. Narcissism was assessed using self-report measures and emotion regulation with self-report questionnaires as well as an experimental regulation task. During this task, participants were presented with pictures of sad/happy faces with the instruction to indicate their subjective emotions via button press. Depending on the condition, participants either indicated their natural response or applied cognitive control strategies to regulate their own subjective emotions. Results indicate no relationship between grandiose and vulnerable narcissism and emotion regulation ability, irrespective of sex. Individuals high on vulnerable narcissism use the maladaptive regulation strategy suppression more frequently than individuals with low expressions. Individuals high on grandiose narcissism, in contrast, seem to avoid the suppression of positive emotions and do not express negative emotions in an uncontrolled manner. Interestingly, while grandiose narcissism was not associated with depressive symptoms, vulnerable narcissism correlated positively with depressive symptoms and anhedonia. Findings of this study underline the need to differentiate between grandiose and vulnerable manifestations of narcissism. Against our expectation, narcissism was not related to emotion regulation performance. In line with previous research, grandiose narcissism seems less harmful for mental health, while vulnerable narcissism is associated with psychological problems and the use of rather maladaptive emotion regulation strategies, i.e., suppression. Future research should investigate the relationship between pathological narcissism and emotion regulation also by extending the scope to other relevant regulation strategies.

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.

Serum Testosterone and Cortisol Concentrations After Single-Dose Administration of 100-Mg Transdermal Testosterone in Healthy Men.

The growing interest in testosterone's effects on men's social behaviors, in particular aggressive, risk-taking, or status maintenance behaviors, is accompanied by a paucity of dose-dependent pharmacokinetic data. Examining the neurophysiological effects of transdermal testosterone typically includes a 4h delay before further brain-behavior measurements. Nevertheless, high heterogeneity regarding the timing of follow-up measurements and dosage remains. In a double-blind placebo-controlled design, we examined the short-term pharmacokinetic profile of 100-mg transdermal testosterone (Testotop®) to determine the optimal time for detecting testosterone-mediated effects. Across two studies, 35 healthy men received a single dose of testosterone and placebo in two separate sessions. In study one (n = 16), serum testosterone and cortisol were assessed serially every 30 min up to 2 h posttreatment. In study two (n = 19), we assessed serum testosterone and cortisol at baseline, 2 h, and 4.15 h (255 min) posttreatment. Relative to baseline and placebo, transdermal testosterone significantly increased total serum testosterone concentrations 90 min posttreatment, reaching maximum concentration between 2 h and 3 h posttreatment. Albeit elevated, serum testosterone levels gradually decreased between 2 h and 4 h following treatment. Transdermal testosterone did not suppress cortisol release. Instead, cortisol concentrations decreased according to cortisol's known circadian rhythm. Unlike previous findings showing significant testosterone concentration increases as soon as 60 min and as late as 3 h post 150-mg testosterone treatment, our 100-mg testosterone manipulation significantly increased testosterone concentrations 90 min following treatment. These pharmacokinetic data are important in facilitating the optimization of timing parameters for future testosterone challenge studies.

Attention control and its emotion-specific association with cognitive emotion regulation in depression.

Individuals with major depression show impaired control of attention and emotions. Both processes are conceptually similar and might share common mechanisms. The current study aims to examine attention control and its association with cognitive emotion regulation in depression. 26 patients with a history of major depression (14 females) and 26 healthy controls (14 females) performed an emotional face-word Stroop task and a cognitive emotion regulation task while undergoing fMRI. Patients and controls showed a similar behavioral performance in both tasks. Across groups, participants who were less distracted from happy faces by the incongruent word "sadness" (Stroop task) were better at regulating their happiness (emotion regulation task). Notably, both the Stroop and emotion regulation task recruited the left supramarginal gyrus. Additionally, only patients showed a relative attentional disengagement from positive compared to negative stimuli in the Stroop task. Attention control and cognitive emotion regulation capabilities appear to be linked at both the behavioral and neural level. Shared mechanisms suggest that emotional disturbances in depression may be improved by interventions that target attention control, particularly regarding the processing of positive stimuli.

Implicit and Explicit Motivational Tendencies to Faces Varying in Trustworthiness and Dominance in Men.

Motivational tendencies to happy and angry faces are well-established, e.g., in the form of aggression. Approach-avoidance reactions are not only elicited by emotional expressions, but also linked to the evaluation of stable, social characteristics of faces. Grounded in the two fundamental dimensions of face-based evaluations proposed by Oosterhof and Todorov (2008), the current study tested whether emotionally neutral faces varying in trustworthiness and dominance potentiate approach-avoidance in 50 healthy male participants. Given that evaluations of social traits are influenced by testosterone, we further tested for associations of approach-avoidance tendencies with endogenous and prenatal indicators of testosterone. Computer-generated faces signaling high and low trustworthiness and dominance were used to elicit motivational reactions in three approach-avoidance tasks, i.e., one implicit and one explicit joystick-based paradigm, and an additional rating task. When participants rated their behavioral tendencies, highly trustworthy faces evoked approach, and highly dominant faces evoked avoidance. This pattern, however, did not translate to faster initiation times of corresponding approach-avoidance movements. Instead, the joystick tasks revealed general effects, such as faster reactions to faces signaling high trustworthiness or high dominance. These findings partially support the framework of Oosterhof and Todorov (2008) in guiding approach-avoidance decisions, but not behavioral tendencies. Contrary to our expectations, neither endogenous nor prenatal indicators of testosterone were associated with motivational tendencies. Future studies should investigate the contexts in which testosterone influences social motivation.

The regulation of positive and negative emotions through instructed causal attributions in lifetime depression - A functional magnetic resonance imaging study.

Adequate emotional control is essential for mental health. Deficiencies in emotion regulation are evident in many psychiatric disorders, including depression. Patients with depression show, for instance, disrupted neural emotion regulation in cognitive regulation regions such as lateral and medial prefrontal cortices. Since depressed individuals tend to attribute positive events to external circumstances and negative events to themselves, modifying this non-self-serving attributional style may represent a promising regulation strategy. Spontaneous causal attributions are generally processed in medial brain structures, particularly the precuneus. However, so far no study has investigated neural correlates of instructed causal attributions (e.g. instructing a person to intentionally relate positive events to the self) and their potential to regulate emotions. The current study therefore aimed to examine how instructed causal attributions of positive and negative events affect the emotional experience of depressed individuals as well as its neural bases. For this purpose pictures of sad and happy faces were presented to 26 patients with a lifetime major depression (MDD) and 26 healthy controls (HC) during fMRI. Participants should respond naturally ("view") or imagine that the person on the picture was sad/happy because of them ("internal attribution") or because something else happened ("external attribution"). Trait attributional style and depressive symptoms were assessed with questionnaires to examine potential influential factors on emotion regulation ability. Results revealed that patients compared to controls show a non-self-serving trait attributional style (i.e. more external attributions of positive events and more internal attributions of negative events). Intriguingly, when instructed to apply specific causal attributions during the emotion regulation task, patients and controls were similarly able to regulate positive and negative emotions. Regulating emotions through instructed attributions (internal/external attribution>view) generally engaged the precuneus, which was correlated with patients' trait attributional style (i.e. more precuneus activation during external>view was linked to a general tendency to relate positive events to external sources). Up-regulating happiness through internal (compared to external) attributions recruited the parahippocampal gyrus only in controls. The down-regulation of sadness (external>internal attribution), in contrast, engaged the superior frontal gyrus only in patients. Superior frontal gyrus activation thereby correlated with depression severity, which implies a greater need of cognitive resources for a successful regulation in more severely depressed. Patients and controls did not differ in activation in brain regions related to cognitive emotion regulation or attribution. However, results point to a disturbed processing of positive emotions in depression. Interestingly, increased precuneus resting-state connectivity with emotion regulation brain regions (inferior parietal lobule, middle frontal gyrus) was linked to healthier attributions (i.e. external attributions of negative events) in patients and controls. Adequate neural communication between these regions therefore seem to facilitate an adaptive trait attributional style. Findings of this study emphasize that despite patients' dysfunctional trait attributional style, explicitly applying causal attributions effectively regulates emotions. Future research should examine the efficacy of instructed attributions in reducing negative affect and anhedonia in depressed patients, for instance by means of attribution trainings during psychotherapy.

Imaging the up's and down's of emotion regulation in lifetime depression.

Reappraisal is a particularly effective strategy for influencing emotional experiences, specifically for reducing the impact of negative stimuli. Although depression has repeatedly been linked to dysfunctional behavioral and neural emotion regulation, prefrontal and amygdala engagement seems to vary with clinical characteristics and the specific regulation strategy used. Whereas previous neuroimaging research has focused on down-regulating reactions to emotionally evocative scenes, the current study compared up- and down-regulation in response to angry facial expressions in patients with depression and healthy individuals. During the initial viewing of faces, patients with depression showed hypoactivation particularly in areas implicated in emotion generation, i.e., amygdala, insula and putamen. In contrast, up-regulating negative emotions yielded stronger recruitment of core face processing areas and posterior medial frontal cortex in patients than in controls. However, group differences did not extend to resting-state functional connectivity. Recurrent depression was inversely associated with amygdala activation specifically during down-regulation, but differences in medication status may limit the current findings. Despite a pattern of reduced neural emotional reactivity in mainly medicated patients, their 'successful' recruitment of the regulation network for up-regulation might point toward an effective use of reappraisal when increasing negative emotions. Future studies need to address how patients might benefit from transferring this ability to adaptive goals, such as improving interpersonal emotion regulation.

Electrophysiological correlates of oxytocin-induced enhancement of social performance monitoring.

Altered performance monitoring has been demonstrated after administration of different pharmacological compounds and in various clinical populations, such as excessive neurophysiological responses to mistakes in anxiety disorders. Here, a novel social pharmacological approach was applied to investigate whether oxytocin administration (24 IU) enhances performance monitoring for errors that have negative consequences for another individual, so-called social mistakes. Healthy male volunteers (N = 24) participated in a placebo-controlled crossover design. EEG measures were obtained while pairs of participants performed a speeded choice reaction-time task in an individual and social context. Following oxytocin administration, error-related negativity amplitudes were increased for social compared with individual mistakes. This increase was not found in the placebo condition. No effects of oxytocin were present in the individual context. The current study shows that oxytocin enhances performance monitoring specifically for social mistakes. This outcome is in line with a presumed role for oxytocin in salience attribution to social cues and underlines its context-dependency. Combining these processes may thus open up new research avenues and advance our understanding of individual differences in performance monitoring and oxytocin responses from a social neurocognitive, pharmacological and clinical perspective.

Oxytocin reduces amygdala responses during threat approach.

Oxytocin reduces amygdala responses to threatening social stimuli in males and has been suggested to facilitate approach-related processing by either decreasing anxiety or intensifying salience. The current administration study tested whether oxytocin either reduces or enhances amygdala responses during threat approach in a placebo-controlled randomized, double-blind, between-subjects design with 52 healthy males undergoing fMRI during a social approach-avoidance task. Oxytocin decreased amygdala activation during threat approach and not during threat avoidance. This neural effect supports oxytocin's social anxiolytic effects and provides a neuroendocrine mechanism promoting social approach. The findings may yield clinical implications for individuals suffering from dysregulations of social approach such as patients with anxiety disorders.