Markus Heinrichs

Oxytocin Increases Trust in Humans

Trust pervades human societies. Trust is indispensable in friendship, love, families and organizations, and plays a key role in economic exchange and politics. In the absence of trust among trading partners, market transactions break down. In the absence of trust in a countrys institutions and leaders, political legitimacy breaks down. Much recent evidence indicates that trust contributes to economic, political and social success. Little is known, however, about the biological basis of trust among humans. Here we show that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions. We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks. On the contrary, oxytocin specifically affects an individuals willingness to accept social risks arising through interpersonal interactions. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour.

Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress

BACKGROUND The presence of social support has been associated with decreased stress responsiveness. Recent animal studies suggest that the neuropeptide oxytocin is implicated both in prosocial behavior and in the central nervous control of neuroendocrine responses to stress. This study was designed to determine the effects of social support and oxytocin on cortisol, mood, and anxiety responses to psychosocial stress in humans. METHODS In a placebo-controlled, double-blind study, 37 healthy men were exposed to the Trier Social Stress Test. All participants were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before stress, and either social support from their best friend during the preparation period or no social support. RESULTS Salivary free cortisol levels were suppressed by social support in response to stress. Comparisons of pre- and poststress anxiety levels revealed an anxiolytic effect of oxytocin. More importantly, the combination of oxytocin and social support exhibited the lowest cortisol concentrations as well as increased calmness and decreased anxiety during stress. CONCLUSIONS Oxytocin seems to enhance the buffering effect of social support on stress responsiveness. These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions.

Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine

The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are evolutionarily highly conserved mediators in the regulation of complex social cognition and behaviour. Recent studies have investigated the effects of OXT and AVP on human social interaction, the genetic mechanisms of inter-individual variation in social neuropeptide signalling and the actions of OXT and AVP in the human brain as revealed by neuroimaging. These data have advanced our understanding of the mechanisms by which these neuropeptides contribute to human social behaviour. OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.

Oxytocin Shapes the Neural Circuitry of Trust and Trust Adaptation in Humans

Trust and betrayal of trust are ubiquitous in human societies. Recent behavioral evidence shows that the neuropeptide oxytocin increases trust among humans, thus offering a unique chance of gaining a deeper understanding of the neural mechanisms underlying trust and the adaptation to breach of trust. We examined the neural circuitry of trusting behavior by combining the intranasal, double-blind, administration of oxytocin with fMRI. We find that subjects in the oxytocin group show no change in their trusting behavior after they learned that their trust had been breached several times while subjects receiving placebo decrease their trust. This difference in trust adaptation is associated with a specific reduction in activation in the amygdala, the midbrain regions, and the dorsal striatum in subjects receiving oxytocin, suggesting that neural systems mediating fear processing (amygdala and midbrain regions) and behavioral adaptations to feedback information (dorsal striatum) modulate oxytocins effect on trust. These findings may help to develop deeper insights into mental disorders such as social phobia and autism, which are characterized by persistent fear or avoidance of social interactions.

Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence

BACKGROUND Oxytocin is known to reduce anxiety and stress in social interactions as well as to modulate approach behavior. Recent studies suggest that the amygdala might be the primary neuronal basis for these effects. METHODS In a functional magnetic resonance imaging study using a double-blind, placebo-controlled within-subject design, we measured neural responses to fearful, angry, and happy facial expressions after intranasal application of 24 IU oxytocin compared with placebo. RESULTS Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly. Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem. CONCLUSIONS Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence. Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior.

Oxytocin, vasopressin, and human social behavior.

There is substantial evidence from animal research indicating a key role of the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in the regulation of complex social cognition and behavior. As social interaction permeates the whole of human society, and the fundamental ability to form attachment is indispensable for social relationships, studies are beginning to dissect the roles of OT and AVP in human social behavior. New experimental paradigms and technologies in human research allow a more nuanced investigation of the molecular basis of social behavior. In addition, a better understanding of the neurobiology and neurogenetics of human social cognition and behavior has important implications for the current development of novel clinical approaches for mental disorders that are associated with social deficits (e.g., autism spectrum disorder, social anxiety disorder, and borderline personality disorder). This review focuses on our recent knowledge of the behavioral, endocrine, genetic, and neural effects of OT and AVP in humans and provides a synthesis of recent advances made in the effort to implicate the oxytocinergic system in the treatment of psychopathological states.

Intranasal Oxytocin Increases Positive Communication and Reduces Cortisol Levels During Couple Conflict

BACKGROUND In nonhuman mammals, the neuropeptide oxytocin has repeatedly been shown to increase social approach behavior and pair bonding. In particular, central nervous oxytocin reduces behavioral and neuroendocrine responses to social stress and is suggested to mediate the rewarding aspects of attachment in highly social species. However, to date there have been no studies investigating the effects of central oxytocin mechanisms on behavior and physiology in human couple interaction. METHODS In a double-blind placebo-controlled design, 47 heterosexual couples (total n = 94) received oxytocin or placebo intranasally before a standard instructed couple conflict discussion in the laboratory. The conflict session was videotaped and coded for verbal and nonverbal interaction behavior (e.g., eye contact, nonverbal positive behavior, and self-disclosure). Salivary cortisol was repeatedly measured during the experiment. RESULTS Oxytocin significantly increased positive communication behavior in relation to negative behavior during the couple conflict discussion (F = 4.18, p = .047) and significantly reduced salivary cortisol levels after the conflict compared with placebo (F = 7.14, p = .011). CONCLUSIONS These results are in line with animal studies indicating that central oxytocin facilitates approach and pair bonding behavior. Our findings imply an involvement of oxytocin in couple interaction and close relationships in humans.

Effects of intranasal oxytocin on emotional face processing in women

The neuropeptide oxytocin (OXT) has previously been found to reduce amygdala reactivity to social and emotional stimuli in healthy men. The present study aimed to investigate the effect of intranasally administered OXT on brain activity in response to social emotional stimuli of varying valence in women. In a functional magnetic-resonance imaging study, sixteen women were presented with fearful, angry, happy and neutral facial expressions after a single dose of 24IU OXT or a placebo administration in a within-subject design. Group analysis revealed that the blood-oxygen-level-dependent (BOLD) signal was enhanced in the left amygdala, the fusiform gyrus and the superior temporal gyrus in response to fearful faces and in the inferior frontal gyrus in response to angry and happy faces following OXT treatment. This effect was independent of fixation pattern to specific sections of the facial stimuli as revealed by eye tracking and independent of basal plasma levels of OXT, estradiol, and progesterone. The results are at odds with the previously reported effects found in men. Future studies should include both sexes to determine a possible sexual dimorphism in the neural effects of OXT, considering gonadal steroids and OXT receptor affinity.

Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis

Following the assumption that stressors play an important part in the etiology and maintenance of psychiatric disorders, it is necessary to evaluate parameters reflecting stress-related physiological reactions. Results from these examinations may help to deepen the insight into the etiology of psychiatric disorders and to elucidate diagnostic uncertainties. One of the best-known stress-related endocrine reactions is the hormonal release of the hypothalamic-pituitary-adrenal (HPA) axis. Dysregulations of this axis are associated with several psychiatric disorders. Profound hyperactivity of the HPA-axis has been found in melancholic depression, alcoholism, and eating disorders. In contrast, posttraumatic stress disorder, stress-related bodily disorders like idiopathic pain syndromes, and chronic fatigue syndrome seem to be associated with diminished HPA activity (lowered activity of the adrenal gland). Hypotheses referring to (a) the psychophysiological meaning and (b) the development of these alterations are discussed.

Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder

Patients with generalized social anxiety disorder (GSAD) exhibit heightened activation of the amygdala in response to social cues conveying threat (eg, fearful/angry faces). The neuropeptide oxytocin (OXT) decreases anxiety and stress, facilitates social encounters, and attenuates amygdala reactivity to threatening faces in healthy subjects. The goal of this study was to examine the effects of OXT on fear-related amygdala reactivity in GSAD and matched healthy control (CON) subjects. In a functional magnetic resonance imaging study utilizing a double-blind placebo-controlled within-subjects design, we measured amygdala activation to an emotional face matching task of fearful, angry, and happy faces following acute intranasal administration of OXT (24 IU or 40.32 μg) and placebo in 18 GSAD and 18 CON subjects. Both the CON and GSAD groups activated bilateral amygdala to all emotional faces during placebo, with the GSAD group exhibiting hyperactivity specifically to fearful faces in bilateral amygdala compared with the CON group. OXT had no effect on amygdala activity to emotional faces in the CON group, but attenuated the heightened amygdala reactivity to fearful faces in the GSAD group, such that the hyperactivity observed during the placebo session was no longer evident following OXT (ie, normalization). These findings suggest that OXT has a specific effect on fear-related amygdala activity, particularly when the amygdala is hyperactive, such as in GSAD, thereby providing a brain-based mechanism of the impact of OXT in modulating the exaggerated processing of social signals of threat in patients with pathological anxiety.