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The neural mechanisms supporting social bonds between adult men remain uncertain. In this double-blind, placebo-controlled study, we investigate the impact of intranasally administered oxytocin (OT) and vasopressin (AVP) on behavior and brain activity among men in the context of an iterated Prisoner’s Dilemma game, which models a real-life social situation. fMRI results show that, relative to both AVP and placebo, OT increases the caudate nucleus response to reciprocated cooperation, which may augment the reward of reciprocated cooperation and/or facilitate learning that another person can be trusted. OT also enhances left amygdala activation in response to reciprocated cooperation. Behaviorally, OT was associated with increased rates of cooperation following unreciprocated cooperation in the previous round compared with AVP. AVP strongly increased cooperation in response to a cooperative gesture by the partner compared with both placebo and OT. In response to reciprocated cooperation, AVP increased activation in a region spanning known vasopressin circuitry implicated in affiliative behaviors in other species. Finally, both OT and AVP increase amygdala functional connectivity with the anterior insula relative to placebo, which may increase the amygdala’s ability to elicit visceral somatic markers that guide decision making. These findings extend our knowledge of the neural and behavioral effects of OT and AVP to the context of genuine social interactions.

Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary preclinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebocontrolled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner’s Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses of males more similar to responses of females in the placebo group and vice-versa, raising the prospect of an inverted u-shaped dose response to central OT levels. These findings emphasize the need to fully characterize the effects of intranasal OT and AVP in both males and females and at multiple doses before widespread clinical application will be warranted.

Social integration and social support have a substantial influence on individual health and longevity, an effect assumed to be mediated through reduced stress reactivity in support recipients. However, considerable variability in individual responses to social support has been documented, suggesting that the beneficial effect of social support interacts with early experiences, genetically influenced differences in biological systems mediating social behavior, personality traits, and psychopathology. Here we outline the historical background of social support research, including epidemiological studies, laboratory studies, and field studies on the subject of social support and health, with regard to different psychobiological effector systems. Most recent research has focused on brain mechanisms which link social integration or social support with reduced neural threat responses. As numerous mental disorders are associated with considerable social impairment, understanding the potentially underlying mechanisms of neural plasticity in relation to social support, stress buffering and health in these disorders can help tailor new diagnostic and treatment strategies. Thus, theories of socially-driven emotional learning and memory, as presented in this review, might eventually lead to psychobiology-based treatment concepts for mental disorders involving social deficits.

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Objective: Adult attachment has been suggested to mediate the effect of social support on stress protection. The purpose of this study was to investigate the effects of adult attachment and social support on psychological and endocrine responses to psychosocial stress.Methods: Sixty-three healthy men who were married or cohabiting were randomly assigned to receive either instructed social support from their partner or no social support before being exposed to a standardized psychosocial stressor (Trier Social Stress Test). Attachment was determined using the Experiences in Close Relationships -Revised questionnaire (ECR-R). State anxiety, mood, and salivary cortisol levels were repeatedly assessed before and after stress.Results: Secure attachment was associated with stronger decreases in state anxiety levels following stress exposure. More importantly, the combination of social support and secure attachment exhibited the lowest anxiety levels after stress (interaction effect). Social support alone reduced cortisol responses to stress, whereas secure attachment did not influence cortisol concentrations.Conclusion: This first study on the interaction of adult attachment and social support in terms of psychological and endocrine stress responses concurs with previous studies suggesting an important protective role of attachment for psychological stress responsiveness. However, attachment did not directly moderate cortisol responses to acute stress. ABSTRACT Objective:Adult attachment has been suggested to mediate the effect of social support on stress protection.The purpose of this study was to investigate the effects of adult attachment and social support on psychological and endocrine responses to psychosocial stress. Methods:Sixty-three healthy men who were married or cohabiting were randomly assigned to receive either instructed social support from their partner or no social support before being exposed to a standardized psychosocial stressor (Trier Social Stress Test). Attachment was determined using the Experiences in Close Relationships -Revised questionnaire (ECR-R). State anxiety, mood, and salivary cortisol levels were repeatedly assessed before and after stress. Results:Secure attachment was associated with stronger decreases in state anxiety levels following stress exposure. More importantly, the combination of social support and secure attachment exhibited the lowest anxiety levels after stress (interaction effect). Social support alone reduced cortisol responses to stress, whereas secure attachment did not influence cortisol concentrations. Conclusion:This first study on the interaction of adult attachment and social support in terms of psychological and endocrine stress responses concurs with previous studies suggesting an important protective role of attachment for psychological stress responsiveness. However, attachment did not directly moderate cortisol responses to acute stress.