ReviewOxytocin, vasopressin, and human social behavior
Introduction
In non-human mammals, receptors for the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) are distributed in various brain regions [94] associated with the central nervous control of stress and anxiety and with social behavior, including parental care, pair-bonding, social memory, and social aggression. Specifically, OT seems both to enable animals to overcome their natural avoidance of proximity and to inhibit defensive behavior, thereby facilitating approach behavior [24], [26], [28], [45], [84], [124], [147], [164]. AVP has primarily been implicated in male-typical social behaviors, including aggression, pair-bond formation, scent marking, and courtship [24], [28], [45], [104], [165].
Aside from its effects on social behavior, OT shows significant binding in the limbic system, including the amygdala [80], [81], [94], [132], and decreases anxiety and the neuroendocrine response to stress in social interactions [11], [27], [120], [123], [158], [159]. In contrast, AVP seems to play an anxiogenic role, with elevated AVP expression in the hypothalamic paraventricular nucleus being associated with increased behavioral and neuroendocrine anxiety levels [117]. In addition, Ferris and colleagues [49] showed that the orally active AVP V1a receptor antagonist SRX251 selectively blocks aggressive behavior in hamsters. At a cellular level, Huber and colleagues [80] reported that distinct populations of neurons in the amygdala are activated by OT and AVP receptor stimulation, through which these peptides modulate the integration of excitatory information from the amygdala and cerebral cortex in opposite manners. These results suggest that the endogenous balance between OT and AVP receptor expression and activation may set distinct, individually tuned levels for the activation of the autonomic fear response. In general, centrally active AVP seems to be associated with increased vigilance, anxiety, arousal, and activation, while OT has behavioral and neural effects associated with reduced anxiety, relaxation, growth, and restoration. Thus, both peptide hormones are important in social stress and in social interaction, and in turn, a dysregulated activity may be associated with mental disorders of psychosocial relevance. While much of the knowledge regarding the ability of OT and AVP to regulate social interactions is based on data from animals using centrally administered agonists and antagonists or knockout mice, initial studies suggest similar social and stress-related effects of both neuropeptides in humans (for review, see [12], [68]).
Here, we review recent advances in the endeavor to understand the role of OT and AVP in human social behavior. In the first part of this review, we summarize the methodological approaches in human neuropeptide research and examine the significance of OT in stress-responsiveness, anxiety and prosocial behavior. In the second part, we address the role of AVP in social behavior. Finally, we conclude by outlining the clinical implications for mental disorders that are associated with social deficits, and provide a synthesis of the interactions of anxiety and stress, social approach behavior, and the oxytocinergic system.
Section snippets
Methodological approaches in human neuropeptide research
Our current knowledge of the behavioral effects of neuropeptides in humans is based on: (i) correlational studies measuring OT or AVP in urine, saliva, blood or CSF, (ii) correlational studies involving genotyping of receptor polymorphisms, and (iii) experimental studies manipulating the availability of OT or AVP using intravenous or intranasal administration. All of these approaches bear different levels of invasiveness and side effects and do not have an equivalent informative value in terms
Social stress and anxiety
In animal studies, OT has been found to be released peripherally and within the brain in response to both physical and psychological stress and fearful situations [120], [121]. Intracerebral OT has been shown to inhibit the stress-induced activity of the hypothalamic–pituitary–adrenal (HPA) axis responsiveness [119], [123] and the activity of the amygdala in the modulation of the autonomic fear response [80]. Numerous studies on the inhibitory influence of OT on stress-responsive neurohormonal
Arginine vasopressin and human social behavior
Whereas OT plays a key role both in prosocial behavior and in the central nervous control of stress and anxiety, AVP has primarily been implicated in male-typical social behaviors, including aggression and pair-bond formation, and in stress-responsiveness [55]. Although most of the studies conducted thus far on human social behavior have focused on OT, few studies on AVP suggest behavioral effects similar to those found in animal research.
Coccaro and colleagues [33] examined the relationship
Clinical perspectives
As social behavior in health is tightly regulated, and dysfunctional alterations can result in a psychopathological state, OT and AVP have been considered to play an important role in the development of a variety of mental disorders. Aside from social anxiety disorder, social deficits are associated with autism spectrum disorders, obsessive-compulsive disorder, borderline personality disorder, depression, and other mental disorders. In the following, we review studies that addressed the role of
Conclusions
Based on the enormous advances in animal models of the role of neuropeptides in social cognition and behavior, recent human studies suggest that the basic social effects of OT and AVP from animal research may also be applicable to human social interaction. Although the translation of behavioral and neurobiological findings from animal studies to humans generally bears the risk of drawing oversimplified parallels between rodents and humans, the initial findings are encouraging in terms of
Acknowledgments
This work was supported by grants from the Swiss National Science Foundation (SNSF PP001-114788) (to M.H.) and the Research Priority Program “Foundations of Human Social Behavior” at the University of Zurich (to M.H. and B.v.D.), and by a grant of the German Research Foundation (DFG Do1312/1-1) (to G.D.).
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