In this review we summarize the results and conclusions of five studies as presented in a symposium at the 42nd annual meeting of the International Society for Psychoneuroendocrinology, in New York in September 2012. Oxytocin administration has received increasing attention for its role in promoting positive social behavior and stress regulation, and its potential as a therapeutic intervention for addressing various aspects of psychiatric disorders. However, it has been noted that the observed effects are not uniformly beneficial. In this paper we present five new studies each concluding that contextual and interindividual factors moderate the effects of oxytocin, as well as peripheral oxytocin levels. These findings are in accordance with the recent idea that oxytocin administration may increase sensitivity to social salience cues and that the interpretation of these cues may be influenced by contextual (i.e. presence of a stranger versus friend) or interindividual factors (i.e. sex, attachment style, or the presence of psychiatric symptoms). When social cues in the environment are interpreted as "safe" oxytocin may promote prosociality but when the social cues are interpreted as "unsafe" oxytocin may promote more defensive and, in effect, "anti-social" emotions and behaviors. Likewise, oxytocin appears to promote such agonistic tendencies in individuals who are chronically pre-disposed to view the social milieu in uncertain and/or in negative terms (e.g., those with borderline personality disorder, severe attachment anxiety and/or childhood maltreatment). In all, these studies in pre-clinical animal, healthy humans and patients samples further reinforce the importance of considering both contextual and interindividual factors when trying to understand the role of oxytocin as a biological substrate underlying social bonding and stress regulatory processes and when studying the effects of oxytocin administration in particular in patients with (increased risk for) psychiatric disorders.

Significance Statement-Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.