Oxytocin is a neuropeptide that has been implicated in several prosocial behaviors, such as trust, empathy and social affiliation, and might contribute to mental health disorders marked by social disturbances. Indeed, Chapter 1 indicated that the accumulated evidence points to interactions between oxytocin, and various neuroendocrine, neurotransmitter, and inflammatory processes in the emergence of depressive disorders. However, the perspective was discussed that oxytocin does not uniformly enhance prosocial behaviors, but instead increases the salience of social cues, so that positive and negative events might elicit exaggerated responses that influence affective states. The current studies examined the role of oxytocin in relation to various stressors and mental health outcomes. In Study 1 (N = 288), it was determined that a genetic variant on the oxytocin receptor gene (OXTR) moderated the influence of early-life events in relation to later depressive symptoms. In the absence of this polymorphism individuals who experienced early-life maltreatment displayed high levels of depressive symptoms, but this was not evident in the presence of this polymorphism. In essence, in the absence of the polymorphism, prosocial behaviors are present, but so is social sensitivity, potentially rendering individuals more vulnerable to the effects of early-life adversity. Study 2 (N = 128) revealed that individuals carrying the same ‘prosocial’ genetic variant on the OXTR were more emotionally sensitive and biologically reactive to social ostracism, further supporting the social sensitivity view. Consistent with this, in Study 3 (N = 243), individuals carrying a genetic variant on a gene that controls for oxytocin release (CD38 gene), which had previously been viewed as a ‘protective’ variant, displayed poorer peer and parental relationships and enhanced suicidal ideation. Finally, Study 4 (N = 67) revealed that although oxytocin was inversely related to distrust scores and baseline cortisol levels, this hormone was unaffected by a stressor or the presence of social support. These studies highlight the role of oxytocin in stressor responses, social sensitivity and, in turn, vulnerability to mental health outcomes. At the same time, the data also suggest that interpreting the findings solely on the basis of a prosocial framework may be too narrow.