Lost connections: Oxytocin and the neural, physiological, and behavioral consequences of disrupted relationships.

In humans and rodent animal models, the brain oxytocin system is paramount for facilitating social bonds, from the formation and consequences of early-life parent-infant bonds to adult pair bond relationships. In social species, oxytocin also mediates the positive effects of healthy social bonds on the partners' well-being. However, new evidence suggests that the negative consequences of early neglect or partner loss may be mediated by disruptions in the oxytocin system as well. With a focus on oxytocin and its receptor, we review studies from humans and animal models, i.e. mainly from the biparental, socially monogamous prairie vole (Microtus ochrogaster), on the beneficial effects of positive social relationships both between offspring and parents and in adult partners. The abundance of social bonds and benevolent social relationships, in general, are associated with protective effects against psycho- and physiopathology not only in the developing infant, but also during adulthood. Furthermore, we discuss the negative effects on well-being, emotionality and behavior, when these bonds are diminished in quality or are disrupted, for example through parental neglect of the young or the loss of the partner in adulthood. Strikingly, in prairie voles, oxytocinergic signaling plays an important developmental role in the ability to form bonds later in life in the face of early-life neglect, while disruption of oxytocin signaling following partner loss results in the emergence of depressive-like behavior and physiology. This review demonstrates the translational value of animal models for investigating the oxytocinergic mechanisms that underlie the detrimental effects of developmental parental neglect and pair bond disruption, encouraging future translationally relevant studies on this topic that is so central to our daily lives.