A developmental working model of the social buffering of the hypothalamic–pituitary–adrenal (HPA) axis in humans. Early-life social experiences are thought to shape the later effectiveness of social buffering of the HPA axis. Additionally, two sets of biological mechanisms are proposed to mediate the effect of social support on HPA reactivity to stressors: oxytocinergic functioning, including patterns of oxytocin release and receptor distribution; and PFC-based safety signaling/neural priming by stimuli associated with attachment figures. The role of other biological mediators (e.g., dopamine, serotonin, opioids, epinephrine, norepinephrine) has been suggested by some studies with nonhuman animals, but more research is needed to characterize their role in the social buffering of the HPA axis in humans. OT = oxytocin; vmPFC = ventromedial prefrontal cortex; Epi = epinephrine; NE = norepinephrine. Reprinted with permission from Hostinar, C. E., Sullivan, R. M., & Gunnar, M. R. (2014). Psychobiological mechanisms underlying the social buffering of the HPA axis: A review of animal models and human studies across development. Psychological Bulletin, 140(1), 256-282. Copyright 2014 by the American Psychological Association.