Psychobiological mechanisms underlying the social buffering of the hypothalamic-pituitary-adrenocortical axis: a review of animal models and human studies across development

Abstract

Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social.

Figure 1. A Developmental Working Model of Social Buffering of the HPA Axis in Humans

OT = oxytocin, vmPFC = ventro-medial prefrontal cortex, Epi = epinephrine, NE = norepinephrine.

Figure 2. Neurobiology of Stress

The primary sensory and association cortices relay information to the medial and orbital prefrontal cortex. The anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC) and orbital prefrontal cortex (OFC) then transmit signals to subcortical structures involved in the stress response. The ACC, mPFC and OFC are reciprocally interconnected with each other and with the amygdala. Both the hippocampus and the amygdala also maintain connections to the locus coeruleus (LC) which releases norepinephrine (NE) to brain areas involved in alerting. The ACC, mPFC, OFC, and amygdala, as well as the hippocampus, all provide inputs to the hypothalamus. Nuclei in the lateral hypothalamus activate highly interconnected nuclei in the brainstem, that regulate the sympathetic (norepinephrine, NE and epinephrine, EPI) and parasympathetic (acetylcholine, ACH) nervous system via pathways traveling through the spinal cord to preganglionic nuclei or to target organs (e.g. the adrenal medulla). In the paraventricular region of the hypothalamus, corticotropin releasing hormone is produced, which travels through the hypophysial portal system to the anterior pituitary gland, stimulates the production and release of adrenocorticotropic hormone (ACTH). ACTH stimulates cells in the adrenal cortex to produce glucocorticoids (GC, cortisol in humans). Adapted from Gunnar and Davis (2003, p. 117). This material is reproduced with permission of John Wiley & Sons, Inc. (Copyright © 1999–2012).