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Review
, 66, 733-67

The Neuroendocrinology of Social Isolation

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Review

The Neuroendocrinology of Social Isolation

John T Cacioppo et al. Annu Rev Psychol.

Abstract

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter of a century. Although the focus of research has been on objective social roles and health behavior, the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others. Accordingly, population-based longitudinal research indicates that perceived social isolation (loneliness) is a risk factor for morbidity and mortality independent of objective social isolation and health behavior. Human and animal investigations of neuroendocrine stress mechanisms that may be involved suggest that (a) chronic social isolation increases the activation of the hypothalamic pituitary adrenocortical axis, and (b) these effects are more dependent on the disruption of a social bond between a significant pair than objective isolation per se. The relational factors and neuroendocrine, neurobiological, and genetic mechanisms that may contribute to the association between perceived isolation and mortality are reviewed.

Keywords: animal models; loneliness; social endocrinology; social genomics; social isolation; social neuroscience.

Figures

Figure 1
Figure 1
Schematics of the hypothalamic-pituitary-adrenocortical (HPA) axis, the sympathetic adrenomedullary (SAM) axis, and the innervation of the lymph node tissue by the sympathetic nervous system (SNS). The HPA axis controls circulating glucocorticoid (GC) levels through a cascade that starts with signals from the prefrontal cortex [e.g., medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC)] and limbic regions [e.g., amygdala, bed nucleus stria terminalis (BNST)] to the paraventricular nucleus of the hypothalamus, which secretes corticotropin-releasing hormone (CRH) into the hypophyseal portal circulatory system. This activity stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH travels through the blood to the adrenal cortex, where it acts on melanocortin type 2 receptors to stimulate the secretion of GC hormones (cortisol in humans and most mammals; corticosterone in rodents) into circulation. GC regulation is accomplished systemically via a negative feedback loop involving higher structures of the HPA axis (notably the hippocampus), whereby increases in circulating cortisol concentrations inhibit CRH secretion from the hypothalamus and diminish the production of ACTH in the pituitary gland by binding to glucocorticoid and mineralocorticoid receptors (GR and MR, respectively); both processes lead to a decrease in cortisol secretion from the adrenal gland. The SAM axis controls circulating epinephrine (EPi) levels. The SNS, through preganglionic neurons (the splanchnic nerve), projects from the central nervous system directly to cells in the adrenal medulla, which secretes primarily EPi (in addition to smaller amounts of norepinephrine and dopamine) into the circulatory system, where it serves to heighten metabolism and increase available energy. In addition, there is direct SNS nerve fiber delivery of norepinephrine into immune system organs such as the lymph nodes, spleen, and thymus; immune cells coordinate responses to tissue injury and infection. Artwork courtesy of Tianyi Li, adapted for publication by Annual Reviews.

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