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Review
. 2014 Nov;140(6):1464-504.
doi: 10.1037/a0037618. Epub 2014 Sep 15.

Toward a neurology of loneliness

Stephanie Cacioppo  1 , John P Capitanio  2 , John T Cacioppo  1
Affiliations
Review

Toward a neurology of loneliness

Stephanie Cacioppo et al. Psychol Bull. 2014 Nov.

Abstract

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter century. The brain is the key organ of social connections and processes, however, and the same objective social relationship can be experienced as caring and protective or as exploitive and isolating. We review evidence that the perception of social isolation (i.e., loneliness) impacts brain and behavior and is a risk factor for broad-based morbidity and mortality. However, the causal role of loneliness on neural mechanisms and mortality is difficult to test conclusively in humans. Mechanistic animal studies provide a lens through which to evaluate the neurological effects of a member of a social species living chronically on the social perimeter. Experimental studies show that social isolation produces significant changes in brain structures and processes in adult social animals. These effects are not uniform across the brain or across species but instead are most evident in brain regions that reflect differences in the functional demands of solitary versus social living for a particular species. The human and animal literatures have developed independently, however, and significant gaps also exist. The current review underscores the importance of integrating human and animal research to delineate the mechanisms through which social relationships impact the brain, health, and well-being.

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Figures

Figure 1
Figure 1
Schematic representation of socially isolated brain. A: Anatomy of the isolated human brain. Sagittal view of the human brain. Main human brain areas shown to be associated with perceived social isolation (loneliness) are labeled. B: Effects of perceived social isolation on biology. Perceived social isolation (loneliness) in humans is associated with higher tonic vascular resistance, blood pressure and hypothalamic pituitary adrenocortical (HPA) activation, and lower inflammatory control, immunity, and sleep salubrity. C: Effects of perceived social isolation on human brain activation. When lonely, compared to nonlonely, individuals view unpleasant pictures of people versus objects, they show higher activation of the visual cortex and lower activation of temporo-parietal junction (TPJ). Lonely individuals also show increased activation of the ventral striatum to pleasant objects than pleasant people, while nonlonely individuals show the reverse pattern (i.e., stronger activation of the ventral striatum to pleasant people than objects). Decreased activation in the dorsomedial prefrontal cortex (dmPFC) is also observed when participants in a lonely condition view negative social scenes. D: Effects of social isolation on brain structures and mechanisms (based on animal models). Animal studies permit more invasive biological measures and manipulations. Animal studies of social isolation indicate low neurogenesis, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in hippocampus; low glucocorticoid receptor (GR) expression and 5alpha RI mRNS, and high corticosterone levels in the prefrontal cortex; low cAMP response element binding protein (CREB) in the ventral striatum; large size of the primary visual cortex, and low NGF and weight of the visual cortex; and low cell proliferation in the amygdala (see Table 1 for information on these animal models). Copyright © Hank Grebe/VisualPhotos.
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