Research in social epidemiology suggests that the absence of positive social relationships is a significant risk factor for broad-based morbidity and mortality. The nature of these social relationships and the mechanisms underlying this association are of increasing interest as the population gets older and the health care costs associated with chronic disease escalate in industrialized countries. We review selected evidence on the nature of social relationships and focus on one particular facet of the connection continuum – the extent to which an individual feels isolated (i.e., feels lonely) in a social world. Evidence indicates that loneliness heightens sensitivity to social threats and motivates the renewal of social connections, but it can also impair executive functioning, sleep, and mental and physical well-being. Together, these effects contribute to higher rates of morbidity and mortality in lonely older adults.

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.

In 1978, when the Task Panel report to the US President’s Commission on Mental Health emphasized the importance of improving health care and easing the pain of those suffering from emotional distress syndromes including loneliness, few anticipated that this issue would still need to be addressed 40 years later. A meta-analysis (Masi et al., 2011) on the efficacy of treatments to reduce loneliness identified a need for well-controlled randomized clinical trials focusing on the rehabilitation of maladaptive social cognition. We review assessments of loneliness and build on this meta-analysis to discuss the efficacy of various treatments for loneliness. With the advances made over the past 5 years in the identification of the psychobiological and pharmaceutical mechanisms associated with loneliness and maladaptive social cognition, there is increasing evidence for the potential efficacy of integrated interventions that combine (social) cognitive behavioral therapy with short-term adjunctive pharmacological treatments.

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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.