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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