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One is the deadliest number: the detrimental effects of social isolation on cerebrovascular diseases and cognition

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Abstract

The deleterious effects of chronic social isolation (SI) have been recognized for several decades. Isolation is a major source of psychosocial stress and is associated with an increased prevalence of vascular and neurological diseases. In addition, isolation exacerbates morbidity and mortality following acute injuries such as stroke or myocardial infarction. In contrast, affiliative social interactions can improve organismal function and health. The molecular mechanisms underlying these effects are unknown. Recently, results from large epidemiological trials and pre-clinical studies have revealed several potential mediators of the detrimental effects of isolation. At least three major biological systems have been implicated: the neuroendocrine (HPA) axis, the immune system, and the autonomic nervous system. This review summarizes studies examining the relationship between isolation and mortality and the pathophysiological mechanisms underlying SI. Cardiovascular, cerebrovascular, and neurological diseases including atherosclerosis, myocardial infarction, ischemic stroke and Alzheimer’s disease are given special emphasis in the context of SI. Sex differences are highlighted and studies are separated into clinical and basic science for clarity.

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Acknowledgments

Financial support for B.F. and J.C. generously provided by NIH/NINDS Grant Psychosocial Stress and Behavioral Response to Stroke (5R01NS077769) as well as NIH/NINDS Grant Chromosomal and Hormonal Contributions to Sex Differences in Ischemic Stroke (5R01NS055215). Financial support was also received in the form of an American Heart Association undergraduate student summer fellowship awarded to J.C.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT, 06030, USA

    Brett Friedler, Joshua Crapser & Louise McCullough

  2. The Stroke Center at Hartford Hospital, 85 Jefferson St., 6th floor, Hartford, CT, 06106, USA

    Louise McCullough

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  1. Brett Friedler
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  2. Joshua Crapser
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Correspondence to Brett Friedler.

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B. Friedler and J. Crapser contributed equally to this work.

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Friedler, B., Crapser, J. & McCullough, L. One is the deadliest number: the detrimental effects of social isolation on cerebrovascular diseases and cognition. Acta Neuropathol 129, 493–509 (2015). https://doi.org/10.1007/s00401-014-1377-9

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