Loneliness is a subjective feeling associated with a lack of social interactions in combination with several internal factors relating to personality. Increasingly, loneliness is becoming viewed as a risk factor for several major negative health outcomes.
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Social isolation and loneliness are both sources of chronic stress and hypervigilance that lead to reduced sleep quality, physiological changes in cardiovascular health, impaired immune function, neuroendocrine effects, and elevated cortisol levels.
Alongside physiological ill-health, loneliness is associated with cognitive decline, depression, and premature mortality
What is loneliness?
Although loneliness, in combination with social isolation, has been associated with ill-health, determining causality is difficult as studies are observational. Biological pathways have been suggested as an explanation for the effect of loneliness on the body.
These include levels of protective hormones which lead to adverse effects on the cardiovascular system, downregulation of the immune system, and dysregulation of the neuroendocrine system because of lack or poor quality of sleep.
Moreover, loneliness increases the likelihood of individuals initiating harmful health behaviors such as excess alcohol consumption, overeating, smoking, and casual sexual activity as a form of psychological relief. Loneliness is a subjective emotion that results from social isolation, or because of a lack of trust and connection with those around them.
Loneliness, inflammation, and stress
Loneliness has been associated with biomarkers of inflammation (interleukin-6, fibrinogen, and C-reactive protein). Chronic inflammation is implicated in the development of cardiovascular disease and other chronic conditions which are associated with premature mortality.
Alongside hormonal effects, psychological stresses can trigger the autonomic nervous system and hypothalamic-pituitary-adrenocortical (HPA) access, and chronic activation of these systems can exert wear-and-tear effects on the cardiovascular, immune, and metabolic systems.
Although loneliness is associated with systemic inflammation and wear-and-tear effect in the nervous system, the direction of causality has not been determined.
Loneliness as a mortality risk factor
Loneliness significantly increases the risk of premature death from all causes and is thought to rival the risk post by smoking, obesity, and physical inactivity. The overall odds of mortality due to loneliness are 1.5, which is comparable to light smoking (15 cigarettes/day) exceeds the risks posed by obesity on type attention.
These figures have been derived from an analysis of 148 studies across 300 and 8849 individuals over 7.5 years and demonstrated that the effect of loneliness was independent of other risk factors.
Loneliness as a cardiovascular risk factor
A recent systematic review followed by a meta-analysis of 16 longitudinal regional studies demonstrated that the risk of coronary heart disease is approximately 29%, and stroke 32%.
This association is comparable to anxiety and job stresses which are also considered risk factors for the development of coronary heart disease. This finding corroborates a body of existing evidence that demonstrates that loneliness is predictive of low morbidity and mortality.
With regards to other cardiovascular conditions, loneliness has been shown to increase systolic blood pressure; this effect can be harmful in older individuals when arterial stiffness increases with age. This is termed total peripheral resistance and is the main cause of elevated systolic blood pressure and individuals up to 40 years old.
An increase in blood pressure can lead to premature arterial stiffening and further increasing the risk of systemic blood pressure increase. As a result, lonely individuals can develop structural changes in arteries that promote the deposition of collagen and decreased elasticity of vessels.
The molecular pathways affected by loneliness
There have been several proposed mechanisms of loneliness associated with cardiovascular disease. Loneliness activates the HPA access and the sympathetic nervous system. This subsequently leads to a change in behavior which includes physical inactivity and sleep deprivation.
The activation of the sympathetic nervous system enhances a process termed monocytopenia in the bone marrow which causes an expansion in pro-inflammatory white blood cells. The sympathetic nervous system also stimulates the movement of monocytes from the spleen.
Over time, social stress can lead to resistance to glucocorticoids, regulation of proinflammatory gene expression, and increased cytokine production by immune cells. Glucocorticoids are hormones that govern several physiological functions. They are involved in suppressing inflammatory, allergic, and immune disorders as well as altering blood glucose and lipolysis.
These effects serve to modulate immune function to prevent overreaction and damage to the tissue under stress. Resistance to glucocorticoids subsequently results in inflammation, muscle atrophy, central adiposity, hepatic steatosis, osteoporosis, insulin resistance, hypertension, depression, and insomnia.
Cytokines can also exacerbate glucocorticoid resistance. This resulting increase in inflammation and oxidative stress may be involved in the development of atherosclerotic plaques and increased blood pressure.
The release of epinephrine and norepinephrine from the brain and adrenal gland can also induce vasoconstriction which is also enhanced by glucocorticoid resistance. Further, glucocorticoid resistance can also reduce the expression of endothelial nitric oxide synthase, which results in decreased production of nitric oxide. This subsequently impairs vasodilation.
This further contributes to increased blood pressure. Although these pathways are implicated in the physiological changes in the body, the causal role of these mechanisms has not been demonstrated.
Understanding the association and causal pathways between loneliness and ill-health is necessary so that strategies and interventions to combat loneliness can be developed.
References:
- Malcolm M, Frost H, Cowie J. Loneliness and social isolation causal association with health-related lifestyle risk in older adults: a systematic review and meta-analysis protocol. Syst Rev. 2019;8(1):48. doi: 10.1186/s13643-019-0968-x.
- Xia N, Li H. Loneliness, Social Isolation, and Cardiovascular Health. Antioxid Redox Signal. 2018;28(9):837-851. doi:10.1089/ars.2017.7312
- Steptoe A, et al. Social isolation, loneliness, and all-cause mortality in older men and women. Proc Natl Acad Sci U S A. 2013;110(15):5797-801. doi: 10.1073/pnas.1219686110.
- Leigh-Hunt N, et al. An overview of systematic reviews on the public health consequences of social isolation and loneliness. Public Health. 2017;152:157-171. doi: 10.1016/j.puhe.2017.07.035.
- Barnes TL, et al. Cumulative effect of loneliness and social isolation on health outcomes among older adults. Aging Ment Health. 2021:1-8. doi: 10.1080/13607863.2021.1940096.
- Valtorta NK, et al. Loneliness and social isolation as risk factors for coronary heart disease and stroke: systematic review and meta-analysis of longitudinal observational studies. Heart. 2016;102(13):1009-1016. doi:10.1136/heartjnl-2015-308790.
- Heinrich LM, Gullone E. The clinical significance of loneliness: a literature review. Clin Psychol Rev. 2006;26(6):695–718.
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