Loneliness is widely recognized as a health risk factor, linked to conditions like cardiovascular disease, psychiatric disorders, and increased risks for stroke and dementia. However, new research challenges this assumption.
A large UK Biobank study provides "compelling" evidence that loneliness may be a potential surrogate marker rather than a causal risk factor for most diseases assessed, researchers concluded.
"Instead, loneliness may act as a surrogate marker, explained by factors such as socioeconomic status, health behaviors, depressive symptoms, metabolic factors, and comorbidities," study investigator Jihui Zhang, PhD, with Guangzhou Medical University in Guangzhou, China, told Medscape Medical News. These factors explained more than 79% of the associations between loneliness and disease.
The study was published online on September 16 in Nature Human Behavior.
Disease Predictor?
The researchers analyzed behavioral, genetic, and hospitalization data from 476,100 individuals in the UK Biobank who were followed for a median of 12 years.
Loneliness was linked to a higher risk for 13 out of 14 disease categories and 30 out of 56 individual diseases, including cardiovascular diseases, mental and behavioral disorders, infectious diseases, and diseases of the nervous, respiratory, and endocrine systems.
The diseases most strongly associated with loneliness were posttraumatic stress disorder, depression, anxiety, schizophrenia, and chronic obstructive pulmonary disease.
Of the 30 diseases associated with loneliness, 26 had genetic data available for Mendelian randomization (MR) analyses.
The results of these genetic analyses indicated noncausal associations with loneliness for 20 out of 26 diseases, including cardiovascular diseases, type 2 diabetes, obesity, chronic liver diseases, chronic kidney disease, most neurologic diseases, and other common diseases.
Potentially causal associations were observed for only six diseases — hypothyroidism, asthma, depression, psychoactive substance abuse, sleep apnea, and hearing loss.
"Ultimately, socioeconomic factors, health behaviors, metabolic factors, baseline depressive symptoms, inflammatory factors, and comorbidities explained more than 79% of the associations between loneliness and disease," the investigators wrote.
The implication, the investigators note, is that only addressing loneliness is unlikely to reduce the risks for most diseases. "Instead, our findings highlight the necessity of addressing the subsequent risk factors related to loneliness, including unfavorable lifestyle behaviors, depressive symptoms, or comorbidities, to improve health outcomes," they wrote.
The MR findings, they added, "reinforce the idea that loneliness could be a pivotal and amenable target for preventing certain groups of diseases such as depression and substance abuse."
Caveats, Cautionary Notes
Commenting on the study for Medscape Medical News, Richard B. Slatcher, PhD, distinguished professor, Department of Psychology, University of Georgia, Athens, Georgia, said all of the findings are "consistent with what we already know from a lot of research on social disconnection — that loneliness is associated with a lot of physical and mental health outcomes."
Slatcher noted that the study makes two main points.
"The first is that links between loneliness and several of the health outcomes examined shrink or disappear when you control for other things like depression and health behaviors. The authors argue that this means loneliness is what they call a 'proxy' cause — that is, not the true cause," he explained.
"Take, for example, depression. Depression accounted for much of the effects of loneliness and health. So, could loneliness simply be a proxy here? It could be. Or alternatively, it could be that depression is a key mechanism (ie, an explanatory factor) through which loneliness impacts physical health. In this scenario, loneliness causes depression, which in turn causes health problems. So, you would have a sort of causal chain here. However, the authors never tested this idea," Slatcher said.
The second main point, he noted, is that the data point to a dissociation between observational and genetic evidence regarding the associations of loneliness with multiple diseases.
"Implicit in the overall message in this paper is that if the genetic proxies for loneliness have a weaker effect on health than observed loneliness, that there is some sort of disagreement between the genetic and observed loneliness. But I see these as very much in agreement," he said.
"Loneliness is only partially driven by genetics (and we still have a very rudimentary understanding of genetic underpinnings of psychological phenomena like loneliness). The rest of loneliness is driven by the environment, like how many friends someone has, being rejected by people, where you live, etc.," he said.
"So, because risk for loneliness is only partially driven by genetic variability, it's no surprise at all (to me and probably to most other health psychologists) that a genetic proxy for loneliness is going to show less robust associations with diseases than the associations between observed loneliness (ie, actual loneliness) and diseases," Slatcher added.
The study had no commercial funding. Zhang and Slatcher had no relevant conflicts of interest.