Immune responses to loneliness similar in monkeys and people

Can loneliness make you sick?

Loneliness is more than just a socio-emotional condition; it can be a significant cause of poor health, and is of special concern in the elderly.

Also known as perceived social isolation, loneliness reflects a discrepancy between desired and actual social relationships, and has been known to be a major risk factor for chronic illness and mortality in humans for more than a quarter century. Loneliness is not a uniquely human phenomenon, however; in most socially living species, there is likely to be a subset of individuals that are dissatisfied with the quantity and quality of their social relationships. A study published in 2014 demonstrated this phenomenon in rhesus macaques.

Although the risk factors have been well understood, the molecular mechanisms by which loneliness can affect health have not been well defined.

A new report, involving both humans and rhesus monkeys as subjects, significantly expands our understanding of these health-related mechanisms by focusing on gene expression in leukocytes — cells of the immune system that are involved in protecting the body against bacteria and viruses.

The study team included researchers from UCLA, the California National Primate Research Center (CNPRC) at UC Davis, and the University of Chicago.

Lead authors Steven Cole, PhD, UCLA School of Medicine, John Capitanio, PhD, Core Scientist in the Brain, Mind, and Behavior Unit at the CNPRC, UC Davis, and John Cacioppo, PhD, University of Chicago published their important findings today in the high impact journal Proceedings of the National Academy of Sciences (“Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation”, Cole et al, PNAS Nov 23, 2015).

The human study examined gene expression in leukocytes collected annually in a study that lasted more than five years. In humans, loneliness at one time point was associated at a later time point with increased expression of genes that lead to inflammation, a decreased expression of genes related to protection from viruses, and an increased percentage in blood of monocytes, a specific type of leukocyte that is involved in many immune responses, including inflammation. Loneliness was also associated with increased concentrations of norepinephrine, a marker of the sympathetic nervous system, which is responsible for the flight or fight response. Together these results suggested that the effect of loneliness on health may be mediated by the impact loneliness has on the sympathetic nervous system, which in turn affects monocyte numbers and leukocyte gene expression.

At the CNPRC, the monkey study was performed to see if similar changes were evident, to provide more detail about these mechanisms, and to understand how loneliness can affect disease. The parallels were striking – lonely monkeys showed a similar pattern of gene expression for increased inflammation and reduced anti-viral responses, higher levels of norepinephrine, and elevated monocyte numbers.

Rhesus monkeys are a highly social nonhuman primate species, and the animals in this study lived outdoors in large, half-acre field corrals, in a rich social environment consisting of 80–150 animals. Animals were identified as lonely, when just like in humans, there was a discrepancy in the desired and actual social relationships.

“Importantly, our study describes a naturally occurring model of loneliness. Animal models of loneliness are usually induced models – for example an animal is physically separated from its companions. Our research suggests loneliness in monkeys can occur even in the presence of others – just like in humans” emphasizes Dr. Capitanio.

The monkey studies extended the human studies by showing that it is a specific subset of monocytes that was increased in the lonely animals. Moreover, there were indications in the monkey studies that the machinery that controls gene transcription was also compromised.