BehindTheMedspeak: Is loneliness genetic?

Long story short: In a study published yesterday in the journal Genome Biology, all 22,000 human genes of two groups of volunteers — the most and least lonely on an accepted loneliness scale — were compared.

209 genes stood out in the loneliest people, and "A big fraction of them seemed to be involved in the basic immune response to tissue damage," said Steve Cole, a molecular biologist at U.C.L.A. who worked on the study.

Here is a link to the BBC's report on the findings; that story follows.

Why loneliness may damage health

US scientists may have uncovered a genetic reason why lonely people may have poorer health.

The UCLA research, published in Genome Biology, found certain genes were more active in people who reported feelings of social isolation.

Many of the genes identified have links to the immune system and tissue inflammation - which may be damaging.

Other studies have shown clear links between lack of social support and illnesses such as heart disease.

The biological impact of social isolation reaches down into some of our most important basic internal processes — the activity of our genes.

The researchers said that quality, not quantity, of friendships, appeared to be important.

The link between genes and loneliness has been explored before - a recent Dutch study of 8,000 twins also pointed to the connection.

The UCLA research looked in more detail at which genes might be involved.

They took 14 volunteers and assessed their level of social interaction using a scoring system.

They then looked at genetic activity in their white blood cells and tried to compare the results.

In their "lonely" volunteers, various genes tended to be "over expressed" compared with those at the opposite end of the scoring scale.

These often had known links to the body's mechanisms for fighting off disease, such producing inflammation. Too much inflammation can damage tissues and cause disease.

Other genes, including those thought to be important in fighting viruses and producing immune antibodies, were less active compared with the non-lonely volunteers.

Dr Steven Cole, who led the study, said: "What this shows us is the biological impact of social isolation reaches down into some of our most important basic internal processes — the activity of our genes.

"These findings provide molecular targets for our efforts to block the adverse health effects of social isolation."

He said the differences he found were not connected to other factors such as the age, wealth or health of the people involved, but were specifically connected to their feelings of social isolation.

They were unconnected with the size of the person's social network.

Dr Cole said: "What counts, at the level of gene expression, is not how many people you know, it's how many you feel really close to over time."

He said that in future, the gene profile he'd identified might help doctors work out whether therapies to ease loneliness were effective.

Professor Andrew Steptoe, who carries out research into the biological effects of psychological conditions at University College London, said that the findings were "plausible".

He said: "We know that social isolation and lack of social support may compromise your health.

"We can say there is an association here, but we can't say definitively that the social isolation is causing any change in gene expression."

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Here is a link to the abstract of the study; the abstract itself follows.

Social regulation of gene expression in human leukocytes

Background: Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates.

Results: DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-kB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways.

Conclusions: These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.

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Here is a link to a press release about the work.