Loneliness Alters Genes Related to Immunity

[Hopeful]

and can cause increased inflamation: http://www.reuters.com/article/blogB...GPzEhlLZMlYJWk

Hopeful

[AlaskaAngel]

Were the genes measured before the loneliness? (Was the loneliness a result of the genetic makeup in the first place, or were the genes actually altered as they become lonely?)

[Hopeful]

followed by a link to the provisional pdf:

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.

http://genomebiology.com/content/pdf...7-8-9-r189.pdf

Hopeful

[R.B.]

Food and environmental factors alter gene expression.

So you could be looking at other factors as well. Maybe people are more emotionally vulnerable because of dietary factors. {More likely than would appear to be the case at face value}

Then that is combined with a host of life indignities and realities in all their human complexity.

It is interesting and not unexpected that it emotion and behaviour link to the inflammatory pathways.

I have just downloaded the PDF - looks like it will be a fascinating read and of particular interest.

Many thanks for posting.


RB

[Sandy in Silicon Valley]

Hi,

I still think the CORRELATION of inflammatory & immunity characteristics linked with loneliness doesn't indicate whether they co-exist, or one follows the other.

For example, an alternative hypothesis could be that people with inflammatory tendencies might have more pain, and shun social contact more due to experiencing unpredictable pain that is socially-inhibiting. Similarly, someone whose immune system is compromised might, biologically, be more prone to stay away from closeness with other people, due to the risk of infection (whether the risk is conscious or more of a biological "fight or flight" reflex to having high vulnerability to infection/ disease.

Just some thoughts. If anyone can boil down the other articles that were cited, and explain how causality is determined by them, I'd appreciate the info!

(((hugs)))
Sandy in Silicon Valley

[Hopeful]

For anyone who wants to tackle the provisional pdf, the authors don't claim causality, just a relationship.

Hopeful

[Hopeful]

“This study provides the first systematic analysis of genome-wide transcriptional alterations as a potential mechanism of social-epidemiological influences on human health. Individuals who experience themselves as chronically isolated from others have an increased risk of several inflammation-related diseases, and the broad pattern of leukocyte transcriptional alterations identified in this study provides a framework for understanding that risk at the molecular level. . . . This study has identified a clear genomic fingerprint of social isolation, and defined candidate transcription control pathways that may shape its expression, but several limitations must be considered when interpreting these results. First, the present findings are based on a relatively small number of individuals sampled from the low and high extremes of a social-epidemiological risk dimension, and thus require replication in larger samples that are more broadly representative of the total variation in human social phenotypes. However, it is remarkable that the size and inter-individual consistency of transcriptional alterations associated with subjective social isolation is sufficiently pronounced to reach high levels of statistical significance in a relatively small sample. It is unclear whether alterations in inflammatory signaling and gene transcriptional alteration might be observed in other tissues. It is also unclear whether the strong quantitative relationship between subjective social isolation and leukocyte transcriptional profiles observed here stems from a causal effect of social processes on gene expression (for example, via the neuroendocrine system), or whether differential gene expression in the immune system might instead drive variations in social behavior (for example, via effects of pro-inflammatory cytokines and prostaglandins on the central nervous system function.) The effects of acute “sickness behavior” are unlikely to explain the present results because this study analyzed long-term individual differences in experienced loneliness (that is, consistently expressed over at least three years). However, longitudinal studies will be required to rule out the possibility that variations in chronic inflammation might potentially influence long-term individual differences in social behavior. This study’s identification of a plausible neuroendocrine mediator or transcriptional alteration (GR signaling), which is known to relate to social phenotype in humans and is causally impacted by experimental social isolation in animal models, is consistent with social influences on gene expression. Experimental manipulations of long-term social behavior may ultimately be required to definitively establish causation in the human clinical setting. What is clear from this study’s ancillary analyses is that relationships between gene expression and social isolation cannot be attributed to correlated differences in other known demographic, psychological, social or medical risk factors (including perceived stress, depression, hostility, socio-economic status, and altered subset distributions within the circulating leukocyte pool). Ancillary analyses controlling for transient variations in loneliness suggest that the transcriptional correlates of chronic subjective social isolation (trait loneliness) do not stem solely from transient variations in state loneliness. A persistent sense of social isolation appears to represent a distinct epidemiological risk factor that is associated with broad alterations in immune cell gene expression linked to reciprocal shifts in the activity of pro- and anti- inflammatory transcription control pathways."

Hopeful

[AlaskaAngel]

I'm just one person interpreting what I read, but one bit extracted from the info provided helped to clarify my impressions:

"In the present study, the functional genomic correlates of subjective social isolation were found to be largely independent of the objective size of an individual’s social network. This result underscores the key role of subjective perceptual processes in transmitting the effects of social factors into physical biology via neuroendocrine alterations, and their subsequent impact on cellular gene expression [4,28,51,52]."

So what does that mean to me? The amount of actual social interaction isn't what is important (so if you are a loner and happen to enjoy being one, you're probably just fine). It is the personal perception of loneliness that is important in this study. I would still have to say that the issue is probably not loneliness per se, but I speculate that if there is an effect generated by a person's perception of their situation it relates to the degree of control the subjects feel they have over their life, and not limited in particular to "loneliness".

Because these measurements were not taken before the individuals became lonely I would still question whether it is cause or effect, which is acknowledged in the article. But the interesting thing about the article is that there is some actual genetic difference that relates to inflammation, whether it is there by cause or effect. Thanks for posting such intriguing information, Hopeful.

A.A.