"The Lone Genome"

(September 18th 2007) Scientists in the United States have published a genomic fingerprint of social isolation. They argue that feelings of social isolation are linked to alterations in the immune system activity. A closer look at the "first systematic analysis of genome-wide transcriptional alterations as a potential mechanism of social-epidemiological influences on human health", from Karin Hollricher.

Recent advances in transcription profiling techniques made it possible to perform genome-wide gene expression analysis in a hypothesis-free manner. Accordingly, researchers all over the world are mining the genome for expression variation, which correlates with any disease. However, is it feasible to assume that complex human behaviour like social isolation also leaves its mark on gene expression?

At least the feeling of social isolation is often accompanied by an increased risk of disease. Could these findings eventually be reflected by variations in the patterns of gene transcription?

Steven Cole from the UCLA School of Medicine, Los Angeles, and the co-authors of his latest paper in Genome Biology (vol. 8:R189) are apparently so convinced. They analysed gene expression profiles in leukocytes of fourteen individuals experiencing low or high levels of subjective social isolation, as identified by their scores in the aptly named UCLA-R Loneliness Scale. Leukocytes from persons identified as feeling socially well-integrated served as a control.

In brief, the main result of the researchers identified 209 genes which were differentially transcribed in the leukocytes of both groups. In "lonely" individuals genes involved in immune activation, transcription control and cell proliferation were up-regulated, whereas genes supporting mature B lymphocyte function and type I interferon response were down-regulated. By applying bioinformatics analyses, the team was able to identify signalling pathways that shape these differences in gene expression, namely reduced activity of the anti-inflammatory glucocorticoid pathway and the pro-inflammatory NF-KappaB/Rel pathway.

These molecular data are consistent with clinical reports describing that socially isolated persons suffer from increased risk of inflammation-mediated diseases, lower resistance to viral infection and impaired humoral immune response. So Cole et al. presumed to write, "This study has identified a clear genomic fingerprint of social isolation".

There is a great danger that this audacious statement over-interprets the pure transcription data that were collected from only eight socially isolated persons. That's why the authors state at the end of the paper that "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."

So far, DNA microarray results in psychiatric fields have been notoriously discordant. For example, despite enormous research efforts, the molecular basis of schizophrenia is still unknown. Furthermore, the results completely depend on the quality and reliability of psychological tests.

Also, Cole et al. are aware that they have created a chicken-and-egg scenario. Are the alterations in gene expression the result of socialisation or does the differential expression of immune-related genes actually drive variation in social behaviour? Thrilling questions, aren't they?

Social regulation of gene expression in human leukocytes
Steve W Cole, Louise C Hawkley, Jesusa M Arevalo, Caroline Y Sung, Robert M Rose and John T Cacioppo
Genome Biology 2007, 8:R189doi:10.1186/gb-2007-8-9-r189
http://genomebiology.com/2007/8/9/R189