There is controversy in the social epidemiology literature about whether the health risks of social isolation stem mainly from an objective lack of social contact (for example, diminishing physical, cognitive, or economic assistance) or from the subjective experience of social isolation (leading to perceptions of threat/uncertainty that activate neuroendocrine stress responses) [2,28,51]. 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]. Moreover, bioinformatics analyses identified several candidate transcription control pathways that could plausibly mediate those effects, including the inflammation-related GR, NF-κB/Rel, and JAK/STAT pathways, as well as the CREB/ATF, IRF1, GATA, and Oct families of transcription factors. These candidate 'social signal transduction pathways' provide a mechanistic basis for understanding social epidemiology in terms of molecular interactions between the human genome and the external socio-environmental stimuli that regulate cellular gene expression [26,48,49].
