The present study utilizes an in vivo genomics-based strategy to identify genes that are differentially expressed in the immune system of people who experience chronically high levels of subjective isolation (loneliness), and to define the upstream transcription-control pathways that mediate those differences. Bioinformatic analyses of differentially expressing promoters [41,42] test the specific hypotheses that immune cells from high-lonely individuals show in vivo, under basal physiological conditions: 1.) decreased activity of the anti-inflammatory glucocorticoid transcription control pathway; and 2.) increased activity of the pro-inflammatory NF-κB/Rel pathway. Results reveal a distinct 'transcriptional fingerprint' of experienced social isolation that includes genomic indications of immune activation, and a reciprocal shift in the activity of pro- and anti-inflammatory transcription control pathways that shape global gene expression in the human immune system.
