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 [1-6], and the broad pattern of leukocyte transcriptional alterations identified in this study provides a framework for understanding that risk at the molecular level. Immune cells from people who report consistently high levels of subjective social isolation (loneliness) showed increased expression of genes controlling basic cellular transcription processes, cell cycle progression, pro-inflammatory cytokine signaling, and prostaglandin synthesis. Against this generalized backdrop of immunological activation, however, several functionally distinct subsets of immune response genes showed selective under-expression, including type I interferon response genes involved in innate antiviral resistance, and genes supporting antibody production and mature B lymphocyte function. These leukocyte transcriptional dynamics are consistent with clinical data indicating a complex pattern of host resistance alterations in social isolates, including increased risk of inflammation-mediated disease [1,2], accompanied by decreased resistance to viral infection [3,4,16,25] and impaired humoral immune response [29]. In addition to providing
