Michael L. M. Murphy, George M. Slavich, Nicolas Rohleder, Gregory E. Miller

Social difficulties during adolescence influence life-span health. To elucidate underlying mechanisms, we examined whether a noxious social event, targeted rejection (TR), influences the signaling pathways that regulate inflammation, which is implicated in a number of health problems. For this study, 147 adolescent women at risk for developing a first episode of major depression were interviewed every 6 months for 2.5 years to assess recent TR exposure, and blood was drawn to quantify leukocyte messenger RNA (mRNA) for nuclear factor-κB (NF-κB) and inhibitor of κB (I-κB) and the inflammatory biomarkers C-reactive protein and interleukin-6. Participants had more NF-κB and I-κB mRNA at visits when TR had occurred. These shifts in inflammatory signaling were most pronounced for adolescents high in perceived social status. These findings demonstrate that social rejection upregulates inflammatory gene expression in youth at risk for depression, particularly for those high in status. If sustained, this heightened inflammatory signaling could have implications for life-span health.