Fast and Slow Gene Expression Changes in Blood Following Acute Social Stress

Social stress is a risk factor for psychiatric disorders and also influences immune function. While it is known that acute social stress impacts the number of immune cells in circulation, the temporal dynamics of stress induced immune-related transcriptional changes in human blood remain unclear. To investigate changes in gene expression, we exposed 26 adults to the Trier Social Stress Test (TSST), and collected blood at baseline, as well as 5, 30, 60 and 90 min after stress. Whole-blood gene expression was profiled using a 5 targeted RNA-sequencing method (STRT). Differential expression was analyzed using linear and cubic models. We observed a total of 54 differentially expressed genes following stress. Fast responses, with a transient peak immediately following stress, were enriched for cytotoxic T cell, NK cell and dendritic cell functions (e.g., GZMB, GNLY, CCL4 and GZMA) and paralleled lymphocyte count changes. In contrast, gradual, linear responses without any evident peak were enriched for neutrophil related genes (e.g., FPR2, PLAUR, CXCR2, AQP9, and QPCT) and did not mirror neutrophil counts, indicating cell intrinsic transcriptional changes. From pathway and transcription factor enrichment analyses, IL-12 family mediated signaling is inferred as a central mechanism linking stress to immune gene regulation. Our results show that acute psychosocial stress induces both fast and slower changes in gene expression in different immune cell populations. The involvement of the IL-12-STAT4 axis and genes such as PLAUR and FPR2 suggests molecular mechanisms through which stress-related immune activation may contribute to vulnerability for anxiety and depressive disorders.