Effect of Chronic Stress on Whole Blood Transcriptome: A Meta-Analysis of Publicly Available Datasets from Rodent Models.

Background: Chronic stress increases risk for neuropsychiatric disorders in humans. By modeling stress-induced changes in animals, we may improve diagnosis or treatment of these disorders. Successful translation benefits from studies with sufficient statistical power and outcome measurements that can be directly compared across species. We performed a meta-analysis to examine the impact of chronic stress on the whole blood transcriptome. Methods: Datasets were systematically identified in Gemma, a database of reprocessed public transcriptional profiling studies; datasets GSE68076, GSE72262, and GSE84185 met inclusion/exclusion parameters. Each study exposed eight-week old mice to chronic stress (5-10 days social defeat stress or 6-8 weeks chronic mild stress). The final sample size was Results: Findings included 23 downregulated and 16 upregulated transcripts in stress-exposed mice (FDR<0.05). Results indicated a down-regulation in gene sets related to B cells, immune response, DNA and chromatin regulation, ribosomal activity, translation, and catabolic cellular processes. Upregulated gene sets related to erythrocytes and oxygen binding. Conclusion: Our results provide molecular insight into stress-related immune dysregulation and add weight to the hypothesis that environmental stress escalates cellular aging, supporting the use of blood transcriptome as a bridge between human and rodent models.