Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics.

BACKGROUND Chronic threat and anxiety are associated with pro-inflammatory transcriptional profiles in circulating leukocytes, but the causal direction of that relationship has not been established. This study tested whether a cognitive-behavioral stress management (CBSM) intervention targeting negative affect and cognition might counteract anxiety-related transcriptional alterations in people confronting a major medical threat. METHODS One hundred ninety-nine women undergoing primary treatment of stage 0-III breast cancer were randomized to a 10-week CBSM protocol or an active control condition. Seventy-nine provided peripheral blood leukocyte samples for genome-wide transcriptional profiling and bioinformatic analyses at baseline, 6-month, and 12-month follow-ups. RESULTS Baseline negative affect was associated with >50% differential expression of 201 leukocyte transcripts, including upregulated expression of pro-inflammatory and metastasis-related genes. CBSM altered leukocyte expression of 91 genes by >50% at follow-up (group × time interaction), including downregulation of pro-inflammatory and metastasis-related genes and upregulation of type I interferon response genes. Promoter-based bioinformatic analyses implicated decreased activity of NF-κB/Rel and GATA family transcription factors and increased activity of interferon response factors and the glucocorticoid receptor as potential mediators of CBSM-induced transcriptional alterations. CONCLUSIONS In early-stage breast cancer patients, a 10-week CBSM intervention can reverse anxiety-related upregulation of pro-inflammatory gene expression in circulating leukocytes. These findings clarify the molecular signaling pathways by which behavioral interventions can influence physical health and alter peripheral inflammatory processes that may reciprocally affect brain affective and cognitive processes.