Cognitive-Behavioral Stress Management Reverses Anxiety-Related Leukocyte Transcriptional Dynamics

Antoni, Michael H.; Lutgendorf, Susan K.; Blomberg, Bonnie; Carver, Charles S.; Lechner, Suzanne; Diaz, Alain; Stagl, Jamie; Arevalo, Jesusa M.G.; Cole, Steven W.

doi:10.1016/j.biopsych.2011.10.007

« Previous Next »Biological Psychiatry
Volume 71, Issue 4 , Pages 366-372, 15 February 2012

Cognitive-Behavioral Stress Management Reverses Anxiety-Related Leukocyte Transcriptional Dynamics

Michael H. Antoni
- Department of Psychology, University of Miami, Coral Gables, Florida
- Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics, Miami, Florida
- Address correspondence to Michael H. Antoni, Ph.D., University of Miami, Department of Psychology, 5665 Ponce DeLeon Boulevard, Coral Gables, FL 33124-0751
Susan K. Lutgendorf
- Department of Psychology, University of Iowa, Iowa City, Iowa
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa
Bonnie Blomberg
- Department of Microbiology and Immunology, University of Miami, Coral Gables, Florida
- Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics, Miami, Florida
Charles S. Carver
- Department of Psychology, University of Miami, Coral Gables, Florida
- Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics, Miami, Florida
Suzanne Lechner
- Department of Psychiatry and Behavioral Sciences, University of Miami, Coral Gables, Florida
- Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics, Miami, Florida
Alain Diaz
- Department of Microbiology and Immunology, University of Miami, Coral Gables, Florida
- Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics, Miami, Florida
Jamie Stagl
- Department of Psychology, University of Miami, Coral Gables, Florida
Jesusa M.G. Arevalo
- School of Medicine, University of California, Los Angeles, Los Angeles, California
Steven W. Cole
- School of Medicine, University of California, Los Angeles, Los Angeles, California
- Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California
- Norman Cousins Center, University of California, Los Angeles, Los Angeles, California

Received 29 May 2011; received in revised form 4 October 2011; accepted 5 October 2011. published online 17 November 2011.

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.

Key Words: Cancer , cognitive-behavioral stress management , gene expression , immune system , inflammation , stress , threat/anxiety