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

Department of Psychology, University of Miami, Coral Gables, 5665 Ponce DeLeon Boulevard, Coral Gables, FL 33124-0751, USA.
Biological psychiatry (Impact Factor: 10.26). 11/2011; 71(4):366-72. DOI: 10.1016/j.biopsych.2011.10.007
Source: PubMed


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.
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.
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.
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.

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    • "What might explain these similar autonomic but disparate immune system findings? Recent work has shown that anxiety seems to be closely linked to activation of NF-KB (Antoni et al., 2012; Koo, Russo, Ferguson, Nestler, & Dunman, 2010), which is a rapid-acting transcriptional factor responsible for increased synthesis and eventual circulation of proinflammatory cytokines under stress (Bierhaus et al., 2003). NF-KB activation is accomplished through occupation and stimulation of β-adrenergic receptors by norepinephrine (Bierhaus et al., 2003; Powell et al., 2013), and, notably, one study has linked state anxiety, but not state anger, with increased occupation of β-adrenergic receptors after controlling for relevant covariates (Yu, Kang, Ziegler, Mills, & Dimsdale, 2008). "
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    • "Previous research has linked stress, threat, and adverse socio-environmental conditions to a conserved transcriptional response to adversity (CTRA) characterized by up-regulated transcription of pro-inflammatory genes and a complementary down-regulation of genes mediating the production of Type I interferon antiviral responses and IgG antibodies (Irwin and Cole, 2011; Antoni et al., 2012; Cole et al., 2012; Cole, 2013). This profile is hypothesized to represent an anticipatory immunological response to increased risk of injury during periods of experienced threat (Irwin and Cole, 2011; Antoni et al., 2012; Cole et al., 2012; Cole, 2013). Based on the 'behavioural immune response' theory (Schaller and Murray, 2008; Thornhill et al., 2010; Schaller, 2011), we hypothesized that pro-inflammatory gene expression would be up-regulated in extraverts and people with high levels of openness to experience (both of whom would be expected to experience elevated risk of injury/infection) and down-regulated in conscientious K. Vedhara et al. individuals with comparatively strong behavioural immune responses. "
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    • "Moreover, they suggest that changes in pro-inflammatory NF-κB-related gene expression are due to the mind-body connection that is generated by the MBSR technique, thus acting on the stress-mediating axes responsible for the expression of the gene. Similar results have been obtained with a group of breast-cancer patients following a psychological intervention [45]. Decreases in feelings of loneliness [16] and those found here in terms of negative affect, are in agreement with the proposal by Quinceno and Vinaccia [23] that, by using relaxation and calming techniques, individuals perceive that there is greater social support, experience feelings of well-being and life satisfaction, obtain better self-awareness and a greater connection with others and with a higher power. "
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