Mindfulness based stress reduction provides psychological benefit and restores immune function of women newly diagnosed with breast cancer: A randomized trial with active control.

BACKGROUND: Women newly diagnosed with breast cancer experience psychological distress, accompanied by reduced Natural Killer Cell Activity (NKCA) and altered levels of cytokines, which may compromise cancer control. Few studies have evaluated psycho-immune outcomes of mindfulness-based stress reduction (MBSR) for women newly diagnosed with breast cancer in comparison to an active control condition. OBJECTIVE: The purpose of this study was to determine whether MBSR benefits psychological, behavioral, and immunological function in women recently diagnosed with breast cancer. DESIGN: After confirmation of breast cancer staging, women diagnosed with early-stage breast cancer (n = 192) were randomized to an 8-week MBSR program or an 8-week active control condition (ACC). The ACC consisted of a series of cancer recovery and health education classes. Both MBSR and the ACC were administered in group format. METHODS: Women completed psychometric instruments and provided blood for NKCA and cytokine levels at pre-, mid-, and completion of program, as well as at 1- and 6-months post-program. One hundred and twenty four women completed all five-assessments (MBSR, n = 63; ACC, n = 61). Hierarchical linear modeling was used to analyze trajectories of outcomes over time and between groups. RESULTS: Compared to the ACC group, women randomized to MBSR exhibited decreasing trajectories of perceived stress, fatigue, sleep disturbance, and depressive symptoms. Further, compared to women randomized to ACC, MBSR women exhibited trajectories demonstrating significantly more rapid restoration of NKCA, accompanied by lower circulating TNF-alpha levels, lower IL-6 production, and greater IFN-gamma production. CONCLUSIONS: These results demonstrate early provision of MBSR for women newly diagnosed with breast cancer provides not only psychological benefit, but also optimizes immune function supportive of cancer control.

Perceived discrimination is associated with the inflammatory response to acute laboratory stress in women at risk for cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death in the United States and exacts a disproportionate toll on minorities. Growing evidence demonstrates that perceived discrimination is a significant contributing factor to psychological distress, chronic low-grade inflammation, and cardiovascular health. However, little is known regarding the extent to which perceived discrimination contributes to the inflammatory response to acute stress. Therefore, the purpose of this study was to examine the influence of perceived discrimination on the inflammatory response to a laboratory acute stress paradigm in women at risk for CVD. A cross-sectional sample of 99 postmenopausal women (50 African American and 49 non-Hispanic White) (mean age 60.2 years) with at least two risk factors for CVD underwent the Trier Social Stress Test (TSST). Subjects completed the Detroit Area Study Discrimination Scale (DAS-DS) Everyday Discrimination subscale and provided blood and saliva samples prior to the TSST and every 15 min up to 90 min post-TSST to measure a pro-inflammatory cytokine, interleukin-6 (IL-6). Perceived discrimination was significantly associated with the salivary IL-6 response to the TSST (b = 0.49, SE = 0.13, p = <0.001) controlling for age, race, marital status, household income, BMI, statin use, childhood maltreatment, depressive symptoms, and subjective social status. Women who reported higher levels of perceived discrimination had higher levels of salivary IL-6 at baseline and following the TSST as compared to women who reported lower levels of perceived discrimination. Results suggest that higher levels of perceived discrimination, regardless of race and socioeconomic status, may heighten levels of inflammation, prior to and following an acute stress exposure. The circulating Il-6 response was associated with BMI only and did not correlate with salivary IL-6. These data suggest that perceived discrimination may contribute to the salivary-IL-6 acute stress response. However, more research is needed to help clarify the complex relationships among stress and salivary proinflammatory cytokines.

During stress, heart rate variability moderates the impact of childhood adversity in women with breast cancer.

Childhood adversity has long-lasting neuro-biological effects that can manifest as exaggerated stress responsivity to environmental challenge. These manifestations include a dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis as well as increased levels of inflammatory mediators in response to stress. In this investigation, vagal parasympathetic activity was assessed for its capacity to moderate the relationship between childhood adversity and stress responsivity (cortisol and inflammation) during an acute laboratory challenge (Trier Social Stress Test-TSST). Thirty women recently diagnosed with breast cancer underwent the TSST during which their heart rate was recorded and saliva samples collected for measurement of cortisol and the proinflammatory cytokine, IL-6. Vagal activity during the TSST was calculated as the high-frequency (HF) component of heart rate variability (HRV). Vagal activity during the TSST moderated the effect of childhood adversity on both the cortisol and the IL-6 response. Women who had lower vagal stress-reactivity during the TSST and reported greater childhood adversity showed a larger rise in cortisol and IL-6 when compared to women with lower childhood adversity. The findings demonstrate that women with exposure to childhood adversity and low vagal stress-reactivity (reduced parasympathetic activity) exhibit an elevated stress response characterized by greater cortisol and proinflammatory cytokine release. Inflammatory burden and HPA dysregulation subsequent to stress may impair cancer control.

Chromatin organization as an indicator of glucocorticoid induced natural killer cell dysfunction.

It is well-established that psychological distress reduces natural killer cell immune function and that this reduction can be due to the stress-induced release of glucocorticoids. Glucocorticoids are known to alter epigenetic marks associated with immune effector loci, and are also known to influence chromatin organization. The purpose of this investigation was to assess the effect of glucocorticoids on natural killer cell chromatin organization and to determine the relationship of chromatin organization to natural killer cell effector function, e.g. interferon gamma production. Interferon gamma production is the prototypic cytokine produced by natural killer cells and is known to modulate both innate and adaptive immunity. Glucocorticoid treatment of human peripheral blood mononuclear cells resulted in a significant reduction in interferon gamma production. Glucocorticoid treatment also resulted in a demonstrable natural killer cell nuclear phenotype. This phenotype was localization of the histone, post-translational epigenetic mark, H3K27me3, to the nuclear periphery. Peripheral nuclear localization of H3K27me3 was directly related to cellular levels of interferon gamma. This nuclear phenotype was determined by direct visual inspection and by use of an automated, high through-put technology, the Amnis ImageStream. This technology combines the per-cell information content provided by standard microscopy with the statistical significance afforded by large sample sizes common to standard flow cytometry. Most importantly, this technology provides for a direct assessment of the localization of signal intensity within individual cells. The results demonstrate glucocorticoids to dysregulate natural killer cell function at least in part through altered H3K27me3 nuclear organization and demonstrate H3K27me3 chromatin organization to be a predictive indicator of glucocorticoid induced immune dysregulation of natural killer cells.

Inflammatory and Epigenetic Pathways for Perinatal Depression.

Depression during the perinatal period is common and can have adverse consequences for women and their children. Yet, the biobehavioral mechanisms underlying perinatal depression are not known. Adverse early life experiences increase the risk for adult depression. One potential mechanism by which this increased risk occurs is epigenetic embedding of inflammatory pathways. The purpose of this article is to propose a conceptual model that explicates the linkage between early life adversity and the risk for maternal depression. The model posits that early life adversity embeds a proinflammatory epigenetic signature (altered DNA methylation) that predisposes vulnerable women to depression during pregnancy and the postpartum period. As proposed, women with a history of early life adversity are more likely to exhibit higher levels of proinflammatory cytokines and lower levels of oxytocin in response to the demands of pregnancy and new motherhood, both of which are associated with the risk for perinatal depression. The model is designed to guide investigations into the biobehavioral basis for perinatal depression, with emphasis upon the impact of early life adversity. Testing this model will provide a better understanding of maternal depressive risk and improve identification of vulnerable women who would benefit from targeted interventions that can reduce the impact of perinatal depression on maternal-infant health.

Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer.

Women respond differentially to the stress-associated with breast cancer diagnosis and treatment, with some women experiencing more intense and/or sustained behavioral symptoms and immune dysregulation than others. Childhood adversity has been identified to produce long-term dysregulation of stress response systems, increasing reactivity to stressors encountered during adulthood. This study determined whether childhood adversity increased vulnerability for more intense and sustained behavioral symptoms (fatigue, perceived stress, and depressive symptoms), poorer quality of life, and greater immune dysregulation in women (N=40) with breast cancer. Evaluation was after breast surgery and through early survivorship. Hierarchical linear modeling was used to examine intra-individual and inter-individual differences with respect to initial status and to the pattern of change (i.e. trajectory) of outcomes. At initial assessment, women exposed to childhood emotional neglect/abuse had greater perceived stress, fatigue, depressive symptoms and poorer quality of life, as well as lower natural killer cell activity (NKCA). Although these outcomes improved over time, women with greater childhood emotional neglect/abuse exhibited worse outcomes through early survivorship. No effect was observed on the pattern of change for these outcomes. In contrast, childhood physical neglect predicted sustained trajectories of greater perceived stress, worse quality of life, and elevated plasma IL-6; with no effect observed at initial assessment. Thus, childhood adversity leaves an enduring imprint, increasing vulnerability for behavioral symptoms, poor quality of life, and elevations in IL-6 in women with breast cancer. Further, childhood adversity predisposes to lower NKCA at a critical time when this immune-effector mechanism is most effective at halting nascent tumor seeding.

Perioperative pain, psychological distress, and immune function in men undergoing prostatectomy for cancer of the prostate.

Prostate cancer is a leading malignancy in men, and prostatectomy is widely used for its treatment. Psychological distress and pain are commonly experienced in the perioperative period, and both can contribute to suppression of the immune response to cancer. This study evaluated perioperative pain, psychological distress, and immune function in men undergoing prostatectomy. Men were evaluated prior to surgery, 1 and 2 days postoperatively and 4-6 weeks postoperatively. Compared to cancer-free men, the prostatectomy group reported increased perceived stress, depression, confusion, and anxiety prior to surgery. During the 2 postoperative days, mood disturbance and anxiety persisted and were accompanied by mild elevations in pain and reduced vigor. At 4-6 weeks postoperative, mood, pain, and immune function were similar to those of the cancer-free group; however, the prostatectomy group continued to report significant elevations in anxiety. Natural killer cell activity (NKCA) was significantly reduced on Day 1 after prostatectomy, but by postoperative Day 2, NKCA returned to a level similar to that of the cancer-free group. The reduction in NKCA was not accompanied by changes in circulating immune cells, demonstrating that this reduction represented a functional change in NKCA. No correlations between immune variables and pain or psychological variables were found, suggesting that the postoperative reduction in NKCA was likely the result of the physical stress of the surgical experience. Suppression of immune defenses during the critical postoperative period can place cancer patients at risk for nascent tumor seeding. Additional interventions are needed to reduce this risk.

The multiple benefits of minimally invasive spinal surgery: results comparing transforaminal lumbar interbody fusion and posterior lumbar fusion.

Minimally invasive transforaminal lumbar interbody fusion (TLIF) offers equivalent postoperative fusion rates compared to posterior lumbar fusion (PLF) and minimizes the amount of iatrogenic injury to the spinal muscles. The objective of this study was to examine the difference in pain perception, stress, mood disturbance, quality of life, and immunological indices throughout the perioperative course among patients undergoing TLIF and PLF. A prospective, nonrandomized descriptive design was used to evaluate these measures among patients undergoing TLIF (n = 17) or PLF (n = 18) at 1 week prior to surgery (T1), the day of surgery (T2), 24 hours postoperatively (T3), and 6 weeks postoperatively (T4). Among TLIF patients, pain, stress, fatigue, and mood disturbance were significantly decreased at the 6-week followup visit (T4) compared to patients who underwent PLF. The TLIF group also demonstrated significantly higher levels (near baseline) of CD8 cells at T4 than the PLF group. Interleukin-6 levels were significantly higher in the TLIF group as well, which may be an indicator of ongoing nerve regeneration and healing. Knowledge concerning the effect of pain and the psychological experience on immunity among individuals undergoing spinal fusion can help nurses tailor interventions to improve outcomes, regardless of the approach used.

Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer.

This investigation used a non-randomized controlled design to evaluate the effect and feasibility of a mindfulness based stress reduction (MBSR) program on immune function, quality of life (QOL), and coping in women recently diagnosed with breast cancer. Early stage breast cancer patients, who did not receive chemotherapy, self-selected into an 8-week MBSR program or into an assessment only, control group. Outcomes were evaluated over time. The first assessment was at least 10 days after surgery and prior to adjuvant therapy, as well as before the MBSR start-up. Further assessments were mid-MBSR, at completion of MBSR, and at 4-week post-MBSR completion. Women with breast cancer enrolled in the control group (Non-MBSR) were assessed at similar times. At the first assessment (i.e., before MBSR start), reductions in peripheral blood mononuclear cell NK cell activity (NKCA) and IFN-gamma production with increases in IL-4, IL-6, and IL-10 production and plasma cortisol levels were observed for both the MBSR and Non-MBSR groups of breast cancer patients. Over time women in the MBSR group re-established their NKCA and cytokine production levels. In contrast, breast cancer patients in the Non-MBSR group exhibited continued reductions in NKCA and IFN-gamma production with increased IL-4, IL-6, and IL-10 production. Moreover, women enrolled in the MBSR program had reduced cortisol levels, improved QOL, and increased coping effectiveness compared to the Non-MBSR group. In summary, MBSR is a program that is feasible for women recently diagnosed with early stage breast cancer and the results provide preliminary evidence for beneficial effects of MBSR; on immune function, QOL, and coping.

Psychologic stress, reduced NK cell activity, and cytokine dysregulation in women experiencing diagnostic breast biopsy.

The purpose of this study was to evaluate a woman's psychological and immunological response to breast biopsy before and after the procedure. Women were enrolled into the study when notified of the need for breast biopsy. Psychological and immunological assessments were made at enrollment, on the day of breast biopsy, as well as 1 month and 4 months after notification of biopsy results. Psychological assessments demonstrated that perceived stress, anxiety, and mood disturbance were heightened before biopsy and remained elevated after biopsy regardless of the diagnosis. Immunologically, the women exhibited reduced natural killer cell activity and INF gamma production before biopsy with reductions significant 1 month after the procedure. In contrast, IL-4, IL-6, and IL-10 production were increased before and after the procedure with most significant increases prior to the procedure and continuing 1 month after the procedure. These results demonstrate that undergoing biopsy of the breast for cancer diagnosis is an emotional experience, characterized by increased perceived stress, anxiety, and mood disturbance. This emotional distress is accompanied by reduced NK cell activity and cytokine dysregulation. The psychological and immunological impact of breast biopsy is not transient, but persists well beyond the actual experience of the biopsy procedure. Noteworthy is the observation that women with benign or malignant biopsy results experienced similar psycho-immune consequences. Hence, these observations are of relevance not only to women diagnosed with malignancy, who face the challenges of cancer treatment and adaptation to illness, but also to women with benign biopsy findings.

Immune function, pain, and psychological stress in patients undergoing spinal surgery.

STUDY DESIGN: This study was an exploratory repeated measures design comparing patients undergoing two magnitudes of surgery in the lumbar spine: lumbar herniated disc repair and posterior lumbar fusion. OBJECTIVE: The present study evaluated and compared the effect of perceived pain, perceived stress, anxiety, and mood on natural killer cell activity (NKCA) and IL-6 production among adult patients undergoing lumbar surgery. SUMMARY OF BACKGROUND DATA: Presurgical stress and anxiety can lead to detrimental patient outcomes after surgery, such as increased infection rates. It has been hypothesized that such outcomes are due to stress-immune alterations, which may be further exacerbated by the extent of surgery. However, psychologic stress, anxiety, and mood have not been previously characterized in patients undergoing spinal surgery. METHODS: Pain, stress, anxiety, and mood were measured using self-report instruments at T1 (1 week before surgery), T2 (the day of surgery), T3 (the day after surgery), and T4 (6 weeks after surgery). Blood (30 mL) was collected for immune assessments at each time point. RESULTS: Pain, stress, anxiety, and mood state were elevated at baseline in both surgical groups and were associated with significant reduction in NKCA compared with the nonsurgical control group. A further decrease in NKCA was observed 24 hours after surgery in both surgical groups with a significant rise in stimulated IL-6 production, regardless of the magnitude of surgery. In the recovery period, NKCA increased to or above baseline values, which correlated with decreased levels of reported pain, perceived stress, anxiety, and mood state. CONCLUSIONS: This study demonstrated that patients undergoing elective spinal surgery are highly stressed and anxious, regardless of the magnitude of surgery and that such psychologic factors may mediate a reduction in NKCA.

Applying the psychoneuroimmunology framework to nursing research.

Psychoneuroimmunology (PNI) provides a distinct perspective regarding the interrelatedness of the nervous, endocrine, and immune systems. PNI explicates the possible means by which behavior and emotion can influence immune function. Moreover, PNI explains the means by which the immune system affects the nervous system and affects psychological response. The interactions among these systems are mediated at the molecular level by cytokines and hormones produced by cells of not just the immune but also the nervous and endocrine systems. These cytokines and hormones affect endocrine and neuronal processes that, in turn, affect mood, emotions, personal perception, as well as the immune response. Analysis of the effect of cytokines and hormones at the molecular, cellular, and peripheral level is under intense investigation. Such analysis will lead to a better understanding of the connections among the psychological, neurological, and immunological systems. This understanding will provide for a holistic perspective upon which better health care can be provided, discomfort minimized, and disease prevented. The use of such a perspective in neuroscience nursing investigation can elicit novel approaches to care.

Neural-immune interactions: implications for pain management in patients with low-back pain and sciatica.

Bidirectional communication between the immune system and the brain and the implications of this communication are emerging concepts in pain research. Although representing a small portion of the disc degeneration syndromes, lumbar herniated discs can cause significant symptoms that may persist even after surgical interventions. Evolving evidence demonstrates that proinflammatory cytokines are a key mediator in the process of disc degeneration as well as in the pain experienced by those afflicted with lumbar herniated discs. Activated immune cells release proinflammatory cytokines, which signal the brain through humoral and neural routes. The brain responds by altering neural activity and promoting further production of proinflammatory cytokines within the brain and spinal cord. Increased local cytokine production by disc tissue irritates spinal nerve roots, resulting in pain and functional changes in neural activity. This review of the current literature explores the importance of cytokine production within the context of lumbar disc degeneration and lumbar spine pain. Furthermore, the significance of the neural-immune interaction will be examined as it relates to pain management and to patient treatment.

Psycho-endocrine-immune response to mindfulness-based stress reduction in individuals infected with the human immunodeficiency virus: a quasiexperimental study.

OBJECTIVES: The purpose of this study was to examine the effects of a structured, 8-week, Mindfulness-Based Stress Reduction (MBSR) program on perceived stress, mood, endocrine function, immunity, and functional health outcomes in individuals infected with the human immunodeficiency virus (HIV). DESIGN: This study used a quasiexperimental, nonrandomized design. METHODS: Subjects were specifically recruited (nonrandom) for intervention (MBSR) or comparison group. Data were collected at pretest and post-test in the MBSR group and at matched times in the comparison group. t Tests where performed to determine within-group changes and between-group differences. RESULTS: Natural killer cell activity and number increased significantly in the MBSR group compared to the comparison group. No significant changes or differences were found for psychological, endocrine, or functional health variables. CONCLUSIONS: These results provide tentative evidence that MBSR may assist in improving immunity in individuals infected with HIV.

Issues in the design and implementation of psychoneuroimmunology research.

Research that uses a psychoneuroimmunology (PNI) framework seeks to determine whether valid associations exist among stress, immune function, and health. These associations are difficult to conclusively determine due to the fact that PNI research is fraught with methodological difficulties. These difficulties arise from the multifaceted and complex nature of the neuro-endocrine-immune network that is the phenomenon of interest in PNI. This article discusses multiple issues of which investigators should be aware when designing and implementing PNI research including (1) the control of potentially immunomodulating variables related to demographics, behavior, and lifestyle; (2) the manner in which stress, endocrine function, immunity, and health outcomes are measured in consideration of the theoretical relevance to the research question, population, or disease entity understudy; (3) the way physiological specimens are procured and stored; and (4) the methods by which assays are performed.

Reduced lymphocyte-mediated antifungal capacity in high-risk infants.

Premature and critically ill infants are highly susceptible to Candida albicans. This study evaluated the lymphocyte-mediated antifungal capacity of infants relative to birth weight, prematurity, and illness severity. Growth inhibition of C. albicans by lymphocytes from preterm and low-birth weight infants was significantly reduced, compared with full-term and normal-weight infants. Lymphocyte growth inhibition of C. albicans is dependent on cell adhesion to the fungus. Compared with full-term infants, lymphocytes from preterm infants had a reduced capacity to adhere to C. albicans. Furthermore, infants with greater severity of illness (score for neonatal acute physiology [SNAP], >or=10) exhibited significantly reduced lymphocyte-mediated antifungal capacity and fungal adhesion. Although gestational age, birth weight, and SNAP were significantly associated with lymphocyte-mediated growth inhibition and adhesion, stepwise regression analysis demonstrated that gestational age best predicted both lymphocyte growth inhibition of and adhesion to the fungus.