Fatigue and Depressive Mood in Chronic Low Back Pain.

PURPOSE: Fatigue is prevalent, problematic, and co-occurs in chronic low back pain. When left untreated, fatigue can increase depressive mood, and intensify pain burden and disability in patients with chronic low back pain. The purpose of this study was to examine the relationship of fatigue to depressive mood, pain severity, and pain interference in patients with chronic low back pain. DESIGN AND METHODS: A cross-sectional design was used to enroll and evaluate adults (n = 67) with chronic low back pain (>6 months) during their visit to an outpatient pain clinic. Participants completed psychometric instruments for fatigue, depressive mood, pain severity, and pain interference. RESULTS: Participants were primarily women (73%), White (59%), with a median age of 59 years (range 22-70 years). Multiple regression models showed significant positive associations between fatigue and depressive mood (SD: 0.025 p = 0.017) with a coefficient of 0.069; fatigue and pain interference (SD: 0.123 p = 0.010) with a coefficient of 0.652; fatigue and pain severity (SD: 0.125 p-value <0.05) with a coefficient of 0.359. After adjusting for demographic factors (age, sex, and race/ethnicity) the associations remained significant. CONCLUSIONS: The findings suggest that fatigue is associated with greater depressive mood, pain severity, and pain interference in adults with chronic low back pain. CLINICAL IMPLICATIONS: Assessing the extent of fatigue and depressive mood as part of pain management may benefit patients with chronic low back, thereby reducing symptom burden.

Impact of a Mindfulness-Based Stress Reduction Program on Psychological Well-Being, Cortisol, and Inflammation in Women Veterans.

BACKGROUND: Women veterans experience higher levels of stress-related symptoms than their civilian counterparts. Psychological stress is associated with greater inflammation and may increase risk for cardiovascular disease (CVD). Mindfulness-based stress reduction (MBSR) has been found to improve psychological well-being in other populations but no randomized controlled trials (RCT) have been conducted examining the impact of MBSR on well-being and inflammation in women veterans at risk for CVD. OBJECTIVE: Determine the effectiveness of MBSR in improving psychological well-being, cortisol, and inflammation associated with CVD in women veterans. DESIGN: The design is a RCT comparing MBSR to an active control condition (ACC) consisting of a health education program. PARTICIPANTS: Women veterans (N=164) with risk factors for CVD from the Chicagoland area participated in the study. INTERVENTION: An 8-week MBSR program with weekly 2.5-h classes was compared to an ACC consisting of an 8-week health promotion education program with weekly 2.5-h classes. MAIN MEASURES: The outcomes were psychological well-being [perceived stress, depressive symptoms, loneliness, and post-traumatic stress disorder (PTSD)] symptoms and stress-related markers, including diurnal salivary cortisol and cytokines interleukin-6 (IL-6) and interferon gamma (IFN-γ). Data were collected at baseline, 4 weeks (mid-point of intervention), 8 weeks (completion of intervention), and 6 months after completion of MBSR or ACC. KEY RESULTS: Compared to the ACC, women who participated in MBSR reported less perceived stress, loneliness, and symptoms of PTSD. Although there were no significant differences between groups or changes over time in IL-6 or IFN-γ, participants in the MBSR program demonstrated a more rapid decline in diurnal salivary cortisol as compared to those in the ACC. CONCLUSIONS: MBSR was found to improve psychological well-being and decrease diurnal salivary cortisol in women veterans at risk for CVD. Health care providers may consider MBSR for women veterans as a means by which to improve their psychological well-being.

Heart Rate Variability and Inflammatory Stress Response in Young African American Men: Implications for Cardiovascular Risk.

Background: African American men have a disproportionately higher incidence of and suffer greater severity and earlier death from cardiovascular disease (CVD). A common feature of many diseases, which disproportionately afflict disadvantaged African Americans, is inflammation. In particular, inflammation plays a decisive role in the pathogenesis of CVD in that persistent inflammation contributes to plaque evolution and destabilization. Adverse childhood experiences increase the risk for adult inflammatory based disease, particularly cardiovascular disease. This inflammatory burden becomes evident during stressful events and may be related to alterations in autonomic nervous system (ANS) activity. We previously reported that African American men who experienced childhood adversity exhibited a greater inflammatory (IL-6) response to acute stress challenge (Trier Social Stress Test - TSST). The purpose of this study was to determine whether altered ANS activity, as measured by heart rate variability (HRV), contributes to a greater proinflammatory response to stress in those exposed to childhood adversity. Methods: Thirty-four African American adult males underwent the TSST while instrumented with Holter monitors to record continuous heart rate for HRV determination. HRV was calculated as the low frequency (LF) to high frequency (HF) heart rate ratio (LF/HF), with higher LF/HF ratios corresponding to higher sympathetic vs. parasympathetic activity. Salivary samples were collected pre- and post-TSST to measure the proinflammatory cytokine IL-6. Childhood adversity was assessed by the Childhood Trauma Questionnaire. Results: Hierarchical linear modeling demonstrated that higher levels of physical abuse were related to a steeper rise in LF/HF ratio during the TSST. Further, a higher LF/HF ratio, in combination with greater exposure to emotional and physical abuse was associated with a greater IL-6 response to the TSST. Conclusions: These findings suggest that adverse childhood experiences associate with an adult phenotype characterized by an altered ANS response to stress as well as a greater proinflammatory (IL-6) response to an acute stressor. Elevations in salivary inflammatory markers have been associated with increased CVD risk. In conclusion, these findings suggest a role for the ANS in the underlying neuro-biological processes whereby childhood adversity predisposes to a more intense inflammatory response to stressful challenge during adulthood.

Social Support Is Inversely Associated With Sleep Disturbance, Inflammation, and Pain Severity in Chronic Low Back Pain.

BACKGROUND: Chronic low back pain (CLBP) is a significant cause of disability, lost wages, and healthcare costs. Inflammatory mediators, such as interleukin-6 (IL-6), have been associated with LBP severity. Patients with CLBP commonly experience sleep disturbance, and poor sleep has been shown to increase pain severity and inflammation. In contrast, social support may benefit patients with CLBP by reducing pain intensity and inflammation. OBJECTIVES: The purpose of this study was to examine the influence of social support on the relationships among sleep disturbance, inflammation, and pain severity in patients with CLBP. METHODS: In a cross-sectional study, men and women with CLBP were enrolled from an outpatient pain clinic. Participants completed psychometric instruments for social support, sleep quality, and pain severity. Blood samples were obtained for measurement of the pro-inflammatory cytokine IL-6 by enzyme-linked immunoassay. RESULTS: Linear regression revealed greater sleep disturbance predicted greater pain severity. In contrast, participants who reported higher social support had lower sleep disturbance and lower pain severity. Mediation analysis revealed sleep disturbance to mediate the relationship between social support and pain, such that sleep disturbance reduced the benefit of social support on pain severity. Furthermore, greater sleep disturbance and lower social support predicted increased IL-6. However, IL-6 did not mediate the relationship between social support and pain. DISCUSSION: The findings suggest that increased social support is associated with lower sleep disturbance, lower inflammation, and lower pain severity in patients with CLBP. Assessing the extent of social support and fostering social support as part of a comprehensive pain management program may benefit patients with CLBP. Interventions to strengthen social support systems and cultivate support from family and/or informal social networks may reduce symptom burden and improve quality of life.

Preliminary evidence for a race-based stress reduction intervention for Black women at risk for cardiovascular disease.

OBJECTIVE: Despite evidence that chronic stress, racism, and discrimination impact the well-being and the risk for cardiovascular disease (CVD) in Black women, there are few evidence-based interventions that improve well-being and reduce the risk for CVD in women of minority groups. The purpose of this pilot study was to evaluate the psychobehavioral and anti-inflammatory benefit of a race-based stress reduction program "Resilience, Stress, and Ethnicity (RiSE) for Black women at risk for CVD. METHODS: Black women were recruited from the Chicagoland community and randomized to either the 8-week RiSE intervention (n = 40) or control group (n = 34). Participants were assessed for coping strategies, psychological distress, and blood levels of TNF-alpha and high sensitivity C-reactive protein (hsCRP) at baseline and at 4 and 8 weeks after baseline. RESULTS: Participation in RiSE was associated with a more rapid decline in the use of avoidance coping (b = -0.3585, SE = 0.1705, p < .01). Reductions over time in TNF-alpha (b = -0.0163, SE = .0087, p = .08) and hsCRP (b= -0.4064, SE = 0.2270, p = .08) approached statistical significance. CONCLUSIONS: Findings provide preliminary evidence in Black women at risk for CVD that RiSE contributes to decreases in avoidance coping. Although preliminary, these results suggest RiSE to be an effective intervention to promote improved coping associated with racism and discrimination in minorities.

A Biopsychosocial Framework to Examine Risk for Type 2 Diabetes in Asian Pacific Islander Immigrants.

There is large disparity in the incidence of Type 2 diabetes (T2D) for Asian Pacific Islanders (APIs), one of the fastest growing minority populations in the United States. It is critical to examine biopsychosocial pathways and vulnerability factors that intensify risk for T2D in API. Increasing evidence links chronic stress to poor health outcomes and accelerated development and progression of diseases of aging, such as diabetes. Immigrant populations face unique life stressors, including the challenges associated with the process of adapting to a new environment, new language, and cultural differences. In addition, immigrants experience high levels of psychological distress related to changes of identity and values, loss of support, discrimination, and disempowerment. The purpose of this article is to propose a biopsychosocial framework to explicate potential mechanistic pathways that link cumulative life stress to risk for T2D in the API immigrant population. Unique to the proposed framework is the emphasis on inflammatory processes and accelerated cellular aging (telomere biology). A deeper understanding of biopsychosocial pathways can lead to tailored and targeted interventions to reduce the incidence of T2D in the API immigrant population.

Behavioral Symptom Clusters, Inflammation, and Quality of Life in Chronic Low Back Pain.

BACKGROUND: Chronic low back pain is a prevalent condition, often involving an inflammatory process. Behavioral symptoms, including depressed mood, fatigue, and sleep disturbance, intensifies pain and reduces quality of life. AIMS: The objectives of this pilot study were to identify behavioral symptom clusters (depressive mood, fatigue, poor sleep) in individuals with chronic low back pain, and to determine whether there are differences in pain, quality of life and inflammation (plasma IL-6) based on cluster membership. DESIGN AND SETTINGS: A cross-sectional study was conducted in a pain clinic. PARTICIPANTS/ SUBJECTS: Participants between ages 21 to 70 years (N=69) were enrolled if they had chronic low back pain for at least six months. METHODS: Participants completed instruments measuring, pain, depressive mood, fatigue, sleep, and demographic form. Blood (10ml) was obtained. Latent class analysis was used to identify clusters. RESULTS AND CONCLUSIONS: Findings revealed a two-class model, with Class 1 characterized by more depressive mood, fatigue, and sleep disturbance compared to Class 2. Class 1 participants reported worse quality of life than those in Class 2. Pain severity and pain interference were not significantly different between the classes. Levels of IL-6 were significantly greater in Class 1 participants compared to Class 2 with higher levels of IL-6 correlating with greater pain severity and sleep disturbances. Logistic regression revealed higher levels of IL-6 predicted Class 1 membership. Behavioral symptoms cluster exist in chronic low back pain patients and impact quality of life. Inflammation may contribute to relationship between behavioral symptoms and pain severity.

Mindfulness Predicts Psycho-behavioral Improvement after Breast Cancer Diagnosis: Influence of Childhood Adversity.

Mindfulness-based interventions provide psychological benefit after breast cancer diagnosis. The aims of this study were to determine whether within-person change in facets of mindfulness predict psycho-behavioral improvements in women with breast cancer, and to assess the influence of childhood adversity on those improvements. Women randomized to the mindfulness arm of a larger trial were evaluated. Psychometric instruments and the Five Facets of Mindfulness Questionnaire were completed pre-, mid-, at completion, one, and six months post program. A subsample completed the Childhood Trauma Questionnaire. Hierarchical linear modeling revealed that significant change in nonjudgment and nonreactivity to inner experience were associated with more rapid decrease in stress, depressive symptoms, fatigue, sleep disturbance, and more rapid increase in quality of life. For women with greater exposure to childhood adversity, a greater increase in nonreactivity to inner experience significantly associated with greater improvements in stress, depressive symptoms, and quality of life.

Yoga for Women With Urgency Urinary Incontinence: A Pilot Study.

OBJECTIVES: The objective of this study was to evaluate the feasibility of a gentle yoga program for women with urgency urinary incontinence (UUI). Also, these preliminary data can evaluate if yoga improves symptom burden, quality of life, and inflammatory biomarkers for women with UUI. METHODS: This prospective nonrandomized single-arm pilot study evaluated the effectiveness of a twice-weekly, 8-week gentle yoga intervention to reduce UUI symptom burden. Changes in symptom burden were measured using the Pelvic Floor Distress Inventory 20. Secondary measures included quality of life, depressive symptoms, sleep, stress, anxiety, and inflammatory biomarkers. Outcomes were evaluated with paired t testing. RESULTS: Twelve women completed the yoga intervention with no adverse outcomes noted. Urgency symptom burden was significantly improved after the intervention (P = 0.01), and women reported an increase in quality of life (P = 0.04) after the yoga intervention. Following the yoga intervention, the majority of women reported symptoms as "much better" (n = 4 [33%]) and "a little better" (n = 5 [42%]), with 3 women (25%) reporting "no change." Women also reported significant reduction in depressive symptoms (P = 0.03) and better quality of sleep (P = 0.03). No significant changes were found in anxiety or stress perception. Plasma levels of the inflammatory biomarker tumor necrosis factor α were reduced after yoga intervention (P = 0.009); however, no significant postyoga changes were found for interleukin 6 or C-reactive protein. CONCLUSIONS: This study provides preliminary evidence that yoga is a feasible complementary therapy that reduces incontinence symptom burden, along with improving quality of life, depressive symptoms, and sleep quality. Additionally, yoga may lower inflammatory biomarkers associated with incontinence.

Project CaLM: A Pilot Intervention Integrating Mindfulness Strategies into Head Start Classrooms.

Using a participatory action research approach, this pilot project examined how mindfulness techniques could be integrated into classroom routines in Head Start programs, which serve children who live below the federal poverty line. In Study 1, we conducted limited-efficacy testing and examined the implementation of our intervention, which we refer to as Project CaLM (Children Learning Mindfulness). Although the study lacked adequate statistical power, when comparing the well-being of children who did and did not receive the intervention, most results were in the expected direction, but were non-significant. Still, findings show that teachers generally implemented Project CaLM at greater frequencies and duration than expected. Study 2 investigated the acceptability of and demand for mindfulness strategies among teachers and parents using both survey and open-ended questions. Results revealed favorable views of and interest in mindfulness practices. Future research should consider extending Project CaLM in terms of sample size and context.

A Behavioral Epigenetics Model to Predict Oral Feeding Skills in Preterm Infants.

BACKGROUND: Preterm infants experience a multitude of prenatal and postnatal stressors, resulting in cumulative stress exposure, which may jeopardize the timely attainment of developmental milestones, such as achieving oral feeding. Up to 70% of preterm infants admitted to the neonatal intensive care unit experience challenges while initiating oral feeding. Oral feeding skills require intact neurobehavioral development. Evolving evidence demonstrates that cumulative stress exposure results in epigenetic modification of glucocorticoid-related genes. Epigenetics is a field of study that focuses on phenotypic changes that do not involve alterations in the DNA sequence. Epigenetic modification of glucocorticoid-related genes alters cortisol reactivity to environmental stimuli, which may influence neurobehavioral development, and is the essence of the evolving field of Preterm Behavioral Epigenetics. It is plausible that early-life cumulative stress exposure and the ensuing epigenetic modification of glucocorticoid-related genes impair neurobehavioral development required for achievement of oral feeding skills in preterm infants. PURPOSE: The purpose of this article is to build upon the evolving science of Preterm Behavioral Epigenetics and present a conceptual model that explicates how cumulative stress exposure affects neurobehavioral development and achievement of oral feeding skills through epigenetic modification of glucocorticoid-related genes. METHODS/RESULTS: Using the Preterm Behavioral Epigenetics framework and supporting literature, we present a conceptual model in which early-life cumulative stress exposure, reflected by DNA methylation of glucocorticoid-related genes and altered cortisol reactivity, disrupts neurobehavioral development critical for achievement of oral feeding skills. IMPLICATIONS FOR PRACTICE AND RESEARCH: Future investigations guided by the proposed conceptual model will benefit preterm infant outcomes by introducing epigenetic-based approaches to assess and monitor preterm infant oral feeding skills. Furthermore, the proposed model can guide future investigations that develop and test epigenetic protective interventions to improve clinical outcomes, representing an innovation in neonatal care.

The relationship between stress and vitiligo: Evaluating perceived stress and electronic medical record data.

Vitiligo is a T-cell mediated skin disorder characterized by progressive loss of skin color. In individuals genetically predisposed to the disease, various triggers contribute to the initiation of vitiligo. Precipitating factors can stress the skin, leading to T-cell activation and recruitment. Though hereditary factors are implicated in the pathogenesis of vitiligo, it is unknown whether precipitating, stressful events play a role in vitiligo. To understand this, we utilized a validated perceived stress scale (PSS) to measure this parameter in vitiligo patients compared to persons without vitiligo. Additionally, we probed a clinical database, using a knowledge linking software called ROCKET, to gauge stress-related conditions in the vitiligo patient population. From a pool of patients in an existing database, a hundred individuals with vitiligo and twenty-five age- and sex-matched comparison group of individuals without vitiligo completed an online survey to quantify their levels of perceived stress. In parallel, patients described specifics of their disease condition, including the affected body sites, the extent, duration and activity of their vitiligo. Perceived stress was significantly higher among vitiligo individuals compared to those without vitiligo. ROCKET analyses suggested signs of metabolic-related disease (i.e., 'stress') preceding vitiligo development. No correlation was found between perceived stress and the stage or the extent of disease, suggesting that elevated stress may not be a consequence of pigment loss alone. The data provide further support for stress as a precipitating factor in vitiligo development.

Qualitative evidence for Resilience, Stress, and Ethnicity (RiSE): A program to address race-based stress among Black women at risk for cardiovascular disease.

OBJECTIVE: Growing evidence demonstrates that perceived discrimination and racism are significant contributing factors to psychological distress, low-grade chronic inflammation, and cardiovascular health disparities among minorities, particularly among Black women. Despite this evidence, there are no evidence-based complementary therapy interventions available to ameliorate chronic stress associated with racism and discrimination. The purpose of this study was to examine the feasibility and effectiveness of a novel, 8-week, group-based stress reduction program, Resilience, Stress and Ethnicity (RiSE), designed to help Black women at risk for cardiovascular disease (CVD) develop effective coping skills for dealing with chronic stress uniquely associated with being a minority. METHODS: We conducted two semi-structured focus groups with Black women (N = 22) following their participation in the 8-week RiSE program. We analyzed the data using constant comparative qualitative methods. RESULTS: Attrition rate was low (13%) with all participants attending at least 6 of the 8 classes. Participants reported high levels of satisfaction with the program and the majority (81%) reported practicing the skills that they learned in real-life stressful situations. In describing the participants' response to the program, four key categories emerged from the data: (1) Increasing awareness of stressors associated with perceived discrimination and racism; (2) Coping with race-based stressors; (3) Coping with other sources of stress; and (4) Increasing sense of empowerment and emotion regulation. CONCLUSIONS: Findings suggest that RiSE is feasible and effective in helping Black women at risk for CVD cope with chronic stress associated with being a minority. Given evidence that perceived discrimination and racism are underlying factors in many inflammatory-based chronic diseases, this research may have broader implications for reducing health disparities across a wide-spectrum of chronic illnesses in which women minorities are disproportionately affected.

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.

Resilience in African American Women at Risk for Cardiovascular Disease: an Exploratory Study.

African Americans (AAs) have a higher risk for cardiovascular disease (CVD) which is not fully explained by traditional CVD risk factors such as smoking, obesity, hypertension, and diabetes. Evidence demonstrates that chronic stress, low subjective status, and lack of social support play important roles in increasing the risk for CVD, particularly in minority women. Increasing evidence demonstrates that resilience may ameliorate the effect of social stressors on the development of CVD. However, little is known about the social context that may influence resilience in AA women. Therefore, the purpose of this exploratory study was to examine the predictors of resilience in AA women at risk for CVD. A cross-sectional sample of AA women (N = 104) participated in the study. Participants completed measures of resilience, subjective social status, social support, and general stress. Findings revealed that participants had low levels of resilience as measured by the Connor-Davidson Resilience Scale (mean = 50.3 ± 11.4) compared to norms. Results of the multiple linear regression analysis demonstrated that both subjective social status in relation to others in the USA (p = 0.021) and perceived social support (p < 0.001) predicted greater level of resilience. The model, controlling for age, marital status, income, level of education, and general stress, accounted for a significant proportion of variance (F[8,75] = 6.6, p < .001), explaining 41.7% of the variation in resilience. Results suggest that subjective social status and social support contribute to perceived resilience in AA women. Additional research is needed to assess the association of subjective social status and social support in longitudinal studies.

Obesity Prevention Behaviors in Asian Indian Adolescent Girls: A Pilot Study.

PURPOSE: The purpose of this pilot study was to evaluate obesity prevention behaviors of Asian Indian adolescent females and determine the relationship of these behaviors to cardiovascular risk factors. DESIGN AND METHODS: A purposive sample of twenty females, 14-18 years of age, was enrolled. Body mass index, percent body fat, waist circumference, and blood pressure were measured to assess cardiovascular risk. Measures of obesity prevention behaviors were physical activity, dietary and sleeping behaviors. To quantify engagement in physical activity, participants wore an accelerometer. The dietary intake was assessed using the web based SuperTracker. Pittsburgh Sleep Quality Index was used to assess sleep behaviors. For data analysis, descriptive statistics was used for demographic characteristics. Correlations were calculated to evaluate the relationship between cardiovascular risk factors and obesity prevention behaviors. RESULTS: The majority of the adolescents did not meet recommended physical activity levels. Most reported unhealthy eating behaviors with higher saturated fat intake correlating with higher percent body fat. The cardiovascular risk measures fell below normative values. However, more time spent in sedentary behaviors was related to higher systolic blood pressure, while poor sleep quality was associated with higher diastolic blood pressure and greater BMI. CONCLUSIONS: The findings support the unhealthy patterns of physical activity, dietary and sleep behaviors in Asian Adolescent girls and the need for promoting healthy behaviors in this at risk population. PRACTICE IMPLICATIONS: The study findings provide a basis for education on healthy behaviors and development of culturally appropriate interventions to prevent obesity.

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.