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.

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.

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.

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.

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.

Relationship of childhood adversity and neighborhood violence to a proinflammatory phenotype in emerging adult African American men: An epigenetic link.

African American men (AAM) who are exposed to trauma and adversity during their early life are at greater risk for poor health over their lifespan. Exposure to adversity during critical developmental windows may embed an epigenetic signature that alters expression of genes that regulate stress response systems, including those genes that regulate the inflammatory response to stress. Such an epigenetic signature may increase risk for diseases exacerbated by inflammation, and may contribute to health disparity. The purpose of this study was to evaluate the extent to which exposure to early life adversity influences the psychological, cortisol, and proinflammatory response to acute stress (Trier Social Stress Test - TSST) in emerging adult AAM, ages 18-25years (N=34). Hierarchical linear modeling was used to examine the cortisol and IL-6 pattern of response to the TSST with respect to childhood adversity factors and DNA methylation of the IL-6 promoter. Findings revealed that in response to the TSST, greater levels of childhood trauma and indirect exposure to neighborhood violence were associated with a greater TSST-induced IL-6 response, and a blunted cortisol response. Reduced methylation of the IL6 promoter was related to increased exposure to childhood trauma and greater TSST-induced IL-6 levels. These results support the concept that exposure to childhood adversity amplifies the adult proinflammatory response to stress, which is related to epigenetic signature.

Exploring Spirituality Among African American Women: Implications for Promoting Breast Health Behaviors.

The purpose of this qualitative study was to gain understanding of the definition, meaning, and function of spirituality to African American women. Four categories emerged that add insight for nurses to develop innovative spiritual-based strategies to promote African American women's positive health behaviors. Implications for promoting breast health behaviors are described.

The Man I Once Knew: Grief and Inflammation in Female Partners of Veterans With Traumatic Brain Injury.

Grief, although traditionally conceptualized as a bereavement-related reaction, is also experienced by significant others in response to the profound cognitive and personality changes associated with a traumatic brain injury (TBI) in a loved one. Grief associated with the death of a loved one is related to increases in proinflammatory cytokines, yet it is not clear whether this is the case for grief experienced by individuals caring for a significant other with TBI. The purpose of this cross-sectional, exploratory study was to examine grief and its association with a proinflammatory cytokine, tumor necrosis factor α (TNF-α), in wives/partners caring for veterans with TBI. Participants completed written measures of grief, perceived stress, and depressive symptoms and provided morning saliva samples for TNF-α analysis. Participants reported levels of grief comparable to those reported in studies evaluating individuals grieving the death of a loved one. Path analysis revealed that grief was not associated with TNF-α; however, participants reporting high levels of blame/anger, a subscale of the grief scale, had higher levels of TNF-α. In addition, both grief and blame/anger were related to increased perceived stress and depressive symptoms; however, path analysis demonstrated that perceived stress and depressive symptoms did not mediate the influence of blame/anger on TNF-α. These findings suggest that blame/anger associated with grief may be related to the elevations in TNF-α exhibited by individuals caring for a loved one with TBI.

Relationships among psychosocial factors, biomarkers, preeclampsia, and preterm birth in African American women: a pilot.

AIM: To explore the relationships among psychosocial factors (optimism, uncertainty, social support, coping, psychological distress), biomarkers (cortisol, cytokines), preeclampsia, and preterm birth in African American women. METHODS: Forty-nine pregnant African American women completed psychosocial questionnaires and had blood collected for biomarkers between 26 and 36 weeks of gestation. Birth outcomes were obtained from birth records. RESULTS: Women reporting higher levels of social support had lower levels of pro-inflammatory cytokines (IL-2, IL-5, and IL-6). Surprisingly, compared with low-risk pregnant women, women diagnosed with preeclampsia reported more optimism and less avoidance, and had lower levels of cortisol and IFN-γ. Similarly, compared to women with full-term birth, women with preterm birth reported higher levels of optimism and lower levels of avoidance, and had lower levels of IL-10. CONCLUSION: Psychosocial factors influence inflammation and pregnancy outcomes. Close assessment and monitoring of psychosocial factors may contribute to improved pregnancy outcomes.

Day-to-day dynamics of associations between sleep, napping, fatigue, and the cortisol diurnal rhythm in women diagnosed as having breast cancer.

OBJECTIVES: To examine whether day-to-day variations in sleep behaviors, ongoing sleep disturbance, and fatigue predict the cortisol diurnal rhythm in women recently diagnosed as having early-stage breast cancer. METHODS: Women (N = 130, mean [standard deviation] age = 55.6 [9.4] years) collected saliva 5×/day/2 days for cortisol. Diaries were used to assess prior-day nap duration, nocturnal awakenings, sleep latency, and morning restfulness. Ongoing fatigue and sleep disturbance were measured using the Multidimensional Fatigue Symptom Inventory and the Pittsburg Sleep Quality Inventory. Data were analyzed using a multilevel growth curve modeling. RESULTS: Greater ongoing fatigue (b = 0.035, p = .032), or sleep disturbance (b = 0.026, p = .006) predicted a slower cortisol decline. Greater ongoing fatigue also predicted higher awakening cortisol (b = 0.154, p = .030) and lower cortisol awakening response (CAR; b = -0.146, p = .005). Longer prior-day naps predicted higher CAR (b = 0.042, p = .050) and a steeper cortisol decline (b = -0.035, p = .003). Longer sleep latency predicted both a greater cortisol linear decline (b = -0.013, p < .001) and a greater quadratic slope curvature (b = 0.0007, p < .001). Feeling less rested in the morning predicted lower awakening cortisol (b = -0.187, p = .004), higher CAR (b = 0.124, p = .016), and a slower cortisol decline (b = 0.023, p = .042). CONCLUSIONS: Both daily variations in sleep behaviors and ongoing sleep disturbance and fatigue are associated with a disrupted cortisol rhythm. In contrast, prior-day napping is associated with a more robust cortisol rhythm. These findings are particularly relevant to women with breast cancer who often experience sleep disturbance and fatigue. Additional research is needed to determine causal pathways between sleep disturbance and dysregulation of the hypothalamic-pituitary-adrenal axis in patients with breast cancer.

Yoga: a biobehavioral approach to reduce symptom distress in women with urge urinary incontinence.

Urge urinary incontinence is a debilitating chronic condition that poses challenges for affected women and the clinicians who care for them. Multicomponent behavioral therapies have shown promise in allowing women to manage their symptoms. New evidence suggests an underlying pathophysiologic inflammatory process for urge urinary incontinence, and complementary therapies that address the psychoneuroimmunology component may improve the health and quality of life for the millions of women with this condition. Yoga, a mind-body therapy, has been shown to reduce inflammation and may help improve symptoms of urge urinary incontinence. More research is necessary to demonstrate the effectiveness of yoga to reduce urge urinary incontinence symptom burden and improve quality of life.

Measurement of the glucocorticoid receptor: relevance to the diagnosis of critical illness-related corticosteroid insufficiency in children.

Diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in children continues to remain difficult and controversial in that no consensus for either exists among pediatric critical care physicians. Critical illness-related corticosteroid insufficiency is defined as a corticosteroid response that is inadequate for the severity of the illness experienced by the patient. Critical illness-related corticosteroid insufficiency manifests as an insufficient corticosteroid mediated down-regulation of proinflammatory cytokines, due to either corticosteroid tissue resistance and/or inadequate circulating levels of cortisol. The tissue resistance is likely due to alterations in the functionality of the intracellular receptor for corticosteroids, the glucocorticoid receptor (GR). This article details the role of the GR during critical illness with a focus upon the measurement of the GR, as a potentially important means by which to clinically assess the level of corticosteroid tissue-resistant in patients suspected of CIRCI. Measurement of the GR may be particularly useful as a means by which to determine the judicious administration of steroids, maximizing their therapeutic potential, whereas minimizing the morbidity that can be associated with their use.

Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer.

INTRODUCTION: This pilot study used a prospective longitudinal design to compare the effect of adjuvant whole breast radiation therapy (WBRT) versus partial breast radiation therapy (PBRT) on fatigue, perceived stress, quality of life and natural killer cell activity (NKCA) in women receiving radiation after breast cancer surgery. METHODS: Women (N = 30) with early-stage breast cancer received either PBRT, Mammosite brachytherapy at dose of 34 Gy 10 fractions/5 days, (N = 15) or WBRT, 3-D conformal techniques at dose of 50 Gy +10 Gy Boost/30 fractions, (N = 15). Treatment was determined by the attending oncologist after discussion with the patient and the choice was based on tumor stage and clinical need. Women were assessed prior to initiation of radiation therapy and twice after completion of radiation therapy. At each assessment, blood was obtained for determination of NKCA and the following instruments were administered: Perceived Stress Scale (PSS), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and Functional Assessment of Cancer Therapy-General (FACT-G). Hierarchical linear modeling (HLM) was used to evaluate group differences in initial outcomes and change in outcomes over time. RESULTS: Fatigue (FACT-F) levels, which were similar prior to radiation therapy, demonstrated a significant difference in trajectory. Women who received PBRT reported progressively lower fatigue; conversely fatigue worsened over time for women who received WBRT. No difference in perceived stress was observed between women who received PBRT or WBRT. Both groups of women reported similar levels of quality of life (FACT-G) prior to initiation of radiation therapy. However, HLM analysis revealed significant group differences in the trajectory of quality of life, such that women receiving PBRT exhibited a linear increase in quality of life over time after completion of radiation therapy; whereas women receiving WBRT showed a decreasing trajectory. NKCA was also similar between therapy groups but additional post hoc analysis revealed that better quality of life significantly predicted higher NKCA regardless of therapy. CONCLUSIONS: Compared to WBRT, PBRT results in more rapid recovery from cancer-related fatigue with improved restoration of quality of life after radiation therapy. Additionally, better quality of life predicts higher NKCA against tumor targets, emphasizing the importance of fostering quality of life for women undergoing adjuvant radiation therapy.

Depressive symptoms and diurnal salivary cortisol patterns among female caregivers of stroke survivors.

Informal caregivers of stroke survivors experience elevated chronic stress and are at risk of developing depressive symptoms. The cumulative effects of chronic stress can increase allostatic load and dysregulate biological processes, thus increasing risk of stress-related disease. Stress-induced alterations in the pattern of cortisol secretion vary with respect to stressor onset, intensity, and chronicity. Little is known about the psychoendocrine response to stress in female caregivers of stroke survivors. The purpose of this study was to examine perceived stress, caregiver burden, and the association between caregiver depressive symptoms and diurnal cortisol in 45 females caring for a significant other who experienced a stroke within the past year. Women completed the Center for Epidemiologic Studies Depression Scale (CES-D) and collected saliva for cortisol upon awakening, 30 min postawakening, noon, and bedtime for 2 consecutive days. Results revealed that women had high levels of perceived stress and caregiver burden. In women with CES-D scores ≥ 16, salivary cortisol levels were significantly lower across the day relative to women with CES-D scores < 16. This difference persisted after adjusting for age, number of caregiving hours per week, perceived social support, and quality of sleep. Younger age was associated with more depressive symptoms as well as lower levels of cortisol at awakening and 30 min postawakening. Results demonstrate that the burden of caregiving increases risk of depressive symptoms and hypocortisolism across the day. Hypocortisolism may contribute to increased risk of depressive symptoms as a result of the loss of glucocorticoid attenuation of stress-induced inflammation.

Glucocorticoid receptor mediated suppression of natural killer cell activity: identification of associated deacetylase and corepressor molecules.

Physical and psychological stressors reduce natural killer cell function. This reduction in cellular function results from stress-induced release of glucocorticoids. Glucocorticoids act upon natural killer cells to deacetylate and transrepress immune response genes through epigenetic processes. However, other than the glucocorticoid receptor, the proteins that participate in this process are not well described in natural killer cells. The purpose of this study was to identify the proteins associated with the glucocorticoid receptor that are likely epigenetic participants in this process. Treatment of natural killer cells with the synthetic glucocorticoid, dexamethasone, produced a significant time dependent reduction in natural killer cell activity as early as 8h post treatment. This reduction in natural killer cell activity was preceded by nuclear localization of the glucocorticoid receptor with histone deacetylase 1 and the corepressor, SMRT. Other class I histone deacetylases were not associated with the glucocorticoid receptor nor was the corepressor NCoR. These results demonstrate histone deacetylase 1 and SMRT to associate with the ligand activated glucocorticoid receptor within the nuclei of natural killer cells and to be the likely participants in the histone deacetylation and transrepression that accompanies glucocorticoid mediated reductions in natural killer cell function.

Epigenetics and psychoneuroimmunology: mechanisms and models.

In this Introduction to the Named Series "Epigenetics, Brain, Behavior, and Immunity" an overview of epigenetics is provided with a consideration of the nature of epigenetic regulation including DNA methylation, histone modification and chromatin re-modeling. Illustrative examples of recent scientific developments are highlighted to demonstrate the influence of epigenetics in areas of research relevant to those who investigate phenomena within the scientific discipline of psychoneuroimmunology. These examples are presented in order to provide a perspective on how epigenetic analysis will add insight into the molecular processes that connect the brain with behavior, neuroendocrine responsivity and immune outcome.

Glucocorticoid dysregulation of natural killer cell function through epigenetic modification.

It is well-established that psychological distress reduces natural killer cell activity (NKCA) and dysregulates cytokine balance. This may be mediated by stress-induced release of glucocorticoids, which have broad effects on the immune system, including the suppression of NKCA and alteration of cytokine production. The purpose of this study was to evaluate epigenetic mechanisms that may underlie the effect of glucocorticoids on NK cells, using the human NK cell line, NK92. Treatment of NK92 cells with the synthetic glucocorticoid, dexamethasone, at a concentration of 10⁻7M, produced a significant reduction in NKCA. Glucocorticoid inhibition was a consequence of not only a reduced capacity of the NK cells to bind to tumor targets but also a reduced production of granule constituents (perforin and granzyme B) with no detectable effect on granule exocytosis. Glucocorticoids also reduced the constitutive and the stimulated production of the cytokines, IL-6, TNF alpha and IFN gamma, and reduced the surface expression of LFA-1. Glucocorticoid treatment also reduced global histone acetylation, the acetylation of histone 4 lysine position 8, and the accessibility of the proximal promoters of perforin, interferon gamma and granzyme B. Histone acetylation was recovered by treatment of the NK cells with a histone deacetylase inhibitor, which also restored NKCA and IFN gamma production. These results demonstrate glucocorticoids to dysregulate NK cell function at least in part through an epigenetic mechanism, which reduces promoter accessibility through modification of histone acetylation status. This epigenetic modification decreases the expression of effector proteins necessary to the full functional activity of NK cells.

Epigenetic patterns associated with the immune dysregulation that accompanies psychosocial distress.

The molecular basis for psychosocial-distress mediated immune-dysregulation is not well understood. The purpose of this study was to determine whether peripheral blood mononuclear cell (PBMC) epigenetic pattern associates with this form of immune dysregulation. Women newly diagnosed with early stage breast cancer were enrolled into the study and psychosocial, immunological and epigenetic assessments were made at diagnosis and four months later, after completion of cancer treatment. At diagnosis women reported increased perceived stress, anxiety, and mood disturbance and the PBMC of these women exhibited reduced natural killer cell activity and reduced production of interferon gamma, which contrasted with results, obtained after completion of treatment. At the epigenetic level, a PBMC subset derived from women at diagnosis exhibited a distinct epigenetic pattern, with reduced nuclear acetylation of histone residues H4-K8 and H4-K12, as well as reduced phosphorylation of H3-S10, when compared to similar cells derived after the completion of treatment. Natural killer cell activity and interferon-gamma production were associated with nuclear acetylation and phosphorylation status of these histone residues. These findings demonstrate associations among nuclear epigenetic pattern and the immune dysregulation that accompanies psychosocial distress.