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Inflammation can have social consequences, which may be relevant to inflammation's link with depression. The current study tests whether a typhoid vaccine increases feelings of social disconnection and avoidance behavior.In two full-day visits at least three weeks apart, 172 postmenopausal breast cancer survivors (Stage I-IIIA) each received a typhoid capsular polysaccharide vaccination and a saline placebo injection in a random sequence. Blood was drawn prior to the injection, as well as every 90 min thereafter for 8 h to assess the inflammatory response (interleukin-6, IL-6; interleukin-1 receptor antagonist, IL-1Ra). At both visits, women completed the Social Connection Scale at 0 and 8.5 h post-vaccination as well as implicit and explicit social avoidance tasks at 7 h post-vaccination.The typhoid vaccine triggered rises in both inflammatory markers (ps 0.01), but it did not impact feelings of social connection (p = .32), or performance on the implicit (p = .34) or explicit tasks (p = .37). Inflammatory rises did not predict feelings of social connection (ps 0.64) or performance on explicit (ps 0.73) or implicit (ps 0.88) social avoidance tasks.Milder inflammatory stimuli may not affect social processes. Higher levels of inflammation or, relatedly, more sickness symptoms may be necessary to recapitulate prior findings of social avoidance.

OBJECTIVE: Colorectal cancer poses a significant threat to both psychological and physical health. This study examined relationships between anxiety and depressive symptoms with pain, fatigue, and inflammation among colorectal patients. METHODS: Colorectal cancer patients (n = 88, stages 0-IV) completed a laboratory-based study visit before undergoing adjuvant cancer treatment. Patients completed questionnaires assessing depressive, anxiety, pain, and fatigue symptoms. A blood sample was also collected to measure c-reactive protein (CRP). Analyses controlled for age, sex, cancer stage, body mass index (BMI), and menopause status. RESULTS: Multiple linear regression analyses showed colorectal patients with higher depressive and anxiety symptoms had greater pain, fatigue, and CRP (ps < 0.03). Approximately one-third of patients with clinically significant depressive (CESD >16) and anxiety symptoms (BAI >16) also had clinically-elevated levels of CRP (>3 mg/L) (ps = 0.02). CONCLUSION: These results extend findings from other cancer subgroups showing heightened symptom burden among patients with depression and anxiety. They also highlight the detrimental role that elevated anxiety and depressive symptoms may play in the physical and biological side effects associated with colorectal cancer.

Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group's 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. ClinicalTrials.gov identifier: NCT00385723.

Objective Breast cancer survivors who experience psychological and physical symptoms after treatment have an increased risk for comorbid disease development, reduced quality of life, and premature mortality. Identifying factors that reduce or exacerbate their symptoms may enhance their long-term health and physical functioning. This study examined how survivors' marital status and marital satisfaction-key health determinants-impacted their psychological and physical health trajectories to understand when, and for whom, marriage offers health benefits. Methods Breast cancer survivors (n=209, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed questionnaires assessing their marital status and satisfaction when applicable, as well as their psychological (depressive symptoms, stress) and physical (fatigue, pain) health at each visit. Results Married women-both those in satisfying and dissatisfying marriages-experienced improvements in their depressive symptoms, stress, and fatigue from pretreatment to 6- and 18-months posttreatment. Unmarried (i.e., single, divorced/separated, or widowed) women's depressive symptoms, stress, fatigue, and pain did not change over time, instead remaining elevated 6 and 18 months after treatment ended. Women in satisfying marriages also had fewer psychological and physical symptoms after treatment than those who were unmarried or in dissatisfying marriages. Conclusions Although marriage was associated with improved psychological and physical health, the gains were most notable when survivors' marriages were satisfying. Thus, the quality of survivors' marriages, rather than the marriage itself, provided the most benefits to their psychological and physical health. This article is protected by copyright. All rights reserved.

Individuals with social anxiety disorder show pronounced perceptual biases in social contexts, such as being hypervigilant to threat and discounting positive social cues. Parasympathetic activity influences responses to the social environment and may underlie these biases. This study examined the associations among social anxiety symptoms, heart rate variability (HRV), and vocal emotion recognition.Female undergraduate students (Women with more social anxiety symptoms had higher emotion recognition accuracy (A parasympathetically-mediated positivity bias may indicate or facilitate normal social functioning in women. Additionally, HRV during a symptom- or disorder-relevant task may predict task performance and reveal parasympathetic differences that are not found at baseline.

PURPOSE: Proton pump inhibitors (PPIs) are used in cancer patients to manage treatment-related gastrointestinal symptoms and to prevent damage to the gastric mucosal lining during treatment. However, PPI use may contribute to cognitive problems. To compare PPI-users and non-users, breast cancer survivors reported cognitive problems in three studies. METHODS: In Study 1, breast cancer survivors (N=209; n=173 non-users, n=36 PPI-users; stages 0-IIIC) rated their cognitive function on the Kohli scale prior to cancer treatment, as well as one and two years later. In Study 2, women (N=200; n=169 non-users, n=31 PPI-users, stages 0-IIIa, M=11 months post-treatment) rated their cognitive function on the Kohli scale and BCPT checklist at three visits over a six-month period. In Study 3, participants (N=142; n=121 non-users, n=21 PPI-users; stages I-IIIa, M=4 years post-treatment) rated their cognitive function on the Kohli scale, BCPT checklist, and Functional Assessment of Cancer Therapy cognitive scale (FACT-cog). RESULTS: In Study 1, PPI-users reported more severe concentration problems (p=0.039) but not memory problems (p=0.17) than non-users. In Study 2, PPI-users reported more severe concentration problems (p=0.022) than non-users, but not memory problems or symptoms on the BCPT (ps=0.11). Study 3’s PPI-users reported more severe memory problems (p=0.002), poorer overall cognitive function (p=0.006), lower quality of life related to cognitive problems (p=0.005), greater perceived cognitive impairment (p=0.013), and poorer cognitive abilities (p=0.046), but not more severe concentration problems (p=0.16), compared to non-users. CONCLUSIONS/IMPLICATIONS: PPI use may impair breast cancer survivors’ memory, concentration, and quality of life.

Background Breast cancer survivors are prone to weakened gut barriers, allowing bacteria to migrate into the blood stream. Gut permeability fuels inflammation, which, among survivors, can elevate risk for comorbid disease development, cancer recurrence, and a poor quality of life; however, survivors’ satisfying relationships can provide health benefits. This longitudinal study used a conceptual model addressing how intimate relationships is associated with health through changes in gut permeability and inflammation. Method Breast cancer survivors (n=139, stages 0–IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women who had an abnormal breast cancer test followed by a benign diagnosis completed visits within a comparable timeframe (noncancer patient controls; n=69). All women completed questionnaires assessing their relationship satisfaction and provided blood samples to assess two bacterial endotoxin biomarkers, lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP) and interleukin 6 (IL-6). Results Within-person multilevel mediation analyses showed that when a survivor’s relationship satisfaction was higher than usual, her own LBP and LBP/sCD14 were lower, which was associated with lower than her own average CRP and IL-6 (95% CIs [-0.0104, -0.0002]). IL-6 was also higher when older survivors, but not younger survivors, experienced higher than usual intestinal permeability (p=.001). These effects of satisfying relationships held after accounting for cancer-related and behavioral factors. Post-hoc analyses showed LBP, sCD14, and LBP/sCD14 were associated with CRP for the cancer survivors, but only LBP and LBP/sCD14 were linked to CRP among the noncancer control patients. Conclusion The gut environment is a new promising candidate for understanding a relationship’s long-term health impact, particularly among those with elevated health risks. Survivors may reap multiple physiological benefits from satisfying relationships.

BACKGROUND: Black breast cancer survivors have greater morbidity and mortality than White survivors. However, evidence comparing Black survivors’ psychological symptoms with their White counterparts has been mixed. Prior studies have not compared Black and White survivor’s distress-related symptom trajectories from pre- to post-treatment – the goal of the current study. METHODS: At three annual visits from shortly after diagnosis to 6 and 18 months post-treatment, 195 women (n=163 White; n=32 Black) reported their cancer-related distress (intrusive thoughts and avoidance), perceived stress, anxiety and depressive symptoms, fatigue, and pain. RESULTS: Adjusting for age, educational attainment, income, treatment type, stage at diagnosis, and physical comorbidities, Black and White breast cancer survivors had different trajectories of cancer-related distress (p=.004), intrusive thoughts about cancer diagnosis and treatment (p=.002), perceived stress (p=.04), emotional fatigue (p=.01), and vigor (p=.02). Specifically, among White women, these distress-related symptoms improved from diagnosis to 6 months post-treatment (ps.09). CONCLUSION: Longitudinal assessment of the same breast cancer survivors from diagnosis to early survivorship revealed that Black and White survivors had divergent trajectories of psychological distress symptoms that were not reliably evident at a single timepoint. Overall, White women reported less psychological distress from pre- to post-treatment, but Black women’s distress remained high from diagnosis to 18 months post-treatment. If left untreated, Black women’s high distress levels may contribute to their poorer health throughout survivorship.

Even healthy older adults experience gastrointestinal (GI) and neurological changes. In fact, the aging process of these two systems are interrelated due the extensive, multifaceted communication network connecting them, termed the gut-brain axis. Age-related modification of the GI environment can influence the bacterial species that survive and thrive there. Additionally, the lifestyle common to older adults in the West, including sedentariness, polypharmacy, and a poor diet, can compound the effect of aging on the GI tract, gut microbiota, and nervous system. Emerging animal and human findings suggest that GI organisms play a major role in gut-brain communication, ultimately shaping neurological aging trajectories by either helping to maintain nervous system function into late life or promoting pathology. Aging and age-related behaviors help to define the gut microbiota's composition and function, but, conversely, the gut microbiota may help to determine late-life functionality and may be harnessed to limit the prevalence of steep neurological decline and diseases. Focusing primarily on clinical research, this review first defines the gut-brain axis, then details age-related GI and nervous system changes, and discusses the impact of age-related lifestyle factors on the GI and nervous systems. The remainder of this review describes cutting-edge research that positions the gut microbiota as an arbiter of age-related neurological decline.

Leptin influences inflammation and tumor growth and leptin signaling is often dysregulated among obese breast cancer survivors. This leads to a lack of satiety and, ultimately, risk for further weight gain. Breast cancer survivors also experience high rates of depression and anxiety, which are linked to leptin production. This study examined how a woman's anxiety and depressive symptoms, in combination with their obesity status, were associated with leptin.Breast cancer survivors (n = 200, stages 0-IIIa) completed a baseline visit before treatment and two follow-up visits, 6 and 18 months after treatment ended. Women completed anxiety and depression measures, and blood samples provided leptin data at each visit. This study related fluctuations in a survivor's own depression and anxiety (i.e., within-person effects), as well as average effects of depression and anxiety (i.e., between-person effects) to changes in leptin depending on BMI.Obese survivors' leptin was significantly higher at visits when they had higher anxiety and depression symptoms than their own average level of symptoms. In contrast, within-person fluctuations in depression and anxiety were not related to leptin levels among non-obese survivors. No significant between-person effects of depression or anxiety on leptin emerged.Leptin is a critical risk factor for recurrence and further health consequences. Our findings highlight how psychological health influences leptin production among breast cancer survivors.These results highlight a biological pathway that may facilitate further weight gain and health risks among distressed, obese breast cancer survivors.

Background The Center for Disease Control (CDC) recently named childhood abuse histories as a public health risk. Clear links between abuse histories and inflammation exist. However, it remains unknown how abuse histories impact inflammatory trajectories throughout adulthood. Accordingly, this study assessed inflammatory trajectories across three visits among healthy adults with and without abuse histories. Method In this secondary analysis of data from a longitudinal observational study of cancer survivors and noncancer controls, 157 noncancer controls (Mage = 55.8, range = 32–83) completed the Childhood Experiences Questionnaire (CTQ), providing data on physical, emotional, and sexual abuse prior to age 18. Cytokines interleukin-6 (IL-6), interleukin 1-beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were collected at the baseline visit and two follow-up visits approximately one (M months = 11.52, SD = 4.10) and two years (M months = 23.79, SD = 4.40) later. To represent inflammatory changes, cytokine data at each visit were combined into a composite z-score. Covariates in all analyses included age, biological sex, race, income, body mass index, menopause status, psychological diagnosis history, and medical comorbidities. Results Compared to their nonabused peers, those who had experienced any type of abuse in childhood demonstrated steeper rises in inflammation across time. Inflammation rose more steeply for individuals with physical and emotional abuse histories compared to those without such histories. Conclusion Overall, these data suggest that childhood abuse histories may quicken age-related increases in inflammation, contributing to accelerated aging, morbidity, and early mortality. These findings provide mechanistic insight into why child abuse is a public health risk.

Background Among breast cancer survivors, elevated inflammation has been linked to greater recurrence risk. Psychological processes, such as cancer-related distress, can pose threats to a survivor’s longevity and wellbeing. Although distress can heighten inflammation, little is known about how fluctuations in distress during and after treatment impact a woman’s own inflammation – the primary question of this study. Methods Breast cancer survivors (n = 165, stages 0-III) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after. At each visit, women completed the Impact of Events Scale to assess cancer-related distress, and a blood sample was collected to measure proinflammatory cytokines IL-6, TNF-α, IL-1β, and IL-8. This longitudinal study related fluctuations in survivor’s own cancer-related distress (i.e., within-person effects), as well as average effects of cancer-related distress between survivors (i.e., between-person effects) to inflammatory changes across visits. Results Women had elevated inflammation at visits where they expressed more cancer-related distress than what was typical. In contrast, the average cancer-related distress was not associated with inflammation. Conclusion Larger increases in a women’s cancer-related distress was linked with higher inflammation across visits. Comparing a survivor’s own cancer-related distress to her average levels may prove useful in identifying links between distress and inflammation.

Background Perceived stress can lead to dysregulated cortisol patterns, including blunted peaks and flatter slopes, which are associated with increased morbidity and mortality risks. Couples’ interdependence provides a prime opportunity for partners’ stress to disrupt a healthy cortisol pattern. This study examined how individuals’ own perceived stress and their partners’ perceived stress shape cortisol levels and slopes across the day, as well as how positive and negative behaviors during conflict discussions impact associations between stress and cortisol. Methods Both partners of a married couple (n = 43 couples, 86 individuals) completed a full day in-person visit. Each partner completed the Perceived Stress Scale, and all couples engaged in a 20-min marital problem discussion which was recorded and later coded for positive and negative behaviors using the Rapid Marital Interaction Coding System (RMICS). Partners also provided five salivary cortisol samples across the day, two samples before the conflict and three after the conflict. The dyadic design and analyses provided a way to account for the interdependent nature of married couples’ data, as well as to use the Actor-Partner Interdependence Model (APIM) to assess the mutual influence of spouses’ stress on cortisol. Results Individuals with more stressed partners had flatter cortisol slopes than individuals with less stressed partners, who showed steeper and thus healthier declines across the day. Individuals’ cortisol levels at the beginning of the day were similar regardless of their partners’ perceived stress, but individuals with more stressed partners had higher cortisol levels 30-min, 1 hr, and 4 hr after the conflict discussion than those with less stressed partners. Couples’ behavior during the conflict moderated the relationship between partner perceived stress and average cortisol; when couples used more negative and less positive behaviors, individuals with more stressed partners had higher average cortisol levels than those with less stressed partners. Conclusion On a day couples experienced conflict, having a partner with higher perceived stress is associated with dysregulated cortisol patterns, including higher levels and flatter slopes, but having a partner with lower perceived stress is linked to steeper and thus healthier cortisol declines. A partner’s stress was particularly consequential for one’s own cortisol when couples used more negative and fewer positive behaviors during a conflict discussion. This research adds to the growing literature on pathways connecting marital interactions to important biorhythms and health.

PURPOSE: A number of studies have shown that self-rated health reliably predicts mortality. This study assessed the impact of perseveration on self-rated health, physical functioning, and physical symptoms (pain, fatigue, breast cancer symptoms) among breast cancer patients. We hypothesized that cancer-related distress would serve as an intervening variable between both worry and rumination and self-rated health, physical functioning, and physical symptoms. METHODS: Women (N=124) who were approximately seven weeks post-surgery but pre adjuvant treatment completed the Impact of Events Scale, the Penn State Worry Questionnaire, and the Rumination Scale. They also rated their pain, fatigue, physical functioning, and self-rated health using the RAND-36 and breast cancer symptoms with the Breast Cancer Prevention Trial Symptom Checklist (BCPT). Covariates included body mass index, age, cancer stage, menopause status, and physical comorbidities. RESULTS: Worry was associated with higher cancer-related distress, which in turn predicted greater pain and breast cancer symptoms, poorer physical functioning, and lower self-rated health. Rumination also predicted greater cancer-related distress, which ultimately contributed to greater pain along with poorer physical functioning and self-rated health. Models with fatigue as an outcome were not significant. CONCLUSIONS: These findings suggest that perseveration can heighten cancer-related distress and subsequent perceptions of physical symptoms and health among breast cancer patients prior to adjuvant treatment. Perseveration early in the cancer trajectory can adversely increase the impact of a cancer diagnosis and treatment on functioning and quality of life.

BACKGROUND: Saturated-fat intake and endotoxemia can impair cognition. However, their acute impact on cognitive performance is unknown. OBJECTIVE: This study assessed the impact of 2 high-fat meals and endotoxemia on attention. METHODS: In this double-blind, randomized crossover trial, 51 women (n = 32 breast cancer survivors, n = 19 noncancer controls; mean ± SD age: 53 ± 8 y) completed the Continuous Performance Test (CPT) and had their blood drawn to assess endotoxemia markers LPS binding protein (LBP), soluble CD14 (sCD14), and the LBP to sCD14 ratio 1 h prior to eating either a high-saturated-fat meal or a high-oleic-sunflower-oil meal. Women again completed the CPT 5 h postmeal. At 1 to 4 wk later, women completed the same protocol but consumed the other meal. RESULTS: In adjusted models, women had more difficulty distinguishing target stimuli from distractors after consuming the high-saturated-fat meal than they did after the oleic-sunflower-oil meal (B = 4.44, SE = 1.88, P = 0.02). Women with higher baseline LBP had less consistent response times (B = 0.002, SE = 0.0008, P = 0.04). Those with higher LBP and LBP:sCD14 were less able to sustain their attention throughout the entire CPT, as reflected by their progressively slower (B = 0.002, SE = 0.0006, P = 0.003; and B = 2.43, SE = 0.090, P = 0.008, respectively) and more erratic (B = 0.003, SE = 0.0008, P

Objective Cross-sectional data have linked gut barrier abnormalities and endotoxemia with depression, even among those without gastrointestinal symptoms. This study examined longitudinal associations between endotoxemia markers and depressive symptoms, as well as the role of inflammation in this relationship. Design At three annual visits, 315 women (n=209 breast cancer survivors, n = 106 non-cancer patient controls, M=55 years old) completed the Center for Epidemiological Studies Depression questionnaire (CES-D) and provided blood samples to assess inflammatory markers – interleukin-6, tumor necrosis factor-alpha, and C-reactive protein – and endotoxemia markers – lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and their ratio. Results Adjusting for key demographic variables, health behaviors, visit 1 depressive symptoms, and cancer status and treatment, women with higher visit 1 LBP and LBP/sCD14 had more depressive symptoms at the two subsequent annual visits. Illustrating the notable impact, a woman at the 75th percentile for LBP or LBP/sCD14 at visit 1 was 18 % more likely to report clinically significant depressive symptoms (CES-D ≥16) at follow-up than a woman in the lowest quartile. Cancer status and treatment type did not modulate this relationship. In contrast, visit 1 depressive symptoms did not predict endotoxemia at follow-up. A significant interaction between LBP/sCD14 and inflammatory burden suggested that visit 1 endotoxemia fueled depressive symptoms only in the context of elevated inflammation. Conclusion These results suggest that endotoxemia, combined with systemic inflammation, can drive depressive symptoms. These findings may implicate bacterial endotoxin translocation from the gut to the bloodstream in depression etiology. Interventions that reduce endotoxemia and inflammation may lessen the risk of depression.

Background Breast cancer survivors with elevated inflammation have a greater risk for cancer recurrence, premature mortality, and comorbid disease development. The psychological stress survivors experience when confronted with a breast cancer diagnosis and cancer treatment can heighten inflammation. Identifying factors that reduce stress and inflammation could lead to improvements in survivors’ long-term health. Accordingly, this study examined the health-enhancing effects of romantic relationships—a key health determinant—on breast cancer survivors’ stress and inflammation. Methods Breast cancer survivors (n = 139, stages 0–IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed self-report questionnaires assessing their romantic relationship satisfaction and perceived stress, and they provided a blood sample for serum markers of inflammation at each visit. The longitudinal design allowed for examination within and between survivors. We conducted multilevel mediation analyses to assess how changes in survivors’ relationship satisfaction were related to changes in stress and inflammation from visit to visit (i.e., within-person effects), as well as how the average effects of relationship satisfaction were associated with average stress and inflammation levels throughout the study (i.e., between-person effects). Results At the within-person level, at visits in which survivors were more satisfied with their relationships, they also perceived less stress, which in turn was related to lower than their own average levels of serum C-reactive protein and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β). At the between-person level, survivors who had greater relationship satisfaction throughout the study had lower perceived stress, which was linked to lower levels of inflammation. Conclusion Breast cancer survivors in satisfying romantic relationships felt less stressed and in turn had lower inflammation throughout cancer treatment. This study illustrates the utility of a within-person approach to not only consider the average effects of relationship satisfaction, but also how changes in their own relationship satisfaction impact stress and inflammation over time. Our findings demonstrate important psychological and immunological pathways through which satisfying relationships may promote breast cancer survivors’ long-term health.