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Purpose The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group. Methods Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1β). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group). Results There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group. Conclusion Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.

Distressed marriages enhance risk for health problems; appetite dysregulation is one potential mechanistic pathway. Research suggests that ghrelin and leptin, appetite-relevant hormones connected to shorter and longer-term energy balance, may differentially affect people with a higher versus lower body mass index (BMI). During this double-blind randomized crossover study, both members of a couple ( N =86 participants) ate a standardized meal at the beginning of two visits. Observational recordings of a marital conflict assessed marital distress. Ghrelin and leptin were sampled pre-meal and post-meal at 2, 4, and 7 hours. Diet quality was measured using the USDA 24-Hour Multiple-Pass Approach. People in more distressed marriages had higher post-meal ghrelin (but not leptin) and a poorer quality diet than those in less distressed marriages, but only among participants with a lower BMI. These effects were consistent for both spouses. Ghrelin and diet quality may link marital distress to its corresponding negative health effects.

Objective: A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis., Methods: The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities., Results: Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users., Conclusions: Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress., (Copyright © 2012 John Wiley & Sons, Ltd.)

Stress and depression consistently elevate inflammation and are often experienced simultaneously, which is exemplified by people in troubled relationships. Troubled relationships also elevate inflammation, which may be partially explained by their ability to engender high levels of stress and depression. People who are stressed, depressed, or in troubled relationships are also at greater risk for health problems than their less distressed counterparts. Inflammation, a risk factor for a variety of age-related diseases including cardiovascular disease, Type II diabetes, metabolic syndrome, and frailty, may be one key mechanistic pathway linking distress to poor health. Obesity may further broaden the health implications of stress and depression; people who are stressed or depressed are often overweight, and adipose tissue is a major source of proinflammatory cytokines. Stress, depression, and troubled relationships may have synergistic inflammatory effects: loneliness, subclinical depression, and major depression enhance inflammatory responses to an acute stressful event. The relationship between distress and inflammation is bidirectional; depression enhances inflammation and inflammation promotes depression. Interesting questions emerge from this literature. For instance, some stressors may be more potent than others and thus may be more strongly linked to inflammation. In addition, it is possible that psychological and interpersonal resources may buffer the negative inflammatory effects of stress. Understanding the links among stress, depression, troubled relationships, and inflammation is an exciting area of research that may provide mechanistic insight into the links between distress and poor health., (© 2013 Wiley Periodicals, Inc.)

Purpose: To identify how child maltreatment is associated with quality of life (QOL) among breast cancer survivors., Patients and Methods: One hundred and thirty two women who had completed treatment for stage 0-IIIA breast cancer within the past 2 years (except for tamoxifen/aromatase inhibitors) and were at least 2 months post surgery, radiation, or chemotherapy completed questionnaires including the Childhood Trauma Questionnaire, the Impact of Events Scale, the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and the Fact-B breast cancer quality of life questionnaire., Results: Women who were abused or neglected as children reported more cancer-related psychological distress, more fatigue and poorer physical, emotional, functional and breast cancer-specific well-being after treatment. These relations were partially explained by the fact that breast cancer survivors reported receiving less support as adults., Conclusion: The findings suggest that child maltreatment is an important predictor of QOL among breast cancer survivors. One reason why this association exists is because those who are maltreated as children report less support as adults. A better understanding of how child maltreatment contributes to breast cancer survivor QOL will help in tailoring and, therefore, enhancing the efficacy of interventions aimed at improving QOL., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This study examined unique versus shared stress and pain-related phenotypes associated with premenstrual dysphoric disorder (PMDD) and prior major depressive disorder (MDD). Sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA)-axis measures were assessed at rest and during mental stress, as well as sensitivity to cold pressor and tourniquet ischemic pain tasks in four groups of women: (1) non-PMDD with no prior MDD (N=18); (2) non-PMDD with prior MDD (N=9); (3) PMDD with no prior MDD (N=17); (4) PMDD with prior MDD (N=10). PMDD women showed blunted SNS responses to stress compared to non-PMDD women, irrespective of prior MDD; while women with prior MDD showed exaggerated diastolic blood pressure responses to stress versus never depressed women, irrespective of PMDD. However, only in women with histories of MDD did PMDD women have lower cortisol concentrations than non-PMDD women, and only in non-PMDD women was MDD associated with reduced cold pressor pain sensitivity. These results suggest both unique phenotypic differences between women with PMDD and those with a history of MDD, but also indicate that histories of MDD may have special relevance for PMDD., (Copyright 2010 Elsevier B.V. All rights reserved.)

Cell barriers are essential for the maintenance and regulation of the microenvironments of the human body. Cell-penetrating peptides have simplified the delivery of bioactive cargoes across the plasma membrane. Here, the passage of three cell-penetrating peptides (transportan, the transportan analogue transportan 10, and penetratin) across a Caco-2 human colon cancer cell layer in vitro was investigated. The peptides were internalized into epithelial Caco-2 cells as visualized by indirect fluorescence microscopy and quantified by fluorimetry. Studies of peptide outflow from cells showed that the peptides were in equilibrium across the plasma membrane. The ability of the peptides to cross a Caco-2 cell layer was tested in a two-chambered model system. After 120 min, 7.0%, 2.8% and 0.6% of added transportan, transportan 10 and penetratin respectively was detected in the lower chamber. Both transportan and transportan 10 reversibly decreased the trans-epithelial electrical resistance of the barrier model, with minimum values after 60 min of 46% and 60% of control respectively. Penetratin did not affect the resistance of the cell layer to the same extent. Although transportan markedly increased the passage of ions, the paracellular flux of 4.4 kDa fluorescein-labelled dextran was limited. In conclusion, the results indicate that the transportan peptides pass the epithelial cell layer mainly by a mechanism involving a transcellular pathway.