Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors Versus Noncancer Controls: Evidence for Accelerated Aging?

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-1ß). 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.

"Struggle to obtain redress": Women's experiences of living with symptoms attributed to dental restorative materials and/or electromagnetic fields.

The aim of this study was to explore the experiences of illness and the encounters with health care professionals among women who attributed their symptoms and illness to either dental restorative materials and/or electromagnetic fields, despite the fact that research on health effects from dental fillings or electricity has failed to substantiate the reported symptoms. Thirteen women (aged 37-63 years) were invited to the study and a qualitative approach was chosen as the study design, and data were collected using semi-structured interviews. The analysis was conducted with a constant comparative method, according to Grounded Theory. The analysis of the results can be described with the core category, "Struggle to obtain redress," the two categories, "Stricken with illness" and "A blot in the protocol," and five subcategories. The core category represents the women's fight for approval and arose in the conflict between their experience of developing a severe illness and the doctors' or dentists' rejection of the symptoms as a disease, which made the women feel like malingerers. The informants experienced better support and confirmation from alternative medicine practitioners. However, sick-leave certificates from alternative medicine practitioners were not approved and this led to a continuous cycle of visits in the health care system. To avoid conflicting encounters, it is important for caregivers to listen to the patient's explanatory models and experience of illness, even if a medical answer cannot be given.

Novel Links between Troubled Marriages and Appetite Regulation: Marital Distress, Ghrelin, and Diet Quality.

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.

Synergistic relationships among stress, depression, and troubled relationships: insights from psychoneuroimmunology.

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.

Beta-blockers may reduce intrusive thoughts in newly diagnosed cancer patients.

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.

A history of depression in women is associated with an altered GABAergic neuroactive steroid profile.

The 3α,5α- and 3α,5ß-reduced metabolites of progesterone, deoxycorticosterone, and dehydroepiandrosterone (DHEA) have potent effects on neurotransmission mediated by GABA(A) receptors, and dysregulation of these receptors has been implicated in depression. Using gas chromatography-mass spectrometry, we compared neuroactive steroid concentrations in women with a history of depressive disorders, but who were in full remission at the time of testing (n=11) to never depressed women (n=17) both before and after a challenge with oral micronized progesterone (300 mg). Serum concentrations of the following were obtained: four progesterone-derived GABAergic neuroactive steroids, the precursor pregnenolone, androstenedione-derived neuroactive steroids, and the precursor DHEA. As an index of conversion of progesterone to neuroactive steroids, we also examined ratios of neuroactive steroids to progesterone following the oral progesterone challenge. Results indicated that both before and after oral progesterone, women with histories of depression showed lower concentrations of all GABAergic neuroactive steroids than never depressed women. Those with a history of depression also had lower cortisol concentrations. Because serum neuroactive steroids are mainly synthesized in the adrenals, we hypothesize that histories of depression may be associated with persistent adrenal suppression. Following the progesterone challenge, ratios of the progesterone-derived neuroactive steroids to plasma progesterone concentrations were elevated in women with depression histories, suggesting there may be an adaptive shift in the metabolism of progesterone that compensates for lower circulating neuroactive steroid concentrations.

Child maltreatment and breast cancer survivors: social support makes a difference for quality of life, fatigue and cancer stress.

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.

Histories of major depression and premenstrual dysphoric disorder: Evidence for phenotypic differences.

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.