Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis.

Adrenergic stimulation adversely affects tumor growth and metastasis, but the underlying mechanisms are not well understood. Here, we uncovered a novel mechanism by which catecholamines induce inflammation by increasing prostaglandin E2 (PGE2) levels in ovarian cancer cells. Metabolic changes in tumors isolated from patients with depression and mice subjected to restraint stress showed elevated PGE2 levels. Increased metabolites, PTGS2 and PTGES protein levels were found in Skov3-ip1 and HeyA8 cells treated with norepinephrine (NE), and these changes were shown to be mediated by ADRB2 receptor signaling. Silencing PTGS2 resulted in significantly decreased migration and invasion in ovarian cancer cells in the presence of NE and decreased tumor burden and metastasis in restraint stress orthotopic models. In human ovarian cancer samples, concurrent increased ADRB2, PTGS2 and PTGES expression was associated with reduced overall and progression-free patient survival. In conclusion, increased adrenergic stimulation results in increased PGE2 synthesis via ADRB2-Nf-kB-PTGS2 axis, which drives tumor growth and metastasis.

Adjusting to life after treatment: distress and quality of life following treatment for breast cancer.

Clinical and anecdotal findings suggest that the completion of cancer treatment may be marked by heightened distress and disrupted adjustment. The present study examined psychological adjustment during the 3 months following treatment among 89 women with stages 0-III breast cancer. Participants completed measures of depression, cancer-related anxiety, cancer concerns, and quality of life at three time points: during treatment, 3 weeks following the end of treatment, and 3 months post-treatment. Post-treatment scores were suggestive of good psychological adjustment among the majority of women. Moreover, distress did not increase following treatment; longitudinal analyses showed no significant changes in depression or recurrence worry, while intrusive thoughts decreased, and quality of life improved. Younger age predicted greater distress across measures. A history of depression or anxiety predicted greater depressive symptomatology, while more extensive treatment predicted greater cancer-related anxiety. Despite the lack of distress endorsed on general depression and anxiety indices, participants reported moderate distress associated with cancer-related concerns, including physical problems, fear of cancer recurrence, and resuming normal life. In sum, while breast cancer survivors demonstrate good adjustment on general distress indices following treatment, some women are at risk for sustained distress. Moreover, significant cancer-related concerns are prevalent and may be important intervention targets.

Illness episodes and cortisol in healthy older adults during a life transition.

Alterations in neuroendocrine functioning and in the neuroendocrine response to stress have been observed in older adults. Stressful life events have also been associated with increased illness vulnerability. However effects of natural life stressors on neuroendocrine functioning and health of the elderly have not been well characterized. This research examines relationships among cortisol, dehydroepiandrosterone sulfate (DHEA-S), distress, and illness episodes in an elderly population experiencing the life transition of housing relocation. Thirty older adults moving to congregate livingfacilities were assessed in their homes 1 month premove and 2 weeks postmove. Twenty-eight nonmoving comparison participants were assessed at similar time points. Assessments included measures of intrusion, cortisol, DHEA-S, and self-reported infectious illness episodes. Movers reported more illness episodes between the two assessments than controls. Significant alterations in neuroendocrine measures were not observed among movers at either time point. Individuals with more intrusive thoughts had higher cortisol levels concurrently and prospectively, but these relationships did not vary by group. Greater intrusion at premove was associated with a greater likelihood of reported illness episodes between the two assessments, but there were no relationships between neuroendocrine factors and illness episodes, and intrusion did not mediate the relationships between group and likelihood of illness. In healthy elders, a temporary life stressor may increase vulnerability to illness but does not

Sense of coherence buffers relationships of chronic stress with fasting glucose levels.

Sense of coherence (SOC) was examined as a buffer of the relationship of chronic stress with fasting glucose and insulin levels. Spouse caregivers of persons with diagnoses of Alzheimer's disease (AD) (n = 73) were compared to controls [spouses of nondemented persons (n = 69)], group-matched on age/gender. After controlling for anger and coronary heart disease (CHD), interactions of SOC and gender explained variance in glucose (but not insulin) at study entry (T1) and 15-18 months later (T2). However, this occurred only in caregivers. At both times SOC and glucose were negatively related in men caregivers but not in women caregivers or in controls. In caregivers (but not controls), SOC at T1 predicted glucose at T2, independent of gender, anger, and glucose at T1; and hassles at T1 appeared to mediate this relationship. Future research should examine SOC as a buffer of other chronic stressors and metabolic variables.

Stress and symptoms in patients with interstitial cystitis: a life stress model.

Objectives. Stress-related exacerbation of interstitial cystitis (IC) symptoms has frequently been reported. Previous research has found stress-related IC symptom exacerbation in an experimental model. However, this relationship has not been objectively examined with daily life stressors. We used a prospective daily symptom diary method to investigate the relationships among stress and bladder symptoms in patients with IC and age-matched healthy controls.Methods. Forty-five previously diagnosed female patients with IC completed a bladder symptom and stress diary nightly for 1 month; 31 female age-matched healthy controls completed a similar diary for 7 days. The symptom questions were modified from the Interstitial Cystitis Data Base study.Results. Patients reported greater mean daily stress, bladder pain, urgency, and daytime and nocturnal frequency than controls (all P values less than 0.001). Among all patients, a significant relationship between stress and urgency was observed. In addition, a significant relationship between stress and pain was observed among patients with moderate and severe disease. As the disease severity increased, more pronounced relationships between stress and the symptoms of urgency and pain were evidenced. Greater stress was associated with greater nocturnal frequency among patients with more severe disease. These stress-symptom relationships were not observed among the controls.Conclusions. Higher levels of stress were related to greater pain and urgency in patients with IC but not in the controls. In addition, the relationship of stress and these IC symptoms was stronger among patients with more severe disease. The results indicate that life stress is associated with greater IC symptoms, particularly among patients whose disease is not well controlled.

Effects of housing relocation on immunocompetence and psychosocial functioning in older adults.

BACKGROUND: The psychological and physical response to moderate life stressors among older adults has not been well characterized. This research examines effects of voluntary housing relocation on distress and immune function in healthy older adults as a model for studying the effects of moderate life stress. METHODS: Thirty older adults moving to congregate living facilities were assessed 1 month premove, 2 weeks postmove, and 3 months postmove. Twenty-eight nonmoving control subjects were assessed at similar time points. Subjects completed psychosocial questionnaires and had early morning blood draws in their homes. Blood samples were assayed for natural killer cell cytotoxicity (NKCC), interleukin-6 (IL-6), and IgG antibody titers to the Epstein Barr virus (EBV) viral capsid antigen. RESULTS: Movers demonstrated decreased vigor and elevated thought intrusion 1 month premove and 2 weeks postmove. By the 3-month follow-up, vigor increased, and intrusion decreased to levels commensurate with the controls. Averaged across all time points, movers showed lower NKCC than controls; however, post-hoc analyses indicate that by the 3-month follow-up time point, these differences were no longer significant. There were no differences between groups in IL-6 or in EBV antibody titers. Independent of the effects of group, higher levels of vigor were associated with greater NKCC at all assessments and with lower EBV titers at 2 weeks postmove. CONCLUSIONS: Findings suggest that in general, healthy older adults recover well psychologically from moderate. temporary life stressors such as moving. Whereas movers showed generally lower NKCC than controls, IL-6 and EBV antibody titers appeared not to be strongly affected by the stress of moving.

Contributions of imagery ability to stress and relaxation.

This study examined the contribution of imagery ability to psychological and physiological responses to stress and relaxation. Individuals (N = 176) participated in two study sessions. In the first session, participants completed the Creative Imagination Scale and were block-randomized to a stress or relaxation condition based on imaging scores. During the second session, stress and mood were assessed before and after participants watched a stressful movie or listened to a relaxation tape. Finger temperature was monitored during the interventions. Changes in temperature and in self-reports of stress and mood indicated that the manipulations were effective. In comparison to low imagers, high imagers reported greater stress after the movie and less stress and negative affect after the relaxation tape. Imagery ability predicted neither levels of negative affect following the stress condition nor changes in positive affect or temperature during the interventions. In the stress condition, expectations of stress partially mediated the relation between imagery ability andpsychological stress. In contrast, expectations of relaxation did not significantly predict responses to the relaxation intervention. These findings suggest that imagery ability is related to greater subjective responses to both stress and relaxation and that, in stressful situations, expectancies may account for some of the effects of imagery ability on perceived stress.

Rapid anxiety assessment in medical patients: evidence for the validity of verbal anxiety ratings.

Rapid assessment of patient anxiety is necessary to insure quality care. A number of self-report measures provide valid and reliable measures of anxiety. These measures can be time-consuming to complete, however, and may be burdensome to medical patients who are in pain or acute anxiety states. Many medical procedures are performed in conditions in which written measures are cumbersome (e.g. patient in supine position), and scoring and interpretation of written measures in a busy clinical setting may be difficult for medical personnel. The present study provides validity data for a verbally administered (0-10) anxiety rating. One hundred and ninety-eight adult interventional radiology patients completed standard measures assessing state anxiety, trait Negative and Positive Affect, and the dimensions of the five-factor model of personality. Verbal anxiety rating was highly correlated with Spielberger's State Anxiety Inventory, showed moderate correlations to the related constructs of neuroticism and trait Negative Affect, and was largely unrelated to theoretically distinct constructs. Verbal anxiety ratings made prior to the invasive procedure also predicted pain and anxiety during the procedure. The verbal anxiety rating also demonstrated sensitivity to changes in anxiety that occurred as a result of changes in situation. Findings support the convergent and discriminant validity of verbal anxiety ratings.

Quality of life and mood in women receiving extensive chemotherapy for gynecologic cancer.

BACKGROUND: Quality of life (QOL) and mood were investigated among women who had received intensive chemotherapy for at least 1 year for advanced gynecologic cancers. Relationships of coping styles to QOL and mood in these patients also were examined. METHODS: Twenty-four patients who had been receiving chemotherapy continuously or intermittently for at least 1 year were recruited into the study. To control for the diagnosis of cancer and for prior hysterectomy, 24 age-matched early stage gynecologic cancer patients not receiving chemotherapy and assessed 1 year following diagnosis were examined as a comparison group. All subjects completed psychosocial assessments at a clinic visit. Medical information was retrospectively abstracted from patient charts. RESULTS: Decrements in physical, emotional, and functional well-being were reported by extensively treated patients, whereas social well-being and satisfaction with the relationship between doctor and patient were close to the norms of the comparison group. Extensively treated patients reported more fatigue and less vigor, but their depression and anxiety did not differ from early stage patients. Almost all extensively treated patients reported that their treatment had been worthwhile. Patients using avoidant coping reported poorer physical and emotional well-being, along with greater anxiety, depression, fatigue, and total mood disturbance. Those using active coping reported better social well-being, better relationships with their doctors, and less overall distress. CONCLUSIONS: This study indicates that gynecologic oncology patients extensively treated with chemotherapy experienced substantial decrements to quality of life, and yet treatment still was considered worthwhile by a majority of patients. Avoidant coping may be a particular risk factor for poor QOL and greater distress.

Stress and symptomatology in patients with interstitial cystitis: a laboratory stress model.

PURPOSE: Although patients with interstitial cystitis frequently report symptom exacerbation due to stress, to our knowledge this association has not been empirically examined. We evaluated the effects of a laboratory mental stress challenge on symptoms of urgency and pain in patients with interstitial cystitis and healthy controls. MATERIALS AND METHODS: A total of 14 females with interstitial cystitis and 14 age matched controls participated in a laboratory session, including a 60-minute baseline measurement, 25 minutes of mental stress tasks and 75 minutes of recovery. Acute symptoms of pain and urgency were assessed at voiding 15 minutes before the stressor, and 25, 70 and 100 minutes after stressor onset. Chronic symptoms were evaluated by questions from the Interstitial Cystitis Data Base survey. RESULTS: Patients reported significantly greater pain and urgency than controls at all 4 voidings (p <0.005). Pain increased in patients from the prestressor point to 25 minutes after stressor onset (p <0.005), remained elevated at 70, and decreased between 70 and 100. At 100 minutes patient pain remained significantly elevated above baseline (p = 0.018). Patient urgency was significantly elevated over baseline by 70 minutes after stressor onset (p <0.001) and significantly decreased between 70 and 100 minutes (p <0.002). Controls had no symptom changes with stress. CONCLUSIONS: These findings indicate that an acute stressor evokes increased symptoms of pain and urgency in patients with interstitial cystitis but not in controls. Findings are consistent with sympathetic effects on inflammatory processes in interstitial cystitis. However, further evaluation of the mechanisms underlying stress related interstitial cystitis symptom exacerbation is needed to provide a more comprehensive understanding of these phenomena.

Perceived health competence and personality factors differentially predict health behaviors in older adults.

OBJECTIVES: Previous studies have shown relationships among personality, perceived efficacy, and proactive health behaviors. Although health behaviors are particularly important among seniors, little is known regarding predictors of health behaviors in older adults. The current study examined the extent to which facets of personality, perceived health competence (PHC), and health status predicted health behaviors among older adults. METHODS: Ninety-seven older adults responded to questionnaires assessing health status, personality, PHC, and level of engagement in certain health behaviors. RESULTS: Whereas higher levels of Conscientiousness and lower levels of Neuroticism predicted a greater likelihood of engaging in social support/relaxation behaviors, after controlling for health status and education, higher levels of PHC predicted greater exercise and dietary/health information-seeking behaviors. DISCUSSION: These findings suggest the importance of considering facets of personality and PHC when evaluating health care strategies for the elderly.

Life stress, mood disturbance, and elevated interleukin-6 in healthy older women.

BACKGROUND: Although adverse effects of severe chronic stress on immunocompetence and physical well-being in older adults have been reported, the immune response to less severe life stress among healthy older adults, particularly among women, is not well understood. Interleukin-6 (IL-6) has been considered a good overall indicator of immune functioning in older adults because of its contribution to the pathogenesis of several age-related conditions such as osteoporosis. Regulation of IL-6 is impaired in elderly adults, and levels of IL-6 increase with stress and depression. This research cross-sectionally examined levels of IL-6 in three groups of healthy older women with varying levels of life stress and mood disturbance and a healthy group of young women. METHODS: Subjects included 18 caregivers of Alzheimer's patients, 17 older women assessed one month before relocation of their residence, 15 nonmoving and noncaregiving older women, and 20 younger women. Subjects completed the Profile of Mood States (POMS) and had early morning blood draws. RESULTS: Alzheimer's caregivers reported significantly greater distress than women of all other groups. IL-6 levels in caregivers were significantly higher than those of all other women. The older women had significantly higher IL-6 than young controls, but there were no significant differences in IL-6 between movers and older controls. Among all women, greater depression and distress were related to higher levels of IL-6. CONCLUSIONS: These findings suggest that in older women, chronic stressors are associated with significant elevations in IL-6 over and above the elevations associated with normal aging, but that moderate stressors may not be related to appreciable elevations in IL-6.

Sense of coherence moderates the relationship between life stress and natural killer cell activity in healthy older adults.

A sense of coherence (SOC) has been found to be a strong predictor of health outcomes and life satisfaction in older adults. This study investigated mood and immune effects of anticipated voluntary housing relocation in 30 healthy older adults and 28 age-matched controls and examined whether SOC would buffer effects of relocation on natural killer (NK) cell activity. Movers completed assessments and had blood drawn 1 month before relocation to congregate living facilities; controls were assessed concurrently. Compared with the control group, movers showed decreased positive mood and NK activity and elevated thought intrusion. Positive mood mediated the relationship of moving with NK activity, whereas SOC moderated this relationship. Low SOC movers had the poorest NK activity; that of high SOC movers was less compromised. These findings are consistent with possible salutogenic contributions of SOC and positive mood to immune function in older adults facing stressful life transitions.

Changes in cognitive coping skills and social support during cognitive behavioral stress management intervention and distress outcomes in symptomatic human immunodeficiency virus (HIV)-seropositive gay men.

OBJECTIVE: We have previously reported decreases in dysphoria, anxiety, and total mood disturbance in symptomatic HIV seropositive gay men after a 10-week cognitive behavioral stress management (CBSM) group intervention. This structured intervention was designed a) to increase cognitive and behavioral coping skills related to managing the distress of symptomatic HIV, and b) to increase social support among group members. Here we examine the relative contribution of changes in coping skills and social support during the intervention period to reductions in dysphoria, anxiety, and distress-related symptoms in this sample. METHODS: Participants were randomized to a 10-week CBSM group intervention or to a wait-list control condition. Coping, social supports, and mood were measured before and after the intervention period. RESULTS: Members of the CBSM group (N = 22) showed significant improvement in cognitive coping strategies involving positive reframing and acceptance, and in social supports involving attachment, alliances, and guidance at the end of the 10-week CBSM program compared with controls (N = 18) who showed decrements in these coping abilities and no changes in social support. Improved cognitive coping, specifically acceptance of the HIV infection, was strongly related to lower dysphoria, anxiety, and total mood disturbance in both conditions. Changes in social support and in cognitive coping skills seem to mediate the effects of the experimental condition on the changes in distress noted during the intervention. CONCLUSIONS: These results suggest that cognitive coping and social support factors can be modified by psychosocial interventions and may be important determinants of the changes in psychological well-being and quality of life during symptomatic HIV infection that can be achieved through this form of intervention.

Cognitive-behavioral stress management decreases dysphoric mood and herpes simplex virus-type 2 antibody titers in symptomatic HIV-seropositive gay men.

This study tested the effects of a 10-week group cognitive-behavioral stress management (CBSM) intervention on mood and immunologic parameters in HIV-seropositive gay men whose disease had progressed to a symptomatic stage. Men were randomized to either CBSM or a modified waiting-list control group. The CBSM intervention significantly decreased self-reported dysphoria, anxiety, and total distress. Individuals who practiced relaxation more consistently had significantly greater drops in dysphoria. The intervention also decreased herpes simplex virus-Type 2 (HSV-2) immunoglobulin G antibody titers. The control group showed no significant changes in either mood or antibody titers. Individual difference analyses revealed that decreases in dysphoria significantly predicted lower HSV-2 antibody titers by the end of the 10-week period. Neither group displayed changes in HSV-Type 1 antibody titers or in CD4+ or CD8+ cell numbers.

Physical symptoms of chronic fatigue syndrome are exacerbated by the stress of Hurricane Andrew.

This study examined the effects of Hurricane Andrew on physical symptoms and functional impairments in a sample of chronic fatigue syndrome (CFS) patients residing in South Florida. In the months after Hurricane Andrew (September 15-December 31, 1992), 49 CFS patients were assessed for psychosocial and physical functioning with questionnaires, interviews, and physical examinations. This sample was made up of 25 CFS patients living in Dade county, a high impact area, and 24 patients in Broward and Palm Beach counties, areas less affected by the hurricane. Based on our model for stress-related effects on CFS, we tested the hypothesis that the patients who had the greatest exposure to this natural disaster would show the greatest exacerbation in CFS symptoms and related impairments in activities of daily living (illness burden). In support of this hypothesis, we found that the Dade county patients showed significant increases in physician-rated clinical relapses and exacerbations in frequency of several categories of self-reported CFS physical symptoms as compared to the Broward/Palm Beach county patients. Illness burden, as measured on the Sickness Impact Profile, also showed a significant increase in the Dade county patients. Although extent of disruption due to the storm was a significant factor in predicting relapse, the patient's posthurricane distress response was the single strongest predictor of the likelihood and severity of relapse and functional impairment. Additionally, optimism and social support were significantly associated with lower illness burden after the hurricane, above and beyond storm-related disruption and distress responses. These findings provide information on the impact of environmental stressors and psychosocial factors in the exacerbation of CFS symptoms.

Changes in cognitive coping strategies predict EBV-antibody titre change following a stressor disclosure induction.

Previous research has shown that emotional disclosure of traumatic or stressful events is associated with facilitating insight into the experience, improving mood, and modulating some aspects of the immune system. The current study examined how cognitive changes and experiential involvement during an emotional disclosure induction protocol relate to immune functioning, as measured by IgG antibody titres to the Epstein-Barr virus viral capsid antigen (EBV-VCA). Seventy-six college undergraduates were randomly assigned to either a disclosure induction or an assessment-only control condition. Experimental subjects met with an experimenter for three weekly 20-min individual sessions during which time they were asked to discuss a stressful or traumatic topic which they had previously discussed only minimally with others. Blood was drawn a week prior to the first session and at one week following the third session. Subjects completed the Impact of Event Scale (IES) after session 1 and at followup, and the extent of experiential involvement in disclosure during each session was assessed by means of the Experiencing Scale. Mood was assessed before and after each disclosure using the Nowlis Mood Adjective Checklist. Although the disclosure induction did not directly affect EBV-VCA antibody titres, individual differences in subjects' ability to involve themselves in the disclosure process and abandon their avoidance of the stressful tropic during the course of the 3-wk period were predictive of antibody decrements. These associations were more pronounced for individuals who disclosed older and more troublesome events.