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

Pain and immunologic response to root canal treatment and subsequent health outcomes.

OBJECTIVE: This study examined the effects of pain and stress associated with a dental procedure, root canal treatment (RCT), on natural killer cell cytotoxicity (NKCC) and the subsequent development of symptoms of upper respiratory illness during the following month. METHODS: Patients (N = 33) were recruited from those scheduled for RCT appointments. Subjects for a non-RCT comparison group (N = 14) were also recruited from dental clinic patients. Peripheral blood was drawn by use of an indwelling catheter three times: just before RCT, 30 minutes after injection of a local anesthetic, and 30 minutes after RCT (a parallel time course was followed for the comparison group.) Blood was assayed for cortisol and NKCC. Subjects completed a health diary in the month after RCT. RESULTS: Patients showed a significant increase in NKCC between baseline and RCT and a significant decrease from RCT to after RCT, whereas the comparison group did not. The NKCC following the RCT was negatively correlated with the pain level during RCT (r = -0.48, p < .01) and pain levels 2 and 6 hours after RCT (r = -0.43, p < .05; r = -0.44 p < .05, respectively). The patient group reported significantly more illness episodes 2 weeks after RCT than the comparison group (Wilcoxon rank sum = 4.78, p = .03). Discriminant function analysis correctly classified 88% of the subjects into the illness category using predictor variables of post-RCT NKCC, stress, and pain levels during RCT (F(3,21) = 8.23, p < .001). CONCLUSIONS: Transitory changes in NKCC associated with pain and stress may be implicated in the development of infectious disease episodes after an acute stressful event.

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.

Effects of stress and relaxation on capsaicin-induced pain.

A sizable body of research has been devoted to understanding the relationship between pain sensitivity and the psychological state of the individual. Considerable disagreement as to the direction of the association still exists. This study examines the effects of 2 experimental manipulations, cognitive/emotional stress and relaxation, on capsaicin-induced pain. Subjects were pretrained in relaxation and then randomized to experimental stress produced by a 20-minute Stroop test, relaxation (tape), or a control condition (neutral video), followed by a capsaicin injection in the forearm. Cardiovascular measures were taken at regular intervals, and cortisol, norepinephrine (NE), and self-reports of arousal (relaxation index) were taken immediately before and after the experimental task. The manipulation significantly interacted with sex to predict capsaicin-induced maximum pain. Women in the stress condition reported greater pain than both men in the stress condition and women in the relaxation condition. Pain was correlated negatively with task-induced changes in NE and cortisol and positively with self-reported arousal (decreased relaxation). However, separate analyses showed that some physiologic indexes of heightened arousal (increased blood pressure and NE) predicted lower pain only in men, whereas subjective increases in arousal predicted higher pain only in women. Multiple hierarchical regression analyses confirmed that physiologic and self-reported arousal predicted pain independently and in opposite directions, and a model including both accounted for 56% of the overall variance. These findings suggest that a unidimensional model of arousal may be insufficient to explain the effects of stress on pain and that these effects operate differently in men and women.

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.

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.

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.

Effects of relaxation and stress on the capsaicin-induced local inflammatory response.

OBJECTIVE: Although stress is known to modulate the inflammatory response, there has been little experimental examination of the effects of stress and stress reduction on inflammation in humans. In particular, the effects of stress and relaxation on neurogenic inflammation have been minimally studied. This study examines the effects of three experimental manipulations: mental stress, relaxation, and control on the local inflammatory response evoked by the intradermal injection of capsaicin, the active ingredient in chili peppers. METHODS: Fifty subjects (28 men and 22 women) were pretrained in relaxation using an imagery-based relaxation tape and then randomized to experimental condition. Subjects participated in an evening reactivity session including 20 minutes of a stress (Stroop test), relaxation (tape), or control (video) manipulation, followed by a capsaicin injection in the forearm. Digitized flare measurements were taken for 1 hour postcapsaicin, and measurements of cardiovascular variables, cortisol, adrenocorticotrophic hormone, and norepinephrine were taken at regular intervals. RESULTS: The size of the maximum capsaicin-induced flare was significantly smaller in the relaxation condition than in the stress or control conditions, which did not differ from each other. Increases in norepinephrine, heart rate, and systolic blood pressure during the experimental task, but not after capsaicin, significantly predicted size of maximum flare and total area under the curve of flare measurements. CONCLUSIONS: These findings suggest that stress reduction may affect local inflammatory processes. Results are consistent with sympathetic modulation of the effects of relaxation on the flare response.

Cognitive-behavioral stress management reduces distress and 24-hour urinary free cortisol output among symptomatic HIV-infected gay men.

BACKGROUND: Stress management interventions can reduce symptoms of distress as well as modulate certain immune system components in persons infected with human immunodeficiency virus (HIV). These effects may occur in parallel with reductions in hypothalamic-pituitary-adrenal (HPA) axis hormones such as cortisol, which has been related in other work to a down-regulation of immune system components relevant to HIV infection. The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on 24-hour urinary free cortisol levels and distressed mood in symptomatic HIV+ gay men. METHODS: Symptomatic HIV-infected gay men who were randomized to either a 10-week group-based CBSM intervention or a 10-week wait-list period provided psychological responses and urine samples pre-post intervention. RESULTS: Of the 59 participants providing matched questionnaire data, men assigned to CBSM (n = 40) showed significantly lower posttreatment levels of self-reported depressed affect, anxiety, anger, and confusion than those in the wait-list control group (n = 19). Among the 47 men providing urine samples (34 CBSM, 13 controls), those assigned to CBSM revealed significantly less cortisol output as compared to controls. At the individual level, depressed mood decreases paralleled cortisol reductions over this period across the entire sample. CONCLUSION: A time-limited CBSM intervention reduced distress symptoms and urinary free cortisol output in symptomatic HIV+ gay men and greater reductions in some aspects of distress, especially depressed mood, paralleled greater decreases in cortisol over the intervention period. If persisting stressors and depressed mood contribute to chronic HPA axis activation in HIV-infected persons, then interventions such as CBSM, which teaches them to relax, alter cognitive appraisals, use new coping strategies, and access social support resources, may decrease distress and depressed mood and normalize HPA axis functioning.

Adjunctive non-pharmacological analgesia for invasive medical procedures: a randomised trial.

BACKGROUND: Non-pharmacological behavioural adjuncts have been suggested as efficient safe means in reducing discomfort and adverse effects during medical procedures. We tested this assumption for patients undergoing percutaneous vascular and renal procedures in a prospective, randomised, single-centre study. METHODS: 241 patients were randomised to receive intraoperatively standard care (n=79), structured attention (n=80), or self-hypnotic relaxation (n=82). All had access to patient-controlled intravenous analgesia with fentanyl and midazolam. Patients rated their pain and anxiety on 0-10 scales before, every 15 min during and after the procedures. FINDINGS: Pain increased linearly with procedure time in the standard group (slope 0.09 in pain score/15 min, p<0.0001), and the attention group (slope 0.04/15 min; p=0.0425), but remained flat in the hypnosis group. Anxiety decreased over time in all three groups with slopes of -0.04 (standard), -0.07 (attention), and -0.11 (hypnosis). Drug use in the standard group (1.9 units) was significantly higher than in the attention and hypnosis groups (0.8 and 0.9 units, respectively). One hypnosis patient became haemodynamically unstable compared with ten attention patients (p=0.0041), and 12 standard patients (p=0.0009). Procedure times were significantly shorter in the hypnosis group (61 min) than in the standard group (78 min, p=0.0016) with procedure duration of the attention group in between (67 min). INTERPRETATION: Structured attention and self-hypnotic relaxation proved beneficial during invasive medical procedures. Hypnosis had more pronounced effects on pain and anxiety reduction, and is superior, in that it also improves haemodynamic stability.

Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and T-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men.

The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on anxious mood, perceived stress, 24-hr urinary catecholamine levels, and changes in T-lymphocyte subpopulations over time in symptomatic HIV+ gay men. Seventy-three men were randomized to either a group-based CBSM intervention (n = 47) or a wait-list control (WLC) condition (n = 26). Men assigned to CBSM showed significantly lower posttreatment levels of self-reported anxiety, anger, total mood disturbance, and perceived stress and less norepinephrine (NE) output as compared with men in the WLC group. At the individual level, anxiety decreases paralleled NE reductions. Significantly greater numbers of T-cytotoxic/suppressor (CD3+CD8+) lymphocytes were found 6 to 12 months later in those assigned to CBSM. Moreover, greater decreases in NE output and a greater frequency of relaxation home practice during the 10-week CBSM intervention period predicted higher CD3+CD8+ cell counts at follow-up.

Quality of life as an outcome measure in gynecologic malignancies.

Health-related quality of life instruments for cancer patients and specifically for gynecologic cancer patients have been developed, validated and applied in clinical trials. More focused investigations of specific symptoms, side-effects and both short- and long-term toxicities are also being pursued. Assessments are now included as part of many cancer treatment trials and some studies are looking at quality of life in survivors. Another area of investigation seeks to define the types of stress and coping mechanisms being used in order to identify predictors of psychologic distress.