Janine Giese-Davis

Depression and cancer: Mechanisms and disease progression

Depression and cancer commonly co-occur. The prevalence of depression among cancer patients increases with disease severity and symptoms such as pain and fatigue. The literature on depression as a predictor of cancer incidence is mixed, although chronic and severe depression may be associated with elevated cancer risk. There is divided but stronger evidence that depression predicts cancer progression and mortality, although disentangling the deleterious effects of disease progression on mood complicates this research, as does the fact that some symptoms of cancer and its treatment mimic depression. There is evidence that providing psychosocial support reduces depression, anxiety, and pain, and may increase survival time with cancer, although studies in this latter area are also divided. Psychophysiological mechanisms linking depression and cancer progression include dysregulation of the hypothalamic-pituitary-adrenal axis, especially diurnal variation in cortisol and melatonin. Depression also affects components of immune function that may affect cancer surveillance. Thus, there is evidence of a bidirectional relationship between cancer and depression, offering new opportunities for therapeutic intervention.

Decrease in Depression Symptoms Is Associated With Longer Survival in Patients With Metastatic Breast Cancer: A Secondary Analysis

PURPOSE Numerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival. METHODS In a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies-Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival. RESULTS Median survival time was 53.6 months for women with decreasing CES-D scores over 1 year and 25.1 months for women with increasing CES-D scores. There was a significant effect of change in CES-D over the first year on survival out to 14 years (P = .007) but no significant interaction between treatment condition and CES-D change on survival. Neither demographic nor medical variables explained this association. CONCLUSION Decreasing depression symptoms over the first year were associated with longer subsequent survival for women with MBC in this sample. Further research is necessary to confirm this hypothesis in other samples, and causation cannot be assumed based on this analysis.

Flattened cortisol rhythms in metastatic breast cancer patients

Allostatic load, the physiological accumulation of the effects of chronic stressors, has been associated with multiple adverse health outcomes. Flattened diurnal cortisol rhythmicity is one of the prototypes of allostatic load, and has been shown to predict shorter survival among women with metastatic breast cancer. The current study compared diurnal cortisol slope in 17 breast cancer patients and 31 controls, and tested associations with variables previously found to be related to cortisol regulation, i.e, abdominal adiposity, perceived stress, social support, and explicit memory. Women with metastatic breast cancer had significantly flatter diurnal cortisol rhythms than did healthy controls. Patients with greater disease severity showed higher mean cortisol levels, smaller waist circumference, and a tendency toward flatter diurnal cortisol rhythms. There were no relations between cortisol slope and psychological or cognitive functioning among patients. In contrast, controls with flatter rhythms showed the expected allostatic load profile of larger waist circumference, poorer performance on explicit memory tasks, lower perceived social support, and a tendency toward higher perceived stress. These findings suggest that the cortisol diurnal slope may have important but different correlates in healthy women versus those with breast cancer.

Effects of Supportive-Expressive Group Therapy on Survival of Patients With Metastatic Breast Cancer A Randomized Prospective Trial

One hundred twenty-five women with confirmed metastatic (n 5 122)or locally recurrent (n 5 3) breast cancer were randomly assigned either to the sup-portive-expressive group therapy condition (n 5 64), where they received educa-tional materials plus weekly supportive-expressive group therapy, or to the controlcondition (n 5 61), where they received only educational materials for a minimumof 1 year. The treatment, 90 minutes once a week, was designed to build new bondsof social support, encourage expression of emotion, deal with fears of dying anddeath, help restructure life priorities, improve communication with family mem-bers and healthcare professionals, and enhance control of pain and anxiety.

Effects of supportive‐expressive group therapy on survival of patients with metastatic breast cancer

This study was designed to replicate our earlier finding that intensive group therapy extended survival time of women with metastatic breast cancer. Subsequent findings concerning the question of whether such psychosocial support affects survival have been mixed.

Traumatic stress symptoms among women with recently diagnosed primary breast cancer

This study examined the concurrent and longitudinal relationships between traumatic stress symptoms and demographic, medical, and psychosocial variables among women recently diagnosed with primary breast cancer. Participants were 117 women drawn from a parent study for women recently diagnosed with primary breast cancer. At baseline, the Impact of Event Scale (IES) total score was related to intensity of postsurgical treatment and lower emotional self-efficacy. At the 6-month follow-up, the IES total score was significantly related to younger age, to the increased impact of the illness on life, and to the baseline IES total score assessment. These results suggest that it is important to intervene for traumatic stress symptoms soon after the diagnosis of breast cancer. Furthermore, these results suggest women at greatest risk are those who are younger, who receive postsurgical cancer treatment, who are low in emotional self-efficacy and whose lives are most affected by having cancer.

Quality of couples' relationship and adjustment to metastatic breast cancer.

This study examined mood disturbance among women with metastatic breast cancer in relationship to partnership status, relationship quality, and partners coping and mood disturbance. These associations were examined within a total sample of 125 metastatic breast cancer patients and a subsample of 48 of these patients and their partners. Partnered and single women were indistinguishable in mood disturbance when household income was statistically controlled. Results also showed that patients were less distressed when they rated the relationship higher in Cohesion--Expression and in Conflict and when their partners reported lower mood disturbance. One possible implication of these results is that in relationships in which a woman has metastatic cancer, she may benefit from open engagement of difficulties and conflict. Furthermore, alleviating her distress may be better achieved by focus on the couple relationship rather than her individual coping.

Depression and stress reactivity in metastatic breast cancer

Objective: Cancer-related distress due to the psychological and physical challenges of metastatic breast cancer (MBC) may result in symptoms of depression, which negatively affects quality and may influence quantity of life. This study investigated how depression affects MBC stress reactivity, including autonomic (ANS) and hypothalamic–pituitary–adrenal (HPA) axis function. Method: Forty-five nondepressed and 45 depressed patients with MBC underwent a modified Trier Social Stress Test (TSST) while affect, cardiovascular, respiratory, and cortisol responses were measured. Results: At study entry, depressed compared with nondepressed patients had significantly lower log cortisol waking rise levels (p = .005) but no other HPA differences. Positive affect (p = .025) and high-frequency heart-rate variability (lnHF) (p = .002) were significantly lower at TSST baseline in depressed patients. In response to the TSST, depressed patients reported significantly lower positive (p = .050) and greater negative affect (p = .037) and had significantly reduced lnHF (p = .031). In secondary analyses, at TSST baseline both low-frequency (lnLF) (p = .002) and very-low-frequency (lnVLF) (p = .0001) heart rate variability were significantly lower in the depressed group. In secondary analyses during the TSST, those who were depressed had significantly lower lnVLF (p = .008) and did not increase aortic impedance reactivity as much as did the nondepressed during the stressor (p = .005). Conclusion: Depression in patients with MBC was associated with alterations in autonomic regulation, particularly reductions in respiratory sinus arrhythmia, a measure of cardiac vagal control, at baseline and during the TSST. In addition, depression was associated with blunted HPA response to awakening. Both MBC groups had relative cortisol hyporesponsiveness to acute stress. ANS = autonomic nervous system; BMI = body mass index; BP = blood pressure; BRC = baroreflex control of heart rate; CO = cardiac output; CVD = cardiovascular disease; DBP = diastolic blood pressure; ECG = electrocardiogram; HDL = high-density lipoprotein; HPA axis = hypothalamic–pituitary–adrenal axis; HR = heart rate; HRSD = Hamilton Rating Scale of Depression; HRV = heart rate variability; ICG = impedance cardiogram; lnHF = natural log of high-frequency HRV; lnLF = natural log of low-frequency HRV; lnVLF = natural log of very low frequency HRV; LDL = low-density lipoprotein; MBC = metastatic breast cancer; MDD = major depressive disorder; ND = nondepressed; PANAS = Positive and Negative Affect Schedule; pCO2 = partial pressure of carbon dioxide; PEP = preejection period; RR interval = time between two consecutive R waves of the ECG; RSA = respiratory sinus arrhythmia; RSATF = transfer function respiratory sinus arrhythmia; SBP = systolic blood pressure; SNRI = serotonin–norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TSST = Trier Social Stress Test; VLDL = very-low-density lipoprotein.

Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer.

Cancer treatment is known to have significant immuno-suppressive/dysregulatory effects. Psychological distress and depression, which often accompany cancer diagnosis and treatment, can also suppress or dysregulate endocrine and immune function. Cell-mediated immunity (CMI) is critical for protection against a host of pathogens to which cancer patients may be particularly susceptible. CMI is also important for defense against some tumors. This study explored relationships among depressive symptoms, cortisol secretion, and CMI responses in 72 women with metastatic breast cancer. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression Scale (CES-D). Saliva was sampled throughout the day over a 3-day period to obtain a physiologic index of diurnal cortisol concentrations and rhythmicity, which is associated with breast cancer survival time. CMI for specific antigens was measured following intradermal administration of seven commonly encountered antigens (tuberculin, tetanus, diphtheria, Streptococcus, Candida, Trichophyton, and Proteus). Analyses adjusting for relevant medical and treatment variables indicated that women reporting more depressive symptoms showed suppressed immunity as measured by lower average induration size. Women with higher mean diurnal cortisol concentrations also showed suppressed immunity as indicated by a decreased number of antigens to which positive reactions were measured. This study highlights the relationships among depression, stress, and immune function in the context of advanced breast cancer.

Mood disturbance in community cancer support groups: The role of emotional suppression and fighting spirit

OBJECTIVE In this cross-sectional study, we tested whether the coping styles of emotional suppression and fighting spirit were associated with mood disturbance in cancer patients participating in professionally led community-based support groups even when demographic, medical, and group support variables were taken into account. METHODS A heterogeneous sample of 121 cancer patients (71% female, 29% male) completed the Courtauld Emotional Control Scale (CECS), the Mini-Mental Adjustment to Cancer Scale (Mini-MAC), a measure of perceived group support, and the Profile of Mood States (POMS). RESULTS Consistent with hypotheses, lower emotional suppression and greater adoption of a fighting spirit, in addition to older age and higher income, were associated with lower mood disturbance. Gender, time since diagnosis, presence of metastatic disease, time in the support group, perceived group support, cognitive avoidance, and fatalism were unrelated to mood disturbance. CONCLUSION Expression of negative affect and an attitude of realistic optimism may enhance adjustment and reduce distress for cancer patients in support groups.