A Structured Psychiatric Intervention for Cancer Patients: II. Changes Over Time in Immunological Measures
01 Aug 1990-Archives of General Psychiatry (American Medical Association)-Vol. 47, Iss: 8, pp 729-735
TL;DR: The results indicate that a short-term psychiatric group intervention in patients with malignant melanoma with a good prognosis was associated with longer-term changes in affective state, coping, and the NK lymphoid cell system.
Abstract: • We evaluated the immediate and long-term effects on immune function measures of a 6-week structured psychiatric group intervention for patients with malignant melanoma. Along with a reduction in levels of psychological distress and greater use of active coping methods, the following immune changes were seen at the 6-month assessment point in the interventiongroup patients (n 35) compared with controls (n = 26): significant increases in the percent of large granular lymphocytes (defined as CD57 with Leu-7) and natural killer (NK) cells (defined as CD16 with Leu-11 and CD56 with NKH1) along with indications of increase in NK cytotoxic activity; and a small decrease in the percent of CD4 (helper/inducer) T cells. At the 6-week follow-up point, the majority of these changes were not yet observable. The results indicate that a short-term psychiatric group intervention in patients with malignant melanoma with a good prognosis was associated with longer-term changes in affective state, coping, and the NK lymphoid cell system. Affective rather than coping measures showed some significant correlations with immune cell changes.
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TL;DR: Acknowledging that health promotion rests on the shoulders not only of individuals but also of their families and communities means that resources must be committed over the next decade to designing, testing, and implementing interventions in this area.
Abstract: In considering new paradigms for the prevention and treatment of disease and disability, we need to incorporate ways to promote social support and develop family and community strengths and abilities into our interventions. There is now a substantial body of evidence that indicates that the extent to which social relationships are strong and supportive is related to the health of individuals who live within such social contexts. A review of population-based research on mortality risk over the last 20 years indicates that people who are isolated are at increased mortality risk from a number of causes. More recent studies indicate that social support is particularly related to survival postmyocardial infarction. The pathways that lead from such socioenvironmental exposures to poor health outcomes are likely to be multiple and include behavioral mechanisms and more direct physiologic pathways related to neuroendocrine or immunologic function. For social support to be health promoting, it must provide both a sense of belonging and intimacy and must help people to be more competent and self-efficacious. Acknowledging that health promotion rests on the shoulders not only of individuals but also of their families and communities means that we must commit resources over the next decade to designing, testing, and implementing interventions in this area.
1,222 citations
TL;DR: The evidence that various cellular and molecular immunological factors are compromised in chronic stress and depression is overviewed and the clinical implications of these factors in the initiation and progression of cancer are discussed.
Abstract: The links between the psychological and physiological features of cancer risk and progression have been studied through psychoneuroimmunology. The persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis in the chronic stress response and in depression probably impairs the immune response and contributes to the development and progression of some types of cancer. Here, we overview the evidence that various cellular and molecular immunological factors are compromised in chronic stress and depression and discuss the clinical implications of these factors in the initiation and progression of cancer. The consecutive stages of the multistep immune reactions are either inhibited or enhanced as a result of previous or parallel stress experiences, depending on the type and intensity of the stressor and on the animal species, strain, sex, or age. In general, both stressors and depression are associated with the decreased cytotoxic T-cell and natural-killer-cell activities that affect processes such as immune surveillance of tumours, and with the events that modulate development and accumulation of somatic mutations and genomic instability. A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to new clinical and treatment strategies.
1,100 citations
TL;DR: A mindfulness meditation–based stress reduction program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses, stages of illness, and ages.
Abstract: Objective: The objective of this study was to assess the effects of participation in a mindfulness meditation‐ based stress reduction program on mood disturbance and symptoms of stress in cancer outpatients. Methods: A randomized, wait-list controlled design was used. A convenience sample of eligible cancer patients enrolled after giving informed consent and were randomly assigned to either an immediate treatment condition or a wait-list control condition. Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention. The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice. Results: Ninety patients (mean age, 51 years) completed the study. The group was heterogeneous in type and stage of cancer. Patients’ mean preintervention scores on dependent measures were equivalent between groups. After the intervention, patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression, Anxiety, Anger, and Confusion and more Vigor than control subjects. The treatment group also had fewer overall Symptoms of Stress; fewer Cardiopulmonary and Gastrointestinal symptoms; less Emotional Irritability, Depression, and Cognitive Disorganization; and fewer Habitual Patterns of stress. Overall reduction in Total Mood Disturbance was 65%, with a 31% reduction in Symptoms of Stress. Conclusions: This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses, stages of illness, and ages. Key words: meditation, cancer, stress, mood, intervention, mindfulness. ANOVA 5 analysis of variance; MANOVA 5 multiple analysis of variance; POMS 5 Profile of Mood States; SOSI 5 Symptoms of Stress Inventory.
1,086 citations
TL;DR: Psychiatric interventions that enhance effective coping and reduce affective distress appear to have beneficial effects on survival but are not proposed as an alternative or independent treatment for cancer or any other illness or disease.
Abstract: Objectives: We evaluated recurrence and survival for 68 patients with malignant melanoma who participated in a 6-week structured psychiatric group intervention 5 to 6 years earlier, shortly after their diagnosis and initial surgical treatment. We also explored the role of several factors as possible predictors of outcome. Design: This was a randomized controlled experimental study. The Cox proportion hazards regression model was used to quantify the relationship between treatment and the outcomes adjusted by the covariates (age, sex, Breslow depth, tumor site, baseline Profile of Mood States Total Mood Disturbance, baseline active-behavioral coping, baseline natural killer cell activity, and treatment [ie, group intervention]). The stepwise procedure was used for covariate selection. Results: For control patients, there was a trend for recurrence (13/34) and a statistically significant greater rate of death (10/34) than for experimental patients (7/34 and 3/34, respectively). We found that being male and having a greater Breslow depth predicted greater recurrence and poorer survival. Analysis of multiple covariates found that only Breslow depth and treatment (ie, group intervention) were significant. Adjusting for Breslow depth, treatment effect remained significant. Finally, baseline affective distress and baseline coping were significant psychobehavioral predictors for recurrence and survival. Surprisingly, higher levels of baseline distress as well as baseline coping and enhancement of active-behavioral coping over time were predictive of lower rates of recurrence and death. Conclusion: Psychiatric interventions that enhance effective coping and reduce affective distress appear to have beneficial effects on survival but are not proposed as an alternative or independent treatment for cancer or any other illness or disease. However, the exact nature of this relationship warrants further investigation.
1,026 citations
TL;DR: This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.
Abstract: Stress does not cause cancer per se, but depression and a lack of social support might influence cancer progression and clinical outcome. Can identification of the molecular and biological mechanisms involved be used to improve patient treatment? Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.
841 citations
References
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Journal Article•
TL;DR: The monoclonal antibody HNK-1, produced against a membrane antigen from the cultured T cell line, HSB-2, defines the first differentiation antigen shown to be selectively expressed on human NK and K cells.
Abstract: A monoclonal IgM antibody (HNK-1) was produced against a membrane antigen from the cultured T cell line, HSB-2 By indirect immunofluorescence, this antibody reacted with certain human cultured T cell lines (HSB-2 and MOLT-4 but not MOLT-3) but not with other lines of B cell or phagocytic cell origin HNK-1 reacted with 151 +/- 71% of normal blood lymphocytes but was unreactive with monocytes, granulocytes, erythrocytes, and platelets HNK-1+ cells separated by a fluorescence-activated cell sorter (FACS) were a homogeneous population of medium sized lymphocytes with abundant neutrophilic cytoplasm containing azurophilic granules HNK-1+ cells were nonadherent, surface Ig-, mostly FcIgG receptor+ and both positive and negative for demonstrable sheep erythrocyte (E) rosetting capability Cell suspensions enriched for E-rosetting T cells and depleted of FcIgG receptor+ cells contained few (6%) HNK-1+ cells Depletion of HNK-1+ cells from blood mononuclear cell populations by complement (C) mediated lysis greatly reduced NK activity against K-562 target cells and K cell lytic activity against antibody-coated chicken red blood cells Treatment with HNK-1 alone or C alone did not affect these activities When the FACS was utilized to separate HNK-1+ and HNK-1- cells from 6 individuals, the HNK-1+ cell population contained almost all of the NK and K cell function The monoclonal antibody HNK-1 thus defines the first differentiation antigen shown to be selectively expressed on human NK and K cells
1,346 citations
Journal Article•
TL;DR: The finding that CD3+,Leu 19+ lymphocytes mediated cytotoxicity against K562 unequivocally demonstrates that a unique subset of non-MHC-restricted cytotoxic CD3+ T lymphocytes are present in the peripheral blood of unprimed, normal individuals.
Abstract: We examined the antigenic and functional characteristics of human peripheral blood lymphocytes that differentially express the CD16 (Leu-11) and Leu-19 (NKH-1) antigens. Leu-19 is a approximately 220,000 daltons protein expressed on approximately 15% of freshly isolated peripheral blood lymphocytes. Within the Leu-19+ subset, three distinct populations were identified: CD3-,CD16+,Leu-19+ cells; CD3+,CD16-,Leu-19+ cells; and CD3-,CD16-,Leu-19bright+ cells. Both the CD3+,CD16-,Leu-19+ and CD3-,CD16+,Leu-19+ populations mediated non-major histocompatibility complex (MHC)-restricted cytotoxicity against the NK-sensitive tumor cell K562 and were large granular lymphocytes. CD3-,CD16+,Leu-19+ NK cells were the most abundant (comprising approximately 10% of peripheral blood lymphocytes) and the most efficient cytotoxic effectors. The finding that CD3+,Leu 19+ lymphocytes mediated cytotoxicity against K562 unequivocally demonstrates that a unique subset of non-MHC-restricted cytotoxic CD3+ T lymphocytes are present in the peripheral blood of unprimed, normal individuals. However, CD3+,CD16-,Leu-19+ cells comprised less than 5% of peripheral blood lymphocytes, and the cytotoxic activity of this subset was significantly less than CD3-,CD16+,Leu-19+ NK cells. Most CD3+,Leu-19+ T cells co-expressed the CD2, CD8, and CD5 differentiation antigens. The antigenic and functional phenotype of peripheral blood CD3+,Leu-19+ cytotoxic T lymphocytes corresponds to the interleukin 2-dependent CD3+ cell lines that mediate non-MHC-restricted cytotoxicity against NK-sensitive tumor cell targets. A small population of Leu-19bright+ lymphocytes lacking both CD3 and CD16 was also observed. This population (comprising less than 2% of peripheral blood lymphocytes) contained both large agranular lymphocytes and large granular lymphocytes. CD3-,CD16-,Leu-19bright+ lymphocytes also mediate non-MHC-restricted cytotoxicity. The relationship of these CD3-CD16-,Leu-19bright+ lymphocytes to CD3+ T cells or CD16+ NK cells is unknown.
1,088 citations
TL;DR: Objective evidence is provided that a supportive group intervention for patients with metastatic cancer results in psychological benefit and mechanisms underlying the effectiveness of this group intervention are explored.
Abstract: • The effects of weekly supportive group meetings for women with metastatic carcinoma of the breast were systematically evaluated in a one-year, randomized, prospective outcome study. The groups focused on the problems of terminal illness, including improving relationships with family, friends, and physicians and living as fully as possible in the face of death. We hypothesized that this intervention would lead to improved mood, coping strategies, and self-esteem among those in the treatment group. Eighty-six patients were tested at four-month intervals. The treatment group had significantly lower mooddisturbance scores on the Profile of Mood States scale, had fewer maladaptive coping responses, and were less phobic than the control group. This study provides objective evidence that a supportive group intervention for patients with metastatic cancer results in psychological benefit. Mechanisms underlying the effectiveness of this group intervention are explored.
824 citations
TL;DR: Blood was drawn twice from 75 first‐year medical students, with a baseline sample taken one month before their final examinations and a stress sample drawn on the first day of final examinations to address the effects of a naturally occurring stressor on components of the immune response.
Abstract: This study addressed the effects of a naturally occurring stressor on components of the immune response. Blood was drawn twice from 75 first-year medical students, with a baseline sample taken one month before their final examinations and a stress sample drawn on the first day of final examinations. Median splits on scores from the Holmes--Rahe Social Readjustment Rating Scale and the UCLA Loneliness Scale produced a 2 X 2 X 2 repeated measures ANOVA when combined with the trials variable. Natural killer (NK) cell activity declined significantly from the first to the second sample. High scorers on stressful life events and loneliness had significantly lower levels of NK activity. Total plasma IgA increased significantly from the first to second sample, while plasma IgG and IgM, C-reactive protein, and salivary IgA did not change significantly.
796 citations
TL;DR: Among married subjects, poorer marital quality was associated with greater depression and a poorer response on three qualitative measures of immune function, and women who had been separated 1 year or less had significantly poorer qualitative and quantitative immune function than their sociodemographically matched married counterparts.
Abstract: Marital disruption is associated with significant increases in a variety of psychologic and physical disorders. In order to examine psychologic and physiologic mediators, self-report data and blood samples were obtained from 38 married women and 38 separated/divorced women. Among married subjects, poorer marital quality was associated with greater depression and a poorer response on three qualitative measures of immune function. Women who had been separated 1 year or less had significantly poorer qualitative and quantitative immune function than their sociodemographically matched married counterparts. Among the separated/divorced cohort, shorter separation periods and greater attachment to the (ex)husband were associated with poorer immune function and greater depression. These data are consistent with epidemiologic evidence linking marital disruption with increased morbidity and mortality.
657 citations