| Attitude and Cancer... does
depression or stress cause cancer or effect cure rates?
There is evidence that the mind has a big impact on the body. People with a high level of stress or chronic depression are more prone to health problems. There have been numerous studies showing the relationship between the mind and the endocrine and immune system (commonly referred to as psychoneuroimmunology).
Some studies have shown a link between personality and the risk of getting cancer. Some studies have shown that a person 's attitude may effect his outcome with cancer. Many studies have shown no relationship between attitude and cancer (either incidence or outcome). So the topic remains controversial. Some studies show a benefit from psychotherapy and others do not (go here, here , here and here). Some other typical studies are noted below.
The connection between depression and cancer has been debated for more than two decades. After publication of two major epidemiologic studies of the Western Electric Company employee cohort that showed a relationship between self-reported depression symptoms and risk of mortality over 17- and 20-year follow-up periods, some imagined that depression would be identified as a risk factor for cancer, much as it had been for cardiovascular disease.However, this initial link proved elusive, and a number of subsequent studies failed to find an association between depression and cancer deaths. Although Linkins suggested that depression predicted cancer mortality in smokers but not in nonsmokers, a meta-analytic review concluded that depression was only a small, marginally significant risk factor for cancer. However, interest in the link between depression and cancer mortality was renewed by the report of Penninx In this prospective study of 4,825 persons aged 71 years and older, an 88% increase in cancer risk was found over a follow-up period of nearly 4 years. Notably, this increase in cancer risk was detected using a standardized and validated measure of depression, the Center for Epidemiological Studies Depression Scale; and the presence of chronic depression, rather than depression at a single period in time, was found to be associated with cancer mortality.
Among persons with a cancer diagnosis, depression occurs at a high rate, with a median point prevalence (15% to 29%) that is approximately three to five times greater than the general population. Unfortunately, depression remains largely underdiagnosed and undertreated in cancer patients, and such chronic depression might impact disease progression. Indeed, investigations examining depression and cancer progression have led to a more consistent set of associations compared with investigations of depression and cancer incidence.However, variable results have also been reported, possibly as a result of the heterogeneity of cancer diagnoses and cancer types. Depression, for example, may impact cancer progression through physiologically relevant mechanisms (eg, increases in proinflammatory cytokine activity) but only in cancers where such pathways are implicated (eg, lymphoproliferative disorders). Moreover, conclusions are often constrained by the use of nonstandardized assessment of depressive symptoms without diagnostic specificity or by the use of varying follow-up times. Interestingly, in studies with longer follow-up time, the results seem to be less definitive, suggesting that intervening health factors are more likely to come into play as survival time is extended.Finally, studies have rarely tested the possibility that underlying physiologic processes driven by tumor biology and tumor burden (eg, increases in inflammation) may produce changes in behaviors, notably fatigue, decreased vigor, and poor sleep. This constellation of symptoms can be promoted by inflammatory processes and might be interpreted as depression.
The study by Steel presents new findings that advance the hypothesis that depression impacts survival times in cancer patients. In a prospective study of 101 patients diagnosed with hepatobiliary cancer, the investigators found that depression (a score of 16 or higher on the Center for Epidemiological Studies Depression Scale) occurred in more than one third of the patients, and these patients showed a significantly shorter survival time. These differences were particularly striking among patients who had evidence of tumor vascular invasion; in this group, depressed patients survived for only 5 months, whereas the nondepressed patients had a survival time more than twice as long at 11 months. Importantly, the analyses adjusted for clinical demographic factors including age, sex, race, alcohol and tobacco use, and life stress. Moreover, cancer type, presence or absence of hepatitis B and/or C, presence or absence of cirrhosis, vascularity of the lesions, and vascular invasion did not significantly account for differences in survival time between depressed and nondepressed patients; however, vascular invasion did have independent effects on survival. It seems that these results might be specific to depression because the link between depression and survival held even after measures of somatic symptoms, including loss of appetite and restless sleep, were removed.
The study by Steel has an additional strength in its exploration of a potential mechanism that might mediate the association between depression and cancer survival. Depression is well recognized to be associated with alterations in cellular immune response and with declines in natural killer (NK) cell activity.The findings reported here extend these observations to depressed patients with hepatobiliary cancer and provide novel evidence in a small subsample of patients (n = 23) that such declines in NK activity correlate with survival time. Statistical analyses yield further provocative evidence that a decline in NK activity is an intermediary step between depression and mortality risk in this patient population. Others have shown that severity of psychological stress is associated with lower NK cell activity in ovarian cancer patients, and this decline is found in peripheral blood as well as in tumor-infiltrating lymphocytes.Animal models further implicate NK cells as a key mechanism in stress-induced tumor progression of experimental mammary adenocarcinoma; this effect is driven by catecholamine-induced suppression of NK activity and prevented by an NK-enhancing intervention, low-dose poly I-C (polyriboinosinic acid-polyribocytidylic acid) injection. However, alternative mechanisms independent of the immune system also require consideration. Depression is well known to be associated with increases of sympathetic catecholamines, and recent data suggest that such stress mediators modulate tumor growth by inducing the release of angiogenic cytokines and promoting angiogenesis and tumor growth. Of further relevance to hepatobiliary carcinoma, in which hepatitis B and hepatitis C viral pathology may play a role, catecholamines and other aspects of neuroendocrine function (eg, glucocorticoids) can modulate viral replication, activate viral oncogenes, and increase tumor metabolism.
The high prevalence of depression in this population and its apparent influence on survival challenge clinicians to identify effective interventions that can ameliorate depressive symptoms with potential impacts on mortality risk. Psychosocial interventions in patients with malignant melanoma are reported to increase measures of NK cell activity along with decreases in depressive symptoms, although a survival advantage of such treatments has not been confirmed. Nevertheless, there is extensive evidence that behavioral interventions are effective in reducing depressive symptoms in cancer patients, at least in the short term. Likewise, interventions with antidepressant medications (eg, paroxetine) reduce major depression incidence among patients undergoing active immunotherapy or chemotherapy. In addition to improving health functioning in these patients, other nonpsychological benefits have also emerged, including possible improved adherence to cancer treatment. Rigorous investigations that examine the efficacy of both pharmacologic and behavioral interventions for the treatment of depression and depressive symptoms in cancer patients are needed. Design of such treatment approaches also needs to be examined and understood within an evidence-based framework of scientific method, with rigorous consideration of the mechanisms by which treatment effects are achieved.
Increasing evidence is accumulating regarding the association between depressive symptoms and increased morbidity and mortality in the general population as well as across several chronic diseases,including cancer.Reviews of the literature conclude that the prevalence of depressive symptoms in people diagnosed with cancer ranges between 22% and 29%.Because of the high prevalence of depressive symptoms in people with cancer and the association with decrements in survival, the underlying biologic mechanisms associated with this link warrant further research.
Although several studies have now confirmed an association between depressive symptoms and increased cancer-related mortality, many of the studies suffer from methodologic flaws including lack of standardized instruments to assess depressive symptoms and the inclusion of other psychiatric diagnoses or psychiatric symptoms under the diagnosis of depression.
At this time, the predominant theory explaining the link between depressive symptoms and survival is modulation of the immune system. Ample evidence exists regarding the relationship between depressive symptoms and immune system modulation both in the general population and in people diagnosed with cancer. Excellent reviews are available that describe in detail the link between depression and immune system modulation; however, many unanswered questions still remain regarding the relationship between depressive symptoms and immune system functioning, including the temporal relationship between depressive symptoms and immune system modulation, differentiation between the effects of stress and depressive symptoms on immune system modulation, dissociation regarding the independent effects of depression on inflammatory and natural killer (NK) immune responses, and understanding the biologic mechanisms underlying subtypes of depressive symptoms.
Understanding the prevalence and physiologic consequences of depressive symptoms in hepatobiliary carcinoma (HBC) is critical because of the expected increase in prevalence of HBC in the next decade and the high rates of distress reported by people diagnosed with this cancer type. The aims of the present study were to assess the prevalence of depressive symptoms in patients with HBC at diagnosis, examine the relationship between depressive symptoms and survival while controlling for sociodemographic and disease-specific variables as well as somatic symptoms of depression, and preliminarily test a mediational model of depression and survival, with immune system modulation as a possible mediator.
Patients and Methods: One hundred one patients diagnosed with HBC were prospectively studied. Depressive symptoms were measured at diagnosis using the Center for Epidemiological Studies Depression Scale (CES-D). Sociodemographic and disease-specific data were gathered from the patients' charts. In a subsample of patients, stress; alcohol, tobacco, and drug use; sleep quality; physical activity; social support; natural killer (NK) cell number and cytotoxicity; and plasma levels of interleukin (IL) -4, IL-5, tumor necrosis factor alpha, and interferon gamma were measured. Survival was measured from date of diagnosis to death.
Results: At diagnosis, 37% of patients reported a CES-D score of 16 (clinical range). Using Cox regression analysis, sociodemographic and disease-specific variables and CES-D score significantly predicted survival. Only vascular invasion (P = .001) and CES-D score 16 (P = .03) were significant predictors. In a subsample of 23 patients, patients who reported a CES-D score of 16 were found to have significantly lower NK cell numbers than patients who reported a CES-D score of less than 16. A robust trend was found in which NK cell number was associated with survival. A mediational model linking depressive symptoms and survival, with NK cell number as a mediator, was preliminarily supported.
cancer: fact or fiction?
Kiecolt-Glaser JK, Eur J Cancer. 1999 Oct;35(11):1603-7. Department of Psychiatry, Ohio State University College of Medicine
There is substantial evidence from both healthy populations as well as individuals with cancer linking psychological stress with immune downregulation. This discussion highlights natural killer (NK) cells, because of the role that they may play in malignant disease. In addition, distress or depression is also associated with two important processes for carcinogenesis: poorer repair of damaged DNA, and alterations in apoptosis. Conversely, the possibility that psychological interventions may enhance immune function and survival among cancer patients clearly merits further exploration, as does the evidence suggesting that social support may be a key psychological mediator. These studies and others suggest that psychological or behavioural factors may influence the incidence or progression of cancer through psychosocial influences on immune function and other physiological pathways.
Psychosocial correlates of cancer relapse and survival: a literature
De Boer MF, Patient Educ Couns. 1999 Jul;37(3):215-30. Department of Head and Neck Surgery, University Hospital Rotterdam Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
This article reviews literature on the psychosocial correlates of cancer relapse and survival from 1979 through 1995. The factors studied were structured according to a theoretical model of coping with cancer. Reviewed studies have shown that factors most frequently evaluated were depression, anxiety, hopelessness/helplessness, hostility, marital status and social involvement. Mainly inconsistent results were found. The strongest evidence for a relationship between psychosocial variables and prognosis was found for social involvement/social support; in 7 of 15 studies a positive relationship was demonstrated, while no negative associations were found. Coping styles e.g., fighting spirit and stoic acceptance, and severe/stressful life events were found to have no conclusive influence on the length of survival. Important determinants of the coping model, such as uncertainty and information given by the specialist were not studied as possible predictors of survival and/or relapse free period. Among the factors that showed no correlation at all was multidimensional health locus of control. For the inconsistent findings, a considerable number of methodologic shortcomings with respect to study design, sample size, measure and statistical analysis are enumerated.