Elsevier

Biological Psychiatry

Volume 54, Issue 3, 1 August 2003, Pages 269-282
Biological Psychiatry

Mood disorders and medical illness
Depression and cancer: mechanisms and disease progression

https://doi.org/10.1016/S0006-3223(03)00566-3Get rights and content

Abstract

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.

Introduction

Depression in patients with cancer has been underdiagnosed and undertreated due, in part, to the belief that depression is a normal and universal reaction to serious disease Newport and Nemeroff, 1998, Rodin and Voshart, 1986, Spiegel, 1996 and, in part, because the neurovegetative signs (weight loss, sleep disturbance) or emotional/cognitive signs of depression are often attributed to the medical illness itself Craig and Abeloff, 1974, McDaniel et al., 1995. Thus, serious medical and psychiatric comorbidity is often overlooked, leading to undertreatment that complicates cancer and depression and at the least adversely affects patients' quality of life.

Section snippets

Depression among cancer patients

Rates of depressive states reported for cancer inpatients are roughly comparable to similarly ill patients with other medical diagnoses (Evans et al 1999). Studies of medical inpatients show that one third report mild or moderate symptoms of depression, and up to one fourth may suffer from major depression (McDaniel et al 1995) or a depressive syndrome Katon and Sullivan, 1990, Atkinson et al., 1988. However, some studies show that rates of major depression among cancer patients are similar to

Depression as a predictor of cancer incidence, progression, and mortality

The literature on the association between depression and subsequent cancer incidence, progression, and mortality is divided, although a preponderance of the studies demonstrate a connection, and only one (Derogatis 1979) showed that depression seemed to have a protective effect against cancer (see review Giese-Davis and Spiegel 2003). At the time of the Giese-Davis and Spiegel (2003) review, the evidence linking depression to cancer incidence was weaker than that connecting it to progression.

Medical effects of psychosocial treatment of depression

These findings raise the possibility that effective treatment of depression and/or anxiety may affect the course of the disease as well as the patient's distress McDaniel et al., 1995, Clarke, 1998. There are 10 published randomized trials that examine this hypothesis (see Table 3). In all of them, both control and intervention groups received standard medical cancer treatment. While they were designed to reduce distress in general and enhance coping rather than treat depressive symptoms per

Depression and treatment adherence

How might depression affect the incidence or progression of cancer? Depression might affect behavior and adherence to medical treatment (Pirl and Roth 1999). Psychological distress interferes with adherence to screening procedures such as mammography (Lerman et al 1994). Interventions specifically designed to improve adherence have done so (Richardson et al 1990); however, in some studies higher depression and anxiety scores have been found to be associated with increased adherence to

Depression and immunity in cancer

The severity of depression and related repressive coping in response to it may have a deleterious effect on immunocompetence in cancer patients (Baltrusch et al 1991). For example, clinician-rated symptoms of depression significantly predict both lower white blood cell counts and natural killer (NK) cell numbers in this population (Andersen et al 1994). Symptoms of chronic depression and a lack of social support predicted reduced NK cell cytotoxicity measured at a 3-month follow-up in breast

Conclusion

There is growing evidence of a relationship between depression and cancer incidence and progression. Depression complicates not only coping with cancer and adherence to medical treatment but also affects aspects of endocrine and immune function that plausibly affect resistance to tumor progression. Some studies of psychotherapeutic interventions that reduce depression have shown that they normalize potential mediators such as cortisol and may slow disease progression. There is good reason to

Acknowledgements

This work was supported by National Institutes of Health grants 5R01 MH047226 from NIMH and 5P01AG018784 from National Institute on Aging and National Cancer Institute.

Aspects of this work were presented at the conference, “The Diagnosis and Treatment of Mood Disorders in the Medically Ill,” November 12–13, 2002 in Washington, DC. The conference was sponsored by the Depression and Bipolar Support Alliance through unrestricted educational grants provided by Abbott Laboratories, Bristol-Myers

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