Depression and Cancer

Abstract & Commentary

By William B. Ershler, MD

Synopsis: This meta-analysis revealed overall increased mortality of up to 25% in patients experiencing depressive symptoms after cancer diagnosis, and a 39% higher risk in patients diagnosed with major or minor depression after cancer diagnosis, based upon 25 independent studies. Given the low number of studies available to date, the effect of depressive symptoms on cancer recurrence did not reach a level of statistical significance.

Source: Satin JR, et al. Depression as a predictor of disease progression and mortality in cancer patients: A meta-analysis. Cancer. 2009;115:5349-5361.

There is a sense held by both patients and oncologists that psychological variables influence the course of cancer. In fact, 85% of cancer patients and 71% of oncologists endorse the belief that psychological variables affect cancer progression.1 Despite this, the evidence for such an association remains inconclusive. Of the psychological variables, depression has been the most commonly studied in the context of cancer progression and mortality. In a striking early study, Shekelle et al demonstrated a two-fold higher mortality rate in depressed cancer patients at 17 years follow-up,2 although this finding has been difficult to replicate.3,4 Furthermore, depression is the only psychological variable more commonly found in cancer patients than in the general public.5 Thus, Satin et al present a meta-analysis of the existing literature to explore the effect of depression on cancer recurrence and mortality.

Using the MEDLINE (National Library of Medicine), PsycINFO (American Psychological Association), CINAHL (EBSCO Electronic Journal Services), and EMBASE (Elsevier) online databases, Satin et al identified prospective studies that examined the association between depressive symptoms or major/minor depression and risk of disease progression or mortality in cancer patients. Two raters independently extracted effect sizes using a random effects model.

Based on three available studies, depressive symptoms were not shown to significantly predict cancer progression (risk ratio [RR] unadjusted = 1.23; 95% confidence interval [CI], 0.85-1.77; p = 0.28). Based on data from 25 independent studies, mortality rates were up to 25% higher in patients experiencing depressive symptoms (RR unadjusted = 1.25; 95% CI, 1.12-1.40; p < 0.001), and up to 39% higher in patients diagnosed with major or minor depression (RR unadjusted = 1.39; 95% CI, 1.10-1.89; p = 0.03). In support of a causal interpretation of results, there was no evidence that adjusting for known clinical prognostic factors diminished the effect of depression on mortality in cancer patients.

Commentary

The present meta-analysis represents a much-needed quantitative synthesis of the often under-powered studies examining depression as a predictor of disease progression and mortality in cancer patients. This is of considerable importance in both theory and practice in determining the risks associated with depression, as well as in providing rationale for psychological intervention with the hopeful benefit of enhancing survival.

As such, this meta-analysis presented reasonable evidence that depression predicts mortality, but not progression, in cancer patients. The associated risk was statistically significant but relatively small. The effect of depression remains after adjustment for clinical prognosticators, suggesting that depression may play a causal role, although how it occurs remains unclear.

Possible mechanisms whereby psychological variables might affect host defenses include activation of the hypothalamo-pituitary-adrenal (HPA) axis, producing a chronic stress pattern observed in a number of biological systems.6-8 Such activation might modulate both innate and acquired immune functions and, thereby, influence tumor progression. These, of course, remain theoretical constructs derived primarily from cellular or experimental animal studies, and their applicability to the human condition remains to be established.

That depression occurs commonly in cancer patients is now well established. It appears also to be true that there is evidence that depression is associated with a significant but small increased risk of mortality. Although treatment of depression in cancer patients is quite successful in reducing subjective distress, it remains to be established whether successful treatment will improve survival. Statin et al argue that in order to demonstrate this, the mediators of depression-associated increased risk need to be identified and a reduction of such demonstrated when appropriate and successful psychological intervention is undertaken. We are quite far from this level of understanding, but it remains an excellent goal for investigators in the rapidly developing field of psycho-oncology.

References

1. Lemon J, et al. Perceptions of the "mind-cancer" relationship by members of the public, cancer patients and oncologists. J Psychosoc Oncol. 2004;21:43-58.

2. Shekelle RB, et al. Psychological depression and 17-year risk of death from cancer. Psychosom Med. 1981;43:117-125.

3. Zonderman AB, et al. Depression as a risk for cancer morbidity and mortality in a nationally representative sample. JAMA. 1989;262:1191-1195.

4. Kaplan GA, Reynolds P. Depression and cancer mortality and morbidity: prospective evidence from the Alameda County study. J Behav Med. 1988;11:1-13.

5. van't Spijker A, et al. Psychological sequelae of cancer diagnosis: a meta-analytical review of 58 studies after 1980. Psychosom Med. 1997;59:280-293.

6. Thaker PH, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006;12:939-944.

7. Reiche EM, et al. Stress, depression, the immune system, and cancer. Lancet Oncol. 2004;5:617-625.

8. Seruga B, et al. Cytokines and their relationship to the symptoms and outcome of cancer. Nat Rev Cancer. 2008;8:887-899. CME Objectives