Source/Disclosures
Source: Cohen L. PloS ONE. 2012;doi:10.1371/journal.pone.0042324.
August 15, 2012
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Depression may shorten cancer survival

Source/Disclosures
Source: Cohen L. PloS ONE. 2012;doi:10.1371/journal.pone.0042324.
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Cancer patients who exhibited symptoms of depression had significantly poorer survival than those who did not, according to study results.

“Our findings, and those of others, suggest that mental health and social well-being can affect biological processes, which influence cancer-related outcomes,” Lorenzo Cohen, PhD, a professor in the general oncology and behavioral science departments and director of the Integrative Medicine Program at The University of Texas MD Anderson Cancer Center, said in a press release. “They also suggest that screening for mental health should be part of standard care.”

Prior studies indicated depression is associated with worse outcomes, although the specific factors involved have been unclear, according to background information in the study.

“Our findings indicate that we’re now able to understand some of the possible biological pathways that explain the association between depression and survival,” Cohen said.

Cohen and colleagues evaluated 217 patients with newly diagnosed metastatic renal cell carcinoma from April 2000 through November 2005. Patients provided blood samples and also completed several questionnaires at the time of study entry. The questionnaires were designed to measure depressive symptoms, quality of life, social support, spirituality and religiosity.

The researchers also collected five saliva samples per day for 3 days from all study participants to measure fluctuations of cortisol. Under normal circumstances, levels of the stress hormone should be high in the morning and drop through the day. Increased levels of cortisol have been observed in patients who exhibit depressive symptoms, according to the researchers.

Sixty-four percent of patients had died at the time of analysis. Those patients lived an average of 1.8 years after diagnosis.

Overall, 23% of patients reported depressive symptoms within a clinical range, as determined by a Centers for Epidemiologic Studies depression score of 16 or higher.

Cox regression models showed that such scores were significantly associated with decreased survival (HR=1.5, 95% CI, 1.00-2.23; P=.05). Patients who exhibited “a flattened cortisol slope” from morning to evening also had shorter survival (HR=1.9; 95% CI, 1.27-2.97; P=.002), according to researchers.

“Our findings provide the first evidence that levels of depressive symptoms are associated with survival time among patients with newly diagnosed advanced [renal cell carcinoma], controlling for disease- and treatment-related factors,” Cohen and colleagues wrote.

The researchers conducted whole-genome profiling to determine whether increased mortality risk associated with greater depressive symptoms may be due to pro-inflammatory gene expression. They compared tissue samples from 15 patients with the highest depressive symptom scores and 15 risk-matched patients with the lowest depressive symptom scores.

The results showed 116 genetic transcripts were upregulated by an average of 50% or more in patients with higher levels of depressive symptoms. The findings indicate the association between survival time and a patient’s psychological condition may be due to a dysregulation in inflammatory biology and cortisol slope, the researchers said.

“While depressive symptoms, inflammatory markers, immune function and gene regulation have been shown to be independently linked to the progression of cancer and survival, the current study is the first to demonstrate a more systemic model of cancer that includes both central and peripheral nervous system function and the influence of psychological well-being on the system,” Cohen and colleagues wrote. “Defining the neural and hormonal mechanisms of such effects could provide new biological targets for adjunctive control of disease progression in the context of [renal cell carcinoma].”

Cohen and colleagues acknowledged several limitations to their study. Several studies have indicated a link between psychological stress and cancer progression in animals, but that causality is difficult to prove in humans. The researchers also were not able to determine patients’ levels of distress or depressive symptoms prior to cancer diagnosis.

Future studies are needed to evaluate whether management of depression, either through pharmacologic interventions or behavioral techniques, can effect survival in cancer patients with mood disorders, the researchers concluded.