Patients with lung cancer, depression have higher inflammation levels
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Moderate to severe depression in patients with lung cancer was linked to elevated inflammation levels, and the biomarkers measuring inflammation predicted poor survival, according to study results published in PLOS ONE.
“We have studied stress, immunity and depression for some time with cancer patients,” Barbara L. Andersen, PhD, professor of psychology at The Ohio State University, told Healio. “A recent prior study showed not only depression at diagnosis, but depressive symptoms thereafter to predict non-small cell lung cancer survival. Being aware that both depression and lung cancer have inflammatory properties, we predicted that significant effects would be found between depression severity and the systemic inflammation markers. What we found was a very robust effect across all the markers, including the specific lung cancer inflammation index.”
In a prospective cohort study, Andersen and colleagues analyzed 186 patients (mean age, 63.25 years; 59.1% men; 84.9% previously/currently smoking) newly diagnosed with stage IV non-small cell lung cancer (NSCLC) for 5 years to determine how depression severity was linked to systemic inflammation ratio (SIR) biomarker levels, both of which are also predictive of survival in this type of cancer.
When assessing depression severity, researcher used patients’ total scores from the Patient Health Questionnaire-9 that ranged from 0 to 27. Based on the total score, the severity of patients’ depressive symptoms were categorized as none/mild (n = 120; 64.5%), moderate (n = 51; 27.4%), moderate to severe (n = 9; 4.8%) or severe (n = 6; 3.2%).
To evaluate SIRs, researcher used patients’ blood and cell counts of neutrophils, lymphocytes and platelets to calculate the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the advanced lung cancer inflammation index (ALI).
Each biomarker was first tested as a predictor of 2-year overall survival and then in relation to depression in multivariate linear regressions.
Of the total cohort, 61% of patients died over 2 years, and 35% of patients had moderate to severe symptoms of depression.
Predictors of poorer overall survival included higher NLR (adjusted HR = 1.91; 95% CI, 1.29-2.84), higher PLR (aHR = 2.08; 95% CI, 1.34-3.22) and lower ALI (aHR = 0.53; 95% CI, 0.34-0.82) in Cox model analyses adjusted for age, sex, race, partner status, education level, employment status and smoking history. These SIRs signaled a greater risk for mortality with higher inflammation levels than lower inflammation levels, according to researchers.
After adjusting for multiple covariates, researchers found an association between depression symptoms and the three inflammation biomarker levels (NLR, P = .02; PLR, P = .02; ALI, P = .009). This finding demonstrates that higher depression levels are linked to increased NLR, increased PLR and decreased ALI values, which as noted above, are predictors of poor overall survival.
A two to three times higher likelihood of having poor PLR and ALI values at diagnosis was found for patients identified as having moderate to severe depression symptoms.
In patients with moderate to severe depression levels, 77% of patients fell above the PLR marker that signaled higher levels of inflammation (PLR 5), whereas only 56% of patients with no/mild depression levels were above this marker.
For ALI ratios, a greater percentage of patients with moderate to severe depression fell below the cutoff than patients with no/mild depression (70% vs. 58%), demonstrating that higher levels of depression are linked to lower ALI.
Lastly, measuring for NLR, patients with no/mild depression were evenly split above (NLR 5) and below (NLR < 5) the cutoff that separated high inflammation from low inflammation. On the other hand, more patients with moderate to severe depression were above the cutoff (58%) than below it (42%).
“Alone these inflammation markers have been reliable predictors of survival not only for lung cancer but other tumors as well,” Andersen told Healio. “Screening of depression and anxiety has been mandated by the Commission on Cancer for accreditation. The American Society of Clinical Oncology will shortly be releasing the updated guideline for depression/anxiety screening and treatment. Thus, screening information can be easily coupled with the determination of inflammatory markers. These data highlight the importance of identifying and treating depression early and vigorously — the same principles that apply when cancer is diagnosed and treated.”
For future studies, Andersen told Healio there are two obvious directions that researchers could take.
“The first is an intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity to extend these findings and discover their biobehavioral mechanisms, with the long term aim to improve patients’ quality of life, treatment responses and longevity,” she said. “The second is to conduct randomized depression trials with patients to reduce depression while simultaneously conducting cell biology and inflammation studies.”
For more information:
Barbara L. Andersen, PhD, can be reached at andersen.1@osu.edu
Reference:
- Depression linked to deadly inflammation in lung cancer patients. https://news.osu.edu/depression-linked-to-deadly-inflammation-in-lung-cancer-patients/ Published March 6, 2023. Accessed March 6, 2023.