According to findings from a study published in PLOS ONE, patients with lung cancer who also suffer from moderate-to-severe depression symptoms could be two to three times more likely to have elevated levels of inflammatory biomarkers, and the biomarkers may aid clinicians in predicting poorer clinical outcomes and survival rates.

The authors wrote, “Depression disproportionately affects lung cancer patients, having the highest rates of all cancers. Systemic inflammation and depression are both predictive of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence are unknown.”

In this study, researchers conducted a prospective cohort study that involved 186 patients who were newly diagnosed with stage IV NSCLC. The average age of participants was 63.25 years; 59.1% were males and 84.9% were classified as currently smoking or had a history of smoking. Patients were followed for up to 5 years, withdrawal from the study, or until death.

The study’s objective was to ascertain the correlation between systemic inflammation ratio (SIR) biomarker levels and patients’ depressive symptoms, with the theory that depression severity would be significantly linked with prognostically poor inflammation.

To evaluate SIRs, the researchers used routine laboratory work, which included 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). The researchers noted that systemic inflammatory biomarkers—NLR, PLR, ALI—are well-recognized predictors of advanced NSCLC survival.

They also used the patient-reported depressive symptom assessment (Patient Health Questionnaire-9 [PHQ-9]), which ranged from a score of 0 to 27 to screen for depression symptoms.

The results revealed that 61% of participants died over a 2-year period, and 35% of patients had moderate-to-severe depressive symptoms. The authors indicated that Cox model analyses confirmed greater NLR and PLR, along with lower ALI, to be predictive of poorer overall survival.

Among those with no/mild depression symptoms with regard to the PLR, 56% of participants were ranked above the PLR cutoff for dangerous levels of inflammation, compared with 42% who were below. Additionally, among individuals with elevated levels of depression, 77% were above the PLR cutoff for high levels of inflammation compared with only 23% who were below.

The authors also indicated that patients with no/mild depressive symptoms were as likely to have low NLRs (<5; 50%) as to have high NLRs (≥5; 50%), and in contrast, among patients with moderate/severe depressive symptoms, considerably more patients had prognostically worse, high NLRs (≥5; 58%) rather than low NLRs (<5; 42%).

The results also indicated that greater levels of depression are correlated with lower ALI. A more significant percentage of patients with moderate-to-severe depression were below the cutoff compared with those with no/mild depression symptoms. The results were reported as 70% versus 58%, respectively.

The authors concluded that even after controlling for other factors related to inflammation biomarker levels, such as demographics and smoking status, individuals with high levels of depression were 1.3 to 3 times more likely to have elevated levels of inflammation.

They wrote, “The clinical significance of depression/systemic inflammation associations found here require further study as individually, the variables are prognostic for NSCLC survival. Intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses and longevity.”

In a news story on the Ohio State University website, Barbra Andersen, PhD, lead author and professor of psychology at the Ohio State University, stated, “Of all cancer patients, those with lung cancer are among those with the highest rates of depression, which makes the findings of our study even more concerning.

Dr. Andersen also stated, “It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw. It is normal to be upset, sad, and anxious about a cancer diagnosis, but it is not normal to have major depression. Depression should not be discounted. This study shows the strong link between depression and inflammation, with both related to poor outcomes.”

Lastly, Dr. Andersen added, “The accumulating data suggest the importance of measuring and treating depression in patients with lung cancer.”

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