Cancer-related inflammation and depressive symptoms: Systematic review and meta-analysis

Abstract

Background: Depressive symptoms in patients with cancer are associated with poor quality of life and decreased survival. Although inflammation is reliably associated with depression in otherwise healthy individuals, the association in patients with cancer remains unclear. Given the high prevalence of cancer-related inflammation, the authors aimed to establish the relationship between inflammation and depression in cancer patients based on extant literature.

Methods: A systematic review and meta-analysis was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and registered under Prospero ID CRD42021226743. Three databases were searched including PubMed, the Cochrane Library, and PsycINFO using the following criteria for inclusion: 1) measurement of a peripheral inflammatory marker, 2) use of a validated tool/scale to measure depression, and 3) a cancer diagnosis. Risk of publication bias was assessed by Funnel plot and Egger test.

Results: Seventy-three studies were included in the systematic review and 54 studies (n = 5017) were included in meta-analyses. Associations with depressive symptoms were significant for peripheral blood interleukin (IL)-6 (standardized mean difference [SMD] = 0.59; 95% confidence interval [CI], 0.35-0.82), I² = 57.9%; tumor necrosis factor (TNF) (SMD = 0.73; 95% CI, 0.35-1.11), I² = 74.1%; and C-reactive protein (CRP) (SMD = 0.57; 95% CI, 0.27-0.87), I² = 0%. IL-5, IL-13, albumin, and neutrophil-to-lymphocyte ratio were associated with depressive symptoms but based on fewer studies. Most cancer settings were represented; the number of studies per inflammatory marker varied from 1 to 52.

Conclusions: Although peripheral inflammatory markers were unevenly studied, the most studied markers (IL-6, TNF, and CRP) were associated with depressive symptoms in cancer patients and may be useful for management of depressive symptoms in the cancer setting.

Lay summary: Peripheral blood inflammatory markers (IL-6, TNF, and CRP) were associated with depressive symptoms in various cancer settings. Although further studies are warranted, these findings may help identify and manage depressive symptoms in patients with cancer.

Keywords: C-reactive protein; cancer; depression; depressive symptoms; inflammation; interleukin-6; meta-analysis; tumor necrosis factor.