Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Misiak, Błażej; Beszłej, Jan Aleksander; Kotowicz, Kamila; Szewczuk-Bogusławska, Monika; Samochowiec, Jerzy; Kucharska-Mazur, Jolanta; Frydecka, Dorota

doi:10.1016/j.pnpbp.2017.04.021

Cited by 83 publications

(41 citation statements)

References 170 publications

(186 reference statements)

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“…15,16 Tumor necrosis factor α, interleukin-6, and interleukin-1β are proinflammatory cytokines that are most commonly and consistently associated with depression. [17][18][19] In lung cancer, biomarkers such as interleukin-6 and tumor necrosis factor α are elevated in patients with depressed states. 20 Nevertheless, the clinical usefulness of this association is complicated by a number of factors.…”

Section: Introductionmentioning

confidence: 99%

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

McFarland

Shaffer

Breitbart

et al. 2018

Cancer

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BACKGROUND: Depression is highly prevalent in lung cancer. Although there is a known association between inflammation and depression, this relationship has not been examined in patients with lung cancer who undergo treatment with immune and other targeted drug therapies. Peripheral blood C-reactive protein (CRP), a marker of systemic inflammation, may help identify metastatic lung cancer patients with inflammation-associated depression. METHOD: Patients with metastatic lung cancer undergoing treatment were evaluated for depression using the Hospital Anxiety and Depression Scale (HADS). Inflammation (CRP and CRP cutoffs ≥1 and ≥3 mg/mL) and demographic and treatment variables were analyzed for association with depression. RESULTS: One hundred nine consecutive participants exhibited an average plasma CRP concentration of 1.79 mg/mL (median, 0.75 mg/mL [standard deviation, 2.5 mg/mL), and 20.7% had a CRP concentration of ≥3.0 mg/mL; 23.9% met depression screening criteria (HADS ≥8). A log transformation of CRP was significantly correlated with depression severity (r = 0.47, P < .001). CRP was the only covariate to predict depression severity (P = .008) in a multivariate model including lung cancer disease subtype and type of systemic treatment. Receiver operating characteristic analysis indicated that CRP had moderate predictive accuracy in identifying elevated depression (area under the curve = 0.74). A cutoff of CRP ≥3.0 generated high specificity (88%) but identified only 50% of those with elevated depression. CONCLUSION: Elevated CRP is associated with depression in patients with metastatic lung cancer. Thus, CRP may identify a subset of lung cancer patients with inflammation-induced depression and may be useful in predicting response to treatments that target inflammation or its downstream mediators on the brain.

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Section: Introductionmentioning

confidence: 99%

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

McFarland

Shaffer

Breitbart

et al. 2018

Cancer

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“…32,33 CRP, along with the proinflammatory cytokines TNF-a, IL-6, and IL-1b, is consistently associated with depression in various patient populations. [34][35][36][37][38] NLR is derived from the absolute neutrophil and lymphocyte counts obtained from a CBC and has been evaluated as a marker of depression and other mood disorders. 39 High NLR is associated with worse cancer-related prognosis 40,41 and has been shown to be associated with a lower chance of benefit from immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Tumor Mutation Burden and Depression in Lung Cancer: Association With Inflammation

McFarland

Jutagir

Miller

et al. 2020

Journal of the National Comprehensive Cancer Network

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Background: Patients with lung cancer with greater systemic inflammation have higher rates of depression. Tumor mutation burden (TMB) predicts immunotherapy response in patients with lung cancer and is associated with intratumoral inflammation, which may contribute to systemic inflammation and depression. This study evaluated whether higher TMB was associated with increased depression and systemic inflammation in patients with lung cancer. Patients and Methods: Patients with metastatic lung cancers were evaluated for depression severity using the Hospital Anxiety and Depression Scale. TMB was measured using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Inflammation was evaluated using C-reactive protein (CRP) level and neutrophilto-lymphocyte ratio (NLR). Results: A total of 96 patients with adequate TMB testing were evaluated. The average number of mutations (TMB) was 10.8 (SD, 10.9). A total of 19% of patients endorsed clinically significant depression symptoms. TMB was significantly correlated with depression severity (r 5 0.34; P5.001) and NLR (r 5 0.37; P5.002) but not CRP level (r 5 0.19; P5.07). TMB was also higher in patients receiving chemotherapy (mean, 12.0) and immunotherapy (mean, 14.4) versus targeted therapy (mean, 4.8). A multivariate model found that TMB (b 5 0.30; P5.01) and CRP level (b 5 0.31; P5.01) were independently associated with depression; there was no significant interaction effect of TMB 3 CRP and depression. A similar multivariate model showed no independent effect for NLR and depression (b 5 0.16; P5.17) after accounting for TMB. Conclusions: These data provide evidence for biologic depression risk in patients with lung cancer who have high levels of TMB. The underlying mechanism of the association is not clearly related to inflammation but warrants further analysis to broadly elucidate the mechanism of biologically derived depression in cancer.

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“…It has been associated with depression and other measures of psychological distress in both medically healthy and chronically ill populations . CRP is a biomarker that has been more consistently associated with depression, along with the proinflammatory cytokines, TNF‐α, interleukin‐6 (IL‐6), and IL‐1β as compared with other depression biomarkers . CRP elevation is also associated with depression severity .…”

Section: Introductionmentioning

confidence: 99%

“…16,20 CRP is a biomarker that has been more consistently associated with depression, along with the proinflammatory cytokines, TNF-α, interleukin-6 (IL-6), and IL-1β as compared with other depression biomarkers. 16,17,21 CRP elevation is also associated with depression severity. 22 There are no studies to date that have evaluated an association between EGFR-mutated NSCLC and CRP.…”

Section: Introductionmentioning

confidence: 99%

Depression and inflammation among epidermal growth factor receptor (EGFR) mutant nonsmall cell lung cancer patients

et al. 2019

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Objectives: Depression is highly prevalent in Non-Small Cell Lung cancer (NSCLC) and is associated with elevated inflammation. However, certain subtypes of driver mutation associated NSCLC such as Epidermal Growth Factor Receptor (EGFR) mutated NSCLC may be associated with less depression given the differences in their underlying biology and disease trajectories. Biological variables such as inflammation, measured by C-reactive protein (CRP), may provide insight into depression variability in EGFR mutant NSCLC. Methods: Patients with EGFR mutant and wild-type metastatic NSCLC were evaluated for depression using the Hospital Anxiety and Depression Scale (HADS) on a continuous scale and meeting depression screening criteria (HADS≥8). Inflammation was measured using CRP. A mediation model was created to understand how inflammation mediates EGFR wild-type associated depression. Results: One hundred out of 120 patients with NSCLC were recruited (83.3% response rate). The 20 participants with EGFR mutant NSCLC had less depression (HADS-D 3.0 versus 5.4) (p<.001), met depression screening criteria less often (p=.047), and exhibited less inflammation [CRP =0.23 mg/ml versus 2.71 mg/ml] (p<.001) in comparison with EGFR wild-type NSCLC. Multivariate linear regression model revealed that only CRP predicted depression (p=.015) while controlling for age and sex. Mediation analysis found that lower CRP partially mediated less depression in EGFR mutant NSCLC. Conclusion: EGFR mutant NSCLC is associated with less depression but the relationship is partially mediated by lower CRP-related inflammation, which is a stronger predictor of depression than EGFR status. Depression in lung cancer varies by subtype and is significantly related to inflammation.

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Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Cited by 83 publications

References 170 publications

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

Tumor Mutation Burden and Depression in Lung Cancer: Association With Inflammation

Depression and inflammation among epidermal growth factor receptor (EGFR) mutant nonsmall cell lung cancer patients

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