Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy

Grosse, Laura; Carvalho, Lívia A.; Birkenhäger, Tom K.; Hoogendijk, Witte J.G.; Kushner, Steven A.; Drexhage, Hemmo A.; Bergink, Veerle

doi:10.1007/s00213-015-3943-9

Cited by 79 publications

(46 citation statements)

References 61 publications

(62 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…To our knowledge, the percentage of memory CD8 + cells has not previously been evaluated specifically in depression, although several studies reported higher levels of CD8 + cells per se , in depressed populations (Grosse et al, 2016a; Pavon et al, 2006). Potentially consistent with our finding, non-responders to treatment with either venlafaxine or imipramine showed higher levels of CD8 + cells compared to depressed subjects who responded to treatment (Grosse et al, 2016a). Additionally, a study of HIV positive women reported that depressive and anxiety symptoms were significantly associated with higher activated CD8 + counts and higher viral load levels suggesting a mechanism by which depression may have a negative effect on HIV disease progression (Evans et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Suzuki

Savitz

Teague

et al. 2017

Brain, Behavior, and Immunity

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A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations. Furthermore, despite evidence that sleep disturbance, which is a core symptom of MDD, is itself associated with alterations in lymphocyte distributions, there is a paucity of studies examining the contribution of sleep disturbance on lymphocyte populations in MDD populations. Here, we measured differences in the percentages of 13 different lymphocytes and 6 different leukocytes in 54 unmedicated MDD patients (partially remitted to moderate) and 56 age and sex-matched healthy controls (HC). The relationship between self-reported sleep disturbance and cell counts was evaluated in the MDD group using the Pittsburgh Sleep Quality Index (PSQI). The MDD group showed a significantly increased percentage of CD127low/CCR4+ Treg cells, and memory Treg cells, as well as a reduction in CD56+CD16− (putative immunoregulatory) NKC counts, the latter, prior to correction for body mass index. There also was a trend for higher effector memory CD8+ cell counts in the MDD group versus the HC group. Further, within the MDD group, self-reported sleep disturbance was associated with an increased percentage of effector memory CD8+ cells but with a lower percentage of CD56+CD16− NKC. These results provide important new insights into the immune pathways involved in MDD, and provide novel evidence that MDD and associated sleep disturbance increase effector memory CD8+ and Treg pathways. Targeting sleep disturbance may have implications as a therapeutic strategy to normalize NKC and memory CD8+ cells in MDD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Suzuki

Savitz

Teague

et al. 2017

Brain, Behavior, and Immunity

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“…[62][63][64] Additionally, T-cell changes seem to predict antidepressant response. [65][66][67] However, our study only measured the entire lymphocyte count, which is too general to capture selective T-cell changes. It is also possible that the association between TMB and depression is mediated by other immune markers, such as TNF-a, IL-6, or IL-1b, rather than CRP, or by factors independent of inflammatory proteins entirely.…”

Section: Discussionmentioning

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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“…In line with our previous report (21), p11 levels in NK cells were correlated with the MADRS depression score in PD(Dep) patients. Zorrilla et al (29) reported a decreased number of NK cells in depressed patients; moreover, Grosse et al (30) reported that NK cell activity is related to antidepressant response. Our data add to the emerging evidence supporting an association between NK cells and a depressive phenotype, even with a comorbidity of PD.…”

Section: Discussionmentioning

confidence: 99%

Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

Green

Zhang

Tiklová

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Individuals with Parkinson’s disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression. We investigated p11 levels in postmortem PD brains and assessed whether peripheral p11 levels correlate with disease severity. Substantia nigra, putamen, and cortical p11 protein levels were assessed in postmortem brain samples from PD patients and matched controls. In a different set of postmortem brains, p11 mRNA expression was measured in dopaminergic cells from the substantia nigra. Both p11 protein and mRNA levels were decreased in PD patients. Peripheral p11 protein levels were investigated in distinct leukocyte populations from PD patients with depression and those without depression. Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores. Given that inflammation plays a role in both PD and depression, it is intriguing that peripheral p11 levels are altered in immune cells in both conditions. Our data provide insight into the pathological alterations occurring centrally and peripherally in PD. Moreover, if replicated in other cohorts, p11 could be an easily accessible biomarker for monitoring the severity of PD, especially in the context of comorbid depression.

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Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy

Abstract: In melancholic MDD, FACS analysis of circulating leukocyte subpopulations might help to discriminate between patients with high or low responsiveness to antidepressant treatment.

Cited by 79 publications

References 61 publications

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

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

Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

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