Objective:To assess the magnitude and direction of associations of depression with C-reactive protein (CRP), interleukin (IL)-1, and IL-6 in community and clinical samples.Methods:Systematic review of articles published between January 1967 and January 2008 in the PubMed and PsycINFO electronic data

Associations of Depression With C-Reactive Protein, IL-1, and IL-6 : A Meta-Analysis

The brain and immune system form a bidirectional communication network in which the immune system operates as a diffuse sense organ, informing the brain about events in the body. This allows the activation of immune cells to produce physiological, behavioral, affective, and cognitive changes that are collectively called sickness, which function to promote recuperation. Fight-flight evolved later and coopted this immune-brain circuitry both because many of the needs of fight-flight were met by this circuitry and this cooptation allowed the immune system to respond to potential injury in anticipatory fashion. Many sequelae of exposure to stressors can be understood from this view and can take on the role of adaptive responses rather than pathological manifestations. Finally, it is argued that activation of immune-brain pathways is important for understanding diverse phenomena related to stress such as depression and suppression of specific immunity.

Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition.

Objective
To conduct a systematic review and meta-analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs).

Method
The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models.

Result
Eighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon-gamma levels were lower in MDD (Hedge's g = −0.477, P = 0.043). Levels of IL-1β, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, and transforming growth factor-beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I2: 51.6–97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index).

Conclusion
Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.

/pdf/peripheral-cytokine-and-chemokine-alterations-in-depression-3u6rtrppnv.pdf

Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies.

This is a broad meta-analysis of the relations of both depression and stressors to immunological assays. The number of study samples (greater than 180) and measures (greater than 40) is much more extensive than any so far. Analyses are done by both fixed and random effects. By a fixed-effects analysis, both major depression and naturally occurring acute stressors are associated with (1) an overall leukocytosis, (2) mild reductions in absolute NK-cell counts and relative T-cell proportions, (3) marginal increases in CD4/CD8 ratios, and (4) moderate decreases in T- and NK-cell function. However, the degree of heterogeneity of the studies' results raises questions about their robustness. Therefore, we also did the first random effects analysis to estimate what is likely to appear in future studies. For depression, the analysis showed the immunological correlates included (1) an overall leukocytosis, manifesting as a relative neutrophilia and lymphoenia; (2) increased CD4/CD8 ratios; (3) increased circulating haptoglobin, PGE(2), and IL-6 levels; (4) reduced NK-cell cytotoxicity; and (5) reduced lymphocyte proliferative response to mitogen. For stressors, the random effects analysis showed that future studies are likely to find the following effects: (1) an overall leukocytosis, manifesting as an absolute lymphocytosis; (2) alterations in cytotoxic lymphocyte levels, CD4/CD8 ratios, and natural killer cell cytotoxicity with the direction of change depending on the chronicity of the stressor; (3) a relative reduction of T-cell levels; (3) increased EBV antibody titers; (4) reduced lymphocyte proliferative response and proportion of IL-2r bearing cells following mitogenic stimulation; and (5) increased leukocyte adhesiveness. The random-effects analysis revealed that for both major depression and naturally occurring stressors the following effects are shared: leukocytosis, increased CD4/CD8 ratios, reduced proliferative response to mitogen, and reduced NK cell cytotoxicity. The implications for these findings for disease susceptibility and the pathophysiology of these conditions is discussed.

The relationship of depression and stressors to immunological assays: a meta-analytic review.

Objectives: This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life, mood states, stress symptoms, lymphocyte counts, and cytokine production. Methods: Forty-nine patients with breast cancer and 10 with prostate cancer participated in an 8-week MBSR program that incorporated relaxation, meditation, gentle yoga, and daily home practice. Demographic and health behavior variables, quality of life (EORTC QLQ C-30), mood (POMS), stress (SOSI), and counts of NK, NKT, B, T total, T helper, and T cytotoxic cells, as well as NK and T cell production of TNF, IFN-, IL-4, and IL-10 were assessed pre- and postintervention. Results: Fifty-nine and 42 patients were assessed pre- and postintervention, respectively. Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality. Although there were no significant changes in the overall number of lymphocytes or cell subsets, T cell production of IL-4 increased and IFN- decreased, whereas NK cell production of IL-10 decreased. These results are consistent with a shift in immune profile from one associated with depressive symptoms to a more normal profile. Conclusions: MBSR participation was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients. This study is also the first to show changes in cancer-related cytokine production associated with program participation.

http://psych415.class.uic.edu/Readings/Carlson,%20Mindfulness%20training%20-%20cancer%20health,%20PsyMed,%202003.pdf

Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients.

One of the most consistently reported findings in depression has been leucocytosis. In 33 in-patients with major depressive disorder, we assessed white blood cell count (WBC) and lymphocyte subsets four times over a period of 6 weeks. The control group consisted of 44 healthy subjects. Shortly after admission, we detected significant increases in the numbers of leucocytes, granulocytes, platelets and monocytes in the depressed patients. Patients who recovered well during hospitalization showed a decrease in monocyte counts, whereas those with slower clinical improvement had significantly higher monocyte counts than the control group. This longitudinal study demonstrates that monocytes may play a role in the acute phase of depression and could provide an explanation for immunological dysfunction in depressive states.

Major depressive disorder is associated with elevated monocyte counts

One, as yet unemployed, approach to investigating immunology in depression is the assessment of the cytokine production by leucocytes, which would allow the determination of immune response under standardized conditions. Thus we measured the production of mitogen-induced cytokines (IL-1 beta, IL-2, IL-6, IL-10, interferon-gamma) and sIL-2R in a whole blood assay, and serum protein levels such as C-reactive protein (CRP), haptoglobin (Hp) and alpha 2-macroglobulin (alpha 2 M) in a longitudinal 6-week study in an attempt to assess leucocyte function during and after acute clinical stage of depression in 39 patients. Shortly after admission to hospital we found higher levels of all measured cytokines in the patients. Serum protein levels were significantly higher in the patients than in controls, and decreased over the study period. Whereas slightly elevated monokine levels in patients tended to reach control values, lymphokines showed a significant decrease over the 6 weeks as compared to baseline. These results suggest that the increase in immune activity seen at the beginning of the study may be followed by a suppressed cell-mediated immune function.

Cytokine production and serum proteins in depression.

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Major depressive disorder is associated with elevated monocyte counts

Cytokine production and serum proteins in depression.