Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder

Haapakoski, Rita; Mathieu, Jean‐Paul; Ebmeier, Klaus P.; Alenius, Harri; Kivimäki, Mika

doi:10.1016/j.bbi.2015.06.001

Cited by 949 publications

(658 citation statements)

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“…Indeed, over the past several decades, data demonstrating increased innate immune responses and inflammation in patients with major depression have dominated the literature . For example, a multitude of studies have described increases in inflammatory cytokines in the peripheral blood and cerebrospinal fluid (CSF) of depressed patients (Howren et al, 2009;Dowlati et al, 2010;Haapakoski et al, 2015). In addition, numerous studies have documented increases in peripheral blood acute-phase reactants, chemokines, and adhesion molecules (Howren et al, 2009;Dowlati et al, 2010;Haapakoski et al, 2015).…”

Section: Foundations For the Hypothesis That The Immune System Plays mentioning

confidence: 99%

“…In addition, numerous studies have documented increases in peripheral blood acute-phase reactants, chemokines, and adhesion molecules (Howren et al, 2009;Dowlati et al, 2010;Haapakoski et al, 2015). In several meta-analyses of this literature, the most well-documented and reproducible findings have included increases in peripheral blood concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) and the acute-phase reactant C-reactive protein (CRP) (Howren et al, 2009;Dowlati et al, 2010;Haapakoski et al, 2015). In addition to increases in inflammatory markers in depressed subjects, a number of polymorphisms in genes associated with inflammation, including IL-1β, IL-6, and TNF, as well as CRP, have been linked to the development of mood and anxiety disorders as well as treatment response (Bufalino et al, 2012;Michopoulos et al, 2015).…”

Section: Foundations For the Hypothesis That The Immune System Plays mentioning

confidence: 99%

“…For example, a multitude of studies have described increases in inflammatory cytokines in the peripheral blood and cerebrospinal fluid (CSF) of depressed patients (Howren et al, 2009;Dowlati et al, 2010;Haapakoski et al, 2015). In addition, numerous studies have documented increases in peripheral blood acute-phase reactants, chemokines, and adhesion molecules (Howren et al, 2009;Dowlati et al, 2010;Haapakoski et al, 2015). In several meta-analyses of this literature, the most well-documented and reproducible findings have included increases in peripheral blood concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) and the acute-phase reactant C-reactive protein (CRP) (Howren et al, 2009;Dowlati et al, 2010;Haapakoski et al, 2015).…”

Section: Foundations For the Hypothesis That The Immune System Plays mentioning

confidence: 99%

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Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

Miller

Haroon

Felger

2016

Neuropsychopharmacol

119

124

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A wealth of data has been amassed that details a complex, yet accessible, series of pathways by which the immune system, notably inflammation, can influence the brain and behavior. These data have opened the window to a diverse array of novel targets whose potential efficacy is tied to specific neurotransmitters and neurocircuits as well as specific behaviors. What is clear is that the impact of inflammation on the brain cuts across psychiatric disorders and engages dopaminergic and glutamatergic pathways that regulate motivation and motor activity as well as the sensitivity to threat. Given the ability to identify patient populations with increased inflammation, the precision of interventions can be further tuned, in conjunction with the ability to establish target engagement in the brain through the use of multiple neuroimaging strategies. After a brief overview of the mechanisms by which inflammation affects the brain and behavior, this review examines the extant literature on the efficacy of anti-inflammatory treatments, while forging guidelines for future intelligent clinical trial design. An examination of the most promising therapeutic strategies is also provided, along with some of the most exciting clinical trials that are currently being planned or underway.

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Section: Foundations For the Hypothesis That The Immune System Plays mentioning

confidence: 99%

Section: Foundations For the Hypothesis That The Immune System Plays mentioning

confidence: 99%

Section: Foundations For the Hypothesis That The Immune System Plays mentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

Miller

Haroon

Felger

2016

Neuropsychopharmacol

119

124

View full text Add to dashboard Cite

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“…In mood disorders, several studies have suggested that the chronic mild inflammation indicated by elevated C-reactive protein (Courtet et al, 2015;Rapaport et al, 2015;Uher et al, 2014) as well as the quantification of the levels of inflammatory cytokines such as IL-6, IL-10 and TNF (de Witte et al, 2014;Ducasse et al, 2015b;Haapakoski et al, 2015;Halaris et al, 2015;Rethorst et al, 2013) could prove to be useful biomarkers for improved diagnosis and the detection of treatment refractoriness (Strawbridge et al, 2015), as well as indicators of the risk of suicide. As an increasing number of inflammatory factors are tested, an emerging picture supports the idea that a complex network of cytokines is involved in the pathophysiology of disease such as major depression (Dahl et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays

Belzeaux

Lefebvre

Lazzari

et al. 2017

Psychoneuroendocrinology

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Cytokines produced by both immune and non-immune cells are likely to play roles in the development and/or progression of psychiatric disorders. Indeed, many investigators have compared the blood cytokine levels in psychiatric patients with those of healthy controls or monitored their levels in patients during disease progression to identify biomarkers. Nevertheless, very few studies have confirmed that such cytokines remain stable in healthy individuals through periods of weeks and months. This is an important issue to consider before using blood cytokine levels as biomarkers of disease traits, disease state, or treatment response. Although multiplex assay technology represents an advance in identifying biomarkers because it allows simultaneous examination of large panels of analytes from a small volume of sample, it is necessary to verify whether these assays yield enough sensitivity and reproducibility when applied to the blood from neuropsychiatric patients. Therefore, we compared two multiplex immunoassays, the bead-based Luminex® (Bio-Rad) and the electro-chemiluminescence-based V-plex® (MesoScaleDiscovery), for the detection and quantification of 31 cytokines, chemokines and growth factors in both the sera and plasma of patients with major depressive episodes (MDE) and age-and sex-matched healthy control subjects during a 30-week period. Although both platforms exhibited low coefficients of variability (CV) between the duplicates in the calibration curves, the linearity was better in general for the V-PLEX® platform. However, neither platform was able to detect the absolute values for all of the tested analytes. Among the 16 analytes that were detected by both assays, the intra-assay reproducibility was in general better with the V-PLEX® platform. Although it is not a general rule that the results from sera and plasma will be correlated, consistent results were more frequent with the V-PLEX® platform. Furthermore, the V-PLEX® results were more consistent with the gold standard ELISA simplex assay for IL-6 in both sera and plasma. The intra-individual variability of the measurements, among the sera and plasma for the 4 samples harvested from each healthy individual, was low for Eotaxin, G-CSF, IL-4, IL-7, IL-9, IL-12p40, IL-12p70, IL-15, MIP-1β, PDGF-BB, TNF, TNF-β and VEGF, but intermediate or high for IFN-γ, IL-6, IL-8, IL-10, and IP10. Together, these data suggest that extreme caution is needed in translating the results of multiplex cytokine profiling into biomarker discovery in psychiatry. Dear Editor,We thank you and the Editor in chief, Robert Dantzer, for reaching the conclusion to ultimately publish our manuscript. Following your suggestion, we changed the tiltle to: "How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays".We were concerned by the persistent negative comments of Reviewer#3, stressing out that our comparison between the two platforms we have worked with suffers a number of theoretical and technical limitations because...

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“…Meta-analyses showed higher blood levels of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), in drugfree depressed patients compared with healthy controls (10)(11)(12)(13). Studies using postmortem brain samples showed elevated gene expression of proinflammatory cytokines in the frontal cortex of people with a history of depression (14,15).…”

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confidence: 99%

Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress

Ren

Ishima

et al. 2016

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

134

156

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Depression is a severe and chronic psychiatric disease, affecting 350 million subjects worldwide. Although multiple antidepressants have been used in the treatment of depressive symptoms, their beneficial effects are limited. The soluble epoxide hydrolase (sEH) plays a key role in the inflammation that is involved in depression. Thus, we examined here the role of sEH in depression. In both inflammation and social defeat stress models of depression, a potent sEH inhibitor, TPPU, displayed rapid antidepressant effects. Expression of sEH protein in the brain from chronically stressed (susceptible) mice was higher than of control mice. Furthermore, expression of sEH protein in postmortem brain samples of patients with psychiatric diseases, including depression, bipolar disorder, and schizophrenia, was higher than controls. This finding suggests that increased sEH levels might be involved in the pathogenesis of certain psychiatric diseases. In support of this hypothesis, pretreatment with TPPU prevented the onset of depression-like behaviors after inflammation or repeated social defeat stress. Moreover, sEH KO mice did not show depressionlike behavior after repeated social defeat stress, suggesting stress resilience. The sEH KO mice showed increased brain-derived neurotrophic factor (BDNF) and phosphorylation of its receptor TrkB in the prefrontal cortex, hippocampus, but not nucleus accumbens, suggesting that increased BDNF-TrkB signaling in the prefrontal cortex and hippocampus confer stress resilience. All of these findings suggest that sEH plays a key role in the pathophysiology of depression, and that epoxy fatty acids, their mimics, as well as sEH inhibitors could be potential therapeutic or prophylactic drugs for depression.brain-derived neurotrophic factor | depression | epoxyeicosatrienoic acid | soluble epoxide hydrolase | resilience

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Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder

Abstract: HighlightsThis meta-analysis confirms a robust link between IL-6, CRP and major depression.The role of TNF-α and IL-1β in major depression remains uncertain.Further mechanistic and immunotherapeutic studies on IL-6 and CRP are needed.

Cited by 949 publications

References 95 publications

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays

Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress

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