Cytokine levels in depressed and non-depressed subjects, and masking effects of obesity

Schmidt, F.; Lichtblau, Nicole; Minkwitz, Juliane; Chittka, Tobias; Thormann, J.; Kirkby, Kenneth C.; Sander, Christian; Mergl, Roland; Faßhauer, Mathias; Stümvoll, Michael; Holdt, Lesca M.; Teupser, Daniel; Hegerl, Ulrich; Himmerich, Hubertus

doi:10.1016/j.jpsychires.2014.04.021

Cited by 137 publications

(130 citation statements)

References 38 publications

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“…For some assays, the proteins could not be detected in more than 60% of the tested sera (Table 2). Indeed, both platforms failed to robustly detect the GM-CSF, IL-1β, IL-2 and IL-5 cytokines for which previous investigations had reported significant variations in expression either during MDE treatment or at baseline in comparison to healthy controls (Biancotto et al, 2013;Dahl et al, 2014;Hernandez et al, 2008;Schmidt et al, 2014;Shelton et al, 2015). These types of inconsistency in the results have already been reported (Breen et al, 2011;Chaturvedi et al, 2011;Dabitao et al, 2011;Dupuy et al, 2013;Fu et al, 2010).…”

Section: Discussionmentioning

confidence: 89%

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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Section: Discussionmentioning

confidence: 89%

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

Belzeaux

Lefebvre

Lazzari

et al. 2017

Psychoneuroendocrinology

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“…It is important to consider that TNF-may not a specific biomarker for PTSD, but rather a general marker of psychopathology. Elevated levels of TNF-have also been observed in other psychiatric disorders, including depression (Himmerich et al 2008, Schmidt et al 2014). Furthermore, given that TNF-is part of a complex network of cytokines, which have also been shown to be elevated in PTSD and other disorders (e.g.…”

Section: Tnf-in Human Studies Of Ptsdmentioning

confidence: 99%

A SYSTEMATIC REVIEW OF TUMOR NECROSIS FACTOR-α IN POST-TRAUMATIC STRESS DISORDER: EVIDENCE FROM HUMAN AND ANIMAL STUDIES

Hussein

Dalton

Willmund³

et al. 2017

Psychiat Danub

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“…In depression, proinflammatory cytokines were found to interact with the HPA axis, to stimulate the serotonin-depleting indolamine-2,3-dioxygenase and to trigger serotonin reuptake [6,8,9]. Levels of proinflammatory cytokines were repeatedly found to be elevated in depressed patients as well as in animal models of depression [6,10,11], potentially representing an inflammation-associated specific subtype of MDD [12,13,14] and a target for new antidepressant treatment strategies [15,16]. …”

Section: Introductionmentioning

confidence: 99%

Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls

et al. 2016

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Background: In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups. Methods: In 60 patients with MDD and 129 controls, 15-min resting-state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness-promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-α, interferon-γ and IL-2 were measured prior to the EEG. Results: Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group × time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant. Conclusions: The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways.

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Cytokine levels in depressed and non-depressed subjects, and masking effects of obesity

Cited by 137 publications

References 38 publications

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

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

A SYSTEMATIC REVIEW OF TUMOR NECROSIS FACTOR-α IN POST-TRAUMATIC STRESS DISORDER: EVIDENCE FROM HUMAN AND ANIMAL STUDIES

Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls

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