Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study

Gimeno, David; Kivimäki, Mika; Brunner, Eric J.; Elovainio, Marko; Vogli, Roberto De; Steptoe, Andrew; Kumari, Meena; Lowe, G. D. O.; Rumley, Ann; Marmot, Michael; Ferrie, Jane E.

doi:10.1017/s0033291708003723

Cited by 512 publications

(418 citation statements)

References 52 publications

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“…Conversely, in a cohort of .3,339 participants with .12 years of follow-up, baseline inflammatory marker levels (CRP and IL-6) were associated with a subsequent risk of depression at followup (36). However, this association was not observed in patients with type 2 diabetes.…”

Section: Resultsmentioning

confidence: 86%

Elevated Levels of hs-CRP Are Associated With High Prevalence of Depression in Japanese Patients With Type 2 Diabetes: The Diabetes Distress and Care Registry at Tenri (DDCRT 6)

et al. 2014

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OBJECTIVEBecause of the absence of data on the direct association between inflammation and depression in patients with diabetes, we examined the association between hs-CRP levels and the high prevalence of depression in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODSCross-sectional data were obtained from 3,573 patients with type 2 diabetes recruited from a Japanese diabetes registry. A multiple logistic regression analysis adjusted for potential confounders was used to assess independent associations between hs-CRP levels and major depression, as defined by the Patient Health Questionnaire-9. RESULTSMean age, BMI, and HbA 1c levels were 66.0 years, 24.6 kg/m 2 , and 7.4% (57.8 mmol/mol), respectively, and 122 patients (3.4%) suffered from major depression. In the age-and sex-adjusted model, the odds ratio (OR) for major depression was 1.86 (95% CI 1.01-3.42; P = 0.045) in the highest CRP quintile compared with that in the 3rd CRP quintile; however, this association disappeared after adjustment for other possible confounders (OR 1.58 [95% CI 0.85-2.94]; P = 0.148). Among patients with a BMI of ‡25 kg/m 2 , a significant association was observed between the highest hs-CRP quintile and major depression (multivariable-adjusted OR 2.69 [95% CI 1.09-7.08]; P = 0.032). CONCLUSIONSWe observed a significant positive association between high hs-CRP levels and depression in patients with diabetes who had a high BMI.In the last decade, several studies have been published that suggest a close association between diabetes and depression. Patients with diabetes have a high prevalence of depression (1), particularly that associated with poor treatment adherence and glycemic control (1,2), and a high prevalence of complications (3). In addition, depression is associated with mortality in these patients (4).

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Section: Resultsmentioning

confidence: 86%

Elevated Levels of hs-CRP Are Associated With High Prevalence of Depression in Japanese Patients With Type 2 Diabetes: The Diabetes Distress and Care Registry at Tenri (DDCRT 6)

et al. 2014

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“…Some correlational work has found that the relationship between inflammatory markers and symptoms of depression or depressed mood is stronger in males than females (Gimeno et al, 2009;Penninx et al, 2003). Conversely, in the context of clinical studies that follow patients using the cytokine interferon-a (IFN-a), some work has found that females who receive IFN-a are at greater risk of developing depression than males (Gohier et al, 2003;Koskinas et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression

Moieni

Irwin

Jevtić

et al. 2015

Neuropsychopharmacol

236

238

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Substantial evidence demonstrates that inflammatory processes may underlie depression for a subset of patients, including work showing that healthy subjects exposed to an inflammatory challenge show increases in depressed mood and feelings of social disconnection. However, despite the fact that depression is two times as likely to occur in females than males, the vast majority of this work has been carried out in males. Thus, the objective of this study was to determine whether females (vs males) would show greater increases in proinflammatory cytokines, depressed mood, and social disconnection in response to an inflammatory challenge. One hundred and fifteen healthy participants (69 female) completed this double-blind, placebo-controlled, randomized clinical trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), depressed mood, and feelings of social disconnection were assessed hourly. Results showed that endotoxin (vs placebo) led to increases in proinflammatory cytokines (TNF-a, IL-6), depressed mood, and feelings of social disconnection. Females exposed to endotoxin showed greater increases in depressed mood and feelings of social disconnection. Furthermore, increases in TNF-a and IL-6 were correlated with increases in social disconnection for females but not for males. These sex differences in the relationships between inflammatory and socioemotional responses to an inflammatory challenge may be particularly important for understanding why females are two times as likely as males to develop depressive disorders.

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“…In support of this hypothesis, depressive symptoms have been shown to be associated with increased serum and plasma concentrations of TNF, IL-6 and C-reactive protein (Dowlati et al, 2010;Goldsmith et al, 2016;Strawbridge et al, 2015;Valkanova et al, 2013). Most importantly, recent longitudinal studies have extended these cross-sectional observations by reporting that increased inflammatory markers in non-depressed individuals predict the later development of major depression (Gimeno et al, 2009;Pasco et al, 2010;van den Biggelaar et al, 2007).…”

Section: Introductionmentioning

confidence: 88%

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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Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study

Cited by 512 publications

References 52 publications

Elevated Levels of hs-CRP Are Associated With High Prevalence of Depression in Japanese Patients With Type 2 Diabetes: The Diabetes Distress and Care Registry at Tenri (DDCRT 6)

Elevated Levels of hs-CRP Are Associated With High Prevalence of Depression in Japanese Patients With Type 2 Diabetes: The Diabetes Distress and Care Registry at Tenri (DDCRT 6)

Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression

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

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