Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71: 171-186. Epub 2009 Feb 2

Department of Psychology, The University of Iowa, 11 Seashore Hall East, Iowa City, IA 52242, USA.
Psychosomatic Medicine (Impact Factor: 3.47). 02/2009; 71(2):171-86. DOI: 10.1097/PSY.0b013e3181907c1b
Source: PubMed


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.
Systematic review of articles published between January 1967 and January 2008 in the PubMed and PsycINFO electronic databases was performed. Effect sizes were calculated as stat d and meta-analyzed, using random-effects models.
Each inflammatory marker was positively associated with depression; CRP, d = 0.15 (95% CI = 0.10, 0.21), p < .001; IL-6, d = 0.25 (95% CI = 0.18, 0.31), p < .001; IL-1, d = 0.35 (95% CI = 0.03, 0.67), p = .03; IL-1ra, d = 0.25 (95% CI = 0.04, 0.46), p = .02. Associations were strongest in clinically depressed patient samples--but were also significant in community-based samples--and when clinical interviews were used. Studies adjusting for body mass index (BMI) had smaller associations, albeit significant. Relationships were inconsistent with respect to age, medication, and sex. Depression was related to CRP and IL-6 among patients with cardiac disease or cancer.
Depression and CRP, IL-1, and IL-6 are positively associated in clinical and community samples and BMI is implicated as a mediating/moderating factor. Continuity in clinic- and community-based samples suggests there is a dose-response relationship between depression and these inflammatory markers, lending strength to the contention that the cardiac (or cancer) risk conferred by depression is not exclusive to patient populations. Available evidence is consistent with three causal pathways: depression to inflammation, inflammation to depression, and bidirectional relationships.

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    • "It has been reported that there is a male preponderance of depression until early adolescence, yet the male to female ratio of depression is 1:1 in childhood in many countries À with the onset of puberty the ratio changes to an increased incidence in females (Piccinelli and Wilkinson, 2000; Merikangas et al., 2009). Meta-analysis by Howren et al. (2009) assessed associations of depression with C-reactive protein (CRP), interleukin (IL)-1, and IL-6 in community and clinical samples and reported a positive correlation between levels of IL-1, IL-6 and CRP and depression with a difference between males and females in IL-6 levels. The skewing of the total result by female group of patients remains remarkable in our result . "
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    ABSTRACT: The present study compares the serum cytokine levels between adolescent depression patients and healthy controls and assesses correlation between depression, anxiety scores and serum levels of eight cytokines. Study also checked the variation in serum levels with medication status (medication free/naïve vs. patients on medication). Following clinical and psychometric assessment of 77 adolescent (aged 13-18 years) depression patients (49 males and 28 females; 56 medication free/naïve) and 54 healthy controls (25 males, 29 females), eight cytokines (IL-1β, IL-2, IL-6, IL-10, TNF-α, IFN-γ, TGF-β1 and IL-17A {denoted IL-17 throughout}) were measured in serum using ELISA. Depressed adolescents had significantly high levels of IL-2 (p<0.001) and IL-6 (p=0.03) as compared to controls. The female population skewed the result of one cytokine (IL-6) in patients. Anxiety scores showed positive correlation (only in female patients) with IL-1β, IL-10 and negative correlation with TGF-β1 and IL-17. The gender effect in relationship between anxiety and cytokines was not straightforward. On comparing study groups on the medication/naïve status, IL-2 and TGF-β1 showed significant difference between the groups (p<0.001, p=0.007 higher in medicated). Depression in adolescents was associated with elevation of proinflammatory serum cytokines with a gender bias for females. Anxiety scores correlated negatively with TGF-β1 and IL-17. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    06/2015; 229(1-2). DOI:10.1016/j.psychres.2015.06.036
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    • "The meta-analysis conducted by Hiles et al. (2012b) found that the association between IL-6 and depression did not significantly differ between smokers and non-smokers and samples analysed by different processing techniques. However, in agreement with our cumulative meta-analysis and previous standard meta-analyses, inclusion of patients using psychotropic medication and the lack of adjustment for overweight/obesity resulted in slightly larger effect size estimates between the levels of CRP, IL-6 and depression (Hiles et al., 2012b; Howren et al., 2009). The observed heterogeneity between study-specific effect estimates was either high (TNF-a and IL-1b) or moderate (IL-6 and CRP). "
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    ABSTRACT: Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d = 0.54, p < 0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d = 0.47, p < 0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d = 0.40, p = 0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d = −0.05, p = 0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression.
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    • "Magnesium is a potent antagonist of the N-methyl-D-aspartate receptor complex [41]. Additionally, magnesium may contribute to lowering systemic inflammation [42], which has been associated with depression [43]. Calcium activates tryptophan hydroxylase in the biosynthetic pathway leading to serotonin synthesis [44]. "
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    ABSTRACT: Although intake of minerals has been suggested to be beneficial against depression, epidemiologic data from free-living settings are limited. The aim of this study was to determine the cross-sectional associations between the intake of magnesium, calcium, iron, and zinc and the prevalence of depressive symptoms in Japanese employees. Participants were 1792 men and 214 women ages 19 to 69 y. Dietary intake was assessed using a validated, brief self-administered diet history questionnaire. Participants with depressive symptoms were defined as those with a scale score of ≥16 on the Center for Epidemiologic Studies Depression Scale. The prevalence of depressive symptoms was 27.8%. Intakes of magnesium, calcium, iron, and zinc were inversely associated with the prevalence of depressive symptoms. The multivariate adjusted odds ratios (95% confidence interval) of having depressive symptoms were 0.63 (0.44-0.91), 0.64 (0.47-0.88), 0.59 (0.40-0.87), and 0.63 (0.45-0.87) in the highest versus lowest tertiles of magnesium, calcium, iron, and zinc, respectively. Results suggest that higher dietary intake of magnesium, calcium, iron, and zinc is associated with lower prevalence of depressive symptoms in Japanese employees. Copyright © 2015 Elsevier Inc. All rights reserved.
    Nutrition 05/2015; 31(5):686-90. DOI:10.1016/j.nut.2014.11.002 · 2.93 Impact Factor
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