The pro-inflammatory profile of depressed patients is (partly) related to obesity

Abstract

Many people with major depressive disorder (MDD) show evidence of systemic inflammation, including elevations in inflammatory factors, but the cause is unclear. The purpose of this analysis was to determine if obesity might contribute to the pro-inflammatory state in MDD patients. Blood was obtained from 135 MDD patients and 50 controls. Serum was extracted and assayed for interleukin (IL) −1β, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), C-reactive protein (CRP), leptin, and adiponectin using single- or multi-plex human immunoassay kits. The primary analysis contrasted IL-6, TNFα, and CRP between MDD and control groups with body mass index (BMI) as a covariate. The other analytes were compared in an exploratory fashion. IL-6 (but not TNFα or CRP) showed significant differences between MDD and controls even after covarying for BMI. Obese controls and obese MDD groups were significantly higher in IL-6 than both lean groups, but the two obese groups did not differ from each other. In the exploratory analyses, the IL-2 level showed robust and significant differences between MDD and controls even after covarying for BMI. Both lean and obese MDD were higher than lean and obese controls. Adiponectin levels were also lower in the MDD sample than controls. Prior findings of higher IL-6, and CRP in MDD patients may be explained, at least in part, based on obesity. High IL-2, however, was associated with depression and not obesity. The results have significant implications for the understanding of pathophysiology and, potentially treatment of MDD.

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

“…Participants with low CRP levels (<1 mg/L) performed markedly better with SSRI monotherapy than participants with higher CRP levels, and this effect was evident as early as the second week of treatment. Proportion of participants with CRP levels ≥1 mg/L (69.8%) and mean levels of CRP (5.1 mg/L) in this study were similar to those reported in the overall US population (Woloshin and Schwartz, 2005) and other studies of depressed patients (Shelton et al, 2015; Wium-Andersen et al, 2013), but higher than what was reported by Uher et al where 45.6% participants had CRP ≥1 mg/L and the mean CRP level was 1.3–1.6 mg/L (Uher et al, 2014). …”

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

“…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).…”

Childhood Maltreatment Is an Independent Risk Factor for Prediabetic Disturbances in Glucose Regulation

“…Previous studies indicate that childhood stress increases the tendencies for pro-inflammatory status, leading to exaggerated cytokine response to stress and decreased sensitivity to inhibitory hormonal signals and hormonal dysregulation (26, 27). In this study, both TNFα and CRP were found to be elevated and positively associated with CM scores.…”