Abstract

Multiple studies show an association between inflammatory markers and major depressive disorder (MDD). People with chronic low-grade inflammation may be at an increased risk of MDD, often in the form of sickness behaviors. We hypothesized that inflammation is predictive of the severity and the course of a subset of MDD symptoms, especially symptoms that overlap with sickness behavior, such as anhedonia, anorexia, low concentration, low energy, loss of libido, psychomotor slowness, irritability, and malaise. We tested the association between basal and lipopolysaccharide (LPS)-induced inflammatory markers with individual MDD symptoms (measured using the Inventory of Depressive Symptomatology Self-Report) over a period of up to 9 years using multivariate-adjusted mixed models in 1147–2872 Netherlands Study of Depression and Anxiety (NESDA) participants. At baseline, participants were on average 42.2 years old, 66.5% were women and 53.9% had a current mood or anxiety disorder. We found that basal and LPS-stimulated inflammatory markers were more strongly associated with sickness behavior symptoms at up to 9-year follow-up compared with non-sickness behavior symptoms of depression. However, we also found significant associations with some symptoms that are not typical of sickness behavior (e.g., sympathetic arousal among others). Inflammation was not related to depression as a unified syndrome but rather to the presence and the course of specific MDD symptoms, of which the majority were related to sickness behavior. Anti-inflammatory strategies should be tested in the subgroup of MDD patients who report depressive symptoms related to sickness behavior.

Highlights

  • Inflammatory markers and depression have an intricate and complex relationship[1,2]

  • We aimed to examine whether diverse inflammatory markers could predict the trajectories of individual symptoms of depression over the course of 9 years, looking at symptoms indicative of sickness behavior

  • We found that the basal inflammation index and the LPS-induced inflammation index-2 predicted many depressive symptoms over the course of 9 years

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Summary

Introduction

Inflammatory markers and depression have an intricate and complex relationship[1,2]. Evidence from meta-analyses suggests that depressed subjects have higher circulating concentrations of acute-phase proteins and proinflammatory cytokines compared with healthy subjects[3,4,5,6,7,8]. The innate and adaptive immune systems are activated. Pro-inflammatory cytokines are produced by macrophages, monocytes, and Another approach to assess inflammation is to stimulating the immune cells and study the clinically important immune disturbances[9,10]. After ex vivo induction of lipopolysaccharide (LPS: the cell membrane of Gramnegative bacteria that strongly induces immunological responses) in whole blood samples, a wide array of pro-inflammatory cytokines are released, which can be measured in the supernatant[9,10]. Fewer studies exist on van Eeden et al Translational Psychiatry (2020)10:235

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