Blood levels of S-100 calcium-binding protein B, high-sensitivity C-reactive protein, and interleukin-6 for changes in depressive symptom severity after coronary artery bypass grafting: prospective cohort nested within a randomized, controlled trial.

Daniel M Pearlman,Todd A Mackenzie,Felix Hernandez,Jeremiah R Brown,Souhel Najjar,Malú G Tansey

doi:10.1371/journal.pone.0111110

Abstract

BackgroundCross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium-binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge.MethodsFifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month follow-up using the Beck Depression Inventory II (BDI-II). The primary outcome of the present biomarker study was acute change in depressive symptom severity, defined as the intra-subject difference between baseline and discharge BDI-II scores. Blood biomarker levels were determined at baseline and 2 days postoperative.ResultsChanges in S-100B levels correlated positively with acute changes in depressive symptom severity (Spearman ρ, 0.62; P = 0.0004) and accounted for about one-fourth of their observed variance (R2, 0.23; P = 0.0105). This association remained statistically significant after adjusting for baseline S-100B levels, age, weight, body-mass index, or β-blocker use, but not baseline BDI-II scores (P = 0.064). There was no statistically significant association between the primary outcome and baseline S-100B levels, baseline high-sensitivity C-reactive protein or interleukin-6 levels, or changes in high-sensitivity C-reactive protein or interleukin-6 levels. Among most participants, levels of all three biomarkers were normal at baseline and markedly elevated at 2 days postoperative.ConclusionsAcute changes in depressive symptom severity were specifically associated with incremental changes in S-100B blood levels, largely independent of covariates associated with either. These findings support the hypothesis that glial activation and injury and blood–brain barrier disruption can be mechanistically linked to acute exacerbation of depressive symptoms in some individuals.

Highlights

A large body of evidence substantiates the association between inflammation and major depressive disorder [1,2,3,4,5,6,7,8,9,10,11,12,13]
Participant characteristics and Beck Depression Inventory II (BDI-II) scores were generally similar among those comprising the biomarker cohort relative to the remaining participants in the Scarecrow trial (Table 1)
Spearman r values and scatterplots for all possible twoterm combinations between and among BDI-II scores and blood biomarker measures are displayed in Table 3 and Figure 2

Summary

Introduction

A large body of evidence substantiates the association between inflammation and major depressive disorder [1,2,3,4,5,6,7,8,9,10,11,12,13]. The prototypical etiologic studies in this regard are the so-called inflammation-challenge paradigms, such as interferon-a administration [36] Among those treated with interferon-a, typically for hepatitis C or cancer, about half experience acuteonset depression in association with systemic inflammatory and neuroimaging abnormalities [5,21,22,23,24,25,26,27,28,29,30,31]. We aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calciumbinding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge

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