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

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.

Blood-brain barrier regulation in psychiatric disorders

“…Additionally, S100β levels seem to be higher in patients with MDD compared to those with bipolar disorder [195] and older patients with MDD have higher levels of S100β compared to younger patients [196]. In a clinical trial comparing coronary artery bypass grafting procedures, changes in levels of S100β positively correlated with changes in depressive symptom severity [197]. In rodent studies, overexpression of S100β in female mice induces depression-like behaviour in the forced swim task [198].…”

Role of Interleukin-6 in Depressive Disorder

“…The result showed that patients with depression had significantly higher levels of serum IL-6 and IL-6-to-IL-10 ratios compared to patients without depression [85]. In fifty patients undergoing coronary artery bypass grafting procedures, depressive symptom severity was measured at baseline, discharged, with a six-month follow-up [86]. Results demonstrated that changes in depression severity were associated with incremental changes in blood levels of S100B, but not IL-6.…”

“…[85] Coronary artery bypass grafting Acute changes in depressive symptom severity were not associated with IL-6 levels. [86] Total knee replacement Plasma IL-6 levels predicted depressive symptoms at three-months following surgery.…”

Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial

“…Several reports have found elevated levels of S100B in peripheral circulation of patients with depression [27][28][29]. Two previous reports have evaluated the association between pre-treatment S100B levels and response to treatment outcomes and found that elevated levels of S100B were associated with better outcomes to antidepressants [30,31]. However, neither of these reports evaluated whether levels of S100B differentially predicted improvement with one antidepressant medication versus another.…”