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

• Published in: PloS one Vol. 9; no. 10; p. e111110
• Main Authors: Pearlman, Daniel M., Brown, Jeremiah R., MacKenzie, Todd A., Hernandez, Felix, Najjar, Souhel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.10.2014; Public Library of Science (PLoS)
• Subjects: Activation; Adult; Aged; Aged, 80 and over; Analysis; Binding proteins; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Blood; Blood levels; Blood-brain barrier; Bone surgery; Brain; Brain injury; Brain research; Bypasses; C-reactive protein; C-Reactive Protein - metabolism; Calcium; Calcium (blood); Calcium-binding protein; Calmodulin; Cardiology; Clinical medicine; Cognition; Coronary artery; Coronary artery bypass; Coronary Artery Bypass - adverse effects; Coronary vessels; Cytokines; Depression (Mood disorder); Depression - blood; Depression - etiology; Discharge; Epidemiology; Female; Grafting; Heart surgery; Humans; Inflammation; Informed consent; Interleukin 6; Interleukin-6 - blood; Interleukins; Male; Medicine; Medicine and Health Sciences; Mental depression; Middle Aged; Postoperative Complications - blood; Prospective Studies; Protein B; Protein binding; Proteins; Randomization; Research and Analysis Methods; S100 Calcium Binding Protein beta Subunit - blood; S100b protein; Sensitivity; Severity of Illness Index; Statistical analysis; Statistical significance; Surgery; Traumatic brain injury; Veins & arteries; New York; United States > US; Maine; New Hampshire
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111110

Cross-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. Fifty 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. Changes 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. Acute 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.