title: 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: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroinflammation Research Group, Epilepsy Center Division, Department of Neurology, NYU School of Medicine, New York, New York, United States of America; The Dartmouth Institute for Health Policy and Clinical Practice, Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Pearlman
authors.affiliation: The Dartmouth Institute for Health Policy and Clinical Practice, Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America; Section of Epidemiology and Biostatistics, Department of Community and Family Medicine, Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America; Section of Cardiology, Department of Medicine, Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Jeremiah R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: The Dartmouth Institute for Health Policy and Clinical Practice, Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America; Section of Epidemiology and Biostatistics, Department of Community and Family Medicine, Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America; Section of Cardiology, Department of Medicine, Audrey and Theodor Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Todd A
authors.initials: TA
authors.lastname: MacKenzie
authors.affiliation: Cardiothoracic Surgery, Eastern Maine Medical Center, Bangor, Maine, United States of America.
authors.forename: Felix
authors.initials: F
authors.lastname: Hernandez
authors.affiliation: Neuroinflammation Research Group, Epilepsy Center Division, Department of Neurology, NYU School of Medicine, New York, New York, United States of America.
authors.forename: Souhel
authors.initials: S
authors.lastname: Najjar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003863:Depression / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood*; D011446:Prospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D002097:C-Reactive Protein