Pearlman Daniel M, Brown Jeremiah R, MacKenzie Todd A, Hernandez Felix, Najjar Souhel
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.
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.
PLoS One. 2014 Oct 20;9(10):e111110. doi: 10.1371/journal.pone.0111110. eCollection 2014.
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.
横断面研究和回顾性研究已将重度抑郁症与胶质细胞激活、损伤以及血脑屏障破坏联系起来，但这些关联尚未进行前瞻性评估。在此，我们旨在确定炎症激发后抑郁症状严重程度的变化与血液中S-100钙结合蛋白B（S-100B）、高敏C反应蛋白和白细胞介素-6水平之间的关系。
从一项随机对照试验中招募了50名未经过筛选的参与者，该试验比较了在有或没有体外循环的情况下进行冠状动脉搭桥手术时神经认知功能下降的风险。使用贝克抑郁量表第二版（BDI-II）在基线、出院时和六个月随访时测量抑郁症状严重程度。本生物标志物研究的主要结局是抑郁症状严重程度的急性变化，定义为基线和出院时BDI-II评分之间的个体内差异。在基线和术后2天测定血液生物标志物水平。
S-100B水平的变化与抑郁症状严重程度的急性变化呈正相关（Spearman ρ，0.62；P = 0.0004），并占其观察到的方差的约四分之一（R2，0.23；P = 0.0105）。在调整基线S-100B水平、年龄、体重、体重指数或β受体阻滞剂使用情况后，这种关联仍然具有统计学意义，但调整基线BDI-II评分后则无统计学意义（P = 0.064）。主要结局与基线S-100B水平、基线高敏C反应蛋白或白细胞介素-6水平，或高敏C反应蛋白或白细胞介素-6水平的变化之间无统计学意义上的显著关联。在大多数参与者中，所有三种生物标志物的水平在基线时正常，在术后2天显著升高。
抑郁症状严重程度的急性变化与S-100B血液水平的增量变化特别相关，在很大程度上独立于与之相关的协变量。这些发现支持了这样一种假设，即胶质细胞激活、损伤和血脑屏障破坏在机制上可能与某些个体的抑郁症状急性加重有关。
