Monocyte and microglial activation in patients with mood-stabilized bipolar disorder
Monocyte and microglial activation in patients with mood-stabilized bipolar disorder
复制标题
DOI：
10.1503/jpn.140183
复制
发表时间：
2015-07-01
影响因子：
4.3
通讯作者：
Landen, Mikael
中科院分区：
文献类型：
--
作者：
Jakobsson, Joel;Bjerke, Maria;Landen, Mikael
背景双相情感障碍与全身炎症机制相关的内科合并症有关。然而，有有限的证据支持神经炎症在双相情感障碍中的作用。在这里，我们测试是否小胶质细胞激活和相关的组织重塑过程相关的双相情感障碍通过分析标记物在脑脊液（CSF）和血清从患者和健康controls.Methods从正常胸腺双相情感障碍患者和健康对照组的血清中取样，和CSF从这些人的一个大的子集取样。检测单核细胞趋化蛋白-1（MCP-1）、YKL-40、可溶性分化抗原14（sCD 14）、金属蛋白酶组织抑制因子-1（TIMP-1）和金属蛋白酶组织抑制因子-2（TIMP-2）的水平，结果221例患者和112例对照者的血清标本和脑脊液标本均经病理证实，来自125名患者和87名对照的样本。我们发现与对照组相比，患者CSF中MCP-1和YKL-40水平升高，血清中sCD 14和YKL-40水平升高;在控制混杂因素（如年龄、性别、吸烟、血-CSF屏障功能、急性期蛋白和体重指数）后，这些差异仍然存在。MCP-1和YKL-40的CSF水平与血清水平相关，而MCP-1和YKL-40的CSF水平的患者和对照组之间的差异是独立的血清levels.Limitations-横断面研究设计排除了因果关系的结论。结论我们的研究结果表明，神经炎症和全身炎症过程参与双相情感障碍的病理生理学。重要的是，大脑中免疫过程的标记物独立于外周免疫活性。
Background Bipolar disorder is associated with medical comorbidities that have been linked to systemic inflammatory mechanisms. There is, however, limited evidence supporting a role of neuroinflammation in bipolar disorder. Here we tested whether microglial activation and associated tissue remodelling processes are related to bipolar disorder by analyzing markers in cerebrospinal fluid (CSF) and serum from patients and healthy controls.Methods Serum was sampled from euthymic patients with bipolar disorder and healthy controls, and CSF was sampled from a large subset of these individuals. The levels of monocyte chemoattractant protein-1 (MCP-1), YKL-40, soluble cluster of differentiation 14 (sCD14), tissue inhibitor of metalloproteinases-1 (TIMP-1) and tissue inhibitor of metalloproteinases-2 (TIMP-2), were measured, and we adjusted comparisons between patients and controls for confounding factors.Results We obtained serum samples from 221 patients and 112 controls and CSF samples from 125 patients and 87 controls. We found increased CSF levels of MCP-1 and YKL-40 and increased serum levels of sCD14 and YKL-40 in patients compared with controls; these differences remained after controlling for confounding factors, such as age, sex, smoking, blood-CSF barrier function, acute-phase proteins and body mass index. The CSF levels of MCP-1 and YKL-40 correlated with the serum levels, whereas the differences between patients and controls in CSF levels of MCP-1 and YKL-40 were independent of serum levels.Limitations The cross-sectional study design precludes conclusions about causality.Conclusion Our results suggest that both neuroinflammatory and systemic inflammatory processes are involved in the pathophysiology of bipolar disorder. Importantly, markers of immunological processes in the brain were independent of peripheral immunological activity.