Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei 112, Taiwan; Institute of Philosophy of Mind and Cognition, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department of Psychiatry, Taipei Veterans General Hospital, Taipei 112, Taiwan; Department of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
J Affect Disord. 2017 Sep;219:172-177. doi: 10.1016/j.jad.2017.04.036. Epub 2017 Apr 21.
Inflammation is reported to play a crucial role in the pathogenesis of bipolar disorder (BD). Higher serum levels of soluble interleukin-6 receptor (sIL-6R), which forms a ligand-receptor complex with the potent proinflammatory cytokine IL-6, have been consistently observed in patients with BD. However, the effect of sIL-6R on neural structure and function remains unclear. This study investigated the association between serum sIL-6R levels and the structural and functional connectivity (FC) of the brain in patients with BD.
Seventy-four stable patients with BD-I or BD-II were enrolled from the outpatient clinic. Structural and resting functional MRI and clinical evaluations were performed in all participants, and serum sIL-6R levels were measured. We used an automated surface-based method (FreeSurfer) to measure cortical thickness and a seed-based FC analysis to derive the FC map of the medial prefrontal cortex (mPFC), a key region implicated in the fronto-limbic disconnection hypothesis of BD. Brain-wise regression analyses of cortical thickness and FC mapping on IL-6 levels were performed using a general linear model.
Higher sIL-6R levels were associated with a thinner cortex in the right middle temporal gyrus. Furthermore, higher sIL-6R levels were associated with increased FC between the mPFC and amygdala, pallidum, putamen, and insula and decreased FC between the mPFC and subgenual anterior cingulate cortex and frontal pole.
The results evidence that higher serum inflammatory marker levels are associated with a severer deficit in structural and connectivity abnormalities implicated in BD.
炎症被认为在双相情感障碍（BD）的发病机制中起关键作用。患有 BD 的患者的血清可溶性白细胞介素-6 受体（sIL-6R）水平升高，sIL-6R 与强效促炎细胞因子 IL-6 形成配体-受体复合物。然而，sIL-6R 对神经结构和功能的影响尚不清楚。本研究调查了 BD 患者血清 sIL-6R 水平与大脑结构和功能连接（FC）之间的关系。
从门诊招募了 74 名稳定的 BD-I 或 BD-II 患者。所有参与者均进行了结构和静息功能 MRI 以及临床评估，并测量了血清 sIL-6R 水平。我们使用自动表面方法（FreeSurfer）测量皮质厚度，并使用基于种子的 FC 分析得出内侧前额叶皮质（mPFC）的 FC 图，mPFC 是与 BD 的额-边缘连接中断假说有关的关键区域。使用一般线性模型对皮质厚度和 FC 映射的 IL-6 水平进行脑区回归分析。
较高的 sIL-6R 水平与右侧颞中回皮质变薄有关。此外，较高的 sIL-6R 水平与 mPFC 与杏仁核、苍白球、壳核和岛叶之间的 FC 增加以及 mPFC 与扣带回前下部和额极之间的 FC 减少有关。
结果表明，较高的血清炎症标志物水平与 BD 中结构和连接异常的更严重缺陷有关。
