Inflammation is associated with depressive symptoms and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited N = 46 healthy controls, and N = 83 depressed cases stratified by CRP (> 3 mg/L: N = 33; < 3 mg/L: N = 50). All completed clinical assessment, venous blood sampling for C-reactive protein (CRP) assay, and brain magnetic resonance imaging (MRI). Micro-structural MRI parameters including proton density (PD), a measure of tissue water content, were measured at 360 cortical and 16 subcortical regions. Resting-state fMRI time series were correlated to estimate functional connectivity between individual regions, as well as the sum of connectivity (weighted degree) of each region. Multiple tests for regional analysis were controlled by the false discovery rate (FDR = 5%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC); and with functional connectivity between pC/pCC, mPFC and hippocampus. Depression was associated with reduced weighted degree of pC/pCC, mPFC, and other nodes of the default mode network (DMN). Thus CRP-related increases in proton density—a plausible marker of extracellular oedema—and changes in functional connectivity were anatomically co-localised with DMN nodes that also demonstrated significantly reduced hubness in depression. We suggest that effects of peripheral inflammation on DMN node micro-structure and connectivity may mediate inflammatory effects on depression.

炎症与抑郁症状有关，先天免疫机制可能是某些重度抑郁症病例的因果关系。全身性炎症也会扰乱大脑功能和微观结构，但它们之间的关系尚不清楚。我们招募了N  = 46 名健康对照者和N  = 83 名按 CRP 分层的抑郁症患者（> 3 mg/L：N  = 33；< 3 mg/L：N = 50）。所有已完成的临床评估、用于 C 反应蛋白 (CRP) 测定的静脉血样和脑磁共振成像 (MRI)。在 360 个皮质和 16 个皮质下区域测量了微观结构 MRI 参数，包括质子密度 (PD)，组织含水量的量度。静息态 fMRI 时间序列与估计各个区域之间的功能连通性以及每个区域的连通性总和（加权程度）相关。区域分析的多项测试由错误发现率 (FDR = 5%) 控制。我们发现 CRP 与楔前叶、后扣带皮层 (pC/pCC) 和内侧前额叶皮层 (mPFC) 中的 PD 显着相关；以及 pC/pCC、mPFC 和海马体之间的功能连接。抑郁症与 pC/pCC、mPFC、和默认模式网络（DMN）的其他节点。因此，CRP 相关的质子密度增加（细胞外水肿的一个合理标志）和功能连接的变化在解剖学上与 DMN 节点共定位，这也表明抑郁症的中心性显着降低。我们认为外周炎症对 DMN 节点微观结构和连通性的影响可能介导炎症对抑郁症的影响。