The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood-brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity. To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts (N=51 patients and N=25 controls) and a second study where peripheral inflammation in N=7 healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100β, that was unchanged. These results suggest a different model of peripheral-to-central immunity interaction whereas peripheral inflammation may cause a reduction in BBB permeability. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms.

中文翻译：

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血清外周 C 反应蛋白增加与健康志愿者和抑郁患者 TSPO 放射性配体的脑屏障通透性降低有关：对炎症和抑郁的影响

外周免疫和中枢免疫之间的关系以及这些最终如何导致抑郁行为一直是使用正电子发射断层扫描 (PET) 进行的许多成像研究的重点。这些研究旨在测试免疫介导的抑郁症模型，该模型提出外周细胞因子和免疫细胞对大脑的直接影响，通过渗漏的血脑屏障引发神经炎症反应，并最终引发抑郁行为。然而，迄今为止，在抑郁症患者队列中使用 PET 放射性配体靶向神经炎症标志物 18 kDa 易位蛋白 (TSPO) 进行的研究表明，大脑处于轻度炎症状态，但中枢免疫和外周免疫之间没有相关性。为了更好地了解增强的外周免疫和神经炎症之间的关系，我们估计了在两项独立研究中收集的两种 TSPO 放射性示踪剂的血液对大脑和血液对脑脊液灌注率，一项针对正常和抑郁队列（N=51 患者和 N=25 对照）中神经炎症的大型横断面研究和第二项研究通过皮下注射干扰素 (IFN)-α 诱导了 N=7 健康对照组的外周炎症。在这两项研究中，我们观察到用 c 反应蛋白 P (CRP) 测量的外周炎症与脑实质和脑脊液的放射性示踪剂灌注之间存在一致的负相关性。重要的是，这种效应与 BBB 渗漏标志物 S100β 没有关联，没有改变。这些结果表明外周与中枢免疫相互作用的不同模型，而外周炎症可能导致 BBB 通透性降低。