Eiff Brandi, Bullmore Edward T, Clatworthy Menna R, Fryer Tim D, Pariante Carmine M, Mondelli Valeria, Maccioni Lucia, Hadjikhani Nouchine, Loggia Marco L, Moskowitz Michael A, Bruner Emiliano, Veronese Mattia, Turkheimer Federico E, Schubert Julia J
Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.
Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SZ, UK.
Brain. 2025 Feb 3;148(2):635-646. doi: 10.1093/brain/awae343.
Although both central and peripheral inflammation have been observed consistently in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression. PET was used to measure regional TSPO expression in the skull and parameninges as a marker of inflammatory activity. This measure was correlated with brain TSPO expression and peripheral cytokine concentrations in a cohort enriched for heightened peripheral and central immunity comprising 51 individuals with depression and 25 healthy controls. The findings reveal a complex relationship between regional skull TSPO expression and both peripheral and central immunity. Facial and parietal skull bone TSPO expression showed significant associations with both peripheral and central immunity. TSPO expression in the confluence of sinuses was also linked to both central and peripheral immune markers. Group-dependent elevations in TSPO expression within the occipital skull bone marrow were also found to be significantly associated with central inflammation. Significant associations between immune activity within the skull, parameninges, parenchyma and periphery highlight the role of the skull bone marrow and venous sinuses as pivotal sites for peripheral and central immune interactions.
尽管在抑郁症中一直观察到中枢和外周炎症，但两者之间的关系仍不明确。轴外免疫细胞可能在介导中枢和外周免疫之间的联系中发挥作用。本研究调查了颅骨骨髓和脑膜旁间隙在介导抑郁症中枢和外周免疫相互作用中的潜在作用。正电子发射断层扫描（PET）用于测量颅骨和脑膜区域的转运体18 kDa 蛋白（TSPO）表达，作为炎症活动的标志物。在一个外周和中枢免疫增强的队列中，该测量值与脑TSPO表达和外周细胞因子浓度相关，该队列包括51名抑郁症患者和25名健康对照。研究结果揭示了颅骨区域TSPO表达与外周和中枢免疫之间的复杂关系。面部和顶骨的TSPO表达与外周和中枢免疫均显示出显著关联。窦汇处的TSPO表达也与中枢和外周免疫标志物相关。枕骨骨髓内TSPO表达的组间依赖性升高也被发现与中枢炎症显著相关。颅骨、脑膜、实质和外周的免疫活动之间的显著关联突出了颅骨骨髓和静脉窦作为外周和中枢免疫相互作用关键部位的作用。
