Zhao Wenming, Zhu Dao-Min, Zhang Yongqi, Zhang Yu, Shen Yuxian, Yu Yongqiang, Zhu Jiajia
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Research Center of Clinical Medical Imaging, Anhui Province, Hefei, China.
Hum Brain Mapp. 2025 Oct 1;46(14):e70371. doi: 10.1002/hbm.70371.
The role of inflammation in the neuropathology of major depressive disorder (MDD) is evident. However, the neural correlates of peripheral inflammation in MDD and their transcriptomic architecture, neurochemical basis, and behavioral relevance have not been systematically investigated. We adopted functional and diffusion magnetic resonance imaging to assess gray matter function and white matter integrity, whose associations with serum C-reactive protein (CRP) levels were explored in a large sample of MDD patients. Further, we examined the spatial relationships of the identified neural correlates of CRP with transcriptome, neurotransmitter, and behavioral domain atlases. Higher serum CRP levels were associated with local gray matter function alterations and widespread white matter integrity changes in MDD patients, but not HC. Moreover, the gray matter functional correlates of CRP in MDD were spatially correlated with functional gene categories involving inflammatory signaling pathways (macrophage activation, NF-κB signaling, and JUN kinase activity), specific neurotransmitters (serotonin, GABA, and glutamate), and diverse behavioral domains (sensorimotor, cognition, emotion, and sleep). In addition, some neural correlates of CRP (anterior cingulate cortex function and superior corona radiata integrity) mediated the relationships of serum CRP with sustained attention and sleep structure in MDD patients. Our findings may not only confirm the role of inflammation in the neuropathology of MDD, but also inform a novel conceptualization of targeting inflammatory processes to treat this disorder.
炎症在重度抑郁症（MDD）神经病理学中的作用是显而易见的。然而，MDD患者外周炎症的神经关联及其转录组结构、神经化学基础和行为相关性尚未得到系统研究。我们采用功能磁共振成像和扩散磁共振成像来评估灰质功能和白质完整性，并在大量MDD患者样本中探讨了它们与血清C反应蛋白（CRP）水平的关联。此外，我们还研究了所确定的CRP神经关联与转录组、神经递质和行为领域图谱的空间关系。较高的血清CRP水平与MDD患者局部灰质功能改变和广泛的白质完整性变化相关，但与健康对照（HC）无关。此外，MDD患者中CRP的灰质功能关联在空间上与涉及炎症信号通路（巨噬细胞活化、NF-κB信号传导和JUN激酶活性）、特定神经递质（血清素、GABA和谷氨酸）以及不同行为领域（感觉运动、认知、情感和睡眠）的功能基因类别相关。此外，CRP的一些神经关联（前扣带回皮质功能和放射冠上部完整性）介导了血清CRP与MDD患者持续注意力和睡眠结构之间的关系。我们的研究结果不仅可能证实炎症在MDD神经病理学中的作用，还可能为针对炎症过程治疗该疾病提供一种新的概念。
