Hua Lin, Zeng Xinglin, Zhang Kaixi, Zhao Zhiying, Yuan Zhen
Faculty of Health Sciences, University of Macau, Macau SAR, China.
Center for Cognitive and Brain Sciences, University of Macau, Macau SAR, China.
Mol Psychiatry. 2025 May 19. doi: 10.1038/s41380-025-03058-1.
Psychosis involves neuroinflammation and oxidative stress, both affecting the glymphatic system, the lymphatic-like, fluid-transport system in the brain. However, it is unclear whether early psychosis is related to impairments in glymphatic functions. In resting-state fMRI, it has been recently established in a number of neurodegenerative diseases that the coupling relationship between cortical blood-oxygen-level-dependent (BOLD) signal and ventricular cerebrospinal fluid (CSF) flow is associated with brain waste clearance, a key glymphatic function that has not been examined in psychosis or any other psychiatric populations. In a large dataset (total n = 137, age = 23.86 ± 4.16), we demonstrated that glymphatic clearance marked by BOLD-CSF coupling was weaker and more delayed in patients with early psychosis compared to healthy controls. BOLD-CSF coupling also varied between the non-affective and affective psychosis groups with group differences most prominent in high-order but not low-order cortical regions. Finally, reduced global BOLD-CSF coupling was associated with cognitive decline and more severe psychotic symptoms. We provided novel evidence highlighting dysregulated coupling between cortical activity and macroscopic CSF flow as a biomarker for early psychosis. Similar to recent observations in neurodegenerative disorders, the association between reduced BOLD-CSF coupling and psychotic symptoms suggested that waste clearance is disrupted in psychosis which shed light on the pathophysiology of this disease from a glymphatic point of view.
精神病涉及神经炎症和氧化应激,二者均会影响类淋巴系统,即大脑中类似淋巴的液体运输系统。然而,早期精神病是否与类淋巴功能受损相关尚不清楚。在静息态功能磁共振成像中,最近在一些神经退行性疾病中发现,皮质血氧水平依赖(BOLD)信号与脑室脑脊液(CSF)流动之间的耦合关系与脑废物清除有关,这是类淋巴的一项关键功能,尚未在精神病患者或任何其他精神科人群中进行研究。在一个大型数据集中(总样本量n = 137,年龄 = 23.86 ± 4.16),我们证明,与健康对照相比,早期精神病患者中以BOLD-CSF耦合为标志的类淋巴清除较弱且延迟。非情感性和情感性精神病组之间的BOLD-CSF耦合也有所不同,组间差异在高阶而非低阶皮质区域最为显著。最后,整体BOLD-CSF耦合降低与认知能力下降和更严重的精神病症状相关。我们提供了新的证据,突出了皮质活动与宏观CSF流动之间失调的耦合作为早期精神病的生物标志物。与神经退行性疾病的近期观察结果相似,BOLD-CSF耦合降低与精神病症状之间的关联表明,精神病患者的废物清除受到破坏,这从类淋巴的角度揭示了该疾病的病理生理学。
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