Biological and Precision Psychiatry, Copenhagen Research Center for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Schizophr Bull. 2022 Nov 18;48(6):1206-1216. doi: 10.1093/schbul/sbac098.
Neuroinflammation and blood-brain barrier (BBB) dysfunction have been observed in patients with psychotic disorders. However, previous studies have mainly focused on selected patients and broad screenings of cerebrospinal fluid (CSF) of patients with recent onset psychosis compared to healthy controls are lacking.
We included 104 patients with recent onset psychotic disorder and 104 individually matched healthy controls. CSF and blood were analyzed for readily available markers assessing neuroinflammation and BBB dysfunction. Primary outcomes were CSF white blood cell count (WBC), total protein, IgG Index, and CSF/serum albumin ratio. Secondary outcomes included additional markers of inflammation and BBB, and analyses of association with clinical variables.
CSF/serum albumin ratio (Relative Mean Difference (MD): 1.11; 95%CI: 1.00-1.23; P = .044) and CSF/serum IgG ratio (MD: 1.17; 95%CI: 1.01-1.36; P = .036) was increased in patients compared to controls. A higher number of patients than controls had CSF WBC >3 cells/µl (seven vs. one, OR: 7.73, 95%CI: 1.33-146.49, P = .020), while WBC>5 cells/µl was found in two patients (1.9%) and no controls. Inpatients had higher serum WBC and neutrophil/lymphocyte ratio (all p-values for effect heterogeneity < .011). Mean CSF WBC (MD: 1.10; 95%CI: 0.97-1.26), protein (MD: 1.06; 95%CI: 0.98-1.15) and IgG index (MD: 1.05; 95%CI: 0.96-1.15) were not significantly elevated.
When comparing a broad group of patients with psychotic disorders with healthy controls, patients had increased BBB permeability, more patients had high CSF WBC levels, and inpatients had increased peripheral inflammation, consistent with the hypothesis of a subgroup of patients with increased activation of the immune system.
神经炎症和血脑屏障（BBB）功能障碍已在精神病患者中观察到。然而，以前的研究主要集中在选定的患者身上，并且缺乏对近期发病的精神病患者与健康对照者进行广泛的脑脊液（CSF）筛查。
我们纳入了 104 例近期发病的精神病患者和 104 例个体匹配的健康对照者。分析了 CSF 和血液中可评估神经炎症和 BBB 功能障碍的现成标志物。主要结局是 CSF 白细胞计数（WBC）、总蛋白、IgG 指数和 CSF/血清白蛋白比值。次要结局包括炎症和 BBB 的其他标志物，以及与临床变量的相关性分析。
与对照组相比，患者的 CSF/血清白蛋白比值（相对平均差异（MD）：1.11；95%CI：1.00-1.23；P =.044）和 CSF/血清 IgG 比值（MD：1.17；95%CI：1.01-1.36；P =.036）升高。与对照组相比，有更多的患者 CSF WBC>3 个/µl（7 例比 1 例，OR：7.73，95%CI：1.33-146.49，P =.020），而有 2 例患者（1.9%）和对照组均无 WBC>5 个/µl。住院患者的血清 WBC 和中性粒细胞/淋巴细胞比值较高（所有效应异质性 P 值<.011）。CSF WBC（MD：1.10；95%CI：0.97-1.26）、蛋白（MD：1.06；95%CI：0.98-1.15）和 IgG 指数（MD：1.05；95%CI：0.96-1.15）均无显著升高。
当将一组广泛的精神病患者与健康对照者进行比较时，患者的 BBB 通透性增加，更多的患者 CSF WBC 水平升高，住院患者外周炎症增加，这与免疫系统激活增加的亚组患者的假说一致。
