Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
Psychoneuroendocrinology. 2012 Dec;37(12):1901-11. doi: 10.1016/j.psyneuen.2012.04.001. Epub 2012 Apr 27.
At present there are strong indications of a shared vulnerability factor for schizophrenia (SZ), diabetes and the metabolic syndrome (metS). In this study we focus on an aberrantly activated monocyte/macrophage system as the shared factor. We measured in SZ patients (n=144), the serum levels of monocyte/macrophage cytokines/chemokines/adipokines CCL2, CCL4, IL-1β, TNF-α, IL-6, PTX3, leptin, adiponectin, PAI-1, OPG and ICAM-1 and compared these levels to healthy controls (HC) (n=138). Using multivariate analysis, we studied the effect of the presence of the disease SZ, the components of the metS including BMI, the levels of lipids (HDL cholesterol and triglycerides (TG)), diabetes (hyperglycemia) and the use of antipsychotic medication, on the serum levels of these immune compounds. We found all measured immune compounds with the exception of PAI-1 and OPG to be elevated in the SZ patient population. Multivariate analysis showed that elevations were linked to gender (ICAM-1, leptin, TNF-α and adiponectin), an increased BMI (leptin, adiponectin), hyperglycemia/diabetes (CCL4, and OPG), reduced HDL-cholesterol or increased levels of TG (adiponectin and PTX3) or the metS (CCL2, leptin and adiponectin). IL-1β and IL-6 were the only immune compounds raised in the serum of patients not affected by any of the included factors. Although many of the immune compounds were found linked to (components of) the metS, the most dominant linkage was found with the disease schizophrenia, confirming earlier reports on increased monocyte/macrophage activation as a key component for understanding the pathogenesis of schizophrenia.
目前有强烈的迹象表明精神分裂症(SZ)、糖尿病和代谢综合征(metS)存在共同的易损性因素。在这项研究中,我们专注于异常激活的单核细胞/巨噬细胞系统作为共同因素。我们测量了 144 名 SZ 患者和 138 名健康对照者(HC)的血清中单核细胞/巨噬细胞细胞因子/趋化因子/脂肪因子 CCL2、CCL4、IL-1β、TNF-α、IL-6、PTX3、瘦素、脂联素、PAI-1、OPG 和 ICAM-1 的水平,并将这些水平与健康对照组进行了比较。通过多元分析,我们研究了疾病 SZ 的存在、metS 的组成部分(包括 BMI、血脂水平(HDL 胆固醇和甘油三酯(TG))、糖尿病(高血糖)和抗精神病药物的使用)对这些免疫化合物血清水平的影响。我们发现除了 PAI-1 和 OPG 之外,所有测量的免疫化合物在 SZ 患者群体中都升高了。多元分析表明,升高与性别(ICAM-1、瘦素、TNF-α和脂联素)、BMI 增加(瘦素、脂联素)、高血糖/糖尿病(CCL4 和 OPG)、HDL 胆固醇降低或 TG 水平升高(脂联素和 PTX3)或代谢综合征(CCL2、瘦素和脂联素)有关。IL-1β 和 IL-6 是血清中未受任何包含因素影响的患者中升高的唯一免疫化合物。尽管许多免疫化合物与(metS 的)成分有关,但与疾病精神分裂症的关联最为明显,这证实了先前关于单核细胞/巨噬细胞激活增加作为理解精神分裂症发病机制的关键因素的报告。