Institute for Behavioral Science, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.
Neuropsychopharmacology. 2021 May;46(6):1140-1144. doi: 10.1038/s41386-020-00867-6. Epub 2020 Sep 22.
Abnormalities in the complement system have been described in patients with schizophrenia, with those individuals having greater frequency of complement component 4A (C4A) alleles and higher C4A transcript levels in postmortem brain tissue. Importantly, abnormalities in C4A and other complement molecules have been associated with synaptic pruning abnormalities that occur during neurodevelopment. A few studies have investigated C4 levels in living patients with schizophrenia, but all of them did so using peripheral blood samples. No studies have examined C4 levels in cerebrospinal fluid (CSF), presumably a better biofluid choice given its intimate contact with the brain. Therefore, we report for the first time on C4 levels in CSF and plasma of patients with schizophrenia. In this study, we obtained CSF in 32 patients with schizophrenia spectrum disorders and 32 healthy volunteers and peripheral blood samples in 33 SSD and 31 healthy volunteers. C4 levels were measured using Abcam ELISA assays. Univariate analysis did not show a statistically significant difference in CSF C4 values between groups. However, a multivariable analysis showed a statistically significant increase in CSF C4 levels between groups after adjusting for sex and age. We also observed a high correlation between CSF C4 levels and age. By contrast, plasma C4 levels were not significantly different between groups. CSF and plasma C4 levels were not significantly correlated. Therefore, the use of CSF samples is critical and should be complementary to the use of peripheral blood samples to allow for a comprehensive understanding of complement C4 abnormalities in schizophrenia.
补体系统异常在精神分裂症患者中已有描述,这些个体在后脑组织中具有更高频率的补体成分 4A(C4A)等位基因和更高的 C4A 转录水平。重要的是,C4A 和其他补体分子的异常与神经发育过程中发生的突触修剪异常有关。一些研究已经调查了活体精神分裂症患者的 C4 水平,但所有这些研究都是使用外周血样本来进行的。没有研究检查过脑脊液(CSF)中的 C4 水平,大概是因为它与大脑的密切接触,所以 CSF 是更好的生物流体选择。因此,我们首次报告了精神分裂症患者 CSF 和血浆中的 C4 水平。在这项研究中,我们获得了 32 名精神分裂症谱系障碍患者和 32 名健康志愿者的 CSF,以及 33 名 SSD 和 31 名健康志愿者的外周血样。使用 Abcam ELISA 测定法测量 C4 水平。单变量分析显示组间 CSF C4 值无统计学差异。然而,多变量分析显示,在校正性别和年龄后,组间 CSF C4 水平有统计学显著增加。我们还观察到 CSF C4 水平与年龄之间存在高度相关性。相比之下,组间血浆 C4 水平无显著差异。CSF 和血浆 C4 水平之间无显著相关性。因此,使用 CSF 样本至关重要,并且应该与使用外周血样本互补,以全面了解精神分裂症中补体 C4 的异常。