Department of Laboratory Medicine, Hunan Provincial People's Hospital, The first affiliated hospital of Hunan Normal University, Changsha, 410005, Hunan, China.
Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.
Int J Med Sci. 2018 Jun 4;15(9):900-906. doi: 10.7150/ijms.24346. eCollection 2018.
Schizophrenia (SZ) is a devastating psychiatric disorder. Validation of potential serum biomarkers during first-episode psychosis (FEP) is especially helpful to understand the onset and prognosis of this disorder. To address this question, we examined multiple blood biomarkers and assessed the efficacy to diagnose SZ. The expression levels of Neuregulin1 (NRG1), ErbB4, brain-derived neurotrophic factor (BDNF), DNA methyltransferases 1 (DNMT1) and ten-eleven translocation 1 (TET1) proteins in peripheral blood of 53 FEP patients and 57 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression including biomarker concentration as covariates was used to predict SZ. Differentiating performance of these five serum protein levels was analyzed by Receiver Operating Characteristic (ROC) curve analysis. We found that patients with SZ present a higher concentration of DNMT1, and TET1 in peripheral blood, but a lower concentration of NRG1, ErbB4 and BDNF than controls. Multivariable logistic regression showed that ErbB4, BDNF and TET1 were independent predictors of SZ, and when combined, provided high diagnostic accuracy for SZ. Together, our findings highlight that altered expression of NRG1, ErbB4, BDNF, DNMT1 and TET1 are involved in schizophrenia development and they may serve as potential biomarkers for the diagnosis of the schizophrenia. Therefore, our study provides evidence that combination of ErbB4, BDNF and TET1 biomarkers could greatly improve the diagnostic performance.
精神分裂症(SZ)是一种严重的精神疾病。在首发精神病(FEP)期间验证潜在的血清生物标志物对于理解这种疾病的发病机制和预后特别有帮助。为了解决这个问题,我们研究了多种血液生物标志物,并评估了其诊断 SZ 的效果。通过酶联免疫吸附测定(ELISA)测定了 53 名 FEP 患者和 57 名健康对照者外周血中神经调节蛋白 1(NRG1)、表皮生长因子受体 4(ErbB4)、脑源性神经营养因子(BDNF)、DNA 甲基转移酶 1(DNMT1)和 ten-eleven 易位酶 1(TET1)的表达水平。使用包含生物标志物浓度作为协变量的多变量逻辑回归来预测 SZ。通过接收者操作特征(ROC)曲线分析分析这五种血清蛋白水平的区分性能。我们发现,SZ 患者外周血中的 DNMT1 和 TET1 浓度较高,而 NRG1、ErbB4 和 BDNF 浓度较低。多变量逻辑回归显示,ErbB4、BDNF 和 TET1 是 SZ 的独立预测因子,当它们联合使用时,对 SZ 具有较高的诊断准确性。总的来说,我们的研究结果表明,NRG1、ErbB4、BDNF、DNMT1 和 TET1 的表达改变参与了精神分裂症的发生,它们可能作为精神分裂症诊断的潜在生物标志物。因此,我们的研究提供了证据表明,ErbB4、BDNF 和 TET1 生物标志物的组合可以极大地提高诊断性能。