Liu Yong, Tang Yamei, Li Cunyan, Tao Huai, Yang Xiudeng, Zhang Xianghui, Wang Xuyi
National Clinical Research Center for Mental Disorders, and Department of Psychaitry, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Psychiatry. 2020 Aug 12;11:760. doi: 10.3389/fpsyt.2020.00760. eCollection 2020.
It is well-known that altered hypothalamus-pituitary-adrenal (HPA) axis process has an important role in the neurodegenerative process in schizophrenia (SZ). However, this neurodegenerative mechanism has not been clarified in SZ. Therefore, the main purpose of this study was to determine HPA axis damage in the first-episode, unmedicated schizophrenia (FES) patients and chronic schizophrenia (CSZ) patients in comparison with healthy controls (HC) by means of quantitative analysis of the peripheral blood mRNA expression of glucocorticoid receptor (GR), GR transcripts containing exons 1B (GR-1B), and neuron specific enolase (NSE) genes and serum cortisol and NSE, a specific serum marker for neuronal damage.
In the present study, 43 FES patients, 39 CSZ, and 47 HC were included. The peripheral blood mRNA expressions for GR, GR-1B, and NSE genes were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Serum cortisol and NSE were analyzed by electrochemiluminescence immunoassay technique.
Levels of GR mRNA were significantly lower in FES and CSZ than that in HC. The expression of GR-1B mRNA was significantly decreased in CSZ when compared with that in FES. Levels of NSE mRNA were significantly lower in CSZ than that in FES patients or HC patients. CSZ patients showed significantly lower cortisol concentrations than FES and HC patients. FES patients showed significantly higher NSE concentrations than CSZ and HC.
Our findings support that there is disrupted HPA axis system in the SZ and suggest that CSZ patients suffer a greater HPA axis damage than FES patients. Our research implicated underlying GR mRNA dysregulation in SZ and the potential importance of the functional GR-1B transcription in CSZ.
众所周知，下丘脑 - 垂体 - 肾上腺（HPA）轴功能改变在精神分裂症（SZ）的神经退行性病变过程中起重要作用。然而，这种神经退行性机制在精神分裂症中尚未阐明。因此，本研究的主要目的是通过对糖皮质激素受体（GR）、含外显子1B的GR转录本（GR-1B）以及神经元特异性烯醇化酶（NSE）基因的外周血mRNA表达进行定量分析，并检测血清皮质醇和NSE（一种神经元损伤的特异性血清标志物），来确定首发未用药精神分裂症（FES）患者和慢性精神分裂症（CSZ）患者相较于健康对照（HC）的HPA轴损伤情况。
本研究纳入了43例FES患者、39例CSZ患者和47例HC。通过实时定量聚合酶链反应（RT-qPCR）测定GR、GR-1B和NSE基因的外周血mRNA表达。采用电化学发光免疫分析技术检测血清皮质醇和NSE。
FES和CSZ患者的GR mRNA水平显著低于HC。与FES相比，CSZ患者GR-1B mRNA的表达显著降低。CSZ患者的NSE mRNA水平显著低于FES患者或HC患者。CSZ患者的皮质醇浓度显著低于FES患者和HC患者。FES患者的NSE浓度显著高于CSZ患者和HC患者。
我们的研究结果支持精神分裂症患者存在HPA轴系统紊乱，并表明CSZ患者比FES患者遭受更严重的HPA轴损伤。我们的研究提示精神分裂症患者存在潜在的GR mRNA失调，以及功能性GR-1B转录在CSZ中的潜在重要性。
