Altered Expression of Glucocorticoid Receptor and Neuron-Specific Enolase mRNA in Peripheral Blood in First-Episode Schizophrenia and Chronic Schizophrenia.

Yong Liu,Xiudeng Yang,Xianghui Zhang,Cunyan Li,Xuyi Wang,Huai Tao,Yamei Tang

doi:10.3389/fpsyt.2020.00760

Abstract

IntroductionIt 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.MethodsIn 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.ResultsLevels 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.ConclusionOur 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.

Highlights

It is well-known that altered hypothalamus–pituitary–adrenal (HPA) axis process has an important role in the neurodegenerative process in schizophrenia (SZ)
We provide further evidence of altered neuron specific enolase (NSE) mRNA in chronic schizophrenia (CSZ), glucocorticoid receptor (GR) mRNA in FES and CSZ and decreased GR transcripts containing exons 1B (GR-1B) mRNA in CSZ compared to FES
Our findings showed no significant difference in serum cortisol levels between the FES and healthy controls (HC) groups (P > 0.05), which is consistent with previous researches [24, 30, 31], while some findings showed that CSZ patients had higher cortisol concentration [22, 29] or no elevated diurnal cortisol level in antipsychotic-naive, putatively at-risk children who present multiple antecedents of SZ or a family history of illness [23]

Summary

Introduction

It is well-known that altered hypothalamus–pituitary–adrenal (HPA) axis process has an important role in the neurodegenerative process in schizophrenia (SZ). This neurodegenerative mechanism has not been clarified in SZ. 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. Rodents and human GR levels are almost completely mediated at transcriptional level, and each non-coding exon variant is regulated by its own promoter, which is conducive to the tissue specificity of GR expression [10,11,12,13]

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