Department of Geriatric Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu, 214151, China.
Combined TCM & Western Medicine Department, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu, 214151, China.
Neurosci Lett. 2021 Feb 16;746:135669. doi: 10.1016/j.neulet.2021.135669. Epub 2021 Jan 21.
This study attempted to analyze the alterations in the mRNA expression levels of autophagy- and apoptosis-related genes in the forkhead box transcription factor O (FOXO) pathway in schizophrenia patients before and after olanzapine treatment. For a total of 32 acute schizophrenic inpatients, clinical data with PANSS were obtained before and after four weeks of olanzapine treatment (mean dose 14.24 ± 4.35 mg/d) along with data from 32 healthy volunteers. The mRNA expression levels of the FOXO pathway genes were measured by real-time qPCR after fasting venous blood was collected and analyzed. The mRNA expression levels of FOXO1, FOXO3A, FASLG, and BCL2L11 were observed to be significantly decreased in acute schizophrenia patients. After four weeks of olanzapine treatment, the expression levels of the first three genes were further reduced, but BCL2L11 expression levels were not significantly changed. The pairwise correlations between the mRNA expression level of FASLG and those of the other three genes were not observed in acute schizophrenia patients, while these relationships were observed in healthy controls. After olanzapine treatment, the FASLG mRNA expression level was restored and exhibited a pairwise correlation with the FOXO3A and BCL2L11 mRNA expression levels but not with the FOXO1 mRNA expression level, and FASLG mRNA expression was also correlated with the duration of the disease. The statuses and correlations of the mRNA expression levels of FOXO pathway-related genes were altered in schizophrenia patients and were affected by olanzapine treatment and the duration of the disease.
本研究试图分析精神分裂症患者在奥氮平治疗前后叉头框转录因子 O（FOXO）通路中自噬和凋亡相关基因的 mRNA 表达水平变化。共纳入 32 例急性精神分裂症住院患者，在奥氮平治疗（平均剂量 14.24±4.35mg/d）前和治疗 4 周后采集空腹静脉血，同时纳入 32 名健康志愿者，应用实时 qPCR 检测 FOXO 通路基因的 mRNA 表达水平。结果发现，急性精神分裂症患者 FOXO1、FOXO3A、FASLG 和 BCL2L11 的 mRNA 表达水平显著降低。奥氮平治疗 4 周后，前 3 个基因的表达水平进一步降低，但 BCL2L11 表达水平无明显变化。急性精神分裂症患者中未观察到 FASLG mRNA 表达水平与其他 3 个基因表达水平之间的两两相关性，而在健康对照组中观察到这些关系。奥氮平治疗后，FASLG mRNA 表达水平恢复，与 FOXO3A 和 BCL2L11 mRNA 表达水平呈两两相关，但与 FOXO1 mRNA 表达水平无关，FASLG mRNA 表达水平与疾病持续时间相关。精神分裂症患者 FOXO 通路相关基因的 mRNA 表达水平状态和相关性发生改变，受奥氮平治疗和疾病持续时间的影响。
