精神分裂症患者脑源性神经营养因子基因多态性与临床症状的关系

Association of the brain-derived neurotrophic factor gene polymorphisms and clinical symptoms in patients with schizophrenia

背景神经发育学说是精神分裂症发病机制的研究重点,脑源性神经营养因子(BDNF)在神经元发育过程中起重要作用,可能是精神分裂症的生物标志物之一。BDNF水平及其基因多态性在精神分裂症的发病机制中具有重要作用,但尚存争议。目的分析精神分裂症患者BDNF水平与健康对照人群的差异,探讨BDNF单核苷酸多态性(SNPs)位点(rs11030101、rs2030324、rs6265)与BDNF水平的关系,并分析其与临床症状的关系,为精神分裂症的治疗提供参考。方法采用病例对照研究,纳入2019年1月-2020年12月在中山市第三人民医院就诊的、符合《精神障碍诊断与统计手册(第5版)》(DSM-5)精神分裂症诊断标准的55例精神分裂症患者为研究对象,同期在中山市第三人民医院工作人员和社会人群中招募健康对照组31名。使用阳性和阴性症状量表(PANSS)评定精神分裂症患者的临床症状。采用酶联免疫吸附法(ELISA法)经酶标仪定标检测精神分裂症患者和对照组血清BDNF水平,采用聚合酶链式反应产物直接测序确定患者组和对照组BDNF的rs11030101、rs2030324、rs6265位点基因型。结果患者组血清BDNF水平低于对照组,差异有统计学意义(t=-3.804,P<0.01)。临床症状方面,BDNF rs11030101位点不同基因型的患者PANSS总评分、兴奋敌对因子评分和抑郁焦虑因子评分差异均有统计学意义(t=2.022、Z=-2.696、-2.467,P<0.05或0.01)。不同位点的各基因型患者血清BDNF水平差异均无统计学意义(Z=1.483、F=2.584、0.417,P均>0.05)。结论精神分裂症患者BDNF水平偏低。BDNF的rs11030101、rs2030324、rs6265位点多态性与血清BDNF水平水平无关,BDNF的rs11030101位点多态性可能会导致精神分裂症患者兴奋敌对、抑郁焦虑等临床症状。血清BDNF水平可能更多地取决于诊断效果而非基因多态性效应。

Background In relation to neurodevelopmental hypothesis in the etiology of schizophrenia,brain-derived neurotrophic factor(BDNF)as a neurotrophin occupies a relatively dominant position in neuronal development and is a potential biomarker for schizophrenia,and previous studies have suggested that its serum concentration and genetic polymorphisms play a vital role in the pathogenesis of schizophrenia,but this remains controversial.Objective To analyze the difference in BDNF serum concentration between schizophrenic patients and healthy controls,and to explore the correlation of three BDNF single nucleotide polymorphism(SNPs)including rs11030101,rs2030324 and rs6265 with BDNF serum concentration and clinical symptoms in patients with schizophrenia,thus providing references for the clinical treatment of schizophrenia.Methods A case-control study was conducted on 55 patients with schizophrenia who attended the Zhongshan Third People's Hospital from January 2019 to December 2020 and met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5),and 31 healthy controls concurrently recruited from the hospital or general population.Positive and Negative Symptom Scale(PANSS)was utilized to evaluate the psychiatric symptoms of patients with schizophrenia.BDNF serum concentration in all participants was measured using enzyme linked immunosorbent assay(ELISA),and the genotype distributions of three BDNF SNPs(rs11030101,rs2030324,rs6265)were investigated by polymerase chain reaction sequence-based typing method.Results BDNF serum concentration in patient group was lower than that in control group,with statistical difference(t=-3.804,P<0.01).In terms of clinical symptoms,PANSS total score,excitement/hostility domain score,and depression/anxiety domain score demonstrated statistical difference among patients with different genotypes at SNP rs11030101(t=2.022,Z=-2.696,-2.467,P<0.05 or 0.01).No statistical difference was noted in BDNF serum concentration in patients with different genotypes at three BDNF SNPs(Z=1.483,F=2.584,0.417,P>0.05).Conclusion Patients with schizophrenia are found to have low BDNF serum concentration,and the three BDNF SNPs(rs11030101,rs2030324,rs6265)are not associated with BDNF serum concentration,whereas the BDNF rs11030101 polymorphism may contribute to the manifestation of clinical symptoms of excitement/hostility and depression/anxiety in patients with schizophrenia.Furthermore,BDNF serum concentration seems to be more dependent on clinical diagnosis effect rather than genetic polymorphism.