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腦源性神經(jīng)營養(yǎng)因子含量和基因多態(tài)性與精神分裂癥的相關(guān)分析

發(fā)布時(shí)間:2018-09-06 14:59
【摘要】:背景與目的: 精神分裂癥,英文名稱為schizophrenia,屬于一種較為常見的精神病。有資料表明,世界范圍內(nèi),精神分裂癥患者的終身患病率約為3.8‰~8.4‰。資料顯示,我國有很多人處于不同程度的精神分裂狀態(tài)。一旦患上精神分裂癥,將會(huì)在不同程度影響患者的生活質(zhì)量和患者的身心健康。目前認(rèn)為遺傳因素、內(nèi)分泌因素、軀體生物學(xué)因素、腦結(jié)構(gòu)變化因素等多方面的原因等均可引發(fā)精神分裂癥。有學(xué)者研究表明,精神分裂癥的發(fā)病和神經(jīng)發(fā)育異常有著密切的關(guān)系,在所有因子中,腦源性神經(jīng)營養(yǎng)因子(brain-derived neurotrophic factor, BDNF)是其中最為關(guān)鍵的因子之一。為此,本研究擬通過分析精神分裂癥患者的臨床表型與腦源性神經(jīng)營養(yǎng)因子基因多態(tài)性、以及血清BDNF濃度的相關(guān)性,為精神分裂癥發(fā)病機(jī)制的探索提供實(shí)驗(yàn)資料。 研究方法: 選取商丘市精神病醫(yī)院住院部的456例病例較為完整的精神分裂癥患者作為研究對象,同時(shí)選取114例正常人作為實(shí)驗(yàn)的對照組。并由同一組經(jīng)驗(yàn)豐富的精神科主治醫(yī)師對實(shí)驗(yàn)組患者進(jìn)行PANSS量表與PSP量表評(píng)分;選取實(shí)驗(yàn)組不同臨床診斷分型患者PSP評(píng)分分析不同精神分裂癥臨床亞型對患者社會(huì)認(rèn)知和社會(huì)功能的影響;采用酶聯(lián)免疫吸附(ELISA)法測定2組標(biāo)本血清中BDNF濃度;采用TaqMan法檢測BDNF基因單核苷酸多態(tài)性(SNP) rs6265和rs11030101位點(diǎn)。分析精神分裂癥患者性別、年齡與血清BDNF濃度的相關(guān)性;分析精神分裂癥不同臨床診斷分型與患者血清BDNF濃度的相關(guān)性;分析不同(SNPs rs6265和rs11030101)基因型、等位基因型分布和聯(lián)合基因型頻率分布與精神分裂癥的相關(guān)性,與患者PANSS和PSP的相關(guān)性。 研究結(jié)果: 實(shí)驗(yàn)組患者PANSS量表評(píng)定Ⅰ型與Ⅱ型患者男女比例、平均病程及平均年齡比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);實(shí)驗(yàn)組患者PSP量表平均評(píng)分為(46.04±16.02),表明患者在發(fā)病時(shí)社會(huì)認(rèn)知和社會(huì)功能已經(jīng)受到了不同程度的損害;實(shí)驗(yàn)組患者不同臨床分型PSP評(píng)分比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);實(shí)驗(yàn)組患者血清BDNF低于對照組,,差異具有顯著性(P0.05);2組患者不同性別血清BDNF濃度比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);2組患者不同年齡血清BDNF濃度比較差異也無統(tǒng)計(jì)學(xué)意義(P0.05);實(shí)驗(yàn)組患者不同的臨床診斷分型患者血清BDNF濃度比較無統(tǒng)計(jì)學(xué)差異(P0.05);實(shí)驗(yàn)組患者的血清BDNF濃度、PSP量表評(píng)分和PANSS量表評(píng)分正交相關(guān)分析表明:患者的PSP評(píng)分與PANSS評(píng)分之間呈負(fù)相關(guān),差異具有顯著性(P0.05),其余各指標(biāo)間無統(tǒng)計(jì)學(xué)意義相關(guān)性(P0.05);2組SNPs rs6265和rs11030101基因型及等位基因比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);2組患者男性患者與女性患者SNPs rs6265和rs11030101基因型、等位基因頻率分布比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);2組患者SNPs rs6265和rs11030101基因型、等位基因頻率分布男女比例比較差異均無統(tǒng)計(jì)學(xué)意義(P0.05);2組患者聯(lián)合基因型(SNPs rs6265rs11030101)頻率分布差異無統(tǒng)計(jì)學(xué)意義(P0.0.5);實(shí)驗(yàn)組患者不同臨床診斷分型SNPs rs6265和rs11030101基因型及等位基因型分布差異無統(tǒng)計(jì)學(xué)意義(P0.05);不同臨床診斷分型患者SNPs rs6265和rs11030101基因型及等位基因分布比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05);實(shí)驗(yàn)組SNPs rs6265和rs11030101不同基因型患者PANSS評(píng)分比較差異無統(tǒng)計(jì)學(xué)意義(P0.05);SNPs rs6265不同基因型患者PSP評(píng)分比較差異無統(tǒng)計(jì)學(xué)意義(P0.05), SNPs rs11030101不同基因型患者PSP評(píng)分G/A最高、A/A最低,差異具有顯著性(P0.05);實(shí)驗(yàn)組患者不同SNPs rs6265和rs11030101基因型血清BDNF濃度比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論: 精神分裂癥患者血清BDNF水平低于正常人。精神分裂癥患者SNPs rs11030101位點(diǎn)不同基因型可能對患者個(gè)人和社會(huì)功能評(píng)分產(chǎn)生影響,其中G/A型患者影響最高,A/A型患者影響最低。
[Abstract]:Background and purpose:
Schizophrenia is a common psychiatric disorder. Data show that the lifetime prevalence of schizophrenia is about 3.8 ~8.4. Data show that many people in China are in different degrees of schizophrenia. At present, it is believed that genetic factors, endocrine factors, somatic biological factors, brain structural changes and other factors can cause schizophrenia. Some scholars have shown that the onset of schizophrenia and neurodevelopmental abnormalities have a close relationship, in all the factors, brain origin. Sexual neurotrophic factor (BDNF) is one of the most important factors in schizophrenia. Therefore, this study intends to analyze the correlation between clinical phenotype and brain-derived neurotrophic factor gene polymorphism, and serum BDNF concentration in schizophrenia, so as to provide an experiment for exploring the pathogenesis of schizophrenia. Information.
Research methods:
A total of 456 schizophrenic patients in the inpatient department of Shangqiu Psychiatric Hospital were selected as the subjects and 114 normal persons as the control group. The PSP score of the severed schizophrenia patients was used to analyze the influence of different clinical subtypes on their social cognitive and social functions; the serum BDNF concentration was determined by enzyme-linked immunosorbent assay (ELISA); the single nucleotide polymorphism (SNP) rs6265 and rs11030101 of BDNF gene were detected by TaqMan method. In addition, the correlation between age and serum BDNF concentration was analyzed; the correlation between different clinical diagnostic types and serum BDNF concentration was analyzed; the correlation between different genotypes (SNPs rs6265 and rs11030101), allele distribution and frequency distribution of combined genotypes and schizophrenia, and the correlation between PANSS and PSP were analyzed.
Research findings:
There was no significant difference in the average course of disease and age between the two groups (P 0.05). The average score of PSP in the experimental group was (46.04 +16.02), indicating that the patients'social cognition and social function had been impaired in different degrees. There was no significant difference in clinical classification PSP score (P 0.05); serum BDNF in experimental group was lower than that in control group, the difference was significant (P 0.05); there was no significant difference in serum BDNF concentration between the two groups (P 0.05); there was no significant difference in serum BDNF concentration between the two groups at different ages (P 0.05). There was no significant difference in serum BDNF concentration among patients with different clinical diagnosis types (P 0.05). The orthogonal correlation analysis of serum BDNF concentration, PSP score and PANSS score showed that there was a negative correlation between PSP score and PANSS score, and the difference was significant (P 0.05). Significance correlation (P 0.05); There was no significant difference in genotype and allele between the two groups (P 0.05); SNPs rs6265 and rs11030101 genotypes and allele frequencies between male and female patients in the two groups had no significant difference (P 0.05); SNPs rs6265 and rs11030101 genotypes and allele frequencies in the two groups had no significant difference (P 0.05). There was no significant difference in the frequency distribution of alleles between men and women (P 0.05); there was no significant difference in the frequency distribution of combined genotypes (SNPs rs6265 rs11030101) between the two groups (P 0.0.5); there was no significant difference in the distribution of genotypes and alleles of SNPs rs6265 and rs11030101 between the two groups (P 0.05). There was no significant difference in the genotype and allele distribution of SNPs rs6265 and rs11030101 among the patients with different clinical diagnosis types (P 0.05); there was no significant difference in the PANSS score between the patients with different genotypes of SNPs rs6265 and rs11030101 in the experimental group (P 0.05); there was no significant difference in the PSP score among the patients with different genotypes of SNPs rs6265. Significance (P 0.05), different genotypes of SNPs rs11030101 patients with the highest PSP score G/A, the lowest A/A, the difference was significant (P 0.05); experimental group of different SNPs rs6265 and rs11030101 genotype serum BDNF concentration difference was not statistically significant (P 0.05).
Conclusion:
The level of serum BDNF in schizophrenic patients was lower than that in normal subjects. Different genotypes at SNPs rs11030101 locus may have an impact on individual and social function scores of patients with schizophrenia, of which G/A type had the highest impact and A/A type had the lowest impact.
【學(xué)位授予單位】:鄭州大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2013
【分類號(hào)】:R749.3

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