精神分裂症和亚甲基四氢叶酸还原酶基因的核心家系研究

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因与中国西北地区汉族精神分裂症的关系。方法应用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP),检测106个精神分裂症核心家系MTHFR基因的C677T和A1298C多态性,采用单倍体相对风险(HRR)和传递不平衡检验(TDT)分析MTHFR基因与精神分裂症的关系。结果①患者组与父母组MTHFR基因C677T和A1298C多态性基因型频率分布差异无统计学意义(x2=0.369,P>0.05;x2=1.214,P>0.05)。②HRR分析显示C677T、A1298C两位点等位基因在病例组和父母对照组的频数分布差异无统计学意义(x2=0.236,P>0.05;x2=3.327,P>0.05)。③TDT检验未发现C677T和A1298C两位点在精神分裂症中存在传递不平衡(x2=0.243,P>0.05;x2=2.123,P>0.05)。结论未发现MTHFR基因C677T和A1298C多态性与精神分裂症存在关联。     

难治性精神分裂症与亚甲基四氢叶酸还原酶基因多态性的关联分析

目的:探讨难治性精神分裂症与亚甲基四氢叶酸还原酶(MTHFR)基因C677T和A1298C多态性的关系。方法:应用聚合酶链反应-限制性片断长度多态性方法(PCR-RFLP)检测102名正常对照、138例难治性精神分裂症患者及97例非难治性精神分裂症患者MTHFR基因的C677T和A1298C多态性。结果:患者组与对照组,难治组与非难治组C677T、A1298C基因型分布差异均无统计学意义(C677T,χ2=4.83,P=0.09;χ2=1.90,P=0.39;A1298C,χ2=1.50,P=0.47;χ2=3.90,P=0.14),而患者组C677T的T等位基因频率显著高于正常对照组(P=0.04),难治组A1298C的C等位基因频率显著高于非难治组(P=0.04)。677TT/1298AA、677CT/1298AC复合基因型患病相对风险度比677CC/1298AA型显著提高(OR=4.13,95%CI=1.26～13.58,P=0.02;OR=2.95,95%CI=1.23～7.07,P=0.01),而在难治组和非难治组中,复合基因型差异无统计学意义。结论:MTHFR基因677T等位基因和677TT/1298AA、677CT/1298AC复合基因型是精神分裂症发病危险因素,MTHFR基因1298C等位基因可能是难治性精神分裂症的危险因子之一。     

亚甲基四氢叶酸还原酶与精神分裂症的相关研究进展

高同型半胱氨酸血症(hyperhomocysteinemia)是出生神经发育缺陷及精神分裂症的一个独立危险因子,亚甲基四氢叶酸还原酶(5,10-Methylenetetrahydrofolatereductase,MTHFR)活力的降低是引起高同型半胱氨酸血症的一个重要原因。关于MTHFR基因结构和功能的研究已基本清楚。本文对MTHFR基因进行相关描述,并对两个多态性C67T和A1298C与精神分裂症关联研究的进展进行概述。     

亚甲基四氢叶酸还原酶与精神分裂症的相关研究进展

高同型半胱氨酸血症（hyperhomocysteinemia）是出生神经发育缺陷及精神分裂症的一个独立危险因子，亚甲基四氢叶酸还原酶（5，10-Methylenetetrahydrofolatereductase，MTHFR）活力的降低是引起高同型半胱氨酸血症的一个重要原因。关于MTHFR基因结构和功能的研究已基本清楚。本文对MTHFR基因进行相关描述，并对两个多态性C67T和A1298C与精神分裂症关联研究的进展进行概述。     

亚甲基四氢叶酸还原酶基因多态性与脑出血的关系

目的　探讨上海地区人群亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与脑出血的关系。方法应用聚合酶链反应 限制性片断长度多态性 (PCR RFLP)技术 ,检测 94例脑出血患者 (脑出血组 )和 10 0名正常人 (对照组 )的MTHFR基因。结果　MTHFR基因第 6 77位核苷酸呈多态性 ,可分为 3种类型 :CC、CT、TT。 3种基因型频率脑出血组分别为 2 2 %、6 3%、15 % ;对照组分别为 4 0 %、4 9%、11% ;两组基因型频率TT∶CC +CT ,差异无显著性 (P >0 0 5 )。T等位基因频率脑出血组 4 6 % ,对照组 35 % ,两组间比较差异有显著性 (P <0 0 5 )。结论　MTHFR基因等位基因 (T)频率与脑出血有关     

N5,10-亚甲基四氢叶酸还原酶基因多态性与脑血管病的关系研究

目的　探讨 N5,1 0 -亚甲基四氢叶酸还原酶 ( MTHFR) 677C→T位点突变与晚发型脑血管病的关系。方法　采用多聚酶链反应 -限制性内切酶片段长度多态性 ( PCR-RFLP)方法测定 1 0 7例脑血管病患者及 78例健康对照组 MTHFR基因多态性。结果　 ( 1 )两组 MTHFR基因型频率分布差异有显著性 ( P <0 .0 1 )。患者组纯合子 ( T/ T)突变频率 ( 2 2 .4% )较对照组 ( 1 9.0 % )升高 ,但统计学差异无显著性 ( P =0 .0 5 7)。杂合子 ( T/ C)频率( 61 .7% )较对照组 ( 4 1 .8% )明显升高 ,差异有显著性 ( P <0 .0 1 )。脑血管病患者发生 T等位基因型频率也较对照组显著升高 ,差异有显著性 ( P <0 .0 1 )。 ( 2 ) MTHFR677C→T突变基因型的患者或 T等位基因型患者患病的危险性较对照组显著增加 ,杂合子患病的危险性更大。结论　MTHFR677C→ T位点突变增加脑血管病的危险性 ,可能是脑血管病的易感基因。     

亚甲基四氢叶酸还原酶基因多态性与脑梗死的相关研究

高同型半胱氨酸 (ｈｏｍｏｃｙｓｔｅｉｎｅ ,Ｈｃｙ)血症为脑血管病独立危险因素 ,亚甲基四氢叶酸还原酶 (ｍｅｔｈｙｌｅｎｅｔｅｔｒａｈｙｄｒｏｆｏｌａｔｅｒｅｄｕｃｔａｓｅ ,ＭＴＨＦＲ)是Ｈｃｙ代谢关键酶 ,ＭＴＨＦＲ基因Ｃ677Ｔ位点突变使酶活性下降。我们探讨了我国汉族人群ＭＴＨＦＲ基因Ｃ677Ｔ位点多态性与脑梗死的相关性。资料和方法 :脑梗死组 2 34例 ,男 1 4 0例 ,女 94例 ,平均年龄 63 9岁 ,来自 1 999年 1 0月至 2 0 0 1年 2月我院神经科病房 ,病例符合第四届全国脑血管病学术会议制定的诊断标准 ,经头颅ＣＴ/ＭＲＩ确…     

亚甲基四氢叶酸还原酶基因多态性与脑梗死的关系

目的 再一次探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血浆同型半胱氨酸(Hcy) 与脑梗死的相关性.方法 采用聚合酶链反应-限制性内切酶长度多态性(PCR-RFLP)方法分析脑梗死病人(260例)与健康人群(242例)的MTHFR基因突变的情况.利用高效液相色谱法测定血浆Hcy水平,并加以对照分析.结果 脑梗死组与对照组MTHFR基因型比较无统计学意义(P=0.140).2组MTHFR的T等位基因频率相比亦无统计学意义(P=0.061).2组Hcy水平比较差异有统计学意义(P＜0.001),Hcy水平与叶酸呈负相关.结论 进一步证实血浆Hcy水平升高是脑梗死的独立危险因素,MTHFR基因突变可能是Hcy升高的主要影响因素.     

亚甲基四氢叶酸还原酶基因多态性与脑出血的相关研究

高浓度的血浆同型半胱氨酸 (homocysteine,Hcy)可通过损伤血管内皮细胞 ,抑制内皮细胞增生及刺激血管平滑肌细胞增生而导致动脉粥样硬化。亚甲基四氢叶酸还原酶(Methylenetetrahydrofolate reductase,MTHFR)是 Hcy代谢关键酶 ,MTHFR基因 C6 77T位点突变导致酶活性下降。我们探讨了我国汉族人群 MTHFR基因 C6 77T位点多态性与脑出血的相关性。1　资料与方法脑出血组 15 6例 ,平均年龄 5 9.2± 8.1岁 ,均为 1999年10月～ 2 0 0 1年 2月我院神经科住院患者 ,病例符合第四届全国脑血管病学术会议制定的诊断标准 ,经头部 CT确诊 ,并除…     

脑血栓形成与亚甲基四氢叶酸还原酶基因多态性的关系

目的　探讨中国汉族人群脑血栓形成与亚甲基四氢叶酸还原酶 (MTHFR)基因多态性及血浆同型半胱氨酸 (Hcy)水平的关系。 方法　利用聚合酶链反应 限制性内切酶长度多态性 (PCR RFLP)方法分析脑血栓形成患者 (75例 )与健康人群 (62名 )的MTHFR基因突变的情况。采用高效液相色谱法测定血浆Hcy水平 ,并加以对照分析。 结果　脑血栓形成组与对照组MTHFR基因型频率CC、CT、TT型分别为 0 41、0 35、0 2 4及 0 58、0 2 3、0 1 9,两组相比差异无显著意义 (P =0 1 37)。患者组与对照组MTHFR的T等位基因频率分别为 0 41和 0 31 ,两组相比差异无显著意义 (P =0 0 67)。脑血栓形成组与对照组血浆Hcy水平分别为 (1 8 3± 7 2 ) μmol/L与 (1 3 6± 5 8)μmol/L ,二者比较差异有显著意义 (P <0 0 0 1 )。两组中MTHFR基因TT型者Hcy水平与CC型比较差异有显著意义 (P <0 0 5) ,Hcy水平与叶酸呈负相关 (患者组 :r =- 0 31 ,P <0 0 1 ;对照组 :r =- 0 2 8,P <0 0 5)。结论　血浆Hcy水平升高是脑血栓形成的危险因素之一 ,MTHFR基因突变可能是血浆Hcy升高的主要影响因素     

Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study

Although schizophrenia has been diagnosed in children, this group of disorders has received too little attention in the clinical and research literature. Preliminary data suggest that early onset schizophrenia (EOS) and very early onset schizophrenia (VEOS) tend to have a worse outcome than adult onset schizophrenia, and seem to be related to a greater familial vulnerability, due to genetic, psychosocial, and environmental factors. Recently, advanced neuroimaging techniques have revealed structural and functional brain abnormalities in some cerebral areas. This paper reports on a case diagnosed as VEOS, with premorbid year-long psychopathological history. The patient showed atypical proton magnetic resonance spectroscopy findings, and normal brain and spine computer tomography and brain magnetic resonance images.     

晚发性和早发性精神分裂症临床特征比较

目的：了解早发性和晚发性精神分裂症的临床特征。方法：用阳性症状量表（SAPS）、阴性症状量表（SANS）评定临床症状;临床疗效总评量表（CGI）、治疗中出现的症状量表（TESS）评定临床疗效及不良反应;用躯体异常量表（Waldrop scale）N量软体征。对早发性精神分裂症和晚发性精神分裂症患者各50例进行对照研究。结果：早发性精神分裂症遗传倾向明显,软体征异常率高,有更明显的阴性症状,治疗效果较差,不良反应更明显。晚发性精神分裂症女性明显多于男性,以幻觉、妄想、偏执观念为主要临床特征．结论：早发性和晚发性精神分裂症各有其临床特征。早发性比晚发性精神分裂症的遗传负荷和胚胎发育异常程度高,治疗效果和预后较差。     

A study of cranial computertomograms in very early and early onset schizophrenia

Summary. The cranial computer-assisted tomograms of 19 patients suffering from schizophrenic psychoses with onset by age of 14 were examined. The emphasis was on the extent of the inner liquor spaces. Compared to healthy controls, at the beginning of illness a significant enlargement was revealed only in the patient group with very early onset schizophrenia (VEOS, onset prior to the age of 12), whereas children with early onset (EOS, 12 to 14 years of age) showed no significant brain pathology. As a second result, an increase in the extent of the inner liquor spaces seems to correlate with the duration of illness. It is therefore concluded that psychoses interfere with neurodevelopmental processes and cause more severe brain pathology in very young children, already detectable at the onset of the illness. EOS, on the other hand, induces progressive morphological abnormalities over the course of the illness. Received February 2, 2001; accepted July 11, 2001     

Comparative study of neuropsychological correlates in schizophrenia with onset in childhood, adolescence and adulthood

Childhood onset schizophrenia (COS) patients have marked neuropsychological deficits in areas of attention, working memory and executive functions. Similar deficits have been found in studies on Adolescent onset (AdOS) and Adult onset schizophrenia (AOS). In this study we compared the neuropsychological profile of COS with AdOS and AOS to test the hypothesis that earlier the onset greater is the severity of illness and greater are the neuropsychological deficits. A sample of 15 patients of COS was compared with 20 patients each of AdOS and AOS group. Assessment of neuropsychological profile was done using standard neuropsychological battery for Indian population. Nahor Benson Test and Bender Visual Motor Gestalt Test were used to assess perceptuomotor functioning. COS patients showed significantly greater deficits on scales of IQ, memory and perceptuomotor skills as compared to AdOS that in turn had greater deficits than AOS. The persistence of differences across the three groups inspite of controlling for education and age suggest that these deficits may have been present even before the onset of illness and was not the result of poor academic achievements. These findings also point towards a brain damage in schizophrenia that occurs on a continuum of severity with COS being the most virulent, AOS being the least and AdOS falling in between these two extremes.     

Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria.

BACKGROUND: The gene encoding the dystrobrevin binding protein (DTNBP1) has been implicated in the pathogenesis of schizophrenia by several association studies. We tried to replicate these findings in a sample of 488 parent-proband trios recruited in Bulgaria. Probands had a diagnosis of schizophrenia (n = 441) or schizoaffective disorder (n = 47). METHODS: We genotyped eight single nucleotide polymorphisms within the gene, four of which had been reported in previous studies, and four identified as informative by our group through direct screening of the gene and genotyping in a sample of cases and control subjects. RESULTS: A significant excess of transmissions was observed for two of the markers, p1635 and p1757, (p =.0009 and.0013, respectively). Analysis of two-, three-, and four-marker haplotypes produced numerous positive results, with six (4% of the total combinations) at p <.001. CONCLUSIONS: These results provide strong support for DTNBP1 as a susceptibility gene for schizophrenia; however, different haplotypes seem to be associated in different studies.     

亚甲基四氢叶酸还原酶基因C677T多态性与先兆型偏头痛相关性的Meta分析

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与先兆型偏头痛(MA)的相关性。方法检索1994年1月~2013年3月MEDLINE、EBSCO、EMBASE数据库及PubMed,以及中国医院知识仓库中文期刊全文库、中国生物医学文献数据库、维普、万方等中文数据库中关于MTHFR基因C677T多态性与MA相关性的文献,按纳入、排除标准选择文献,并采用RevMan 5软件进行Meta分析。结果共纳入18项病例对照研究,其中MA患者4276例,对照者27979例。各研究间具有很强的异质性(P0.05,I2=72%),采用随机效应模型分析。Meta分析显示,MTHFR基因TT基因型发生MA的风险明显高于CT+CC基因型(OR=1.33,95%CI:1.02~1.75,P0.01)。剔除不符合H-W遗传平衡定律的3篇文献后,总的分析结果依然稳定(OR=1.39,95%CI:1.02~1.88,P0.01)。在MA人群中所做种族分层分析结果显示,在地中海人种TT基因型增加了MA的发病风险,而在其他高加索人(包括北欧人种和印度雅利安人种)、芬兰人、土耳其人及日本人的研究并未显示出这种相关性。结论 MTHFR基因C677T多态性与MA相关,其TT基因型个体MA发病的风险增加。这在不同种族间存在一定差别。     

早发精神分裂症静息态脑功能低频振幅研究

目的通过静息态功能磁共振研究早发未用药精神分裂症患者局部脑功能低频振幅(amplitude of low-frequency fluctuation,ALFF)的变化,探讨其静息态下功能异常的脑区。方法收集20例早发未用药精神分裂症患者与20名性别、年龄、受教育年限相匹配的正常对照,分别对其进行全脑静息态功能磁共振扫描,计算ALFF值。结果与对照组相比,患者组左侧额上回、左侧楔前叶、左侧扣带回、左侧枕叶、左侧海马旁回、左侧距状沟ALFF值增高(P0.05,Alpha Sim校正),右侧颞上回和右侧小脑后叶ALFF值降低(P0.05,Alpha Sim校正)。结论早发精神分裂症患者在静息态下有多处脑区ALFF值改变,提示其在静息态下存在脑功能异常。     

A controlled randomized treatment study: the effects of a cognitive remediation program on adolescents with early onset psychosis

OBJECTIVE: To examine if a cognitive remediation program could be a positive supplement to a psychoeducational treatment program for adolescents with early onset psychosis. METHOD: Twenty-six subjects, randomly assigned to cognitive remediation (n = 14) or control group (n = 12), were assessed on cognitive, clinical, psychosocial and behavioural measures. RESULTS: No significant between-group differences in pre- and post-treatment scores were found. This may be due to low statistical power. Exploratory within-group analyses showed that the training group improved on five of the 10 cognitive, and three of the five functioning outcome measures, while the control group improved on three of the cognitive, and one functioning outcome variable. CONCLUSION: Based on these results we cannot conclude that the addition of this cognitive remediation program, yields better results than psychoeducation alone. However, within-group analyses indicate that on specific cognitive functions, as well as on some functioning outcome measures, the remediation program may have a positive effect.