COMT基因rs4680位点与中国汉族人群帕金森病遗传易患性关联性分析

目的 探讨儿茶酚胺氧位甲基转移酶(COMT)基因rs4680位点Val158Met多态性与帕金森病遗传易患性的相关性.方法 采用聚合酶链反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)基因多态性测序方法,分析COMT rs4680位点基因型及等位基因频率在帕金森病患者(437例)和健康对照者(530人)间的分布差异.结果 帕金森病患者G等位基因频率为77.2％,A等位基因频率为22.8％,而在健康对照者分别为74.7％、25.3％,两组间COMTrs4680位点Val158Met等位基因频率分布差异没有统计学意义(P =0.199).各基因型频率在帕金森病患者分别为G/G型57.4％、G/A型39.6％、A/A型3.0％,在健康对照者分别为54.9％、39.6％、5.5％,两组间基因型频率分布差异无统计学意义(P=0.156).在校正性别、年龄混杂因素后经二元Logistic回归分析,COMT rs4680位点各基因型与帕金森病发病风险之间仍无相关性.结论 COMT基因r4680位点Val158Met多态性与中国汉族人群帕金森病易患性可能无关,进一步扩大样本量及在其他不同种族中的研究能更好地确定COMT rs4680位点Val158Met多态性在帕金森病发病风险中的作用.     

儿茶酚胺氧甲基转移酶基因rs4680位点多态性与强迫症的关联研究

目的:探讨儿茶酚胺氧甲基转移酶(COMT)基因多态性(rs4680)与强迫症的关联性。方法:以山东汉族人群中的400例强迫症患者和459名健康对照者为研究对象,按性别、发病年龄分层,采用MassARRAY飞行时间质谱(MALDI-TOF)技术对COMT基因单核苷酸多态性(SNP)位点rs4680进行基因分型,比较各组等位基因、基因型频率。结果:COMT rs4680位点等位基因和基因型频率在强迫症组和对照组分布差异无统计学意义(P 0. 05)。按性别、发病年龄分层后,各强迫症组和对照组该位点等位基因和基因型频率分布差异也无统计学意义(P 0. 05)。结论:COMT基因多态性(rs4680)与强迫症可能不存在关联。     

COMT基因多态性与惊恐障碍临床疗效的关联研究

目的 探索惊恐障碍患者儿茶酚胺-O-甲基转移酶（catechol-O-methyltransferase,COMT）基因多态性（rs4680、rs740603）与艾司酞普兰疗效的关系。方法 纳入惊恐障碍患者69例，正常对照78名。患者组使用艾司西酞普兰固定剂量10 mg/d连续治疗8周，分别在基线及第2、4、8周使用汉密尔顿焦虑量表（Hamilton anxiety scale,HAMA）评估焦虑症状。采用基质辅助激光解吸飞行时间质谱（MALDI-TOF-MS）对所有被试COMT基因rs4680、rs740603位点进行基因分型。结果 患者组与对照组两位点基因型和等位基因分布无统计学差异（P>0.05）。患者治疗第8周时，rs4680的G/G基因型患者HAMA减分率（72.52%±11.38%）大于A/G基因型患者（60.70%±16.25%），差异有统计学意义（P<0.05）。在第2、8周时rs4680不同基因型患者焦虑症状治疗有效率差异有统计学意义（P<0.05）。rs740603不同基因型患者HAMA减分率无统计学差异（P>0.05）。结论 COMT基因多...     

COMT基因多态性与颅脑创伤患者执行功能障碍相关性的研究

目的探讨儿茶酚胺氧位甲基转移酶(COMT)基因多态性与颅脑创伤患者执行功能障碍的相关性。方法选取河北联合大学神经外科颅脑创伤患者168例为病例组和134例健康体检人群为对照组。采集患者静脉血检测COMT基因多态性,应用钟表绘画测验(CDT)、威斯康星卡片测验系统(WCST)对患者进行执行功能评估。结果正常对照组和病例组COMT基因型及等位基因频率之间分布差异无统计学意义(P>0.05);不同教育程度、损伤部位、损伤类型及有无饮酒的颅脑创伤患者间COMT基因型和等位基因频率差异无统计学意义(P>0.05);不同病情程度颅脑创伤患者间COMT基因型差异有统计学意义(P>0.05),而等位基因频率差异无统计学意义(P>0.05)。WCST评测显示携带G/G基因型颅脑创伤患者的完成分类数(CC)分值低于携带GA+AA基因型患者;而持续性错误数(RPE)、完成第一个分类所需应答数(RF)分值高于携带GA+AA基因型颅脑创伤患者(P<0.05)。结论 COMT G/G基因型与颅脑创伤患者执行功能障碍有一定关系,可能是颅脑创伤患者执行功能损伤的风险。     

精神分裂症患者茶酚氧位甲基转移酶基因多态性与利培酮疗效的关系

目的:探讨精神分裂症患者茶酚氧位甲基转移酶(COMT)基因多态性与利培酮疗效的关系。方法:95例精神分裂症患者(患者组)接受利培酮单药治疗12周,治疗前后给予阳性与阴性症状量表(PANSS)、瞬时记忆测评、数字划消测验、瑞文标准推理测试;对患者及95名健康对照者(对照组)进行COMT基因的rs4680、rs165599、rs6267和rs4818位点的多态性分析,比较各基因型患者利培酮治疗后各量表评分的变化。结果:两组间COMT rs4680位点各基因型和等位基因频率、rs4680-rs165599 AG型单倍体频率差异有统计学意义(P0.05或P0.01);治疗前后患者PANSS阴性症状因子评分的变化值在rs4680位点各基因型间比较差异有统计学意义(t=2.383,P=0.019);瞬时记忆测评的变化值在rs165599位点的各基因型间差异有统计学意义(F=4.213,P=0.019);PANSS阴性症状因子、认知损害因子以及瞬时记忆测评的变化值在rs6267位点各基因型间差异有统计学意义(F=4.978,3.495,6.086;P均0.01);PANSS认知损害因子的变化值在rs4818位点的各基因型间差异有统计学意义(F=4.251;P=0.014)。结论:COMT rs4680-rs165599 AG型单倍体携带者可能具有精神分裂症患病风险,COMT基因多态性在一定程度上影响精神分裂症患者利培酮的疗效及认知功能。     

凝血因子Ⅱ、Ⅴ基因多态性与脑梗死的关联研究

目的探讨中国湖南长沙地区汉族人群中凝血因子Ⅱ(FⅡ)、凝血因子Ⅴ(FⅤ)基因单核苷酸多态性与脑梗死之间的关联。方法采用PCR及飞行时间质谱技术对351例确诊为脑梗死的汉族患者(病例组)及417例对照组FⅡ基因rs1799963位点、FⅤ基因rs6025位点进行基因分型。结果病例组FⅡ基因rs1799963位点基因型均为G/G,对照组中基因型为G/G和A/G。病例组与对照组中FⅤ基因rs6025位点基因型均为G/G。对基因型及等位基因频率进行χ2检验示,病例组FⅡ基因rs1799963位点的基因型分布与对照组相比较差异无统计学意义(P0.05);病例组等位基因频率与对照组相比较差异无统计学意义(P0.05)。Logistic回归分析示,FⅡ基因rs1799963位点多态性与脑梗死不相关(P0.05)。结论 FⅡ基因rs1799963位点多态性和FⅤ基因rs6025位点多态性均可能与中国长沙汉族人群脑梗死之间不存在关联。     

谷胱甘肽硫转移酶Pi基因多态性与Alzheimer病的关系

目的研究谷胱甘肽硫转移酶Pi(GSTPi)基因多态性与Alzheimer病(AD)的关系。方法 AD患者48例,按1:2匹配选择与AD患者同性别、同年龄、同文化程度、无血缘关系、认知功能正常、身体健康的96例老人作为正常对照,外周血提取基因组DNA,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测GSTPi基因第5外显子rs1695位点和第6外显子rs1138272位点基因型。结果 rs1695位点存在A/A、A/G和G/G三种基因型;rs1138272位点存在C/C和C/T两种基因型,未发现T/T型。AD组和对照组rs1695位点基因型分布差异无统计学意义(P>0.05),但AD组等位基因G的频率(32.3%)明显高于对照组(21.9%)(P=0.05)。AD组和对照组rs1138272位点基因型分布及等位基因频率差异无统计学意义(P>0.05)。GSTPi基因染色体单体型G/T(即rs1695位点为等位基因G,rs1138272位点为等位基因T)的频率,AD组(9.1%)明显高于对照组(2.4%),差异无统计学意义(P=0.01)。结论 GSTPi基因rs1695位点等位基因G和rs1138272位点等位基因T可增加AD发生的危险,尤其rs1695位点等位基因G可能与AD发病关系更大。     

儿茶酚氧位甲基转移酶基因与注意缺陷多动障碍患儿认知功能的关联研究

目的 探讨儿茶酚氧位甲基转移酶(COMT)基因Va1108/158Met(rs4680)多态性对注意缺陷多动障碍(ADHD)患儿认知功能的影响.方法 对203例中国汉族ADHD患儿进行韦氏记忆测查、Stroop测验及数字划消测查,评定记忆力、反应抑制能力和注意力,并检测COMT基因Va1158Met多态性.按照基因型将样本分为高活性基因型组(92例,ValVal)和中低活性基因型组(111例,ValMet和MetMet),比较两组间各项测查结果的异同.结果 高活性基因型组图片分测验[(11.7±3.1)分]和Stroop测验C部分错误数(0个)的成绩好于中低活性基因型组[分别为(10.8±2.9)分和1个;P＜0.05～0.01].两组其他方面的差异均无统计学意义.结论 COMT基因Val158Met多态性与ADHD患儿的认知功能中的记忆力、反应抑制能力和注意力相关.     

COMT基因多态性与慢性精神分裂症患者认知功能的相关性研究

目的:探讨上海汉族人口中儿茶酚胺氧位甲基转移酶(COMT)基因Val108/158Met多态性与慢性精神分裂症患者认知功能的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对152例慢性精神分裂症患者COMT基因多态性进行检测,并选用连线测验(TMT)、韦氏记忆测验(WMS)、威斯康星卡片分类测验(WCST)对其认知功能进行评定。结果:COMT基因与TMT成绩显著相关,其中高活性G/G基因型患者B部分成绩显著低于低活性A/A基因型患者。COMT基因与WMS成绩显著相关,其中G/G基因型患者记忆商数分、背数分显著低于A/A基因型患者。COMT基因与WCST成绩无显著相关性。结论:COMT基因与慢性精神分裂症患者认知功能具有显著相关性,其中高活性G/G基因型患者认知损害更明显。     

儿茶酚胺氧位甲基转移酶-287A/G基因多态性与精神分裂症的关联性研究

目的 探讨儿茶酚胺氧位甲基转移酶(COMT)基因-287A/G多态性与精神分裂症的关系.方法 纳入232例符合美国精神障碍诊断与统计手册第四版(DSM-Ⅳ)诊断标准的精神分裂症患者和141名正常对照,采用限制性片段长度多态技术测定受试者的COMT基因-287A/G多态性.结果 COMT基因-287A/G多态性突变率为10%,患者组和正常对照组间该多态性基因型及基因频率差异无统计学意义(P＞0.05),按性别分层后比较结果仍同前;不同家族史患者组间的上述差异也无统计学意义;该多态性基因型在精神分裂症阳性亚型、阴性亚型、混合型和对照组中分布差异具有统计学意义(P＜0.05),各亚型与对照组比较差异无统计学意义,但G/G基因型在阴性亚型出现的频率是混合型的6.30倍(OR=6.300),G等位基因在阴性亚型出现的频率是混合型的1.859倍(OR=1.859).结论 COMT基因-287A/C多态性在不同亚型精神分裂症患者中存在差异,G/G基因型和G等位基因可能是精神分裂症阴性亚型的危险因素.     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.     

Summary of Legislation of 1933 of interest to the Department of Mental Hygiene

Psychiatric Quarterly -