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.     

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。     

注意缺陷多动障碍执行功能与儿茶酚胺氧位甲基转移酶基因的关联分析

目的探讨注意缺陷多动障碍(attention-deficit hyperactivity disorder,ADHD)执行功能与儿茶酚胺氧位甲基转移酶(catechol-O-methyltransferase,COMT)基因rs4680多态性位点的关系。方法采用威斯康星分类测验(Wisconsin card sorting test,WCST)对114例符合美国精神障碍诊断与统计手册第四版(mental disorders versionⅣ,DSM-Ⅳ)诊断标准的ADHD儿童与76名正常对照组进行执行功能评估,并应用限制性片段长度多态性的方法进行COMT基因rs4680多态性位点分析。结果 ADHD组的WCST总应答数、完成第一个分类所需应答数和持续性应答数均明显高于正常对照组(P0.05),而完成分类数明显低于正常对照组(P0.01)。ADHD患者中不同基因型组之间WCST概念化水平百分数差异具有统计学意义(P=0.01),A/A组高于G/A组和G/G组(P0.05),G/A组也高于G/G组但无统计学意义(P0.05)。不同基因型组间WSCT其他指标的差异均无统计学意义(P≥0.05)。ADHD组和正常对照组之间COMT基因rs4680多态性基因型及等位基因的分布差异均无统计学意义(P0.05)。结论本研究未发现COMT基因rs4680多态性与ADHD存在关联,但rs4680多态性可能与ADHD的某些执行功能指标有关。     

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...     

儿茶酚胺甲基氧位转移酶(COMT)基因多态与海洛因依赖的关联分析

目的 探讨儿茶酚胺甲基氧位转移酶(COMT)基因多态性与海洛因依赖的相关性.方法 采用TagMan探针SNP基因分型技术对507例海洛因依赖者(患者组)和487名健康者(对照组)的COMT基因上7个单核苷酸多态(SNP)位点(rs737866,rs933271,rs l 544325,r84818,rs4680,rs 174696,rs 174699)进行基因分型和关联分析.结果 COMT基因rs737866,rs933271两位点基因型在病例对照组中存在差异(P=0.047,P=0.011),其等位基因C与海洛因依赖相关(P=0.017,P=0.048).由rs737866-rs933271-rsl544325构建的CTG单倍体型在海洛因依赖者中比例较高.结论 rs737866位点携带C等位基因者具有较高的海洛因依赖易感性.     

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基因多态性与伴TD的精神分裂症患者认知功能的相关性研究

目的探讨中国汉族人口中儿茶酚胺氧位甲基转移酶(COMT)基因Val108/158Met多态性与伴迟发性运动障碍(TD)的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82例伴TD的精神分裂症患者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(1)COMT基因与TMT成绩显著相关,其中高活性G/G基因型PartA成绩显著低于中等活性G/A基因型,PartB成绩也显著低于低活性A/A基因型及中等活性G/A基因型。(2)COMT基因与记忆商数、背数成绩显著相关,其中G/G基因型记忆商数分显著低于A/A及G/A基因型,背数分也显著低于A/A基因型。(3)COMT基因与WCST成绩无显著相关性。结论COMT基因与伴TD的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。     

血清脑源性神经营养因子水平及其基因多态性与首发老年抑郁症认知功能的关系

目的 探求血清脑源性神经营养因子（BDNF）水平及其基因多态性与老年首发抑郁症患 者认知功能障碍的关系。方法 前瞻性连续纳入2014 年4 月至2016 年1 月首都医科大学附属北京安定 医院门诊或住院的60 岁及以上老年首发抑郁症患者。采用汉密尔顿抑郁量表（HAMD-17）、言语流畅性 测验、连线测验A-B、Stroop字色测试和威斯康星卡片分类测试对患者进行抑郁症严重程度及认知功能 的评定，采集患者静脉血测定血清BDNF水平，并提取DNA，测定BDNF rs6265 基因单核苷酸多态性位 点。结果 共80 例老年抑郁症患者纳入本研究。BDNF rs6265 基因型与抑郁障碍严重程度无关（均P＞ 0.05）。HAMD-17 总分与言语流畅性测验、WCST持续性错误数呈负相关（r=-0.239、-0.226，均P＜ 0.05）。 rs6265 VAL/MET 基因型的连线测验A-B 表现较VAL/VAL 基因型差［（62.0±18.9）分比（48.3±18.6）分］， 差异有统计学意义（P＜ 0.05）。血清BDNF水平与认知功能之间无相关性（均P ＞ 0.05），与HAMD-17 评 分呈负相关（r=-0.23，P＜ 0.05）。结论 BDNF rs6265 基因多态性与老年抑郁症患者认知功能损害相关， 而与BDNF 水平无显著关联，提示BDNF 可能通过其他机制影响老年抑郁症认知功能。     

脑源性神经营养因子基因多态性与广泛性焦虑症、强迫症的关联研究

目的 探讨脑源性神经营养因子(Brain-Derived Neurotrophic Factor,BDNF)基因与广泛性焦虑症(Generalizea-Anxiety Disorder,GAD)、强迫症(Obsessive-Compulsive Disorder,OCD)的关联性.方法 以上海及周边地区汉族人群108例GAD患者、148例OCD患者和94名健康对照为研究对象,通过TaqMan探针SNP基因分型技术对BDNF基因及基因上游10kb区域的标签单核苷酸多态性(Single nucleotide polyrmorphism,SNP)位点rs6265和rs11030101进行基因分型.同时以汉密尔顿焦虑量表(HAMA)和耶鲁-布朗强迫量表(Y-BOCS)分别评定GAD和OCD患者的病情.结果 GAD组和对照组之间rs6265位点和rs11030101位点的基因型和等位基因频率分布差异无统计学意义(P＞0.05),表明GAD与两个位点不存在关联.同样,也未见OCD与rs6265位点和rs11030101位点的基因型及等位基因存在关联(P＞0.05),GAD和OCD与上述两个位点的单倍型也未见关联(P＞0.05).在GAD组、OCD组内,上述位点的不同基因型组患者首次发病年龄、HAMA或Y-BOCS评分的差异均无统计学意义(P＞0.05).结论 不支持BDNF基因rs6265和rs11030101多态性与GAD或OCD相关.     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.     

The influence of comorbid depression on seizure severity

PURPOSE: To determine the relation between depressive symptoms and seizure severity among people with epilepsy. METHODS: A postal questionnaire was used to survey a nationwide community sample about seizures and depression. The Seizure Severity Questionnaire (SSQ) assessed the severity and bothersomeness of seizure components. The Centers for Epidemiological Studies-Depression scale categorized levels of depression. RESULTS: Respondents categorized as having current severe (SEV, n = 166), mild-moderate (MOD, n = 74), or no depression (NO, n = 443) differed significantly in SSQ scores (all p < 0.0001). People with SEV or MOD reported significantly worse problems than did those with NO depression for overall seizure recovery (mean, 5.3, 4.9, 4.5, respectively); overall severity (5.0, 4.5, 4.2); and overall seizure bother (5.3, 4.8, 4.4) (all p < 0.005). Cognitive, emotional, and physical aspects of seizure recovery also were rated worse among people with SEV than with NO depression (all p < 0.05). Symptoms of depression were significantly correlated with higher levels of all components of generalized tonic-clonic seizure severity (r = 0.33-0.48; all p < 0.0001), and partial seizures (r = 0.31-0.38; all p < 0.01). CONCLUSIONS: Clinically depressed people with epilepsy reported higher levels of perceived severity and bother from seizures, as well as greater problems with overall seizure recovery than did nondepressed people experiencing similar types of seizures. The pervasive influence of depressive symptoms on reports of seizure activity suggests that people with epilepsy should be screened for depression. These data highlight the importance of detecting and treating depression among people with epilepsy.     

Une phénoménologie de la dépendance à l'alcool. Une expérience primordiale de la « nostrité »

The phenomenological approach to alcoholism interestingly focuses on specific dynamics of interpersonal relationships displaying the founding of the Self from a primary “us” and its original basis in the human feast. Priorities for treatment intervention recommend to involve social setting and relationships of the patients, reaching their active participation to a motivational and long term group treatment, underlying the specific therapeutic effect of world exchanges. Biopsychosocial determination of alcoholism could be primarily based on components of interpersonal relationships. Regarding social background, drinking is one of the most famous supports for the achievement of the feast, a founding marker of present time. Taking an existential point of view, the feast appears as the heart of mankind because it presents a primary “us”, a plural state which indicates the beginning and founding of the Self from the others. During the feast, we regularly have to reach our Self from the “us” while avoiding two main dangers, drunkenness, an increase in the dizziness of upright verticality, and addiction, an opposite vertical surrender to alcohol and falling into in the alcoholic relapse, both situations imply a spatial domination and the disappearance of others. Treatment programs of alcohol addicts need to integrate the necessity of reaching the existential basic trust from the support of a group to the appropriation of the community which can be defined as an original “usness”.