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.     

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。     

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.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.