脂蛋白脂酶基因和对氧磷酶1基因联合作用与脑梗死发病的相关性

目的 探讨脂蛋白脂酶(LPL)、对氧磷酶1(PONl)基因联合作用与脑梗死发病的相关性.方法 选取LPL基因2个SNP和PON1基因2个标签SNP,采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)技术,对705例脑梗死患者和431例对照组人群进行检测,应用UNPHASED软件、等位基因条件分析的方法,分析基因的联合作用与脑梗死的相关性.结果 LPL基因rs328位点G等位基因分布在动脉粥样硬化性脑梗死组与对照组差异显著(x2=4.83,P=0.034,OR=1.47,95％CI=1.03～2.13);rs326位点G等位基因分布在动脉粥样硬化性脑梗死组与对照组差异显著(x2=3.597,P=0.047,OR=1.64,95％CI =1.12～1.84);PON1基因上的rs2299262位点与LPL基因上的rs328位点联合作用与脑梗死的发病具有相关性(x2=6.26,df =2,P=0.043).结论 LPL基因rs328位点G等位基因携带者患大动脉粥样硬化性脑梗死的风险高于非携带者.LPL基因rs326位点G等位基因携带者患大动脉粥样硬化性脑梗死的风险高于非携带者.PON1基因上的rs2299262位点与LPL基因上的rs328位点联合作用与脑梗死的发病具有相关性.     

NOS1基因多态性与腔隙性脑梗死相关性研究

目的:探讨神经元型一氧化氮合酶基因( NOS1)多态性与腔隙性脑梗死发病的关系。方法:本研究共纳入385例腔隙性脑梗死患者和313例对照组人群，以位于NOS1基因的rs9658281和rs2682820位点为遗传标记，采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)技术检测NOS1基因的多态性。结果:Cocaphase 分析表明腔隙性脑梗死组rs9658281位点G等位基因频率较对照组显著增高(x2 =4.135，P=0.042，OR=1.422，95％ CI 1.013～1.997)，这种差异在女性患者更加明显(x2=9.522，P=0.002，OR=2.502，95％ CI 1.398～4.479)。卡方检验表明腔隙性脑梗死组rs9658281位点的GG基因型频率较对照组显著增高(x2=5.862，P=0.015，OR=1.579，95％ CI 1.091～2.286)，这种差异在女性更加明显(x2=13.641，P＜0.0001，OR=3.501，95％CI 1.800～6.810)。经过多因素回归分析调整了传统危险因素的影响后，两组间的差异仍有显著性(P=0.014)。腔隙性脑梗死组和对照组的rs2682820位点的基因型、等位基因频率差异无显著性（P＞0. 05）。结论:NOS1基因rs9658281位点G等位基因与腔隙性脑梗死的发病可能有关。     

文拉法辛临床疗效与γ-氨基丁酸β2受体基因的相关分析

目的 探索γ-氨基丁酸β2受体(GABRB2)基因多态性与五羟色胺-去甲肾上腺素重吸收抑制剂(Serotonin and Norepinephrine Reuptake Inhibitor,SNRI)文拉法辛抗抑郁疗效差异的相关性.方法 对151例抑郁症患者采用文拉法辛治疗6周,以治疗后17项汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)总分≤7为临床痊愈.检测5号染色体上的GABRB2基因的29个标签单核苷酸多态性(Single Nucleotide Polymorphisms,SNP)位点.运用Plink 1.07和Haploview 4.2软件进行29个SNP位点及其构成的单倍型与药物疗效的相关分析.结果 GABRB2基因的rs10071312 和 rs4426954位点的等位基因频率在痊愈组和非痊愈组之间的差异有统计学意义(均P=0.02),rs10071312位点的A等位基因携带者的治疗痊愈率高于G等位基因携带者(OR=4.43),而rs4426954位点的A等位基因携带者的治疗痊愈率低于G等位基因携带者(OR=0.44).有3种单倍型在痊愈组和非痊愈组之间的分布差异有统计学意义,分别是A-A-A-A-G-A (rs7724146-rs10051667-rs2964773-rs12153421-rs2962402-rs4426954,P=0.01),A-A-A-G-A(rs10051667-rs2964773-rs12153421-rs2962402-rs442695,P=0.02)和A-A-A-G-A-G (rs10051667-rs2964773-rs12153421-rs2962402-rs4426954-rs3816596,P=0.03).结论 GABRB2基因多态性可能与文拉法辛治疗的个体化差异有关联.     

精神分裂症患者多巴胺D1受体基因多态性与抗精神病药疗效的关系

目的:探讨精神分裂症患者多巴胺D1受体(DRD1)基因多态性与抗精神病药疗效的关系.方法:300例精神分裂症患者分别给予氯丙嗪(n=78)、利培酮(n=90)、氯氮平(n=132)单一治疗8周;以阳性与阴性症状量表(PANSS)评定疗效;以SNaPshot单核苷酸多态性(SNP)技术检测DRD1基因rs265981、rs4532、rs686和rs265976多态性. 结果:氯氮平总疗效有效组与无效组相比,rs265981基因型T/T、T/C、C/C及等位基因T、C的分布差异有统计学意义(x2=7.101,P=0.029;x2 =4.011,P=0.045);rs265976基因型A/A、A/C、C/C的分布差异有统计学意义(x2=7.124,P=0.028),但其等位基因A、C的分布差异无统计学意义(x2=3.54,P =0.06).氯丙嗪改善阳性症状有效组与无效组相比,rs686等位基因A、G的分布差异有统计学意义(x2=4.427,P=0.035),但其基因型A/A、A/G、G/G的分布差异无统计学意义(x2=3.842,P=0.146).氯氮平改善阴性症状有效组与无效组相比,rs265976基因型A/A、A/C、C/C的分布差异有统计学意义(x2 =5.999,P=0.05),而其等位基因A、C的分布差异无统计学意义(x2=1.051,P=0.305). 结论:DRD1基因rs265981、rs686和rs265976多态性可能对抗精神病药治疗精神分裂症的临床疗效有着重要影响.     

脑源性神经营养因子基因多态性与强迫症的关联研究

目的:探讨脑源性神经营养因子(BDNF)基因与强迫症(OCD)的关联性。方法:190例OCD患者和309个健康对照为研究对象,通过聚合酶链式反应与限制性片段长度多态性(PCR-RFLP)基因分型技术对BDNF基因标签单核苷酸多态性(SNP)位点rs6265进行基因分型。以耶鲁-布朗强迫量表(Y-BOCS)评定OCD患者的病情。结果:OCD组和对照组之间rs6265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)。在起病年龄和性别方面基因型和等位基因频率分布差异也无统计学意义(P>0.05)。结论:BDNF基因rs6265多态性与OCD可能没有关联。     

L型钙离子通道α1C亚基基因多态性与精神分裂症的相关性

目的探讨L型钙离子通道α1C亚基(calcium channel,voltage-dependent,L type,alpha 1C subunit,CACNA1C)基因多态性与精神分裂症的关系。方法纳入118例精神分裂症患者及122名对照,采用变性高效液相色谱法对其CACNA1C基因rs10848683、rs2238032、rs2299661位点进行基因分型,通过病历资料收集患者感知觉障碍、思维障碍、情感障碍和行为障碍等临床表现,采用阳性与阴性症状量表(positive and negative syndrome scale,PANSS)评估患者症状。结果 rs2238032和rs2299661位点基因型和等位基因在患者组与对照组间分布有统计学差异(均P0.05),而rs10848683位点基因型和等位基因分布在组间无统计学差异(P0.05)。rs2238032位点TT基因型(OR=0.394)和rs2299661位点CG(OR=0.326)与精神分裂症的患病风险有关联(均P0.05)。rs10848683位点各基因型患者行为障碍分布有统计学差异(P0.05);rs2238032各基因型患者思维障碍、情感障碍和PANSS得分有统计学差异(均P0.05);rs2299661各基因型患者感知觉障碍、PANSS得分有统计学差异(均P0.05)。单体型分析示,CTC(OR=1.811)、CTG(OR=0.432)和TGC(OR=1.771)与精神分裂症关联有统计学意义(P0.05)。结论 CACNA1C基因多态性与精神分裂症及其临床表现有关联。     

CAMSAP1L1基因多态性与我国中部地区人群癫痫的相关性分析

目的 探讨我国中部地区汉族人群中CAMSAP1L1基因两个SNP位点rs6660197和rs2292096的多态性与癫痫遗传易感性的关系.方法 采取病例对照研究方法,分别选取157例癫痫患者,其中包括122例良性癫痫伴中央颞区棘波（BECT）和35例难治性癫痫（RE）患儿;选取160例正常体检儿童作为研究对象.利用PCR-RFLP的方法测定两个SNP位点多态性分布,并进行统计分析.结果 在所有患者中SNP位点（rs6660197）的基因型（CC,CT,TT）频率和等位基因C频率与对照组比较差异均有统计学意义（P＜0.05）;SNP位点（rs2292096）的基因型（AA,AG,GG）频率两组比较差异无统计意义（P＞0.05）.SNP位点（rs6660197）与我国中部地区汉族人群BECT的易感性相关（P=0.040）,CC为风险基因型,C等位基因为风险因子,与对照组比较OR =1.584,95％ CI：1.046～2.398,P=0.029.RE患者SNP位点（rs2292096）的基因型与对照组比较差异有统计学意义（P=0.028）,A等位基因为风险因子（OR=2.431,95％CI：1.265～4.134,P=0.010）,等位基因频率明显高于对照组（P=0.010）.结论 CAMSAP1L1基因SNP位点（rs6660197）与BECT的易感性相关,而SNP位点（rs2292096）与RE的易感性相关.     

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.     

精神分裂症患者多巴胺D2受体基因多态性与利培酮治疗效应的关联分析

目的:探讨多巴胺D_2受体基因(DRD2)多态性与利培酮治疗精神分裂症临床疗效的关系。方法:纳入汉族精神分裂症患者304例(研究组)和汉族健康对照120名(对照组),研究组服用利培酮8周后以阳性与阴性症状量表(PANSS)评估疗效,同时检测两组DRD2基因rs6275、rs1801028和rs6277位点多态性。结果:rs6277位点在研究组和对照组中的等位基因频率与基因型频率的分布差异有统计学意义(χ~2=8.37,P=0.02)。研究组rs6275(F=15.52,P0.001)、rs1801028(F=19.74,P0.001)和rs6277(F=10.67,P0.001)位点不同基因型在PANSS总分减分率上差异均有统计学意义;同时rs1801028位点不同基因型在阴性症状减分率上差异有统计学意义(F=15.29,P0.001),rs6277位点在阳性症状减分率上差异有统计学意义(F=14.74,P0.001)。结论:DRD2基因rs6277位点多态性与精神分裂症易感性存在关联;不同DRD2基因型患者利培酮疗效可能存在差异。     

脑源性神经营养因子基因多态性与精神分裂症的关联研究

目的:探讨脑源性神经营养因子(BDNF)基因多态性与精神分裂症的关联性.方法:以111例精神分裂症发作期患者与362例正常对照为研究对象,通过TagMan探针单核苷酸多态性(SNP)基因分型技术对BDNF基因及基因上游10 kb区域的标签SNPs rs6265和rs11030101进行基因分型,比较各组间基因型、等位基...     

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.     

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.     

Clobazam for Treatment of Intractable Epilepsy: A Critical Assessment

Summary: Clobazam (CLB), a 1,5-benzodiazepine, is a remarkably effective add-on drug for individual patients with refractory partial epilepsy. CLB has an excellent safety record. As with all benzodiazepines used for treating epilepsy, sedation and withdrawal effects, together with the development of tolerance, limit its usefulness. Recent efforts to prevent or reverse tolerance with intermittent administration of CLB or periodic injection of a benzodiazepine antagonist, flumazenil, are encouraging and justify further investigations.     

La passion de Torquemada et le terrorisme islamique : quelques points de comparaison

This original research compares the doctrinal, psychopathological and operational standpoints of the 15th century Spanish Inquisition (Torquemada) with those of radical Islamism from 1988 to 2005 (Al-Qaeda). The following are reviewed: (a) the main texts codifying the procedure for conducting the criminal investigation of a Holy Office trial (Directorium inquisitorum); (b) the life and work of the grand inquisitor Tomás de Torquemada (1420–1498); (c) the psychopathological relations between passion (passionate psychoses, passionate idealism, paranoid personality) and fanaticism; (d) “the madmen, the enlightened and the criminals” of Islamic terrorism; (e) the cognitive and emotional motives for engagement in the jihadist radicalization of young people; (f) the common principles of monotheistic fanaticism (Inquisition, Al-Qaeda) and the particular dogmas of Islamic terrorism in our time; (g) the operating modes of the Inquisition and the Jihadist holy war. The author concludes that the rigour and seriousness of the inquisitorial judicial procedure, which was precise, individual and personalized, contrasts with the revolutionary pamphlets of Al-Qaeda, which only provide broad guidelines for the modus operandi of the fight against infidels, who are usually random victims.     

Claustration et collectionnisme : réflexions à propos d’un cas de syndrome de Diogène avec vols kleptomaniaques et vengeurs

Social withdrawal is a pathognomonic behaviour that is consistently associated with mental illnesses. Compulsive hoarding can also be interpreted as a pathological behaviour, even when it does not involve kleptomania. Diogenes syndrome (DS) was first described in 1975, and is characterized by both behaviours - social withdrawal and compulsive hoarding. Even though it is often the manifestation of a psychiatric condition, its aetiology is diverse. The most frequent ones are however: dementia, schizophrenia and mental retardation. In this study, we describe an atypical case presenting with DS. Il consists of a young man, seen in a forensic setting, who had been diagnosed with kleptomania in the past, presents with compulsive hoarding, and whose recent thefts were fuelled by revenge. Finally, to our knowledge, the way social withdrawal is viewed is seldom taken into account. We analyse its implication on social withdrawal.     

Neurological soft signs and schizophrenia: a review of current knowledge

Schizophrenia is a frequent and disabling disorder emerging during adolescence or early adulthood. The identification of underlying processes has been hampered by the complex clinical expression and the probable etiological heterogeneity. The frequency of neurological soft signs (NSS) in patients with schizophrenia and their presence early in life (during the first two years) in high risk subjects support the hypothesis that schizophrenia is a "brain disease" reflecting pre- or perinatal insults during development. The growing interest for NSS has lead to multiple studies that are often difficult to compare. The objective of this review is to summarize the current knowledge on NSS, methodological issues and the future perspectives.     

Lacan, lecteur de Minkowski : l'approche structurale

The notion of structure occupies a predominant place in the theory of Lacan. He indicates that was developed from the work of Minkowski. In fact, through his phenomeno-structural approach, Minkowski does not limit himself to purely observable phenomena, but attempts to determine the underlying structure. He refers to the comprehensive phenomenology and psychopathology, and this method provides him with clinical finesse and another means of determining a diagnosis. Thus Lacan has used this as a basis for his approach to structure to develop a theory regarding the individual. This implies that the structure of the individual is based on his relation to language. From this concept, he then develops the clinical structures of neurosis, psychosis, and perversion. These structural landmarks also have an effect on the course of treatment.