精神分裂症患者血清同型半胱氨酸水平的研究

目的观测精神分裂症患者同型半胱氨酸(homocysteine,Hcy)水平,并探讨其与精神病理症状的关系。方法采用病例-对照研究设计。用荧光偏振免疫法(FPLA)检测45例精神分裂症患者(患者组)和45名健康正常人(对照组)的血清Hcy,比较各类患者的Hcy。结果患者组血清Hcy水平[(17.3±5.6)μmol/L]高于对照组[(12±3.6)μmol/L],其高同型半胱氨酸血症(HHcy>17 μmol/L)的发生率明显高于对照组(42.2%比8.9%,Odds Ratio:7.5,95%可信区间为2.3-24.5,P=0.000)。阳性亚型患者Hcy水平[(15.6±4.9)μmol/L]低于阴性亚型患者[(20.4±5.6)mol/L],P<0.01。P因子高分亚组患者Hcy水平[(15.1±5.1)μmol/L]低于低分亚组患者[(19±5.6)μmol/L],P<0.05。Hcy水平与阳性症状总分呈负相关(r=-0.374.P<0.05),与阴性症状总分呈正相关(r= 0.297,P<0.05)。结论精神分裂症患者的血清Hcy水平升高,并与精神病理症状有关。     

利培酮和氟哌啶醇对精神分裂症患者超氧化物歧化酶及催乳素影响的临床对照研究

目的 探讨经第一、二代抗精神病药治疗的精神分裂症患者体内超氧化物歧化酶(SOD)、催乳素(PRL)与精神症状间的关系.方法 符合美国精神障碍诊断与统计手册第4版诊断标准的78例精神分裂症患者,随机分为利培酮组(41例),剂量为6 mg/d;氟哌啶醇组(37例),剂量为20mg/d;观察疗程均为12周.使用阳性和阴性症状量表(PANSS)评定临床疗效.采用放射免疫法在治疗前后分别测定患者血浆SOD及PRL浓度.以30名正常人为正常对照组.结果 利培酮组(40例)、氟哌啶醇组(33例)患者的基线SOD浓度[(794±126)ng/mg Hb,(750±101)ng/mg Hb]均明显高于正常对照组[(483±110)ng/mg Hb],而PRL浓度[(6±7)μg/L,(6±8)μg/L]均明显低于正常对照组[(18±12)μg/L],差异均有统计学意义(P均＜0.05).利培酮组和氟哌啶醇组患者的治疗前SOD与PRL间存在显著负相关(n=70,P＜0.05).治疗第12周末,利培酮组和氟哌啶醇组的SOD浓度[(499±98)ng/mg Hb,(482±76)ng/mg Hb]明显降低,而PRL浓度[(33±19)μg/L,(25±16)μg/L]则明显升高.利培酮组与氟哌啶醇组间治疗前后的SOD、PRL的差异均无统计学意义(P均＞0.05).治疗前后,阴性症状改善与SOD浓度差值(P＜0.05)、阳性症状改善与PRL浓度差值(n=70,P＜0.01)有相关性.结论 精神分裂症患者SOD及PRL浓度异常,两者间存在着相互作用,且对抗精神病药的临床疗效有影响.     

利培酮和氟哌啶醇治疗老年期精神障碍对照研究

目的 比较利培酮和氟哌啶醇治疗老年期精神障碍的疗效和安全性。方法 利培酮组22例,口服利培酮1.34±0.52mg/d;氟哌啶醇组20例,口服氟哌啶醇2.2±0.89mg/d,疗程均为8周。用临床疗效评定量表(CGI),简明精神症状检查量表(BPRS)、阴性症状评定量表(SANS)、汉密顿抑郁量表(HAMD)评价疗效。用药物副反应量表(TESS)评定不良反应。用简易智能量表(MMSE)评定对认知功能的影响。结果 临床总体疗效两组间无显著性差异(P>0.05),利培酮对BPRS各靶症状及阴性症状疗效显著,对阴性症状疗效优于氟哌啶醇(P<0.01),而且可提高MMSE的分值(P<0.01)。两组不良反应均以锥体外系症状和嗜睡为主。两组不良反应发生率无显著性差异(P>0.05)。结论 利培酮和氟哌啶醇对老年期精神障碍均有良好的疗效,利培酮对BPRS和SANS各常见靶症状疗效更显著,副反应小而安全,且不影响认知功能,更适宜于老年病人。     

丙戊酸钠合并氟哌啶醇治疗难治性Tourette综合征

目的 探讨丙戊酸钠合并氟哌啶醇治疗难治性Tourette综合征(TS)的临床疗效和安全性.方法 将93例难治性TS患儿按病例编号分为试验组(58例)和对照组(35例).试验组予丙戊酸钠(400～600 mg/d或15 mg·kg-1·d-1)合并氟哌啶醇(2～6 mg/d)治疗,对照组采取常规治疗[单一或联合使用氟哌啶醇(6～16 mg/d)、泰必利(400～600 m/d)、可乐定(0.15～0.6 mg/d)、安定类药物],共治疗8周.采用YGTSS、国际TS临床信息调查表、儿童行为量表(CBCL)及副反应量表,于治疗前、治疗后第1,3,8周末对两组进行评估.结果 治疗第8周末,试验组的有效率为93%,高于对照组(80%;Z=-4.310,P<0.001);试验组YGTSS总分[(3.50±4.59)分]低于对照组[(7.86±7.03)分;P<0.01],减分率[(83.11±15.13)%]高于对照组[(63.81±27.87)%;P<0.01];试验组的CBCL评分[(11.43±5.27)分]低于对照组[(14.77±6.75)分;t=-2.139,P<0.05];治疗第1周末两组副反应差异无显著性(P>0.05);从第3周末开始试验组副反应评分[(9.26±3.15)分]低于对照组[(11.69±5.51)分;P<0.01],并持续至第8周末.结论 丙戊酸钠合并氟哌啶醇治疗难治性TS,疗效肯定,副反应相对较轻.     

利培酮和氟哌啶醇治疗精神分裂症的双盲对照研究

目的 比较利培酮和氟哌啶醇治疗精神分裂症的疗效及副作用。方法 采用双盲双模拟的研究方法,实验及统计结束后揭盲。疗效评定采用阳性和阴性症状量表(PANSS)、临床总体印象量表(CGI)及临床总体疗效四级评定标准。不良反应采用不良反应量表(TESS)和Simpson-Angus量表(SAS)。观察8周。结果 1)两组在PANSS和BPRS总分较治疗前显著降低(P<0.001)组间无显著性差异。2)两组治疗后PANSS减分率:氟哌啶醇组58.08±21.12％,利培酮组65.37±16.50％。两组间无显著性差异。3)总有效率;氟哌啶醇组64％,利培酮组74.07％。4)TESS表明:两组在失眠、头晕、口干、视物模糊、心动过速、体重增加等项严重程度无显著性差异,在肌强直、震颤、静坐不能等项,两组有显著性差异,利培酮组优于氟哌啶醇组。5)安坦合并用药率,利培酮组显著低于氟哌啶醇组(P<0.05)。结论利培酮和氟哌啶醇一样能有效治疗精神分裂症,但利培酮锥外系副作用更小。利培酮和氟哌啶醇都是有效、安全的抗精神病药物。     

精神分裂症患者血清催乳素和生长激素水平与奎硫平、氟哌啶醇治疗关系的对照研究

目的研究精神分裂症患者血清催乳素(PRL)、生长激素(GH)的基础水平与正常人的差异,以及奎硫平、氟哌啶醇治疗前后PRL、GH的变化。方法采用放射免疫法检测126例精神分裂症患者(包括奎硫平组62例和氟哌啶醇组64例)治疗前和治疗8周后PRL、GH水平,观察这2种药物对PRL、GH的影响及比较两者的差异,并与65名健康者进行对照分析。结果 126例精神分裂症患者的基础PRL、GH水平与对照组比较无显著性差异(P>0．05),奎硫平组治疗后PRL和GH均无显著改变(P>0．05)。氟哌啶醇组治疗后PRL值为(96．20±41．12)μg/L,较治疗前的(20．39±11．26)μg/L显著升高(P<0．01),女性升高更明显,为男性的 2．6倍。氟哌啶醇组治疗后GH值为(1．72±1．32)μg/L,较治疗前的(2．41±11．26)μg/L显著降低(P<0．01)。结论奎硫平治疗精神分裂症患者,对PRL及GH无明显影响,更适合生长期的青少年患者和药物性溢乳、乳房发育患者。     

氯丙嗪和利培酮对精神分裂症患者血糖调节功能影响的动态观察

目的观察抗精神病药在治疗的不同时间精神分裂症患者血糖代谢的变化特点,探讨预防血糖调节功能损害(IGR)的有效方法。方法将213例住院精神分裂症患者分为氯丙嗪组(108例,200~650mg/d)和利培酮组(105例,3~6mg/d),均单一用药,分别于入院时、治疗第1,2,3,6个月末及1年末测定多项血糖浓度并进行对照研究。结果(1)治疗后随时间延长,两组血糖浓度均不断上升。治疗第3个月末餐后2h血糖(2hPBG)和2h糖耐量(2hPG)浓度开始升高,治疗第6个月末空腹血糖(FPG)和空腹糖化血红蛋白(HbA1c)开始升高,治疗1年末所有血糖指标均升高(均P<0.05~0.01)。(2)组内治疗前后比较,氯丙嗪组治疗第3个月末2hPG[(5.77±1.28)mmol/L]和2hPBG[(5.93±1.10)mmol/L]、治疗第6个月末HbA1c[(5.49±0.76)mmol/L]、治疗1年FPG浓度[(5.29±0.71)mmol/L]均高于治疗前[分别为(mmol/L)5.31±0.58,5.48±0.60,5.22±0.50和4.96±0.49],均P<0.05~0.01;利培酮组治疗1年末2hPBG浓度[(5.70±0.89)mmol/L]高于治疗前[(5.35±0.77)mmol/L;P<0.05]。(3)两组比较,氯丙嗪组治疗第3个月末2hPBG和HbA1c[(5.41±0.63)mmol/L]、治疗1年末2hPG[(5.92±1.34)mmol/L]和FPG[(5.29±0.71)mmol/L]浓度均高于利培酮组[分别为(mmol/L)5.55±0.83,5.23±0.50,5.54±0.91,5.08±0.59],均P<0.05~0.01。1年末,两种药物日剂量与各血糖浓度之间无显著相关性(P>0.05)。(4)两组治疗后各时间点IGR的发生率均上升;治疗1年末,氯丙嗪组IGR发生率达36.1%,高于利培酮组(22.9%;P<0.05)。(5)在完成1年观察的198例患者中,51例(25.8%)至少有1次符合IGR血糖浓度标准,但两组间的差异无统计学意义(P>0.05)。结论血糖浓度随药物治疗时间的延长而上升,其中氯丙嗪比利培酮更易引起IGR。     

奥氮平对无血清诱导PC12细胞凋亡的影响

目的:探讨奥氮平对无血清诱导PC12细胞凋亡的保护作用及其机制。方法:以神经生长因子(NGF)诱导后的PC12细胞作为细胞模型,采用无血清培养诱导细胞凋亡。给予奥氮平后,采用MTT法检测细胞活性,流式细胞仪检测细胞凋亡率、细胞周期以及Hoechst33342染色观察细胞形态学的改变。结果:奥氮平(100μM)组培养72h的细胞活性与对照组相比差异显著(P<0·05),奥氮平(12·5、25、50、200μM)组与对照组无明显差异;而各浓度氟哌啶醇组的细胞活性均低于对照组;流式细胞仪结果显示血清组、奥氮平组、氟哌啶醇组、对照组的调亡率依次是17·9%、36·6%、59·8%、51·9%,其中对照组、氟哌啶醇组大部分细胞滞留于G1期;奥氮平组Hoechst33342染色偶见凋亡细胞,以核浓缩为主,而对照组、氟哌啶醇组多见核碎裂。结论:奥氮平能保护PC12细胞免于无血清培养诱导的凋亡,可能是其神经保护作用机制之一。     

反义IGF-ⅠR基因片段诱导胶质瘤细胞凋亡的流式细胞仪分析和电镜观察

目的探讨反义胰岛素样生长因子-Ⅰ受体(IGF-ⅠR)基因片段诱导胶质瘤细胞凋亡的作用及其形态学的变化。方法根据IGF-ⅠRcDNA序列设计其正义、反义基因片段,并对部分碱基进行硫代磷酸修饰。实验分为空白对照组、正义寡核苷酸组和反义寡核苷酸组,应用流式细胞仪检测DNA含量,根据DNA直方图分析凋亡细胞发生率。应用透射电镜观察凋亡细胞的形态学变化。结果经反义寡核苷酸5μmol/L、10μmol/L、15μmol/L、20μmol/L等4种浓度处理的胶质瘤细胞的凋亡率分别为(16.06±3.86)%、(24.52±4.84)%、(36.69±5.53)%和(43.85±5.72)%;而经同样浓度正义寡核苷酸处理的胶质瘤细胞的凋亡率分别为(3.76±1.22)%、(3.14±1.15)%、(2.51±0.93)%和(3.26±1.15)%;空白对照组(野生型)的自然凋亡率为(1.01±0.89)%。反义寡核苷酸组与空白对照组相比差异有显著性意义(P<0.05),而正义寡核苷酸组与空白对照组之间差异则无显著性意义(P>0.05)。透射电镜观察显示,凋亡细胞表现为细胞体积缩小,染色质凝聚,并聚集于核膜下呈新月状或块状,胞膜内陷形成膜包裹的核碎片或细胞器,最后出泡形成凋亡小体。结论反义IGF-ⅠR基因片段可诱导胶质瘤细胞发生凋亡。     

利培酮口服液合并氯硝西泮片治疗精神分裂症急性激越的对照研究

目的:比较利培酮口服液合并氯硝西泮片与氟哌啶醇肌内注射治疗精神分裂症急性激越症状的疗效及不良反应。方法:60例精神分裂症急性激越症状患者,按1:1比例随机分入利培酮口服液(2～6mg/d)合并氯硝西泮片(2～8mg/d)组(利培酮组)或氟哌啶醇肌注(5～20mg/d)组(氟哌啶醇组)治疗,疗程7d。采用阳性和阴性症状量表(PANSS)、阳性和阴性症状量表兴奋因子(PANSS-EC)、病人合作程度评定表、修改版外显攻击行为量表(MOAS)、临床疗效总体评定量表(CGI)评定疗效,采用治疗中出现的症状量表(TESS)、静坐不能评定量表(BAS)、锥体外系副反应量表(SAS),不良事件和实验室检查评定安全性。结果:在治疗7d后,利培酮组和氟哌啶醇组PANSS-EC评分分别为(11.1,3.6)分和(12.9,5.2)分,较治疗前均明显进步(P<0.01),两组间PANSS-EC和PANSS总分差异无统计学意义(P>0.05);利培酮组在阳性因子分、MOAS、合作程度改善方面均优于氟哌啶醇组(P<0.05);肌强直、静坐不能的发生率显著低于氟哌啶醇肌注组(P<0.01)。结论:利培酮口服液合并氯硝西泮片治疗精神分裂症急性激越症状与氟哌啶醇肌内注射疗效相当,在某些方面优于氟哌啶醇肌内注射。     

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.     

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.     

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.     

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.     

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.     

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.