首发精神分裂症患者的糖代谢研究

目的　探讨首发精神分裂症患者的糖代谢情况。方法　对 86例首发精神分裂症患者及 45名健康人进行糖耐量试验(OGTT) ,并检测其空腹血浆胰岛素、C肽的浓度。结果　两组间空腹血糖、餐后 3h血糖、空腹胰岛素、C肽的差异无显著性 ,病例组餐后 1h血糖值 [( 7 89± 1 77)mmol/L]、2h的血糖值 [( 6 2 4± 1 14 )mmol/L]、OGTT血糖曲线下面积 (AUC) [( 18 2 4± 2 76)mmol/(L·h) ]比对照组 [分别为 ( 6 5 4± 1 84)mmol/L ,( 5 88± 2 78)mmol/L ,( 15 86± 1 93 )mmol/L/h ,P分别小于 0 .0 1、0 .0 5、0 0 1]要大 ;组间糖耐量减退 (IGT)的发生率无显著性差异 ( χ2 =0 5 84,P >0 0 5 ) ;偏执型患者组与青春型患者组间的空腹血糖、2h血糖值无显著性差异 (t=1 476,P均大于 0 0 5 ) ;发生IGT的病例组与未发生IGT病例组组间阳性和阴性症状量表 (PANSS)总分及 4个分量表分值的差异无显著性差异 (P均大于 0 0 5 )。结论　首发精神分裂症患者存在餐后高血糖现象。     

氯丙嗪、氯氮平、利培酮对首发精神分裂症患者糖代谢、血脂和体重的影响

目的　探讨氯丙嗪、氯氮平和利培酮对首发精神分裂症患者糖代谢、血脂和体重的影响。方法　将首发精神分裂症患者随机分为 3组 ,每组各 3 0例 ,分别单用氯丙嗪、氯氮平、利培酮治疗。于治疗前、治疗第 3周末和第 6周末做糖耐量试验 ,并检测甘油三酯、胆固醇 ,计算体重指数 [BMI,体重 (kg) /身高 (m2 ) ]。结果　氯氮平组治疗后第 3周末、第 6周末餐后 2h的血糖值和第 6周末BMI值明显高于利培酮和氯丙嗪组 ,与治疗前相比也明显升高 (P <0 0 5 )。利培酮组治疗第 6周末BMI值和餐后 1h血糖值比治疗前明显升高 (P <0 0 5 )。氯丙嗪组治疗第 6周末BMI值比治疗前明显升高 (P <0 0 5 )。结论　氯氮平对精神分裂症患者糖代谢和体重影响最大 ,其次是利培酮 ,氯丙嗪影响最小     

糖化血红蛋白异常在抗精神病药诱发糖代谢疾病中的意义

目的探讨糖化血红蛋白(HBA1C)异常在抗精神病药诱发糖代谢疾病中的意义。方法对152例空腹血糖(FPG)、糖耐量试验2H血糖(2HPG)正常的精神分裂症女性患者,按HBA1C正常/异常分层后随机分HBA1C正常组(115例,以下简称正常组)及HBA1C异常组(37例,以下简称异常组),分别给予利培酮(正常组37例,异常组12例)、氯氮平(正常组40例,异常组13例)及氯丙嗪(正常组38例,异常组12例)治疗,治疗前及治疗第6周后测定各组患者的FPG及2HPG。结果(1)仅氯氮平异常组患者治疗后2HPG[(9·5±1·8)MMOL/L]较治疗前[(7·2±1·4)MMOL/L]增高,差异有统计学意义(P<0·01)。(2)各组内治疗前、后FPG的差异均无统计学意义(P均>0·05)。(3)HBA1C水平因素与药物因素对治疗后2HPG存在交互作用(P<0·01)。(4)氯氮平异常组患者治疗后2HPG高于利培酮异常组[(7·4±1·7)MMOL/L]及氯丙嗪异常组[(7·3±1·6)MMOL/L],差异有统计学意义(P<0·01)。各正常组患者治疗后2HPG的差异均无统计学意义(P均>0·05)。(5)各异常组患者治疗前、后的合计2HPG[(7·1±1·6)MMOL/L],[(8·1±1·9)MMOL/L]均高于各正常组的合计2HPG[(6·2±1·4)MMOL/L],[(6·5±1·4)MMOL/L],差异均有统计学意义(P<0·01,<0·001)。(6)异常组与正常组比较,接受抗精神病药治疗后发生糖代谢疾病的比值比(OR)经标化为9·5,差异有统计学意义(P<0·001)。结论HBA1C异常的精神分裂症患者可能是抗精神病药诱发糖代谢疾病的高危人群。     

精神分裂症患者脑脊液单胺类神经递质含量与疗效

目的:探讨精神分裂症患者脑脊液(CSF)内多巴胺(DA)、高香草酸(HVA)含量的变化及其临床意义。　方法:86例首发精神分裂症,用利培酮治疗6个月,于治疗前及治疗6个月后采用高效液相色谱电化学(HPLC -ECD)法检测CSF中的DA及HVA含量,并与32名健康人进行对照。患者组同时用阳性与阴性症状量表(PANSS)评定临床疗效。　结果:患者组在治疗前CSF中DA和HVA含量分别为(3.2 3±0 .36 ) μmol/L和(1.99±0 .4 9) μmol/L ,显著高于对照组(2 .4 4±0 .32 ) μmol/L和(1. 4 1±0 . 37)μmol/L ;患者组治疗6个月后分别为(2 .4 9±0 .35 ) μmol/L和(1.4 2±0 .2 8) μmol/L。其治疗后降低值与PANSS总分的减分差值呈显著正相关。　结论:精神分裂症患者CSF内DA和HVA含量显著增高,利培酮对精神分裂症的疗效与DA和HVA含量的变化密切相关。同时进一步验证了精神分裂症患者中枢神经系统DA功能亢进的假说。     

利培酮及氯氮平对首发精神分裂症患者认知功能及P300的影响

目的比较利培酮和氯氮平对首发精神分裂症患者认知功能的影响。方法对64例首发精神分裂症采用随机对照研究法观察12周,利培酮组33例,平均有效治疗剂量(4.5±1.2)mg/d,氯氮平组31例,平均有效治疗剂量(269.4±133.3)mg/d。于治疗前后行阴性和阳性症状量表(PANSS)、韦氏记忆量表(WMS)和事件相关电位P300检测。结果首发精神分裂症患者在长时记忆、短时记忆、瞬时记忆及记忆商数(MQ)受损较为明显,与对照组比较有显著性差异(P<0.05)。P300电位成分中P2、N2及P3潜伏期明显延长,P2及P3波幅明显降低,与对照组比较均有显著性差异(P<0.05)。经过12周治疗利培酮和氯氮平组PANSS总分、阳性症状分、阴性症状分及一般精神病理症状分均降低,2组无显著性差异(P>0.05)。利培酮组的WMS的再认、联想及记忆商(MQ)明显高于氯氮平组;2组治疗前后P300各指标均无显著性差异。结论首发精神分裂症患者存在着认知功能障碍,利培酮对首发精神分裂症认知功能的改善明显优于氯氮平。两药均不能改善患者的P300。     

利培酮对精神分裂症患者血浆高香草酸的影响

目的　探讨利培酮对精神分裂症患者中枢多巴胺代谢产物血浆高香草酸 (pHVA)的影响。方法　 30例精神分裂症住院患者 (患者组 )纳入研究 ,利培酮治疗平均剂量为 (3 2± 1 1)mg/d ,共观察 6周。以阳性和阴性症状量表 (PANSS)评定疗效 ,以高效液相库仑阵列电化学检测法测定患者治疗前后的 pHVA含量。 30例健康志愿者作为对照组 ,检测pHVA水平。 结果　 (1)患者组治疗前 pHVA含量 [(7 9± 4 0 ) μg /L]与对照组含量 [(8 8± 4 1) μg /L]的差异无显著性 (P >0 0 5 ) ,而患者组治疗后 pHVA含量 [(5 3± 2 7) μg/L]明显低于治疗前 (P <0 0 1) ;(2 )治疗前患者组 pHVA与PANSS阳性症状评分 [(2 0 7± 4 1)分 ]存在正相关 (r =0 39,P <0 0 0 1) ,与基线PANSS阴性症状评分 [(19 7± 5 1)分 ]存在负相关 (r =- 0 35 ,P <0 0 1) ;(3)基础pHVA含量及其治疗前后差值[(2 6± 1 3) μg/L]与PANSS阳性症状评分减分值 [(10 8± 4 1)分 ]均分别呈正相关 (r =0 4 8,P <0 0 1;r=0 6 0 ,P <0 0 0 1)。结论　患者组治疗前pHVA可部分反映精神分裂症症状 (尤其是阳性症状 )的严重程度 ,基础 pHVA含量及治疗前后pHVA水平的变化与利培酮治疗阳性症状的疗效相关。     

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。     

以阳性或阴性症状为主的精神分裂症患者脑脊液催乳素水平测定

目的　探讨以阳性症状为主 (以下简称阳性 )和以阴性症状为主 (以下简称阴性 )的精神分裂症患者脑脊液催乳素 {PRL)水平及氯氮平治疗前后的变化。方法　对 2 6例阳性精神分裂症患者 (阳性组 )和 2 2例阴性精神分裂症患者 (阴性组 )用氯氮平治疗 6周 ,用简明精神病量表 (BPRS)、阳性症状量表 (SAPS)或阴性症状量表 (SANS)评定疗效。治疗前及治疗 6周末用放射免疫测定法测定患者脑脊液PRL水平。结果　治疗前阳性组PRL水平 [(1.0 8± 0 .39) μg/L]低于阴性组 [(1.34± 0 .4 1) μg/L],P <0 .0 5 ;治疗后阳性组PRL水平 [(1.16± 0 .35 ) μg/L]较治疗前升高 ,阴性组 [(1.2 4± 0 .4 6 ) μg/L]较治疗前降低 ,差异均无显著性 (P >0 .0 5 )。两组治疗后BPRS、SAPS或SANS总分较同组治疗前下降均有极显著性差异 (P <0 .0 1)。结论　阳性和阴性精神分裂症患者脑脊液PRL基础水平有差异 ,氯氮平对精神分裂症患者脑脊液PRL水平影响较小。     

利培酮联合氯氮平治疗精神分裂症阴性症状的对照观察

本组试用利培酮联合氯氮平治疗 2 0例以阴性症状为主的精神分裂症并与单独利培酮和单独氯氮平治疗比较。现将结果报道于后。1　对象和方法1.1　对象　均符合ＣＣＭＤ - 2 -Ｒ中精神分裂症的诊断标准 ,且以阴性症状为主者。年龄、性别不限 ,并随机分成三个组 :①利培酮组 ,其中男 12例 ,女 8例 ;年龄 2 0～ 4 8岁 ,平均年龄 (32 .4± 8.5 )岁 ;平均病期6 .3年。②氯氮平组 ,其中男 9例 ,女 11例 ;年龄 19～ 5 6岁 ,平均年龄 (34.5± 11.4 )岁 ;平均病期 7.8年。③利培酮联合氯氮平组 (以下简称联合组 ) ,其中男 13例 ,女 7例 ;平均年龄 (36 .…     

利培酮和氯氮平治疗首发精神分裂症的疗效及其药费负担的比较分析

鉴于利培酮对精神分裂症的阳性、阴性症状均有较好效果 ,但由于其药价较为昂贵 ,从而限制了临床使用。为此 ,本文选择了利培酮治疗首发精神分裂症 ,并与氯氮平对照 ,旨在评价临床疗效和药物费用之间的关系 ,现报道于后。1　对象与方法1 1　对象　①均符合ＣＣＭＤ - 2 -Ｒ诊断标准[1] 中的首发精神分裂症患者进入研究 ,并排除严重躯体疾病者。②本文共 2 0 4例 ,其中研究组 10 2例 ,男 5 7例 ,女 4 5例 ,年龄 (2 1 4 4± 9 74 )岁 ,病程 (4 6± 1 2 )个月。对照组 10 2例 ,男 5 7例 ,女 4 5例 ,年龄 (2 1 82± 8 4 5 )岁 ,病程 (4 9± 3 4 )…     

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.