阴性精神分裂症认知功能改善与HVA和5-HIAA的关系

目的：探讨阴性精神分裂症认知功能的改善与ＨＶＡ和５－ＨＩＡＡ变化的关系。方法：对１３例阴性精神分裂症在氯氮平治疗前和治疗８周后分别采用韦氏成人记忆量表（ＷＭＳ）,数字划消测验和威期康星卡片分类测验（Ｗｉｓｃｏｎｓｉｎ ｃａｒｄ ｓｏｒｔｉｎｇ ｔｅｓｔ,ＷＣＳＴ）评估其记忆、注意及执行功能,采用高效液相色谱－电化学检测测定其治疗前和治疗后脑脊液中ＤＡ代谢产物高香草酸（ＨＶＡ）和５－ＨＴ代谢产物五羟     

氯氮平对慢性难治性精神分裂症的疗效与5—羟色胺2A受体基 …

目的 探讨与氯氮平对慢性难治性精神分裂症疗效有关的５－羟色胺２Ａ（５－ＨＴ２Ａ）受体基因的基因型及其他相关因素。方法 抽取１０４例慢性难治性精神分裂症患者,给予氯氮平≥４００ｍｇ／ｄ治疗２个月。治疗前后用阴性和阳性症状量表（ＰＡＮＳＳ）评定氯氮平疗效,按ＰＡＮＳＳ的减分率≥３０％和≤３０％将氯氮平治疗的患者分为有效组和无效组,用聚合酶链反应扩增及限制性片段长度多态性（ＰＣＲ－ＲＦＬＰｓ）技术测定患     

精神分裂症d－芬氟拉明激发的神经内分泌反应与临床症状的关系

目的探讨ｄ－芬氟拉明（ｄ－ＦＦ）激发的神经内分泌反应与精神分裂症临床症状的关系。方法把１５例精神分裂症患者在氯氮平治疗前、后行ｄ－ＦＦ激发试验，同时以简明精神病评定量表（ＢＰＲＳ）、阳性症状量表（ＳＡＰＳ）、阴性症状量表（ＳＡＮＳ）评定精神症状。结果混合型患者治疗前基础皮质醇（ＣＯＲ）值、治疗后ｄ－ＦＦ激发的ＣＯＲ值及治疗前、后ｄ－ＦＦ激发的催乳素（ＰＲＬ）值均显著高于阳性型。症状评分与激素反应有一定的相关关系。结论提示精神分裂症的发生可能与中枢５－羟色胺／多巴胺（５－ＨＴ／ＤＡ）功能失平衡有关。     

精神分裂症治疗前后脑脊液5-羟色胺代谢变化的对比研究

目的　观察精神分裂症患者脑脊液５羟色胺（５ Ｈ Ｔ） 及其代谢产物５羟吲哚醋酸（５ Ｈ Ｉ Ａ Ａ） 和其前体物质色 氨酸（ Ｔ Ｒ Ｐ）的功能状态，以及经氯丙嗪治疗后上述物质的代谢变化。方法　应用 Ｈ Ｐ Ｌ Ｃ 法对４０ 例未经治疗的精神分裂症（ 阳性症状为主） 患者与１５ 例非中枢神经系统疾病对照者作上述物质的比较，其中２７ 例精神分裂症患者在接受氯丙嗪治疗８ 周后复查了上述物质。结果　精神分裂症组疗前脑脊液５ Ｈ Ｉ Ａ Ａ 浓度比对照组显著为低，治疗后各物质浓度均显著降低。结论　支持有关精神分裂症５ － Ｈ Ｔ 代谢障碍的假说，认为５ － Ｈ Ｔ 功能低下可能系阳性症状为主精神分裂症的易感标志，该型的症状发生与转归主要与多巴胺的代谢障碍有关。     

抑郁症患者脑脊液生长抑素及单胺代谢产物浓度与临床症状的关系

目的 探讨抑郁症患者脑脊液生长抑素（ＳＳ）和单胺代谢产物浓度与临床症状的关系,以及神经递质之间的相互作用。方法 应用放射免疫测定方法和高效液相色谱法,测定２３例抑郁症患者脑脊液ＳＳ和５－羟色胺（５－ＨＴ）代谢产物５－羟吲哚之酸（５－ＨＩＡＡ）、去甲肾上腺素（ＮＥ）代谢产物３－甲基－４－羟－苯乙二醇（ＮＨＰＧ）及多巴胺（ＤＡ）代谢产物高香草酸（ＨＶＡ）的浓度。临床症状评估采用汉密尔顿抑郁量表（ＨＡＭ     

中枢5－HT相对代谢率与精神分裂症临床特征分析

应用高压液相色谱（ＨＰＬＣ）对符合ＣＣＭＤ－２精神分裂症诊断标准的６７例患者脑脊液中５－ＨＴ、５－ＨＩＡＡ进行了测试，并以５－ＨＩＡＡ／５－ＨＴ作为相对代谢率，并以其中位数为界值分为高５－ＨＩＡＡ／５－ＨＴ比值组和低５－ＨＩＡＡ／５－ＨＴ比值组，结果发现，低比值组的ＢＰＲＳ阳性症状显著高于高比值组，而ＢＰＲＳ及其阴性症状和非特异症状两组无显著差异。相关分析发现，５－ＨＩＡＡ与ＢＰＲＳ及其阳性症状呈显著负相关，５－ＨＩＡＡ／５－ＨＴ与ＢＰＲＳ的阳性症状呈显著负相关，提示５－ＨＴ代谢低下与阳性症状有关。     

以阴性症状为主的精神分裂症患者认知功能与局部脑血流的 …

目的 动态观察药物对局部脑血流量（ｒＣＢＦ）的影响,探索以阴性症状为主的精神分裂症患者潜隐的局部脑功能异常。方法 对２１例符合Ａｎｄｒｅａｓｏｎ阴性精神分裂症标准的患者（以下简称患者组）于氯氮平治疗前后进行威斯康星卡片分类测验（ＷＣＳＴ）和单光子发射计算机断层扫描（ＳＰＥＣＴ）检查,以４０名正常人为对照组（其中２８名为ＷＣＳＴ对照组,１２名为ＳＰＥＣＴ对照组）。结果 患者组氯氮平治疗前后ＷＣＳＴ的     

中枢5—HT相对代谢率与精神分裂症临床特征分析

应用高压液相色谱对符合ＣＣＭＤ－２精神分裂症诊断标准的６７例患者脑脊液中５－ＨＴ、５－ＨＩＡＡ进行了测试，并以５－ＨＩＡＡ 作为相对代谢率，并以其中位数为界值分为高５－ＨＩＡＡ／５－ＨＴ比人且和低５－ＨＩＡＡ／５－ＨＴ比值组，结果发现，低比值组的ＢＰＲＳ阳性症状显著高于高比值组，而ＢＰＲＳ及其阴性症状和非特异症状两组无显著差异。相关分析发现，５－ＨＩＡＡ与ＢＰＲＳ及其阳性症状呈显著负相关，５－ＨＩ     

精神分裂症患者脑脊液促甲状腺激素水平研究

目的比较Ⅰ型与Ⅱ型精神分裂症患者治疗前、后脑甲状腺功能状态及其中枢调节方面的差异。方法电抽搐治疗（ＥＣＴ）Ⅰ型精神分裂症、氯氮平治疗Ⅱ型精神分裂症；在治疗前、后测定促甲状腺激素（ＴＳＨ）含量、简明精神病评定量表（ＢＰＲＳ）、阳性症状评定量表（ＳＡＰＳ）、阴性症状评定量表（ＳＡＮＳ）。结果Ⅰ型精神分裂症患者脑脊液ＴＳＨ值略高于Ⅱ型；ＥＣＴ对Ⅰ型患者脑脊液ＴＳＨ水平有双向调节功能，调节效应好；氯氮平对Ⅱ型患者脑脊液ＴＳＨ水平的调节功能和效应低下；治疗前后脑脊液ＴＳＨ增（减）值Ⅰ型较Ⅱ型大（Ｐ＜００１）。结论提示精神分裂症患者Ⅰ型与Ⅱ型脑甲状腺功能状态及其中枢调节不同     

氯丙嗪和氯氮平对血清催乳素和生长素的影响

目的：探讨精神分裂症患者用氯丙嗪和氯氮平治疗前后血清催乳素（ＰＲＬ）、生长素（ＧＨ）的变化及其与临床疗效的关系。方法：采用固定剂量的氯丙嗪和氯氮平治疗首发精神分裂症患者５６例,疗程８周;在治疗前后评定简明精神病评定量表（ＢＰＲＳ）,并用放射免疫法测定治疗前后血清中ＰＲＬ和ＧＨ浓度,以２０例健康者为对照。结果：氯丙嗪组及氯氮平组基础ＰＲＬ水平皆较正常对照组显著为高。用氯丙嗪治疗后ＰＲＬ水平显著升高,且与ＢＰＲＳ减分值显著相关;用氯氮平治疗后ＰＲＬ水平变化不明显,且与ＢＰＲＳ减分值无显著相关。两组ＧＨ基础水平相仿;治疗后两组ＧＨ水平皆显著下降,但与ＢＰＲＳ减分值无显著相关。结论：支持精神分裂症多巴胺（ＤＡ）功能亢进假说,精神分裂症患者可能有中枢５－羟色胺（５－ＨＴ）功能障碍。     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.