抑郁症患者自杀与脑脊液单胺代谢产物的关系

目的：探讨抑郁症患者自杀与脑脊液单胺代谢产物之间的关系。方法：应用高效液相色谱法，测定24例抑郁症患者(自杀组10例，无自杀组14例)及25例对照组5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)，去甲肾上腺素(NE)代谢产物3-甲基-4-羟苯乙二醇(MHPG)及多巴胺(DA)代谢产物高香草酸(HVA)的浓度。结果：抑郁症自杀组5-HIAA浓度显著低于对照组，男性自杀组5-HIAA浓度、HVA浓度和HVA／MHPG比值均显著低于男性对照组，女性则无显著差异：结论：抑郁症患者自杀可能与5-HT和DA功能低下以及DA和NE之间的关系改变有关。     

病毒性脑炎患者脑脊液5-羟色胺、多巴胺改变及其与精神异常的关系

目的探讨病毒性脑炎患者脑脊液5-羟色胺(5-HT)、多巴胺(DA)等的改变及其与精神异常的关系。方法采用高效液相色谱法(HPLC)检测69例病毒性脑炎患者和21例其他疾病患者对照脑脊液的5-HT、DA及其代谢产物5-羟吲哚乙酸(5-HIAA)和高香草酸(HVA)的水平。结果①患者组脑脊液的5-HT、5-HIAA和5-HIAA/HVA比值明显低于对照组(P<0.01),5-HT/DA比值低于对照组(P<0.05),而HVA明显高于对照组(P<0.01)。②患者组划分亚组后进一步比较的结果显示,除无精神异常组的5-HT和对照组的差异无统计学意义外(P>0.05),其余上述指标有或无精神异常组与对照组的差异均有统计学意义(P<0.05);有精神异常组脑脊液中的5-HIAA低于无精神异常组(P<0.05);阳性症状为主组脑脊液中的5-HT、5-HIAA、5-HT/DA和5-HIAA/HVA比值低于阴性症状为主组(P<0.05),5-HT、5-HIAA和5-HIAA/HVA比值低于无精神异常组(P<0.05),而阴性症状为主组与无精神异常组各指标差异无统计学意义。结论病毒性脑炎患者脑脊液中可能存在5-HT和DA功能失衡,且这种失衡可能与患者出现的精神症状有关。     

抑郁症晨重夕轻特征与生物学的关系

目的:探讨抑郁症患者临床症状晨重夕轻的特征与血浆皮质醇、细胞因子浓度的关系。方法:采用放射免疫法、酶联免疫吸附法对55例双相障碍(抑郁相)和抑郁发作诊断标准的抑郁症患者及38名正常对照组早7:00、晚7:00血浆皮质醇、IL-6、IL-2浓度进行测定,比较各指标早、晚浓度及早晚差值在抑郁症晨重夕轻组和无晨重夕轻组以及正常对照组的差异。结果:抑郁症晨重夕轻组和无晨重夕轻组早间的皮质醇浓度、早晚之间的皮质醇浓度差值均较正常对照组显著增高;晨重夕轻组晚间的血IL-6浓度较正常对照组显著增高,两组的IL-6早晚的差值与正常对照组相比有显著性差异;晨重夕轻组和无晨重夕轻组晚间IL-2水平均明显低于正常对照组。结论:抑郁症患者不管临床症状有无晨重夕轻的特征,均存在血浆皮质醇浓度早晨高于晚上和血浆IL-6浓度晚上高于早晨的异常改变。     

抑郁症时CSF中胺代谢产物

为了评价情感障碍患者中枢神经递质的更新,人们广泛地研究了腰段脑脊液(CSF)中胺代谢产物高香草酸(HVA)和5-羟吲(口朶)乙酸(5-HIAA)的浓度,但研究结果至今仍有分歧。本文研究重症抑郁症患者CSF中胺代谢产物HVA和5-HIAA与各实验结果间的关系。方法:实验组为30名未用药的单相抑郁症住院患者(男14,女16),平均年龄36.4岁,均符合Spitzer等的研究用诊断标准。对照组30名,与实验组年龄、性别相匹配,无躯体和精神疾病。所有受试者均住院研究。采集实验组和对照组CSF,用Subhash的高压液相电化学检测法分析CSF样本中HVA和5-HIAA。取实验组患者血样分析血小板单胺氧化酶(MAO)、红细胞腺苷脱氨酶活性(ADA)、血浆多巴胺β-羟化酶等。将资料作统计分析。     

抑郁症昼夜节律变化与免疫功能的关系

目的:探讨抑郁症昼夜节律的特征与细胞因子浓度的关系. 方法:对符合美国精神障碍诊断和统计手册第4版重性抑郁发作诊断标准的49例患者(抑郁症组)和38名健康人(对照组),采用酶联免疫吸附法测定其早7:00和晚7:00血浆白细胞介素-1β(IL-1β)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)及肿瘤坏死因子(TNF)的浓度,比较各指标早、晚浓度及早晚差值在抑郁症组中有晨重夕轻、无晨重夕轻和对照组之间的差异. 结果:抑郁症组中不论有、无晨重夕轻,其早晨IL-1β浓度及TNF浓度均明显低于对照组(P均<0.05或P<0.01));晚间IL-6浓度均较对照组显著增高(P均<0.05),IL-2浓度较对照组显著降低(P均<0.01);IL-6浓度早晚差值均较对照组显著增大(P均<0.05).结论:抑郁症患者在晚间存在广泛的免疫激活,血浆IL-6的昼夜节律较对照组有异常改变.     

慢性应激对大鼠认知及脑脊液单胺类神经递质的影响

目的探讨慢性应激对大鼠脑单胺类神经递质以及认知功能影响的研究。方法75只SD大鼠随机分为对照组(25只)和慢性应激组(50只),后者以束缚浸水应激方式连续应激21天,每日记录大鼠体重及进食量并进行两组比较,三周后行水迷宫实验、大鼠脑单胺类神经递质测定。结果(1)应激组大鼠体重的增加、进食量较对照组明显减少(P<0.05);(2)水迷宫实验:应激组大鼠的游出时间较对照组明显增加(P<0.05),但错误次数无明显差异(P>0.05)。(3)大鼠脑脊液单胺类神经递质含量(ug/L):5-HT、5-HIAA及MHPG的含量应激组明显低于对照组(P<0.05),NA、DA及HVA在应激组均为升高,但无显著差异(P>0.05)。结论慢性束缚浸水应激三周使大鼠脑脊液中5-HT、5-HIAA及MHPG的含量降低,但对认知功能无明显影响。     

脑脊液5-羟色胺和多巴胺及其代谢产物在病毒性脑炎和精神分裂症鉴别诊断中的价值

目的探讨脑脊液5-羟色胺（5-HT）、多巴胺（DA）及其代谢产物水平在病毒性脑炎和精神分裂症鉴别诊断中的价值。方法对病毒性脑炎和脑膜脑炎患者（简称病脑组）67例、精神分裂症患者37例和病例对照患者21例采用高效液相色谱法（HPLC）检测其脑脊液中5-HT、DA、5-羟吲哚乙酸（5-HIAA）和高香草酸（HVA）水平,并进行比较。结果（1）病脑组5-HT、5-HIAA、5-HIAA／HVA和5-HT／DA均明显低于病例对照组（P〈0．05～0．01）,而HVA则明显高于病例对照组（P〈0．01）;病脑组脑脊液中5-HIAA、5-HIAA／5．HT和5-H｜AA／HVA日月显低于精神分裂症组（均P〈0．01）,而HVA／DA则高于精神分裂症组（P〈0．05）;精神分裂症组脑脊液中5-HIAA／5-HT高于病例对照组（P〈0．05）,5-HT／DA低于病例对照组（P〈0．05）。（2）病脑组有精神症状者脑脊液中5-HIAA浓度低于无精神症状者（P〈0．05）,5-HT、5．HIAA、5-HIAA／5．HT和5-HIAA／HVA均低于精神分裂症组（P〈0．05～0．01）,而HVA／DA高于精神分裂症组（P〈0．05）。结论病毒性脑炎患者脑脊液中可能存在5-HT和DA系统失衡;脑脊液中5-HT、DA及其代谢产物的水平可能有助于病毒性脑炎和精神分裂症的鉴别诊断。     

帕金森病伴发抑郁的神经递质改变

目的探讨帕金森病伴发抑郁的神经递质改变.方法用抑郁自评量表(CESD)和汗密尔顿抑郁量表(HAMD)评出帕金森病伴发抑郁患者33例,其中轻度抑郁24例,重度抑郁9例;另取阑尾炎、腹股沟疝、内、外混合痔等25例为对照组.应用日本岛津6A高效液相色谱仪,岛津电化学检测器对两组患者进行了脑脊液(CSF)中单胺类神经递质代谢产物5-羟吲哚已酸(5-HIAA)和3-甲氧-4羟苯乙二醇(MHPG)的含量测定.并进行统计处理.结果两组均数用近似法t检验,(两总体方差不齐)以-x±S表示,结果显示患者组中的5-HIAA和MHPG含量均低于对照组,差异有非常显著性.结论本组通过测定5-HT的代谢产物5-HIAA和NA的代谢产物MHPG,证实了PD伴发患者抑郁的患者其CSF中5-HIAA和MHPG含量显著减少,抑郁症状被认为与5-HT和(或)NA的缺乏有关.本文显示PD伴发抑郁有其生化病理基础.     

阻塞性脑积水患者之脑室脑脊液的高香草酸及5-羟吲哚乙酸的浓度

高香草酸(HVA)及5-羟吲噪乙酸(5-HIAA)分别为中枢神经介质多巴胺(DA)及5-羟色胺(5-HT)之主要代谢产物,这些代谢产物在CSF中的浓度反映着CNS中DA或5-HT之浓度以及DA或5-HT能神经元之活动.从脑组织释放出来的HVA及5-HIAA进入侧脑室及第三脑室之CSF,主要通过第四脑室脉络丛被再吸收入血液中.因此这些代谢产物在侧脑室CSF中之浓度为蛛网膜下腔中的三倍.Andersson等于1966年曾观察到在脑积水患儿脑脊液中5-HIAA浓度增高,并提出这是一种早期脑积水之诊断特征,Maira等人曾报道,在有正常颅压脑积水之Hakin综合症患者中脊髓蛛网膜下腔之脑脊液HVA浓度降低,当前多数的观点认为诊断急性     

脑脊液的高香草酸和5—羟吲哚乙酸

脑脊液的高香草酸(HVA),5-羟吲哚乙酸(5-HIAA)分别为多巴胺(DA),5-羟色胺的代谢产物,它们的测定有助于了解各种脑疾患时脑内氨基酸的代谢情况。脑脊液采取的部位是脑室,脊髓蛛网膜下腔等,至今报导最多的是由腰椎穿刺得的脊髓液HVA,5-HIAA分析。但是由于HVA,5-     

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.