早发型与晚发型抑郁症遗传效应比较

目的:了解早发型与晚发型单相抑郁症之间是否存在遗传效应的差异. 方法:对符合中国精神障碍分类与诊断标准第3版抑郁发作诊断标准的115例单相抑郁症患者,以初发病年龄30岁为界,分为早发组47例和晚发组68例.对照组230名,无精神疾病,与患者组无血缘关系.对所得资料行单因素分析,用多基因阈值理论进行遗传率的估算. 结果:早发组有精神疾病家族史者为55.3%(26/47),显著高于晚发组35.3%(24/68);早发组一级亲属心境障碍和单相抑郁症发生率分别为9.1%(23/252)和7.9%(20/252),显著高于晚发组一级亲属的4.8%(23/479)和3.6%(17/479);两组一级亲属单相抑郁症发生率均显著高于对照组一级亲属的0.2%.早发组加权平均遗传率及标准误(96.3±1.3)%高于晚发组(75.7±1.2)%,脑部CT器质性改变亦少于晚发组(P<0.05或P<0.01). 结论:早发型及晚发型单相抑郁症均有明显的遗传效应,但二者的遗传效应存在差异.     

单相抑郁症遗传效应的性别差异

目的探讨男性和女性抑郁症的遗传效应及差异。方法采用严格的纳入标准,对符合中国精神障碍分类方案与诊断标准第3版(CCMD-3)抑郁发作诊断标准的单相抑郁症患者115例(男38例,女77例)应用家族史法进行研究,用多基因阈值理论进行遗传率的估算。结果女性和男性患者组有精神疾病家族史者分别为46.75%(36/77)和36.84%(14/38),而两组一级亲属心境障碍发生率分别为7.21%(38/527)和3.92%(8/204),但上述差异均无统计学意义(P>0.05)。女性患者组一级亲属单相抑郁症发生率(6.07%)较男性患者组一级亲属(2.45%)高,二者均较对照组一级亲属(0.24%)高;女性单相抑郁症加权平均遗传率及标准误(86.77±5.77)%较男性(60.10±12.24)%高;上述差异均有统计学意义(P<0.05)。结论男、女性单相抑郁症均有明显的遗传效应,但二者的遗传效应存在差异。     

晚发型单相抑郁症遗传方式的研究

目的 探讨晚发型单相抑郁症的遗传实方式.方法 采用严格的纳入标准,对符合中国精神疾病分类方案与诊断标准第3版（CCMD-3）抑郁发作诊断标准,首次发病年龄＞30岁的68例单相抑郁症患者用医学遗传数学方法中分离分析和多基因阈值理论进行遗传实方式的研究.结果 晚发型一级亲属单相抑郁症加权平均遗传率及标准误为（75.7±1.2）%,预期发病率为5.0%,与实际发病率3.6 %相比较无显著性差异（u=1.5,P＞0.05）.结论 晚发型单相抑郁症的遗传方式符合多基因遗传.     

单、双相抑郁症自杀行为遗传效应的比较研究

目的　探讨单、双相抑郁症患者自杀行为的遗传效应有否差异。方法　对1 1 5例单相抑郁症及1 84例双相抑郁症患者应用家族史法进行研究,用多基因阈值理论进行遗传率的估算。结果　单、双相抑郁症患者自杀危险性均较其一级亲属高;患者一级亲属自杀危险性均较对照组一级亲属高;单相抑郁症患者自杀危险性较双相抑郁症患者高;单相抑郁症患者一级亲属自杀危险性较双相抑郁症患者一级亲属高;单相抑郁症患者自杀行为的加权平均遗传率及标准误较双相抑郁症的高,均有显著性差异。结论　单、双相抑郁症患者自杀行为均有明显的遗传效应;单、双相抑郁症患者自杀行为遗传效应存在差异,更应注意对单相抑郁症患者及一级亲属自杀行为进行监测、预防。     

首发抑郁症遗传效应及方式的初步研究

目的探讨首发抑郁症的遗传效应及方式。方法对107例首发抑郁症患者的一至三级亲属(共4439人)进行家族史调查,用分离分析和多基因阈值理论进行遗传方式研究。结果(1)先证者中有精神疾病家族史者占430%(46例),其中有抑郁症家族史者占有精神疾病家族史者的61%(28/46)。(2)一至三级亲属中抑郁症的患病率为087%(29例),高于群体患病率(002%;P<001);其中女性患病率(136%)高于男性(041%,P<001)。一、二、三级亲属患病率分别为746%、037%和005%,前两者均高于群体患病率(P<001);各级亲属的女性患病率均高于男性,其中一级亲属女性患病率为1612%,男性患病率为844%(P<001)。(3)校正后分离率为020,与隐性遗传分离率025比较,差异无统计学意义(P>005);加权平均遗传率及标准误为(10973±526)%;一、二、三级亲属的预期患病率分别为720%、062%和013%,与实际患病率(分别为747%、037%和005%)比较,差异均无统计学意义。结论首发抑郁症具有明显的遗传效应,可能符合具有隐性主基因效应的多基因遗传方式。     

单相抑郁症患者自杀行为遗传效应及遗传方式的研究

目的探讨单相抑郁症患者自杀行为的遗传效应及方式。方法 采用严格的纳入标准,对115例抑郁症患者应用家族史法进行研究,用医学遗传数学方法中分离分析和多基因阈值理论进行遗传方式的探讨,并与对照组(395名)比较。结果 单相抑郁症患者自杀危险性较其一级亲属高(P<0.01),单相抑郁症患者一级亲属自杀危险性较对照组高(P<0.01),有自杀行为患者的一级亲属较无自杀行为患者的一级亲属自杀危险性高(P<0.05)。单相抑郁症自杀行为的加权平均遗传率及标准误为(70.16±0.79)％;一级亲属自杀行为预期发病率为3.1％,实际发病率为2.6％,两者差异无显著性意义(P>0.05)。结论 单相抑郁症自杀行为有明显的遗传效应,其遗传方式符合多基因遗传。     

早发型单相抑郁症患者遗传方式的研究

目的:探讨早发型单相抑郁症患者的遗传方式. 方法:采用严格的纳入标准,对符合中国精神障碍分类与诊断标准第3版抑郁发作诊断标准、首次发病年龄≤30岁的47例单相抑郁症患者采用医学遗传数学方法中分离分析和多基因阈值理论进行遗传方式的探讨. 结果:早发型一级亲属单相抑郁症加权平均遗传率及标准误为(96.3±1.3)％；预期发病率为9.37％,与实际发病率7.94％相比较差异无统计学意义(u=0.7814,P＞0.05). 结论:早发型单相抑郁症患者遗传方式符合多基因遗传.     

广泛性焦虑遗传效应和遗传方式研究

目的探讨广泛性焦虑的遗传效应和遗传方式. 方法对80例符合中国精神障碍分类与诊断标准第3版广泛性焦虑诊断标准的患者,应用家族史法进行研究,采用分离分析法和多基因阈值理论进行遗传模式的探讨. 结果广泛性焦虑患者一级亲属发病危险性显著较对照组高(P＜0.01);广泛性焦虑校正分离率为0.225,与常染色体隐性遗传的分离率0.25相比较,差异无显著性(P＞0.05);广泛性焦虑加权平均遗传率和标准误为(61.70±5.10)%;一级亲属的预期发病率为8.9%,实际发病率为7.5%,二者差异无显著性(P＞0.05). 结论广泛性焦虑具有遗传效应,其遗传方式符合常染色体隐性遗传或多基因遗传.     

抑郁症患者自杀的遗传效应研究

目的：了解抑郁症患者自杀行为与遗传的关系，提供有关遗传预测的资料。方法：对近二年连续住我院符合ＣＣＭＤ－２－Ｒ抑郁症诊断标准的６３例抑郁症患者及其一级亲属进行了遗传效应的研究，以无精神疾病者２６９人为对照组。所得资料行单因素分析，用多基因阈值理论估算自杀行为的遗传率。结果：索引病例中有自杀行为者较其一级亲属高（Ｐ〈０．００１）。一级亲属中发生自杀行为的危险性较对照组高（Ｐ〈０．０１），有自杀行为的     

性别与情感性疾病单、双相的关系

双相情感性疾病患者的家族成员中,既有双相也有单相病人,作者最近对122名双相病人的盲性家族研究和家族史研究发现,11例患躁狂症(双相)的亲属中6例是男性,5例是女性。而在29例患单相抑郁症的亲属中9例是男性,20例是女性。对照组的家族成员中,只有一名患双相情感性疾病的女病人。但有26人患单相抑郁症,其中2例男性,24例女性。双相组和对照组索引病例的亲属     

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.