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。     

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     

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。     

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.     

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研究

目的 探讨单相抑郁症的遗传效应.方法 采用严格的纳入标准,应用家族史法对108例单相抑郁症患者及其一级亲属(700人)进行研究.108例患者均符合中国精神疾病分类方案与诊断标准第2版修订本抑郁症及美国精神障碍诊断和统计手册第4版重症抑郁障碍的诊断标准.结果 在一级亲属中,单相抑郁症的患病率为4.1%(29例),高于群体发病率0.02%(4/19 223,x2=693.44,P<0.01);有单相抑郁症阳性家族史者占25.0%(27例),高于其他精神疾病阳性家族史者(12.9%,14例;x2=44.65,P<0.01);双亲之一患单相抑郁症其子代患同病的风险为24%,双亲均患单相抑郁症其子代患同病的风险为75%,差异有显著性(x2=4.33,P<0.05);单相抑郁症加权平均遗传率及标准误为(96.5+4.5)%.结论 单相抑郁症具有明显的遗传效应.     

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.     

精神分裂症和抑郁症患者一级亲属注意功能研究

目的:探索精神分裂症、抑郁症患者一级亲属的注意功能特征。方法:对41例精神分裂症先证者的62例一级亲属、34例抑郁症先证者的55例一级亲属进行持续性操作测验(CPT)检测,并以54例精神正常者作为对照。结果:在反应时间分测验中,精神分裂症亲属组和抑郁症亲属组所有的CPT指标均高于对照组(P<0.05或P<0.01);大多数指标低于相应的患者组(P<0.05或P<0.01)。在X分测验中,针对靶刺激,上述两个亲属组的大多数CPT指标高于对照组(P<0.05或P<0.01);部分指标低于相应的患者组(P<0.05或P<0.01)。精神分裂症或抑郁症患者的部分CPT指标分别与其一级亲属呈显著性正相关(P<0.05或P<0.001)。在针对靶刺激的8项指标中,抑郁症亲属组有4项指标低于精神分裂症亲属组(P<0.05或P<0.01)。结论:精神分裂症和抑郁症患者的一级亲属都呈现出注意功能缺陷,但他们的CPT表现形式有所不同。从而提示,注意缺陷有可能是精神障碍的一项遗传易感因子,但他们并非精神分裂症所特有。     

单相抑郁症的遗传方式探讨

目的　探讨单相抑郁症的遗传方式。方法 对108例（男32例,女76例）单相抑郁症家系采用分离分析和多基因阈值理论进行遗传方式的探讨。结果　单相抑郁症加权平均遗传率为（96.5±4.5）％,预期发病率为4.35％,与实际发病率4.14％相比较无显著性差异;未发现父-子同病的情况。结论　单相抑郁症的遗传方式为多基因遗传方式,并提示单相抑郁症可能与X连锁显性遗传方式有关。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.