原发性失眠症患者认知功能的研究

目的:探讨原发性失眠症患者认知功能损害的特点。方法:采用神经心理测验包括韦氏记忆(数字累加、视觉再认、视觉再生、联想学习)、数字广度、数字划消、连线测验和威斯康辛卡片分类测验(WCST)分别对35例原发性失眠症患者(失眠组)和30名健康对照者(正常对照组)进行注意力、记忆力、执行功能等方面的测评;同时应用匹兹堡睡眠质量指数量表(PSQI)、抑郁自评量表(SDS)、焦虑自评量表(SAS)分别评定失眠及伴随的焦虑、抑郁症状的严重程度。结果:失眠组在数字累加、视觉再认、视觉再生、联想学习、数字广度测验的数字倒背、数字划消测验中的注意力失误率、连线测验B及BA完成时间和WCST测验的各项成绩(除正确应答数外)均明显差于正常对照组(F=4.646~28.224,P0.05或P0.01)。失眠组数字累加分与病程呈负相关(r=-0.558,P=0.001);联想学习分与PSQI评分呈负相关(r=-0.405,P=0.019);连线测验B-A时间与病程呈正相关(r=0.405,P=0.019);WCST持续错误百分比与SDS分呈正相关(r=0.309,P=0.045)。结论:原发性失眠症患者存在广泛认知功能损害,其病程、失眠程度以及伴随的焦虑抑郁情绪是导致认知功能损害的影响因素。     

缓解期双相情感性精神障碍患者认知功能

目的:了解缓解期双相情感性精神障碍患者认知功能损害的特点。方法:采用逻辑记忆、视觉再生记忆、连线测验A和B、数字广度测验、威斯康星卡片分类测验(WCST)及字色混淆测验(stroop)对62例缓解期双相情感性精神障碍患者(患者组)和62名健康者(对照组)进行有关言语学习和记忆、非言语学习和记忆、注意以及执行功能的神经心理学评定,比较两组间认知功能的差异。结果:患者组在即刻逻辑记忆、延迟逻辑记忆、连线测验A和B、WCST正确应答数、完成分类数、持续性错误数以及Stroop C-W操作分上均显著低于对照组(P<0.05~0.01)。结论:双相情感性精神障碍患者的认知缺陷有其特点。     

儿童少年期精神分裂症患者及其一级亲属认知功能的对照研究

目的:探讨儿童少年期精神分裂症患者及其一级亲属的认知功能状况. 方法:对40例儿童少年期精神分裂症患者(患者组)、80名父母(患者父母组)及22名同胞(患者同胞组)采用注意力测验、WMS-R-逻辑记忆、数字广度、连线测验A和B、词汇流畅性测验、Stroop色词测验及威斯康星卡片分类测验(WCST)评定其认知功能,并与59名健康儿童(健康儿童对照组)及其父母(健康儿童父母组)80名进行比较. 结果:患者组除词汇流畅性测验以外,其他测验成绩差于健康儿童对照组;患者同胞组除数字顺背、词汇流畅性测验、连线测验-A、WCST正确应答数、WCST完成第1个分类应答数以外,其他测验成绩差于健康儿童对照组(P均＜0.001);患者父母组除数字顺背、词汇流畅性测验、连线测验-A以外,其他测验成绩差于健康儿童父母组(P＜0.01或P＜0.001).儿童精神分裂症患者与其父母在注意力测验、WMS-R-逻辑记忆、数字倒背、彩色文字阅读和彩色文字颜色阅读、WCST完成分数上呈正相关(r =0.350～0.615,P＜0.05或P＜0.001). 结论:儿童少年期精神分裂症患者及其一级亲属均存在广泛的认知功能缺陷,但患者的认知功能障碍更为严重.     

首发强迫症患者注意抑制与临床症状相关性研究

目的探讨首次发病的强迫症(obsessive-compulsive disorder,OCD)患者的注意抑制功能与临床症状相关性。方法对88例强迫症患者(obsessive-compulsive disorder,OCD)及与其人口学资料相匹配的85名健康被试(heath controls,HC)采用Stroop任务、数字符号、连线测验等实验评估注意抑制,采用帕多瓦强迫量表和耶鲁布朗强迫量表评估临床症状。结果 OCD组在数字符号数目、Stroop任务中"色-字"的错误数方面成绩逊于HC组,差异有统计学意义[(47.39±7.86)个,(41.12±6.39)个,t=-5.745,P0.001;(OCD:(5.48±4.38)分,HC:中位数2,下四分位数1,上四分位数4),Z=-3.678,P0.001]。OCD患者Stroop任务中"色-字"错误数与耶鲁布朗强迫量表中强迫思维分量表评分呈正相关(r=0.226,P=0.034)。结论强迫症患者临床症状严重程度与注意抑制功能密切相关。     

双相情感障碍I型患者病情缓解后认知功能的1年随访研究

目的:探讨双相情感障碍I型患者认知功能的损害特点。方法:纳入66例缓解期双相情感障碍I型患者和66名正常对照者,随访1年,分别采用数字符号、数字广度(顺背、倒背)、连线测验A(TMT-A)、连线测验B(TMT-B)和威斯康星卡片分类测验(WCST)评定,比较基线和1年后认知功能的变化。两次评定时要求患者均处于缓解期。结果:①患者组数字符号、数字广度(顺背、倒背)、TMTA、TMT-B和WSCT(总错误数和持续错误数)成绩均差于正常对照组(P均0.01),1年后这种损害持续存在,并且保持稳定不变(P0.05)。②患者组顺背、倒背、TMT-A和数字符号均与病程显著相关(P0.05或P0.01),患者组顺背、TMT-A和数字符号均与职业情况显著相关(P0.05或P0.01),未发现任何认知功能指标与发病年龄和缓解时间相关(P0.05)。结论:双相情感障碍I型患者病情缓解后仍存在明显的注意、记忆和执行功能损害,并且这种损害1年后持续存在,无进一步恶化。     

精神分裂症患者健康同胞的神经认知功能研究

目的 分析精神分裂症患者健康同胞的神经认知功能. 方法 采用Stroop测验、数字符号编码测验、符号搜索测验、定步调听觉连续加法任务测验及威斯康星卡片分类测验评估30例精神分裂症患者健康同胞(来源于自2010年10月至2012年4月在中山大学附属第三医院精神科住院的精神分裂症患者的健康同胞)及同期体检正常的43名对照者的神经认知功能. 结果 精神分裂症患者健康同胞在Stroop单词(P=0.016)、Stroop色-词(P=0.001)、符号搜索正确数(P=0.005)、符号搜索错误数(P=0.025)、符号搜索总分(符号搜索正确数减去错误数)(P=0.041)、威斯康星卡片分类测验正确数(P=0.015)、威斯康星卡片分类测验随机错误数(P=0.005)及威斯康星卡片分类测验完成分类数(P=0.041)的得分明显差于正常对照组,差异有统计学意义(P＜0.05). 结论 精神分裂症患者健康同胞可能存在执行功能及信息处理速度等神经认知功能缺陷.     

首次发病的青少年精神分裂症患者执行功能的研究

目的:探讨首次发病的青少年精神分裂症患者执行功能及其与精神症状的关系. 方法:采用威斯康星卡片分类测验(WCST)及韦克斯勒记忆量表第3版(WMS-Ⅲ)空间广度测验测试75例首次发病的青少年精神分裂症患者(病例组)和80名健康对照者(对照组)的执行功能;病例组同时应用阳性和阴性症状量表(PANSS)评定病情. 结果:病例组WCST的错误总数、持续反应数和持续错误数显著高于对照组,正确总数显著低于对照组(P均＜0.01);WMS-Ⅲ总分和空间广度逆行分显著低于对照组(P均＜0.05).病例组PANSS阴性症状分与WMS-Ⅲ空间广度逆行分及总分负相关(r=-0.276,r=-0.230;P均＜0.05);阳性症状分与WCST完成分类数负相关(r=-0.258,P＜0.05);一般病理学总分与WMS-Ⅲ空间广度逆行分负相关(r=-0.244,P＜0.05). 结论:首次发病的青少年精神分裂症患者执行功能显著受损,并与病情有关.     

双相障碍稳定期患者认知损害的性别差异

目的 探讨双相障碍Ⅰ型稳定期患者认知损害的性别差异.方法 采用数字符号、数字广度、视觉再生、连线测验A(TMT-A)、连线测验B(TMT-B)、威斯康星测验(WSCT)和汉诺塔测验(TOH),检测218例双相障碍Ⅰ型患者(患者组)和318名正常对照(对照组)的注意、记忆和执行功能,并比较2组间的性别差异.结果 分组主效应:患者组在数字符号、数字广度顺背、数字广度倒背、数字广度总分、TMT-A时间、TMT-B时间、视觉再生、WSCT分类数、言语流畅性动物总数、TOH总分、TOH任务数、TOH平均计划时间、TOH平均执行时间、WSCT总错误数、WSCT持续错误数、言语流畅性重复数的成绩均低于对照组(F=66.60、16.10、17.06、20.38、98.77、66.33、23.75、5.65、62.08、21.51、22.08、10.15、19.33,x2=21.53、33.17、12.78),差异有统计学意义(P均＜0.05).性别主效应:患者组与对照组女性在数字符号测验中的成绩优于男性(F=7.13,P＜0.05),其中男性对照组和患者组分别为(53.30±12.30)分和(46.14±11.72)分,女性分别为(55.38±14.30)分和(47.82±11.95)分;在汉诺塔平均计划时间均短于男性,差异有统计学意义(F=5.13,P＜0.05),其中男性对照组和患者组分别为(5.28±2.65)分和(6.36±3.77)分,女性分别为(5.15±2.82)分和(5.52±3.07)分;2组在分组和性别的交互作用无统计学意义(P＞0.05).结论 稳定期双相障碍患者存在认知损害,其某些注意和执行功能可能存在性别差异.     

首发精神分裂症病人治疗前后认知功能改变及其与精神症状的相关研究

目的探讨利培酮治疗对未服药首发精神分裂症患者认知功能的影响,以及认知功能与症状变化的关联。方法采用威斯康星卡片分类测验、数字广度测试、词语流畅性测试、Stroop测试、连线测试评估42例首发未服药精神分裂症患者的执行功能、工作记忆、信息处理速度等变化;阳性和阴性症状量表评定患者精神症状;多元回归分析探讨认知功能与精神症状的关联。结果治疗前,患者组威斯康星测验持续错误数较对照组多(P0.001),完成分类数较对照组少(P=0.009);数字广度测试及词语流畅性分数(Ps0.001)均降低;Stroop及连线测试完成时间均较对照组延长(Ps0.001)。治疗后,患者组Stroop_B(P=0.022)、Stroop_C(P=0.033)完成时间较治疗前减少。治疗前连线测试A/B成绩越差,则阴性症状及总症状(Ps0.05)越严重;连线测试A成绩越差,阳性症状的改善越少(P=0.019)。结论精神分裂症患者发病早期存在认知功能损害;急性期治疗可改善精神病性症状及信息处理速度,但不改善执行功能及工作记忆;提示患者早期信息处理受损可能更接近状态性生物学标记,而执行功能、工作记忆受损更接近素质性生物学标记。     

首次发病的强迫症患者的认知功能

目的探讨首次发病的强迫症患者的认知功能特点。方法采用韦氏智力测验(Wechsler adult intelligence scale,WAIS)、韦氏记忆测验(Wechsler memorys cale,WMS-R)、Stroop测验、连线测验(trail-making test,TMT)A和B、威斯康星卡片分类测验(Wisconsin card sorting test,WCST)对首次发病的强迫症患者30例和正常对照32名进行认知功能评估。结果患者组WMS-R中图片回忆、再认、联想学习等3项成绩均较正常对照组差(P0.05),而Stroop测验中的读字色测验的错误数和用时、TMT-B时间、TMTB-A时间等4项成绩也差于正常对照组(P0.05)。此外,患者组WCST中的完成分类数、正确应答数、错误应答数、持续错误数等4项成绩均较正常对照组差(P0.01)。结论首次发病的强迫症患者存在记忆、注意和执行功能损害。     

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.     

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.