以阳性或阴性症状为主的精神分裂症患者脑脊液催乳素水平测定

目的　探讨以阳性症状为主 (以下简称阳性 )和以阴性症状为主 (以下简称阴性 )的精神分裂症患者脑脊液催乳素 {PRL)水平及氯氮平治疗前后的变化。方法　对 2 6例阳性精神分裂症患者 (阳性组 )和 2 2例阴性精神分裂症患者 (阴性组 )用氯氮平治疗 6周 ,用简明精神病量表 (BPRS)、阳性症状量表 (SAPS)或阴性症状量表 (SANS)评定疗效。治疗前及治疗 6周末用放射免疫测定法测定患者脑脊液PRL水平。结果　治疗前阳性组PRL水平 [(1.0 8± 0 .39) μg/L]低于阴性组 [(1.34± 0 .4 1) μg/L],P <0 .0 5 ;治疗后阳性组PRL水平 [(1.16± 0 .35 ) μg/L]较治疗前升高 ,阴性组 [(1.2 4± 0 .4 6 ) μg/L]较治疗前降低 ,差异均无显著性 (P >0 .0 5 )。两组治疗后BPRS、SAPS或SANS总分较同组治疗前下降均有极显著性差异 (P <0 .0 1)。结论　阳性和阴性精神分裂症患者脑脊液PRL基础水平有差异 ,氯氮平对精神分裂症患者脑脊液PRL水平影响较小。     

氯氮平治疗对以阳性或阴性症状为主的精神分裂症患者血清一氧化氮含量的影响

目的　探讨以阳性症状为主 (以下简称阳性 )或阴性症状为主 (以下简称阴性 )的精神分裂症患者用氯氮平治疗前后血清一氧化氮 (NO)含量变化及其与疗效的关系。方法　对 32例阳性患者、30例阴性患者均用氯氮平 (30 0mg/d)治疗 8周。用阳性症状评定量表 (SAPS)和阴性症状评定量表 (SANS)评定其疗效。治疗前及治疗第 8周末分别检测血清NO含量 ,并与 2 8名健康志愿者 (对照组)比较。结果　治疗前阳性组、阴性组及对照组血清NO含量分别为 :(5 9± 16 ) μmol/L、(2 6± 7) μmol/L和 (38± 11) μmol/L ,三组间的差异有非常显著性 (P <0 0 1)。治疗前阳性组血清NO含量与SAPS总分呈显著正相关 (r =0 6 92 ,P <0 0 1) ;阴性组血清NO含量与SANS总分呈显著负相关(r=- 0 916 ,P <0 0 1)。治疗第 8周末阳性组血清NO含量降低至 (39± 8) μmol/L ,其NO降低值与SAPS减分率之间呈显著正相关 (r=0 86 8,P <0 0 1) ;阴性组血清NO含量升高至 (32± 8) μmol/L ,显著高于治疗前 (P <0 0 5 ) ,但仍低于对照组 (P <0 0 1)。NO升高值与SANS减分率呈负相关(r=- 0 916 ,P <0 0 1)。结论　以阳性症状为主与以阴性症状为主的精神分裂症患者血清NO含量的差异有显著性 ;患者血清NO含量变化与疗效之间高度相关。氯氮平可能     

儿童精神分裂症患者血清神经元特异性烯醇化酶和髓鞘碱性蛋白的研究

目的探讨儿童精神分裂症患儿血清神经元特异性烯醇化酶(NSE)和髓鞘碱性蛋白(MBP)的含量及其与精神病理改变的关系。方法选择儿童精神分裂症患儿32例(患者组)与30例正常儿童作对照(对照组),采用北方生物技术研究所提供的NSE100RLA试剂和上海产SN682型全自动r记数仪,测定其血清中NSE和MBP含量。以阳性和阴性症状量表(PANSS)评定儿童精神分裂症患儿的精神症状。结果患者组NSE[(20.6±7.2)μL/L]和MBP[(8.1±4.8)μL/L]含量明显高于对照组[(8.2±3.0)μL/L和(4.4±0.4)μL/L],(经t检验,P均0.01)。在患者组中,血清NSE与MBP呈正相关(r=0.69,P0.01);血清NSE和MBP与PANSS总分均呈正相关(NSE:r=0.66,MBP:r=0.68,P均0.01)。结论精神分裂症患儿血清NSE和MBP含量均升高,并与精神病理性变化密切相关。     

长期治疗的慢性精神分裂症患者血清脑源性神经营养因子水平的研究

目的探讨血清脑源性营养因子(BDNF)浓度与长期抗精神病药治疗的慢性精神分裂症患者精神病理症状间的关系。方法检测81例慢性精神分裂症患者和45名正常人血清的BDNF浓度,比较2组及各类抗精神病药治疗的患者间血清BDNF浓度的差异;采用阳性和阴性症状量表(PANSS)评定精神病理症状,分析血清BDNF浓度与PANSS评分间的关系。结果①患者组血清BDNF浓度显著低于正常对照[(7.3±2.6)vs(9.9±4.3)ng/mL,P<0.001];②利培酮、氯氮平、典型抗精神病药3组间血清BDNF浓度差异有统计学意义(F=6.25,P<0.01),利培酮组显著低于氯氮平组[(5.1±1.7)vs(7.8±2.7)ng/mL,P<0.05];③患者组中血清BDNF浓度与PANSS阴性症状分呈负相关(r=-0.307,P=0.005)。结论长期抗精神病药物治疗的慢性精神分裂症患者血清BDNF浓度下降,利培酮治疗组显著低于氯氮平治疗组,阴性症状越明显的患者BDNF水平越低。     

利福平对氯氮平血药浓度及疗效的影响

目的 :探讨利福平对氯氮平血药浓度及疗效的影响。　方法 :采用自身对照的方法 ,对 30例伴肺结核的精神分裂症患者在原氯氮平治疗的基础上合用利福平 (4 5 0mg/d) ,治疗 6周。以阳性症状与阴性症状量表 (PANSS)评定疗效 ,用高效液相色谱法 (HPLC)测定氯氮平稳态血药浓度。　结果 :合用利福平前与合用后 2、6周末的氯氮平血药浓度分别为 (4 38± 183) μg/L、(10 2± 4 1) μg/L和 (91± 30 ) μg/L ,差异有非常显著性 (F =87 32 ,P <0 0 1)。 30 % (8例 )患者阳性精神症状加重。　结论 :利福平可显著降低氯氮平血药浓度和疗效 ,导致精神分裂症患者阳性症状加重     

精神分裂症患者脑脊液单胺类神经递质含量与疗效

目的:探讨精神分裂症患者脑脊液(CSF)内多巴胺(DA)、高香草酸(HVA)含量的变化及其临床意义。　方法:86例首发精神分裂症,用利培酮治疗6个月,于治疗前及治疗6个月后采用高效液相色谱电化学(HPLC -ECD)法检测CSF中的DA及HVA含量,并与32名健康人进行对照。患者组同时用阳性与阴性症状量表(PANSS)评定临床疗效。　结果:患者组在治疗前CSF中DA和HVA含量分别为(3.2 3±0 .36 ) μmol/L和(1.99±0 .4 9) μmol/L ,显著高于对照组(2 .4 4±0 .32 ) μmol/L和(1. 4 1±0 . 37)μmol/L ;患者组治疗6个月后分别为(2 .4 9±0 .35 ) μmol/L和(1.4 2±0 .2 8) μmol/L。其治疗后降低值与PANSS总分的减分差值呈显著正相关。　结论:精神分裂症患者CSF内DA和HVA含量显著增高,利培酮对精神分裂症的疗效与DA和HVA含量的变化密切相关。同时进一步验证了精神分裂症患者中枢神经系统DA功能亢进的假说。     

晚发精神分裂症患者局部脑血流及认知功能的研究

目的　探讨晚发精神分裂症患者局部脑血流 (rCBF)及认知功能损害的特点。方法　对2 1例首次发病年龄≥ 5 0岁的精神分裂症患者进行脑单光子发射计算机体层摄影术 (SPECT)检查 ,并采用阳性和阴性症状量表 (PANSS)、简易精神状态量表 (MMSE)、中国修订韦克斯勒成人智力量表、韦克斯勒记忆量表 (WMS)及威斯康星卡片分类测验等进行评定 ,经利培酮 [(2 7± 0 8)mg/d ,2次 /d]治疗 8周后 ,其中 11例患者 (PANSS减分率大于 2 5 % )再次完成上述测定。 2 0名正常人完成SPECT、MMSE及WMS测定。结果　 (1)治疗前患者组左额叶、左顶叶、双侧颞下、双侧基底节及右丘脑 (P <0 0 1)的放射性计数比值 (RAR)低于对照组 (P <0 0 5 ) ,且左额叶RAR (0 85± 0 11)低于右额叶(0 86± 0 10 ;P =0 0 13) ;其MMSE评分 (2 3 33± 4 10 )低于对照组 [(2 8 35± 1 6 3)分 ,P <0 0 1];WMS总分及其大部分测验项目分亦均低于对照组 (P <0 0 1或 0 0 5 )。 (2 )治疗后患者组仅MMSE分[(2 4 73± 4 4 5 )分 ]、WMS的定向因子分 [(3 82± 1 0 8)分 ]和背数因子分 [(5 0 0± 3 4 9)分 ]高于治疗前[分别为 (2 2 4 5± 3 98)分、(3 18± 1 0 8)分和 (2 6 4± 3 88)分 ;P <0 0 5 ],而各脑区rCBF及其余认知功能的变化均无显     

首发精神分裂症患者血液中神经元特异性烯醇化酶和髓鞘碱性蛋白的改变

目的 通过测定首发精神分裂症患者髓鞘碱性蛋白(MBP)和神经元特异性烯醇化酶(NSE),探讨是否有神经系统损伤。方法 选择88例首发精神分裂症患者(患者组)和30例对照(对照组)测定血液中MBP和NSE,采用双抗体夹心酶标免疫分析法检测。并在入组第1天及第8周后分别评定阳性和阴性症状量表(PANSS)量表。结果 患者组MBP[(7.9±4.5)μg/L]和NSE[(19.4±6.9)μg/L]含量明显高于对照组[(4.3±0.4)μg/L,(8.0±2.8)μg/L],t:12.70,P<0.01;t=7.20,P<0.01。患者组MBP和NSE与PANSS总分减分率呈负相关(r=-0.236,P=0.025:r=-0.298,P=0.005)。结论 精神分裂症患者可能存在神经系统损伤,且受损程度可能与疗效有关。     

精神分裂症患者奥氮平治疗的血药浓度与剂量及临床效应的关系

目的　观察奥氮平治疗精神分裂症的血药浓度与剂量和临床效应的关系。方法　 6 0例精神分裂症患者 ,其中男 4 0例 ,女 2 0例 ;入组时阳性和阴性症状量表 (PANSS)总分≥ 70分 ,随机分为 :奥氮平低剂量组 (0 0 9mg·kg-1·d-1) 15例 ,中剂量组 (0 .18mg·kg-1·d-1) 30例 ,高剂量组(0 36mg·kg-1·d-1) 15例 ,疗程为 8周。在治疗前及治疗后第 2 ,4 ,6 ,8周末评定PANSS、临床疗效总评量表和副反应量表 (TESS)。采用高效液相色谱法测定治疗后第 4 ,8周末奥氮平血浓度。结果　 (1)血药浓度与日剂量呈正相关 (r =0 5 6 7,P <0 0 1)。 (2 )血药浓度 10～ 2 0 μg/L组的疗效明显优于 <10 μg/L组 (P <0 0 5 ) ;与 >2 0 μg/L组的差异无显著性 (P >0 0 5 )。(3)血药浓度与TESS评分无相关 (r=0 2 4 7,P >0 0 5 ) ;与丙氨酸转氨酶升高呈正相关 (r =0 35 ,P <0 0 5 )。结论　奥氮平是一种有效的抗精神病药 ,有效血药浓度的低限为 10 μg/L ;血药浓度测定对指导临床用药具有实际意义。     

强迫症、抑郁症及焦虑症患者血小板5-羟色胺浓度的对照研究

目的　研究 5 羟色胺 ( 5 HT)在强迫症发病中的作用及强迫思维与强迫动作亚组、抑郁症及焦虑症患者间血小板 5 HT含量的差异。方法　采用高效液相色谱法 ,分别测定 2 9例强迫症患者 [(强迫症组 ,根据Y BOCS强迫量表因子得分将其分为强迫思维 ( 16例 )、强迫动作 ( 7例 )和混合性( 6例 ) 3组 ]、2 0例抑郁障碍患者 (抑郁症组 )、17例焦虑障碍患者 (焦虑症组 )和 2 8名正常人 (正常人组 )的血小板 5 HT含量。结果　强迫症组血小板 5 HT水平 [( 139± 172 ) μg/L]低于正常人组 [( 2 4 8±2 15 ) μg/L]及焦虑症组 [( 397± 4 0 1) μg/L],差异具有显著性 (P =0 0 39;P =0 0 2 0 ) ;与抑郁症组 [( 2 0 2± 16 2 ) μg/L]的差异无显著性 ( P >0 0 5 ) ;强迫思维 [( 85± 6 6 ) μg/L]与强迫动作组 [( 16 9± 10 0 ) μg/L]间血小板 5 HT含量的差异有显著性 (P =0 0 2 5 )。结论　强迫症患者 5 HT浓度变化与抑郁障碍患者趋同 ,与焦虑障碍患者的差异有显著性 ;单纯强迫思维者的 5 HT浓度与单纯强迫动作患者的差异有显著性     

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.