抑郁症首次发病患者额叶三维磁共振氢质子波谱分析研究

目的探讨抑郁症首次发病患者额叶灰、白质可能存在的神经生化异常。方法对24例首次发病抑郁症患者(抑郁症20例,双相障碍抑郁发作者4例;抑郁症组)进行磁共振常规扫描及应用三维磁共振氢质子波谱(1HMRS)检查,测量双侧额叶背外侧白质和前部扣带回皮质的N-乙酰天门冬氨酸(NAA)、胆碱复合物(CHO)、肌醇(MI)和肌酸(CR)的绝对值,计算NAA、CHO、MI与CR的比值,并与21名正常对照者(对照组)作比较。结果(1)抑郁症组患者前额叶扣带回皮质CHO[(772±59)MMOL/L]、MI[(131±39)MMOL/L]的绝对值及CHO/CR(2·3±0·4)、MI/CR(0·39±0·14)均高于对照组[分别为(663±70)MMOL/L,(99±26)MMOL/L,2·0±0·4,0·30±0·01],差异均有统计学意义(P均<0·01);而NAA的绝对值及NAA/CR与对照组的差异无统计学意义(P>0·05)。(2)抑郁症组患者额叶背外侧白质内NAA、CHO、MI的绝对值以及NAA/CR、CHO/CR、MI/CR的比值与对照组的差异均无统计学意义(P均>0·05)。结论抑郁症患者额叶扣带回皮质的CHO、MI绝对值以及CHO/CR、MI/CR比值均增高。     

不同浓度氯氮平对小鼠空腹血糖和骨骼肌葡萄糖转运蛋白4基因表达的影响

目的探讨氯氮平对雄性C57BL/6小鼠空腹血糖和骨骼肌葡萄糖转运蛋白4(GLUT4)基因表达的影响。方法将63只雄性C57BL/6小鼠随机分为3组,每组21只,分别灌胃给予蒸馏水、氯氮平4mg/kg及氯氮平20mg/kg,于给药后3h、1周、4周以试纸法测定各组空腹血糖,用逆转录-聚合酶链反应测定GLUT4mRNA表达。结果(1)灌药后3h、1周氯氮平4mg/kg组和氯氮平20mg/kg组空腹血糖和GLUT4mRNA的表达与空白对照组相比,差异无统计学意义(P>0.05);(2)灌药后4周氯氮平4mg/kg组和20mg/kg组的空腹血糖值[(5.6±0.5)mmol/L和(5.8±0.5)mmol/L]高于空白对照组[(4.6±0.6)mmol/L],而GLUT4mRNA的表达(0.50±0.14和0.48±0.12)却低于空白对照组(0.85±0.27),差异均有统计学意义(P<0.01)。结论氯氮平可以慢性升高空腹血糖,降低GLUT4mRNA的表达,可能是抗精神病药长期应用后血糖升高的发生机制之一。     

氯氮平和利培酮对首发精神分裂症患者糖代谢影响的研究

目的　探讨氯氮平和利培酮对首发精神分裂症患者糖代谢的影响。方法　 6 8例首发精神分裂症患者随机分为两组 ,分别给予氯氮平治疗 ( 34例 ,氯氮平组 )和利培酮治疗 ( 34例 ,利培酮组 )。两组患者治疗前和治疗后第 4周末做糖耐量试验 ,测定空腹胰岛素、C肽、甘油三酯、胆固醇、瘦素 ,并测量身高、体重 ,计算体重指数 [BMI,体重 (kg) /身高 (m2 ) ]。共观察 4周。结果　治疗第 4周末 ,氯氮平组餐后 1h、2h的血糖值 [分别为 ( 8 6± 1 8)mmol/L和 ( 6 7± 1 1)mmol/L]比治疗前 [分别为( 7 4± 2 2 )mmol/L和 ( 5 8± 1 4 )mmol/L]明显升高 (P <0 0 5 ,P <0 0 1) ,而利培酮组无明显变化。治疗后氯氮平组 ( 2 0 % ,7例 )患者糖耐量减低的发生率高于利培酮组 ( 3% ,1例 ) ,差异有显著性 ( χ2 =3 972 ,P <0 0 5 )。结论　氯氮平对首发精神分裂症患者餐后血糖值的影响大于利培酮     

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。     

首发精神分裂症患者氯氮平治疗前后血浆白细胞介素6,13及可溶性白细胞介素6受体水平的变化

目的探讨首发精神分裂症患者氯氮平治疗前后血浆白细胞介素6(IL6)、白细胞介素13(IL13)及可溶性白细胞介素6受体(sIL6R)水平的变化。方法采用双抗体夹心ABC放射免疫吸附法,对30例(男10例,女20例)首发精神分裂症患者(患者组)氯氮平治疗前后及28名(男13名,女15名)健康对照者(对照组)的血浆IL6、IL13及sIL6R水平进行检测。结果(1)患者组治疗前[(202±26)ng/L]后[(217±28)ng/L]血浆IL6水平均明显高于对照组[(181±36)ng/L],差异均有统计学意义(均P<005)。患者组氯氮平治疗后血浆IL6水平高于治疗前(P<005)。(2)患者组治疗第6周末血浆sIL6R水平[(23±20)ng/L]比治疗前[(34±16)ng/L]明显下降,差异有统计学意义(P<005)。(3)患者组治疗前血浆IL13水平[(16±12)ng/L]明显低于对照组[(24±18)ng/L],差异有统计学意义(P<005),治疗第6周末[(22±14)ng/L]比治疗前有所升高。(4)经相关及多元回归分析,患者组治疗第6周末血浆IL6水平的增高幅度与氯氮平治疗剂量呈正相关,差异有统计学意义(r=0722,P=0000);治疗前血浆sIL6R水平与阳性症状分呈正相关(r=0379,P=0020),血浆IL13水平与阴性症状分(r=-0602,P=0000)及阳性和阴性症状量表总分(r=-0334,P=0035)呈负相关;治疗前后IL13的变化幅度与阴性症状分减分率呈正相关(r=0611     

氯丙嗪和利培酮对精神分裂症患者血糖调节功能影响的动态观察

目的观察抗精神病药在治疗的不同时间精神分裂症患者血糖代谢的变化特点,探讨预防血糖调节功能损害(IGR)的有效方法。方法将213例住院精神分裂症患者分为氯丙嗪组(108例,200~650mg/d)和利培酮组(105例,3~6mg/d),均单一用药,分别于入院时、治疗第1,2,3,6个月末及1年末测定多项血糖浓度并进行对照研究。结果(1)治疗后随时间延长,两组血糖浓度均不断上升。治疗第3个月末餐后2h血糖(2hPBG)和2h糖耐量(2hPG)浓度开始升高,治疗第6个月末空腹血糖(FPG)和空腹糖化血红蛋白(HbA1c)开始升高,治疗1年末所有血糖指标均升高(均P<0.05~0.01)。(2)组内治疗前后比较,氯丙嗪组治疗第3个月末2hPG[(5.77±1.28)mmol/L]和2hPBG[(5.93±1.10)mmol/L]、治疗第6个月末HbA1c[(5.49±0.76)mmol/L]、治疗1年FPG浓度[(5.29±0.71)mmol/L]均高于治疗前[分别为(mmol/L)5.31±0.58,5.48±0.60,5.22±0.50和4.96±0.49],均P<0.05~0.01;利培酮组治疗1年末2hPBG浓度[(5.70±0.89)mmol/L]高于治疗前[(5.35±0.77)mmol/L;P<0.05]。(3)两组比较,氯丙嗪组治疗第3个月末2hPBG和HbA1c[(5.41±0.63)mmol/L]、治疗1年末2hPG[(5.92±1.34)mmol/L]和FPG[(5.29±0.71)mmol/L]浓度均高于利培酮组[分别为(mmol/L)5.55±0.83,5.23±0.50,5.54±0.91,5.08±0.59],均P<0.05~0.01。1年末,两种药物日剂量与各血糖浓度之间无显著相关性(P>0.05)。(4)两组治疗后各时间点IGR的发生率均上升;治疗1年末,氯丙嗪组IGR发生率达36.1%,高于利培酮组(22.9%;P<0.05)。(5)在完成1年观察的198例患者中,51例(25.8%)至少有1次符合IGR血糖浓度标准,但两组间的差异无统计学意义(P>0.05)。结论血糖浓度随药物治疗时间的延长而上升,其中氯丙嗪比利培酮更易引起IGR。     

汉族人群载脂蛋白（a）五核苷酸重复序列基因多态性与动脉硬化性？…

目的　研究载脂蛋白 (a) [Apo(a) ]五核苷酸重复序列 (PNR)基因多态性与动脉硬化性脑梗死 (ABI)的关系。方法　 1998年 3～ 12月收治的ABI患者 82例 ,男 5 4例 ,女 2 8例 ,平均年龄 6 8岁。健康对照组 15 3名 ,男 86名 ,女 6 7名 ,平均年龄 6 2岁。分别检测血清脂蛋白A [Lp(a) ]、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)、甘油三酯 (TG)、载脂蛋白AⅠ(ApoAⅠ )及载脂蛋白B(ApoB)水平。同时采用聚合酶链反应结合高压聚丙烯酰胺凝胶电泳检测Apo(a) 5′调控区五核苷酸重复序列基因的多态性 ,并加以对照分析。结果　ABI患者Lp(a) [(2 40±2 2 5 )mg/L]、TC[(4.7± 0 .7)mmol/L]、TG[(1.7± 0 .6 )mmol/L]和LDL C[(2 .8± 0 .6 )mmol/L]水平明显高于对照组 [(134± 98)mg/L、(4.3± 0 .7)mmol/L、(1.1± 0 .5 )mmol/L和 (2 .8± 0 .6 )mmol/L],HDL C水平 [(0 .9± 0 .2 )mmol/L]明显低于对照组 [(1.0± 0 .4)mmol/L];两组ApoAⅠ [(1.1± 0 .2 )mmol/L ,(1.2± 0 .2 )mmol/L]、ApoB[(0 .9± 0 .1)mmol/L ,(0 .9± 0 .2 )mmol/L]比较 ,差异无显著意义 ;ABI组中重复序列数为 5的等位基因频率 (0 .0 98)明显高于正常对照组 (0 .0 2 6 ) ,重复序列数为 9的等位基因频率 (0 .0 73)     

氯氮平及其代谢产物对大鼠胰岛细胞胞内钙的影响

目的从胞内钙离子水平探讨氯氮平及其代谢产物对离体大鼠胰岛细胞内分泌功能的影响。方法分别用低浓度(3.3mmol/L)和高浓度(16.7mmol/L)的葡萄糖Hank′s液经灌流装置孵育诱导,以终浓度为1μmol/L的氯氮平、去甲基氯氮平和N-氧化氯氮平分别作用于分离培养的大鼠胰岛细胞,并设两种浓度葡萄糖的空白对照组,以Fluo-4/AM为荧光探针,应用激光扫描共聚焦显微镜,动态监测不同药物作用于胰岛细胞后胞内钙荧光强度的变化。结果(1)低糖条件下,氯氮平组[(22±4)%]和去甲基氯氮平组[(49±6)%]胞内[Ca2+]i均低于空白对照组[(93±6)%;P<0.01];与未加处理因素前(0min)相比,氯氮平组和去甲基氯氮平组的胞内[Ca2+]i随时间的延长而降低(P<0.05~0.01),且氯氮平的抑制作用强于去甲基氯氮平(P<0.01)。(2)高糖条件下,氯氮平组[(62±10)%]和去甲基氯氮平组[(18±8)%]胞内[Ca2+]i亦均低于空白对照组[(94±5)%;P<0.01];与未加处理因素前(0min)相比,氯氮平组和去甲基氯氮平组的胞内[Ca2+]i随时间的延长而降低(P<0.05~0.01),其中去甲基氯氮平的抑制作用强于氯氮平(P<0.01)。N-氧化氯氮平组对胞内[Ca2+]i的影响不大(P>0.05)。结论氯氮平及去甲基氯氮平均降低胰岛细胞胞内[Ca2+]i,从而抑制胰岛素分泌。     

首发精神分裂症患者的糖代谢研究

目的　探讨首发精神分裂症患者的糖代谢情况。方法　对 86例首发精神分裂症患者及 45名健康人进行糖耐量试验(OGTT) ,并检测其空腹血浆胰岛素、C肽的浓度。结果　两组间空腹血糖、餐后 3h血糖、空腹胰岛素、C肽的差异无显著性 ,病例组餐后 1h血糖值 [( 7 89± 1 77)mmol/L]、2h的血糖值 [( 6 2 4± 1 14 )mmol/L]、OGTT血糖曲线下面积 (AUC) [( 18 2 4± 2 76)mmol/(L·h) ]比对照组 [分别为 ( 6 5 4± 1 84)mmol/L ,( 5 88± 2 78)mmol/L ,( 15 86± 1 93 )mmol/L/h ,P分别小于 0 .0 1、0 .0 5、0 0 1]要大 ;组间糖耐量减退 (IGT)的发生率无显著性差异 ( χ2 =0 5 84,P >0 0 5 ) ;偏执型患者组与青春型患者组间的空腹血糖、2h血糖值无显著性差异 (t=1 476,P均大于 0 0 5 ) ;发生IGT的病例组与未发生IGT病例组组间阳性和阴性症状量表 (PANSS)总分及 4个分量表分值的差异无显著性差异 (P均大于 0 0 5 )。结论　首发精神分裂症患者存在餐后高血糖现象。     

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     

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.