利培酮和氯氮平对首发精神分裂症患者血浆细胞因子的影响

目的 比较利培酮和氯氮平对首发精神分裂症患者血浆细胞因子影响的差异。方法 用酶联免疫吸附法(ELISA)测定利培酮和氯氮平两组各30例患者治疗6周前后的血浆白细胞介素-2(IL-2)、可溶性白细胞介素-2受体(sIL-2 R)、白细胞介素-6(IL-6)及可溶性白细胞介素-6受体(sIL-6R)的浓度,两组间进行比较,每组治疗前后各自进行比较。结果 两组间比较,血浆细胞因子水平无显著性差异(P>0.05);治疗前后各自进行比较,每组血浆IL-2及sIL-6R水平显著下降(P<0.05),IL-6水平显著升高(P<0.05),sIL-2R治疗前后无显著性差异(P>0.05)。结论 利培酮和氯氮平治疗均对首发精神分裂症患者的IL-2、IL-6及sIL-6R水平产生显著性影响,对sIL-2R水平影响不显著;利培酮和氯氮平对首发精神分裂症患者细胞因子水平的影响基本一致。     

精神分裂症患者的性激素分泌变异

为研究精神分裂症患者垂体促性腺激素及外周性激素的功能状态，探讨性激素水平改变与性有关症状和药物治疗的关系，采用放射免疫法测定６０例（男４０例，女２０例）精神分裂症患者的血清促卵泡激素（ＦＳＨ）、黄体生成素（ＬＨ）、催乳素（ＰＲＬ）、睾丸酮（Ｔ）、雌二醇（Ｅ２）等激素水平，并与２０名（男女各１０名）正常人对照。结果显示，试验组中男性ＬＨ和女性ＰＲＬ水平明显低于对照组，女性患者的Ｔ与Ｅ２水平显著升高。按性有关症状的有无分为两组，两组间性激素水平无显著性差异。药物治疗前后男患者ＰＲＬ，女患者ＦＳＨ、ＰＲＬ、Ｔ和Ｅ２等激素分泌改变非常显著。氯丙嗪、舒必利可致明显的高ＰＲＬ血症，但氯氮平无明显影响。提示精神分裂症患者性腺轴存在功能失调。性有关症状与性激素水平改变无关。抗精神病药治疗可导致性激素分泌紊乱。     

氯氮平与利培酮对精神分裂症患者血糖的影响

目的　探讨氯氮平与利培酮对精神分裂症患者血糖的影响。方法　对 6 0例精神分裂症患者分为氯氮平组和利培酮组 ,进行为期 8周的治疗 ,采用自身对照 ,比较用药前后血糖浓度。结果　氯氮平组治疗后血糖浓度显著升高 (P <0 .0 5 ) ;利培酮组治疗后血糖无明显变化 (P >0 .0 5 )。结论　氯氮平可引起精神分裂症患者血糖升高 ;利培酮则无明显影响     

奎硫平与氯氮平对精神分裂症病人心电图影响的对照研究

目的：探讨奎硫平对病人心电图的影响。方法：95例精神分裂症患者随机分成实验组(49例)及对照组(46例)，分别使用奎硫平与氯氮平治疗。于治疗前及治疗后4周、8周检查心电图。结果：奎硫平与氯氮平对精神分裂症病人的心电图均有影响，但奎硫平组所致心电图改变发生率明显低于氯氮平组(P＜0．01)，心电图异常程度轻，以窦性心动过速为主。结论：奎硫平可引起心电图发生改变，但其发生率低，心电图改变程度轻，安全性较大。     

氯氮平、利培酮对精神分裂症患者白细胞介素-2的影响

目的 了解氯氮平、利培酮对首发精神分裂症偏执型患者血清白细胞介素-2(IL-2)的影响,并探讨IL-2与精神病理的关系。方法 对58例首发精神分裂症偏执型患者给予氯氮平或利培酮治疗,分别在治疗前和治疗后第4、8周末、6月末用酶联免疫吸附法检测血清IL-2水平,并用阳性和阴性症状量表(PANSS)评估精神症状及其变化。结果 两组患者治疗后第4、8周末血清IL-2水平均显著低于治疗前;不同药物对IL-2影响差异无显著性;治疗前IL-2水平与SPANSS总分、阳性症状分呈显著正相关;治疗后8周末血清IL-2减分值与阳性症状减分值呈显著正相关;利培酮组患者治疗后第8周末血清IL-2减分值与利培酮日量呈显著相关。结论 氯氮平和利培酮有相似的免疫抑制作用,血清IL-2与精神分裂症精神病理之间有一定的关系。     

Pharacogenetic effects of dopamine transporter gene polymorphisms on response to chlorpromazine and clozapine and on extrapyramidal syndrome in schizophrenia

A number of studies have investigated the effectiveness of the dopamine transporter (SLC6A3) Gene as an antipsychotic target. However, the focus has mainly been on a 40-bp variable number of a tandem repeat (VNTR) in the 3′-region and results have been inconsistent. To fully evaluate SLC6A3 as a therapeutic antipshycotic target we investigated association of the gene with responses to chlorpromazine and clozapine and with chlorpromazine-induced extrapyramidal syndrome (EPS) in the Chinese schizophrenia population. Six polymorphisms across the whole region of this gene were analyzed, namely rs2652511 (T-844C) and rs2975226 (T-71A) in the 5′-regulatory region, rs2963238 (A1491C) in intron 1, a 30-bp VNTR in intron 8, rs27072 and the 40-bp VNTR in the 3′-region. We found that the polymorphic marker, rs2975226, showed significant association of allele and genotype frequencies with response to clozapine (allele-wise: adjusted p = 0.00404; genotype-wise: adjusted p = 0.024), and that patients with the T allele had a better response to the drug. The haplotype block constructed from the first three markers near the 5′-region showed significant association with response to clozapine (for haplotype T-T-A: p = 0.0085; for haplotype C-A-C: p = 0.0092). We did not identify any significant association of the six genetic variants or haplotypes with EPS after Bonferoni correction. Our findings suggest that the 5′-regulatory region of SLC6A3 plays an important role in response to clozapine and that its role in EPS needs to be replicated in a large-scale well designed study.     

精神分裂症患者事件相关电位药物治疗前后对照研究

目的 探索精神分裂症事件相关电位（ERPs）特征及非典型抗精神病药物治疗对其的影响。方法 22例从未用过抗精神病药或停药两周以上的精神分裂症患者以及15例健康受试者进行ERPs检查。然后22例患者分别给予利培酮或氯氮平治疗6周，观察治疗后患者ERPs的变化经情况。结果 与正常受试者比较，治疗前精神分裂症患者表现P3波幅降低，治疗后P3幅值降低得到改善。利培酮治疗可明显增加P3幅值，氯氮平治疗P3幅值增加较少。结论 精神分裂症患者ERPs异常主要表现P3幅值降低，利培酮治疗可显著改善这种异常。     

奥氮平与氯氮平治疗精神分裂症的对照研究

目的 评价奥氮平治疗精神分裂症的疗效和副作用。方法 将39例精神分裂症患者随机分成2组，分别给予奥氮平与氯氮平治疗8周，采用PANSS．CGI评价临床疗效，TESS评价不良反应。结果 奥氮平组与氯氮平组之间疗效无显著性差异，奥氮平组治疗前后PANSS减分率45．7％，有效率78．90％；氯氮平组治疗前后PANSS减分率44．9％，有效率75．0%；氯氮平组副反应明显高于奥氮平组。结论 奥氯平是一种安全有效的新型抗精神病药。     

Effect of treatment duration on plasma levels of clozapine andN-desmethylclozapine in men and women

Plasma levels of clozapine and its major metabolites,N-desmethylclozapine and clozapine-N-oxide, were measured in 18 schizophrenic patients at different times (4, 6 and 24 weeks) during the course of treatment with multiple doses of the drug, by using high performance liquid chromatography (HPLC) with UV detection. Plasma levels of clozapine andN-desmethylclozapine were significantly higher in females than in males after 4 and 6 weeks, but not after 24 weeks, of treatment. No sex difference was found at any time with respect to plasma levels of clozapine-N-oxide.     

One year treatment with haloperidol or clozapine fails to alter neostriatal D1- and D2-dopamine receptor sensitivity in the rat

Rats were treated continuously with either haloperidol (HAL), clozapine (CLOZ) or tap water for one year. There were no differences between age-matched control and antipsychotic drug (APD) treated groups regarding the effects of the D₁-agonist (+)-SKF 38393 or the D₂-agonist quinpirole on striatal cAMP content. However, the combination of SKF (10 μM) and quinpirole (1 μM) produced a marked synergistic response in HAL-treated animals as compared to controls. Our data fail to support the hypothesis that APD produce their neurological side effects by inducing D₂-receptor hypersensitivity in the basal ganglia. However, the results do suggest that chronic APD treatment alters the interaction between D₁- and D₂-neostriatal receptors.