Increased serum S100B in never-medicated and medicated schizophrenic patients

S100B is a calcium-binding protein, which is produced primarily by glial cells. It modulates the proliferation and differentiation of neurons and glia by affecting protective and apoptotic mechanisms. Recently, several studies have shown increased serum S100B levels in patients with schizophrenia, suggesting that S100B might be relevant to the pathophysiology of schizophrenia. S100B levels were assessed using ELISA in the serum of 80 never-medicated early-stage and 82 medicated chronic schizophrenia patients and 97 healthy controls subjects. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed significantly increased serum S100B levels in both never-medicated and medicated patients compared to normal controls (both p < 0.0001). S100B in never-medicated patients was also markedly increased, compared with medicated patients (p < 0.0001). S100B changes observed were irrespective of neuroleptic medication, gender, age, and smoking. Increased S100B levels in the early stage of schizophrenia suggest that glial cell activation or structural damage may be part of a neurodegenerative process in schizophrenia. The lower S100B levels in chronic than early-stage patients further suggest that antipsychotic treatment may reduce this neurodegeneration.     

Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: Association with dyskinetic movements

Several studies show that calcium-binding protein S100B is increased in schizophrenia and may be involved in the pathogenesis of tardive dyskinesia (TD). We therefore compared serum S100B levels in normal controls (n = 60), schizophrenic patients with (n = 32) and without TD (n = 50). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that patients with TD had higher serum S100B levels than normals and those without TD. Serum S100B levels were positively correlated with AIMS scores in patients with TD. These data suggest that increased S100B levels may be related to neuro-degeneration, associated with TD pathophysiology.     

精神分裂症伴发迟发性运动障碍的血清S100B蛋白浓度研究

目的 比较伴发和未伴发迟发性运动障碍(tardive dyskinesia,TD)的慢性精神分裂症患者血清S100B蛋白的浓度,探索S100B蛋白在TD发生中的作用.方法 采用酶联免疫吸附法检测95例伴发TD(TD组,n ＝ 40)与未伴发TD(非TD组,n ＝ 55)的慢性精神分裂症患者和40名正常对照的血清S100B蛋白浓度,比较3组间的差异;采用阳性和阴性症状量表(positive and negative syndrome scale,PANSS)评定精神病理症状,采用异常不自主运动量表(abnormal involuntary movement scale,AIMS)评定TD严重程度,分析血清S100B蛋白浓度与精神病理症状、TD严重程度的关系.结果 TD组、非TD组和对照组的血清S100B蛋白浓度分别为(0.17 ± 0.04)μg/L、(0.15 ± 0.02)μg/L和(0.10 ± 0.03)μg/L,3组的差异有统计学意义(F ＝ 53.07,P ＜ 0.01),前两者均明显高于对照组(P ＜ 0.01),且TD组高于非TD组(P ＜ 0.01).TD组血清S100B蛋白浓度与AIMS总分正相关(r ＝ 0.52,P ＜ 0.01).结论 TD患者血清S100B蛋白浓度较非TD患者还高,而且与TD严重程度正相关,提示胶质细胞功能异常可能在TD发生、发展过程中可能起一定作用.     

首发未服药精神分裂症患者血清S100B蛋白浓度变化

目的 探讨血清S100B蛋白浓度与首发未服用抗精神病药的精神分裂症患者精神病理症状间的关系.方法 采用酶联免疫(ELISA)方法 检测64例首发未服用抗精神病药精神分裂症患者和66名正常对照的血清S100B蛋白浓度,比较2组间的差异;采用阳性和阴性症状量表(PANSS)评定精神病理症状,分析血清S100B蛋白浓度与PANSS评分、患者年龄、发病年龄、病程间的关系.结果 ①患者组血清S100B浓度明显高于对照组,筹异有统计学意义[(0.27±0.13)μg/L vs(0.11±0.04)μg/L,t=10.89,P＜0.001];②患者组中偏执型、瓦解型、未分化型、残留型4个亚组间血清S100B浓度的差异有统计学意义(F=4.63,P=0.006),残留型组明显高于偏执型组(P=0.001)、瓦解型组(P=0.012);且各亚型组均明显高于对照组(P＜0.001).③患者组血清S100B浓度与年龄、总病程、PANSS总分及其阴性症状因子分相关(r为0.36、0.46、0.42、-0.38,P均小于0.005).结论 首发未服药的精神分裂症患者血清S100B浓度升高,并与某些病理症状尤其是阴性症状关联,在一定程度上可反映疾病严重程度.     

精神分裂症血浆S100B蛋白测定及临床意义探讨

目的探讨精神分裂症急性期血浆S100B蛋白水平及临床意义。方法用ELISA法检测血浆S100B蛋白含量。应用阳性和阴性症状量表（PANSS）评定精神症状。结果精神分裂症60例急性期血浆S100B蛋白水平（0．063±0．054μg／1）显著高于对照组（0．019±0．009μg／1，P〈0．001）；治疗6周后血浆S100B蛋白水平（0．079±0．093μg／L）与治疗前（0．063±0．054μg／L）差异不显著（P〉0．05）；治疗后血浆S100B持续增高者PANSS阴性症状评分较高。结论S100B持续增高与精神分裂症阴性症状相关。S100B绝对浓度可作为阴性症状发生的预测因子。     

Memory impairment correlates with increased S100B serum concentrations in patients with chronic schizophrenia

Astrocyte activation indicated by increased S100B is considered a potential pathogenic factor for schizophrenia. To investigate the relationship between astrocyte activation and cognitive performance, S100B serum concentration, memory performance, and psychopathology were assessed in 40 first-episode and 35 chronic schizophrenia patients upon admission and after four weeks of treatment. Chronic schizophrenia patients with high S100B were impaired concerning verbal memory performance (AVLT, Auditory Verbal Learning Test) compared to chronic and first-episode patients with low S100B levels. The findings support the hypothesis that astrocyte activation might contribute to the development of cognitive dysfunction in schizophrenia.     

A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

奎的平与氯氮平治疗以阴性症状为主的精神分裂症对照研究

目的　比较奎的平与氯氮平对以阴性症状为主的精神分裂症的疗效和副反应。方法　对 72例以阴性症状为主的精神分裂症住院患者 ,随机分别用奎的平与氯氮平治疗 ,疗程 12周 ;于治疗前及治疗后 1、2、4、8、12周末用阴性症状量表 (SANS)、简明精神病量表 (BPRS)评定临床疗效 ,用副反应量表 (TESS)评定药物副反应。结果　奎的平组与氮氮平组治疗前后SANS、BPRS总分及减分比较差异无显著性 (P >0 0 5 ) ,各组治疗后SANS、BPRS总分与治疗前比较差异有极显著性 (P <0 0 1) ,奎的平在兴趣社交缺乏因子方面的疗效优于氯氮平 (P <0 0 5 ) ;奎的平组的副反应较氯氮平组少而轻。结论　奎的平对以阴性症状为主的精神分裂症有肯定的疗效 ,在某些方面优于氯氮平 ,安全性较高     

利培酮和氯氮平对精神分裂症阴性症状的疗效及不良反应比较

目的比较利培酮与氯氮平对精神分裂症阴性症状的疗效和不良反应。方法应用利培酮和氯氮平治疗精神分裂症各２０例，其阴性症状评定量表评分≥６５分者入组。用阴性症状评定量表（ＳＡＮＳ）评定疗效，用副反应量表（ＴＥＳＳ）评定药物不良反应。结果利培酮和氯氮平对精神分裂症阴性症状的疗效相当，起效时间为２周。两药的副反应不同，利培酮多见锥体外系反应，而氯氮平多见心动过速、嗜睡、流涎、便秘等。结论利培酮对精神分裂症阴性症状有效、疗效与氯氮平相当。     

Association between serum testosterone levels and the severity of negative symptoms in male patients with chronic schizophrenia

OBJECTIVES: Dysfunction of the hypothalamic-pituitary-gonadal axis may contribute to the pathophysiology of schizophrenia. Recent neuroendocrinological studies have suggested that gonadal sex hormones, including androgens and estrogen, play a significant role in the pathophysiology of schizophrenia. The purpose of this study was to determine any correlation between negative symptoms and the plasma levels of free testosterone, total testosterone, dehydroepiandrosterone sulfate, estradiol, and prolactin with consideration to depressive symptoms, extrapyramidal symptoms (EPS), and other factors including differences in age, diurnal variation of the serum hormone levels, and body fat composition. METHODS: The subjects were 35 male inpatients with chronic schizophrenia aged 20-39 years. The patients' psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). The Calgary Depression Scale for Schizophrenia (CDSS) and the Drug-induced EPS scale (DIEPSS) were also used to exclude the effects of depression or drug-induced movement disorders. RESULTS: The PANSS negative scores had a significant inverse correlation with the serum total and free testosterone levels. The other hormone levels were not correlated with the PANSS negative scores. Moreover, a partial correlation analysis showed an inverse correlation between the PANSS negative subscores and the serum total and free testosterone levels after controlling for the DIEPSS and/or CDSS scores and age. CONCLUSIONS: This study indicates that total and free testosterone may play an important role in the severity of negative symptoms in male patients with schizophrenia.     

氟西汀合并氯氮平治疗精神分裂症临床观察

目的：观察氟西汀合并氯氮平治疗精神分裂症阴性阴性症状的疗效和副反应。方法：将40例男性慢性精神分裂症病人平分为研究组（氟西汀加的氯氮平）和对照组（安慰剂加氯氮平），分别评定疗效及副反应。并同步测定氯氮平与N-去甲基氯氮平的血浓度。结果：治疗8周后研究组PANSS总分、阴性因子分比治疗前明显降低，且阴性因子分值显著低于对照组，同期氯氮平及N-去甲苦氯氮平血浓度明显升高。结论：氟西汀合并氯氮平能明显改善精神分裂症病人的阴性症状，并少有副反应。     

维思通与氯氮平治疗以阴性症状为主的精神分裂症的疗效对照研究

目的探索维思通对以阴性症状为主的精神分裂症的疗效与副反应。方法对８０例以阴性症状为主的精神分裂症住院患者，用维思通与氯氮平随机对照，采用ＳＡＮＳ、ＢＰＲＳ和临床疗效总评进行评定。结果维思通的疗效优于氯氮平，而副反应发生率也较低。结论维思通是治疗以阴性症状为主的精神分裂症较理想的药物     

精神分裂症患者认知功能损害与阴阳性症状的关系

目的：探讨精神分裂症认知功能损害与阴性、阳性症状的关系。方法:至73例入组的患者随机给予利培酮、氯氮平治疗12周,并于治疗前、后盲法评定Wisconsin卡片分类测验（WCST）,Wechsler记忆测验（WMS）,阴状症状评定量表（SANS）与阳性症状评定量表（SAPS）。结果：治疗前精神分裂症患者的阴性症状、阳性症状均与认知功能有显著相关。主要与执行功能相关;注意障碍与记忆相关。治疗后,仅SAPS中怪异行为得分与WCST的持续反应数、持续错误数显著相关。结论：精神分裂症的认知功能损害是原发性的,并不是在阳性、阴性症状基础上产生的。     

脑震荡患者血清S100B蛋白的变化与认知功能障碍的相关性

目的 分析脑震荡患者血清S100B含量变化与认知功能损害的相关性,探讨血清S100B水平在脑震荡认知障碍预后判断中的意义. 方法 采用酶联免疫法分别测定126例脑震荡患者急诊入院后6h、12h和第3天的血清S100B浓度,并和同期轻型单纯脑外伤患者比较.脑震荡患者常规治疗后,于入院后第1天、第14天及3个月后进行简易智能精神状态检查量表(MMSE)评估,将S100B浓度与MMSE评分进行相关性分析. 结果入院6 h、12 h后脑震荡组患者血清S100B浓度均明显高于对照组,差异有统计学意义(P＜0.05).入院6 h血清S100B浓度与各时段MMSE评分均具有相关性(P均＜0.05);入院12 h、第3天血清S100B浓度与各时段MMSE评分均无相关性(P均＞0.05). 结论 脑震荡患者早期(6 h)血清S100B含量异常升高,并与认知功能损害有明显相关性,可作为认知功能损害预后判断的重要指标.     

氯氮平与氟哌啶醇对血清一氧化氮含量的影响

目的：观察氯氮平与氟哌啶醇对精神分裂症患者血清一氧化氮(NO)含量的影响。方法：对122例精神分裂症患者随机分为氯氮平组和氟哌啶醇组，并分别再分为阳性症状为主(阳性组)和阴性症状为主(阴性组)。分别用氯氮平或氟哌啶醇治疗8周。治疗前和治疗第2、4、8周末分别检测血清NO含量，并观察各组之间NO动态变化。选择30名健康者为对照组。结果：治疗前血清NO含量两阳性组均显著高于正常对照组，两阴性组均显著低于正常对照组。两阳性组之间和两阴性组之间差异均无显著性；治疗后两阳性组血清NO含量均逐渐下降，到第8周末接近正常水平，与对照组相仿。而氯氮平组的阴性组逐渐上升，与治疗前比较，第4、8周末差异显著，第8周末与对照组相仿；氟哌啶醇组的阴性组逐渐上升，但与治疗前比较，到第8周末差异显著，与对照组比较差异仍显著。治疗后两阳性组差异无显著性；两阴性组，第2、4周末差异无显著性，第8周末有显著差异。结论：氯氮平和氟哌啶醇对精神分裂症患者血清NO含量有影响，阳性症状为主患者的血清NO含量降低，阴性症状为主患者血清NO含量升高，且氯氮平升高以阴性症状为主患者血清NO含量的作用较氟哌啶醇更为明显。     

Amisulpride: efficacy in the management of chronic patients with predominant negative symptoms of schizophrenia

Amisulpride is a dopamine D2/D3-selective antipsychotic drug with potent antipsychotic efficacy in acute exacerbations of schizophrenia. It also possesses substantial efficacy in chronic schizophrenic patients with enduring predominant negative symptoms. This unique property has been demonstrated in a series of short (6 weeks) and medium-/long-term (6–12 months) double-blind placebo-controlled studies. The patients in these studies were carefully selected and assessed to avoid confounding results with non-specific changes in other symptom domains. The results not only show effects on negative symptoms at the optimal dose of 100 mg/day, but also significant improvement in global functioning. The effect observed in short-term studies was maintained over longer treatment periods (6–12 months). Amisulpride was well tolerated with a safety profile similar to placebo. These results open a new therapeutic approach for negative symptoms, one of the most disabling aspects of schizophrenia. Received: 25 July 2000 / Accepted: 26 July 2001     

急性液化石油气中毒大鼠血清S100B和髓鞘碱性蛋白的检测及意义

目的 研究急性液化石油气(LPG)中毒大鼠血清S100B和髓鞘碱性蛋白(MBP)的变化.方法 健康雄性成年SD大鼠54只按随机数字表法分为正常对照组(n=6)、20%LPG中毒组(n=24)和50%LPG中毒组(n=24).后2组大鼠分别吸入20%、50%LPG,对照组吸入等体积的空气.在中毒1、2、3、7 d时每组取6只大鼠进行神经功能缺损评分(NSS),ELISA法检测血清样本S100B和MBP的含量.结果 与正常对照组比较,20%LPG组中毒1 d、50%LPG组中毒1 d和2 d时NSS评分均较高,差异有统计学意义(P＜0.05);在1 d和2 d时,20%LPG组和50%LPG组大鼠血清S100B、MBP均高于正常对照组,且50%LPG组高于20%LPG组,差异有统计学意义(P＜0.05);3 d时50%LPG组血清S100B、MBP高于正常对照组和20%LPG组,差异有统计学意义(P＜0.05);大鼠LPG中毒1 d时NSS评分、血清S100B、MBP浓度最高,与其它时间点比较差异均有统计学意义(P＜0.05),后随时间延长逐渐恢复.结论 LPG中毒大鼠血清S100B和MBP同时升高,提示胶质细胞参与LPG中毒对神经系统的损害.

Abstract：

Objective To observe the changes of serum S100B and MBP in rats with liquid petroleum gas poisoning. Methods Fifty-four healthy adult male SD rats were randomized into normal control group (n=6), 20% LPG poisoning group (n=24) and 50% LPG poisoning group (n=24). Rat models of liquid petroleum gas poisoning were established in the later 2 groups, and controls were given the same volume of air. The rats of each group(n=6) were scored with neurological severity scale (NSS) and the blood serum was collected on the 1st, 2nd, 3nd and 7th d of poisoning, respectively. The levels of S100B and MBP were detected by euzymelinked immunosorbent assay (ELISA).Results As compared with the scores of NSS in the normal control group, those on the 1st d of poisoning in the 20% LPG poisoning group and those on the 1st and 2nd d of poisoning in the 50% LPG poisoning group were significantly higher (P＜0.05). The levels of Sl00B and MBP in 20% and 50% LPG poisoning groups were higher than those in the control group on the 1st and 2nd d of poisoning (P＜0.05); the levels of S100B and MBP in 50% LPG poisoning group were higher than those in 20% LPG poisoning group on the 1st and 2nd d of poisoning (P＜0.05). The levels of S 100B and MBP in 50% LPG poisoning group were higher than those in 20% LPG poisoning group and normal control group on the 3rd of poisoning (P＜0.05). The NSS scores and the levels of S100B and MBP in rats with LPG poisoning enjoyed the highest scores or levels on the 1st d of poisoning and those decreased after that. Conclusion The levels of S100B and MBP of rats with LPG poisoning increase, indicating that gliocytes participate in the mechanism of nervous system injury in rats with liquid petroleum gas poisoning.     

精神分裂症记忆与阳性、阴性症状的研究

目的探讨精神分裂症患者记忆特点及与阳性、阴性症状的关系。方法采用修正的加工分离记忆实验程序测试精神分裂症患者记忆变化情况,用PANSS评定精神分裂症患者阳性、阴性症状分。结果精神分裂症外显记忆与对照组比较明显受损(P0.05),其文字概念和图像概念实验类型驱动的内隐记忆成绩与对照组比较也受损(P0.05);阳性症状为主的患者外显记忆成绩均高于阴性症状为主的患者组(P0.05);阳性症状为主的患者内隐记忆成绩与以阴性症状为主的患者组之间的差异无统计学意义(P0.05);阳性症状与外显记忆无显著相关关系(P0.05),阴性症状与外显记忆呈显著负相关关系(P0.01);阳性症状、阴性症状与内隐记忆均无显著相关关系(P0.05)。结论精神分裂症外显记忆严重受损,而内隐记忆不同程度的受损;外显记忆与阳性症状无相关性,与阴性症状有显著相关;内隐记忆与阳性、阴性症状均无明显相关性。     

硫酸镁对急性重型颅脑损伤患者血清S100B浓度和预后的影响

目的观察急性重型颅脑损伤(asTBI)后血清S100B浓度的变化及其与预后的关系,研究硫酸镁对asTBI患者血清S100B浓度和预后的影响。方法69例患者随机分为硫酸镁治疗组(n=34)和常规治疗对照组(n=35)。按入院时GCS评分分为特重组(GCS3～5分)和重型组(GCS6～8分),于入院时,伤后1、4、7、14天,检测血清镁、S100B浓度和GCS评分。治疗组首剂给予25%硫酸镁16ml静脉滴注,15分钟输完,继予25%硫酸镁60ml静脉滴注,匀速24h输完。对照组除未用硫酸镁外其余治疗与治疗组完全相同。伤后3个月时纪录GOS评分。结果与健康对照组比较,asTBI后血清镁离子浓度下降(P0.05),血清S100B浓度升高,特重组(ssTBI)S100B浓度高于重型组(sTBI)(P0.05)。伤后第4、7天,治疗组血清S100B浓度低于对照组(P0.05)。入院时血清S100B浓度高于1.2μg/L者预后不良,其敏感度为(sensitivity,SEN)为75.8%,特异度(specificity,SPE)为69.4%。治疗组与对照组预后的比较无统计学意义(P0.05)。结论asTBI后,血清镁离子浓度下降,血清S100B浓度升高,且伤情越重,血清S100B浓度越高,预后越差。早期应用硫酸镁提高asTBI患者血清镁离子浓度可降低伤后第4、7天血清S100B浓度,提示硫酸镁具有一定的神经保护作用,但并不能改善预后。