Statistical differentiation between direct and indirect effects of neuroleptics on negative symptoms

The differentiation between primary and secondary negative symptoms in schizophrenia (Carpenter et al. 1985) is an important issue. Path analysis allows to estimate statistically whether, and in which degree, the effect of a neuroleptic on negative symptoms is mediated by effects on positive, extrapyramidal, and depressive symptoms (Möller et al. 1995). If certain causal relationships are theoretically assumed—as proposed by Carpenter et al. (1985)—then path analysis can be applied to estimate the quantitative degree of these relationships, although the causal directions cannot be inferred from path analysis itself. Especially it can be estimated whether there is sufficient evidence for a “direct effect” of neuroleptic treatment on (primary) negative symptoms, an effect which is not mediated by positive, extrapyramidal, and/or depressive symptoms. We show the correspondence between the applied path model and several simple regression equations which can be estimated with standard statistical software. Moreover, we report some Monte Carlo studies showing that the results reported by Möller et al. (1995)— a “direct effect” of risperidone (6 mg) on negative symptoms compared with haloperidol (20 mg) — cannot be explained by a path model in which, everything else being equal, positive symptoms depend on negative symptoms instead of the other way around.     

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。     

利培酮合用米氮平治疗精神分裂症阴性症状的研究

目的　探讨米氮平治疗精神分裂症阴性症状的疗效和安全性。方法　将 86例以阴性症状为主的住院精神分裂症患者随机分为研究组对对照组 ,分别给予利培酮合用米氮平及单用利培酮治疗 ,疗程 12周 ,用PANSS、TESS评定疗效和安全性。结果　疗后 4周两组PANSS总分、阳性因子分、阴性因子分及 8、12周末两组PANSS总分和各因子分与疗前比较差异有显著性 (P <0 0 5或P <0 0 1)。治疗后 8、12周两组间比较PANSS总分及阴性因子分差异有显著性 (P <0 0 5或P <0 0 1)。结论　米氮平治疗精神分裂症阴性症状疗效较好 ,副作用少。     

利培酮与舒必利治疗以阴性症状为主的精神分裂症对照研究

目的比较利培酮与舒必利对以阴性症状为主的精神分裂症的疗效及安全性。方法对62例以阴性症状为主的精神分裂症住院患者,随机分为利培酮组与舒必利组,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。结果利培酮组与舒必利组治疗前后SANS、BPRS总分及减分比较差异无显著性(P0.05),各组治疗后SANS、BPRS总分与治疗前比较差异有极显著性(P0.01),而利培酮的副反应较舒必利少而轻。结论利培酮对以阴性症状为主的精神分裂症有肯定疗效,且安全性高。     

Increased serum S100B in elderly, chronic schizophrenic patients: negative correlation with deficit symptoms

In schizophrenia, elevations of serum and CSF S100B levels have been reported and related to state of the disease and negative symptoms. In elderly chronic schizophrenic inpatients with stable medication, S100B may be increased and correlated to psychopathology and neuropsychological deficits.

We have measured serum levels of S100B in 41 elderly, chronic schizophrenic patients and 23 age- and gender-matched controls using an immunoluminometric assay. In patients, we assessed detailed psychopathology and neuropsychological performance and determined serum levels of haloperidol, clozapine and its two main metabolites desmethylclozapine and clozapine metabolite N-oxid by HPLC.

S100B levels were increased in elderly chronic schizophrenic patients compared to healthy controls. In patients, levels were negatively correlated with deficit symptoms and positively with age. There were no significant differences of S100B between medication groups and no correlation with serum levels of antipsychotics or neuropsychological scores.

Elevations of S100B in elderly chronic schizophrenic patients may be related to an active disease process lasting until old-age. Correlations point to the impact of S100B in neuroplasticity and ageing. Post-mortem studies should clarify the presence of altered S100B function in the brain and its relationship to neuroplastic or neurodegenerative processes.     

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     

氨磺必利治疗精神分裂症阴性症状的对照研究

目的探讨氨磺必利治疗精神分裂症阴性症状的效果。方法采用随机数字表法将符合《中国精神障碍分类与诊断标准第3版》(CCMD-3)精神分裂症诊断标准的72例精神分裂症患者分为氨磺必利组(研究组)和利培酮组(对照组)各36例,观察8周。采用阳性与阴性症状量表(PANSS)评定疗效,副反应量表(TESS)评定不良反应。结果经8周治疗,两组PANSS总分均较治疗前低(P均0.01)。氨磺必利组与利培酮组有效率分别为88.9%和86.1%,差异无统计学意义(P0.05)。但氨磺必利组阴性症状评分减分与利培酮组比较,差异有统计学意义(P0.05)。治疗结束时两组TESS评分差异无统计学意义(P0.05)。结论氨磺必利对精神分裂症阳性症状的疗效与利培酮相当,而对精神分裂症的阴性症状的疗效优于利培酮。     

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。     

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。     

利培酮合并舍曲林治疗精神分裂症阴性症状的研究

目的探讨舍曲林合并利培酮治疗精神分裂症阴性症状的疗效及安全性。方法将86例以阴性症状为主的住院精神分裂症患者随机分为研究组(舍曲林 利培酮)和对照组(利培酮 安慰剂)。在治疗前及治疗后4、8、12周,用阳性与阴性症状量表(PANSS)、不良反应量表(TESS)评定疗效和安全性。结果治疗后8、12周,两组PANSS总分、阴性因子分比较差异有统计学意义(P<0.05)。研究组阴性因子各项症状评分低于对照组,差异有统计学意义(P<0.05或P<0.01)。而两组TESS评定无统计学意义(P>0.05)。结论舍曲林合并利培酮治疗精神分裂症阴性症状安全有效,副作用少。     

精神分裂症阴性症状的研究进展

精神分裂症是一种病因未明的异质性疾病,其临床表现多样,几乎涵盖了精神科的全部症状群。20世纪80年代,英国精神病学家Crow 提出将精神分裂症分为阳性症状与阴性症状两型［1］。阳性症状与阴性症状的划分,更有利于精神分裂症病因学、发病机制等方面的研究。精神分裂症的阴性症状主要表现为思维贫乏、情感淡漠、愉快感缺乏／社会退缩、意志缺乏、注意障碍,阴性症状较阳性症状更易影响患者的生活质量,增加功能性疾病,增加经济负担,且预后更差［2－3］。     

美多巴及舒必利治疗精神分裂症阴性症状的对照研究

目的探讨美多巴、舒必利治疗精神分裂症阴性症状的效果。方法用美多巴、舒必利分别合并抗精神病药物及单用抗精神病药物对各３０例住院精神分裂症病人进行１３周的对照研究，用阴性症状量表（ＳＡＮＳ）、简明精神病量表（ＢＰＲＳ）、副反应量表（ＴＥＳＳ）于治疗前后评定。结果美多巴、舒必舒利与单用抗精神病药物对阴性病状治疗有效率分别为５０％、５３３％和２０％。结论美多巴、舒必利合并抗精神病药均能提高对阴性症状的疗效，提示精神分裂症存在生物学异质性。     

氯丙咪嗪与舒必利辅助治疗精神分裂症阴性症状的对照研究

目的： 比较氯丙咪嗪、舒必利辅助治疗精神分裂症阴性症状的效果。　方法： 使用氯丙咪嗪、舒必利分别作为氯氮平的辅助用药与单用氯氮平对８８ 例以阴性症状为主的精神分裂症病人进行对照研究; 以简明精神病评定量表、阴性症状量表和副反应量表进行评定。　结果： 合并氯丙咪嗪组、舒必利组及单用氯氮平组对阴性症状的治疗显效率分别为６９％ 、３１％ 、１３３３％ 。　结论： 氯氮平合并氯丙咪嗪治疗能有效地改善精神分裂症的阴性症状。     

利培酮合并氯硝西泮口服与氟哌啶醇肌注后换利培酮口服治疗精神分裂症兴奋激越症状的随机对照研究

目的比较利培酮口服液合并氯硝西泮片与氟哌啶醇肌注控制精神分裂症兴奋激越症状的疗效和安全性,以及在兴奋激越控制后以利培酮口服液替换氟哌啶醇肌注的疗效及安全性。方法纳入33例兴奋激越的精神分裂症患者：18例随机分入利培酮组,利培酮口服液（2～6ml/d）合并氯硝西泮（4～8mg/d）,第6天起氯硝西泮逐渐减量,共观察47d;15例分入氟哌啶醇组,前5天氟哌啶醇肌注（10～20mg/d）,第6天起逐渐替换为利培酮口服液（2～6ml/d）,共观察47d。以阳性与阴性综合征量表（PANSS）、Barnes静坐不能量表（BAS）,类帕金森综合征量表（SAS）评定疗效和不良反应。结果第5天末利培酮组和氟哌啶醇组PANSS兴奋激越因子分的平均（标准差）减分值分别为6.9（3.8）分,8.2（4.7）分,t=0.85,P=0.403,PANSS总分平均减分值分别为41.1（13.5）分,47.7（14.2）分,t=1.31,P=0.199。第5天末利培酮组的SAS评分低于氟哌啶醇肌注组[分别为0（0）分,2（9）分,Z=2.72,P=0.006]。结论利培酮口服液合并氯硝西泮片剂可有效安全地治疗精神分裂症急性兴奋激越。用氟哌啶醇肌注控制兴奋激越后直接换利培酮口服液,也能保持疗效。     

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.     

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     

奥氮平治疗精神分裂症阴性症状对照研究的Meta分析

目的探讨奥氮平治疗精神分裂症阴性症状的疗效和不良反应的差异。方法应用Meta分析对13项奥氮平与其他抗精神病药物治疗精神分裂症阴性症状对照研究的文章进行再分析，评价其合并效应量大小和综合显著性检验。结果1．奥氮平治疗前后的自身对照，合并效应量d=-2．77，95％CI（-4．83，-0．70），Х^2=89．03，P〈0．01；2．奥氮平与对照药物在第2周末和治疗后组间的比较，分别为d=-0．14，95%ACI（-0．31，0．04），Х^2=4．56，P〉0．05；Y合并=-0．10，95％CI（-0．22，0．03），Х^2=3．20，P〉0．05；提示两组疗效没有显著差异；3．奥氮平的不良反应显著少于对照组药物。结论奥氮平与对照组的疗效相仿，但副作用少。     

氟哌啶醇癸酸酯维持治疗阴阳性症状的对照研究

本文报告５个机构合作研究的结果。随机分层抽取社区中精神分裂症患者，进行一年前瞻性抗精神病药物治疗的对照研究，共２９２例，内氟哌啶醇癸酸酯（ＨＤ）治疗１５５例（ＨＤ组），原药维持１３７例（对照组）。结果显示ＨＤ维持治疗对阴性和阳性症状的有效率为６３～８００％，阴／阳性症状有效率为６６％。ＢＰＲＳ量表各国子分６个月和１２个月无显著差异．但ＳＡＮＳ量表各因子分１２个月比６个月有时明显进步。ＨＤ对阴性症状、ＢＰＲＳ量表因子Ⅱ、Ⅲ、Ⅴ和ＳＡＮＳ量表各因子的疗效均优于对照组。     

Social cognition and negative symptoms in psychosis

This study examined the relationship between negative symptoms and social cognition in individuals with psychosis. Although negative symptoms were associated with social cognition, stereotyped thinking, which is cognitive in nature, emerged as the most significant predictor, suggesting that cognition rather than symptoms may have a greater impact on social cognition.     

Effects of haloperidol and risperidone on psychomotor performance relevant to driving ability in schizophrenic patients compared to healthy controls

The effects of antipsychotic treatment on the psychomotor performance and driving ability of schizophrenic patients is subject of investigation. The present study was designed to evaluate the effects of an atypical neuroleptic (risperidone) in comparison to a conventional dopamine antagonist neuroleptic (haloperidol) on several dimensions of psychomotor performance (visual perception, attention, reaction time, and sensorimotor performance) considered to be of relevance in evaluating driving fitness. Psychomotor performance was assessed by means of the ART 90 (act-and-react test), a computerized test battery which is frequently used in diagnosis of psychomotor performance. The 40 participating patients were examined at discharge following psychopathological stabilisation; 20 received haloperidol medication, 20 received the atypical neuroleptic risperidone. Nineteen healthy individuals were studied as a control group. Our findings indicate a remarkably reduced psychomotor performance in both groups of schizophrenic patients compared to healthy controls. We did find a significant but low correlation between age and some items of the RST3 and between age and the tracking performance on the PVT. The younger patients showed a better test performance than older patients. The BPRS-score was significantly correlated with only two items of the RST3. However, patients under treatment with risperidone showed significantly better results compared to patients treated with haloperidol. Only one (5%) subject passed all subtests without major failures and could be regarded as competent to drive. Among patients with risperidone, seven patients (35%) passed all test parameters without major failures. Clinical implications of these findings are discussed.