Effects of antipsychotics on cognitive performance in drug-naive schizophrenic patients

It has been reported that antipsychotics may improve cognitive function in the treatment of schizophrenia. The present study examined the effect of haloperidol and risperidone on cognitive performance in schizophrenic patients. 95 healthy subjects and 68 schizophrenic patients were recruited for comparison of cognitive function. As 20 of the 68 schizophrenic patients were drug-naive, they were randomly divided into two groups and double-blinded for treatment with either haloperidol or risperidone for an 8-week period. Each subject received Wisconsin Card Sorting Test (WCST) and Maze paradigms for cognitive function performance. For schizophrenic patients, the Positive and Negative Syndrome Scale (PANSS) was used for evaluation of clinical symptoms. Results demonstrated that in both WCST and Maze paradigms the 68 schizophrenic patients had worse cognitive performance compared with healthy subjects. Of the 20 drug-naive schizophrenic patients from the 68 in-patients, both haloperidol and risperidone improved the clinical symptoms. Maze tasks performance was improved progressively after haloperidol and risperidone treatment, although improvement was greatest with risperidone. Both haloperidol and risperidone had no evident effect on WCST performance. Our findings suggest that Maze paradigms may be an ideal tool for evaluation of pharmacological treatment effects on cognitive function in schizophrenic patients. Furthermore, risperidone may have more treatment benefits than haloperidol on cognitive performance in drug-naive schizophrenic patients.     

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。     

The effect of treatment with risperidone,olanzapine or phenothiazines on cognitive functions in patients with schizophrenia

INTRODUCTION: Theaimofthestudywastocomparetheeffectsofrisperidone, olanzapine and phenothiazines on cognitive functions in schizophrenia during short-term (4 &#45 6 weeks) and long-term (3 &#45 4 months) treatment. METHOD: Seventy patients with schizophrenia were investigated: 30 treated with risperidone, 20 with olanzapine and 20 with phenothiazines, in standard doses. Psychometric measurements were made with the Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests included the Trail Making Test (TMT), the Stroop Test and the Wisconsin Card Sorting Test (WCST). RESULTS: PANSS negative symptoms decreased significantly after risperidone and olanzapine, did not change after short-term, and improved marginally after long-term, phenothiazine treatment. Risperidone treatment resulted in significant amelioration of performance on all neuropsychological tests after both short- and long-term treatment. Olanzapine gave benefit on five out of seven subtests, although in most instances this effect was noted only after long-term treatment. Olanzapine was inferior to risperidone in improving WCST performance. Treatment with phenothiazines brought about improvement on two subtests while the results on three showed significant deterioration. CONCLUSION: The results obtained suggest that novel antipsychotics show differential effect on cognition, with risperidone especially improving working memory; however, their effect on negative symptoms and cognitive functions is better than that of typical neuroleptics.     

3种抗精神病药对精神分裂症认知功能的影响

目的:探讨阿立哌唑、利培酮和氯丙嗪对首发精神分裂症患者认知功能的影响。方法:56例首发精神分裂症患者分为阿立哌唑组(n=18)、利培酮组(n=24)和氯丙嗪组(n=14),在治疗前和治疗6周进行阳性与阴性症状量表(PANSS)评分,威斯康星卡片分类测验(WCST)、连线测验(A和B)、韦氏成人智力量表(WAIS)中的数字符号和数字广度(顺、逆)测验等神经心理测验。结果:治疗6周后,3组PANSS评分均明显下降,3组之间差异无显著性。阿立哌唑组和利培酮组各项认知功能指标均有不同程度的改善,而氯丙嗪组只有2项(WCST中持续反应数和数字广度测验)较治疗前显著好转。连线测验B阿立哌唑组显著优于利培酮组,其余各指标两组间差异无显著性。阿立哌唑组除WCST中持续反应数、完成分类数和数字广度测验外,其余各指标均显著优于氯丙嗪组;利培酮组除WCST中持续反应数外,其余各指标均显著优于氯丙嗪组。结论:阿立哌唑和利培酮对首发精神分裂症患者认知功能的改善作用相当,均显著优于氯丙嗪。     

阿立哌唑、利培酮及氯丙嗪对精神分裂症疗效及认知功能的影响

目的探讨非经典抗精神病药阿立哌唑、利培酮及传统抗精神病药氯丙嗪治疗精神分裂症的疗效及对认知功能的影响。方法将148例符合CCMD-3诊断标准的精神分裂症病人随机分为阿立哌唑组（48例）、利培酮组（52例）和氯丙嗪组（48例），观察12周，分别于治疗前及治疗后4、8、12周采用阳性症状与阴性症状量表（PANSS）、不良反应量表（TESS）评定疗效和不良反应；治疗前及治疗后12周采用韦氏成人记忆测检（WMS）及威斯康星卡片分类测验（WCST）测定。结果与治疗前比较，三组治疗后12周PANSS总分及各因子分显著下降（P〈0．01），但三组之间无显著差异；利培酮、氯丙嗪组的不良反应发生率高于阿立哌唑组（P〈0．05），主要表现为肌强直、震颤等锥体外系等不良反应；阿立哌唑、利培酮组WMS和WCST评分均有显著改善，而氯丙嗪组治疗前后则无差异。结论阿立哌唑、利培酮及氯丙嗪治疗精神分裂症均有效，且疗效相当，阿立哌唑所致锥体外系不良反应较少，阿立哌唑、利培酮对认知功能有改善作用，而氯丙嗪则对认知功能无影响。     

利培酮与氯氮平对精神分裂症患者认知功能影响的对照研究

目的：观察利培酮与氯氮平对精神分裂症患者认知功能的影响。方法：将80例精神分裂症住院患者随机分为两组,并分别予以利培酮与氯氮平治疗12周,于入组前及治疗结束时测查威斯康星卡片分类测验,韦氏记忆测验,阳性和阴性症状量表,并与正常人比较,借以分析两药对认知功能的影响。结果：两组间在威斯康星卡片分类测验,韦氏记忆测验,阳性和阴性症状量表中的认知因子分上并无显著性差异,治疗前后比较利培酮组（40例）在记忆,阳性和阴性症状量表中的认知因子分及威斯康星卡片分类测验中的完成分类数和概念的水平,其百分数有显著差异,而氯氮平组（33例）仅在阳性和阴性症状量表中的认知因子及威斯康星卡片分类测验中的概念水平,其百分数有显著差异,在威斯康星卡片分类测验中完成第一个分类的次数有增加趋势。结论：利培酮对认知功能障碍的治疗作用优于氯氮平。     

The effect of neuroleptic treatments on executive function and symptomatology in schizophrenia: a 1-year follow up study

Cognitive dysfunctions (as in memory, attention and executive function) have been recognized as fundamental features of schizophrenia. Executive dysfunction is a major obstacle to functional outcome, community functioning and rehabilitation success and it is crucial to assess the effects of so-called neuroleptic (NLP) medications in this domain of cognitive functioning. Risperidone, an atypical NLP, has been reported to improve executive function in schizophrenia (SZ), but there is controversy regarding these findings. The aim of the current study was to assess the differential effects of risperidone (2-6 mg) and conventional (2-40 mg haloperidol) NLPs on executive skills in 31 individuals with SZ over a 12-month period. The performance of both NLP groups was compared to the performance of 17 age- and education-matched healthy controls. In this randomized, double blind study, the Wisconsin Card Sorting Test (WCST) was administered at baseline, 3, 6, and 12 months after initiating medication. The relationship between executive functioning and the course of clinical symptoms, as assessed by the Positive and Negative Syndrome Scale (PANSS) was also investigated. Results showed that, relative to healthy controls, individuals with SZ showed marked impairment in WCST from baseline through 12 months of treatment. Also, participants under haloperidol or risperidone NLP medication performed similarly on the WCST at all assessment periods showing that risperidone and haloperidol do not differ in their effect on executive functioning. Risperidone treatment, however, was more effective in the reduction of negative symptoms. The differential efficacy of risperidone over negative symptoms and WCST performance strongly suggests that the executive impairments are to some extent the result of brain abnormalities independent of those that produce the major psychopathology manifestations seen in SZ.     

具阴性症状精神分裂症的病程与其认知功能改善的相关性分析

目的探讨具阴性症状的精神分裂症病人的病程与其认知功能改善的关系。方法对60例具阴性症状的精神分裂症病人在氯氮平或利培酮治疗前后进行阴性症状评定量表（SANS）、简明精神病评定量表（BPRS）评定精神症状;用Wisconsin卡片分类测验（WCST）,Wechsler记忆测验（WMS）、Wechsler成人智力量表（WMS—RC）评定认知功能;以及对病程与认知功能的改善程度进行比较和相关性分析。结果WMS理解量袭分的前后差值与病程为0—5年和病程为11—15年有显著差异（P〈0．05）,在WSCT测验中总测验数的差值与病程为0—5年、6—10年和11—15年比较有显著差异（P〈0．05）,持续错误数的改善在病程为6—10年和11—15年两个组,有显著差异（P〈0．05）;WAIS—RC和WMS前后的差值与病程元相关性（P〉0．05）。结论具阴性症状的精神分裂症的部分认知功能改善程度与病程有关。     

利培酮合并赛来昔布治疗对精神分裂症首次发病患者认知功能的影响

目的 探讨利培酮合并赛来昔布对精神分裂症首发患者认知功能的影响.方法 符合美国精神障碍诊断与统计手册第4版诊断标准的精神分裂症首次发病(以下简称首发)住院患者90例,随机分到利培酮+赛来昔布组(研究组,46例)或利培酮+空白剂组(对照组,44例),观察治疗时间均为12周.认知功能评定使用阳性和阴性症状量表、汉密尔顿抑郁量表、威斯康星卡片分类(WCST)、重复性神经心理测查系统(RBANS).结果 治疗第12周末,研究组PANSS总分及分量表分低于对照组(P均＜0.05);研究组HAMD评分低于对照组;两组患者RBANS测验总分及部分分量表评分均较基线明显提高,差异均有统计学意义(P均＜0.05);WCST部分因子分均较基线有明显改善,差异均有统计学意义(P均＜0.05);两组间各量表评分的差异均无统计学意义(P均＞0.05).研究组男性患者的延时记忆量表分明显高于女性患者,差异有统计学意义(F=4.8;υ=1.0,38;P=0.03),且临床症状的改善与认知功能的提高存在显著相关性(P＜0.05).结论 利培酮具有改善首发精神分裂症患者认知功能的作用;赛来昔布对男性患者的延时记忆有改善作用.     

氯氮平和维思通对精神分裂症认知功能的影响

目的：比较氯氮平和维思通对精神分裂症对知功能的影响,以阴性症状为主。方法对５７例接受氯氮平或维思通治疗的精神分裂症病人,采用韦氏记忆量表,数字划销测验、威斯康星卡片分类测验评估其治疗前和治疗８周后记忆、注意及执行功能。结果氯氮平和维思通能显著改善记忆,注意及执行功能,氯氮平对以阳性症状为主分裂症的注意改善优于维思通,维思能对以阴性症状为主分裂症图片成绩优于氯氮平,结论两种药物均有助于改善精神分理解     

抗精神病药对精神分裂症患者认知功能的影响

目的：比较利培酮和氯氮平对精神分裂症患者认知功能的影响。方法：对58例精神分裂症患者随机分成两组,分别给予利培酮、氯氮平治疗8周。治疗前和治疗8周末分别进行简明精神病评定量表(BPRS)、韦氏成人记忆量表修订本(WMS-RC)、威斯康星卡片分类测验(WCST)和数字划销测验(CT)评定,比较利培酮和氯氮平对精神分裂症患者认知功能的影响。结果：两组8周后,各项检查项目均有显著好转。结论：利培酮和氯氮平均能改善精神分裂症患者的认知功能。     

精神分裂症认知障碍及其与阴性阳性症状的关系

目的 探索精神分裂症认知障碍特点及其与阴性阳性症状之间的关系。方法 比较32例从未用过抗精神病药或停药2周以上的精神分裂症患者以及15例健康受试者的事件相关电位(ERPs)和威斯康星卡片分类测验成绩(WCST),并进行相关分析。结果 与正常受试者比较,多个位点N2和P3波潜伏期延长,P3波幅降低。WCST中分类完成数偏少,持续错误数和总错误数增加。N2潜伏期和波幅与PANSS阳性症状分呈负相关,而WCST总错误数与PANSS总分和阴性症状总分正相关。结论精神分裂症病人存在中枢信息处理障碍,认知障碍与阴性阳性症状之间具有一定的内在联系。     

Does risperidone act better in schizophrenic patients who have a family or obstetric history?

Purpose: The aim of the study was to assess the effect of treatment with risperidone on psychopathological symptoms and cognitive deficits in schizophrenic patients, in relation to family history, obstetric complications and duration of the illness. Methods: Fifty schizophrenic inpatients (29 males, 21 females), aged 16–50 (mean 28 years), with duration of the illness 1–15 (mean 4 years) who successfully completed a 3-month risperidone treatment were included into the study. Family history of psychiatric illness and the presence of obstetric complications were estimated by a semistructured questionnaire. Schizophrenic symptoms were assessed using the Positive and Negative Symptoms Scale (PANSS). Cognitive abilities were measured by neuropsychological “frontal lobe” tests: Trail Making Test (TMT), part B, Stroop Color Word Interference Test, part B, and Wisconsin Card Sorting Test (WCST). The clinical and neuropsychological evaluation was performed before and after 3 months of risperidone treatment, in doses 2–6 mg (mean 4.2 mg/day). Results: Before treatment, patients with family history had significantly higher intensity of negative symptoms, and obtained worse results on WCST perseverative errors (PE) and correct categories (CC). These measures were also impaired in subjects with obstetric complications. Additionally, in patients with obstetric complications, total and general PANSS psychopathology was higher and the results of Stroop B were worse. After a 3-month treatment with risperidone, no difference between respective groups was observed both in psychopathology and in neuropsychological tests. Patients with obstetric complications had higher degree of improvement on positive and negative symptoms and on TMT-B than the remaining ones. Patients with longer duration of the illness had less improvement on positive symptoms with risperidone treatment. Conclusions: The results of this study show that treatment with risperidone results in better compensation of psychopathological (negative symptoms) and neuropsychological (working memory) deficits in patients who have a family history and/or obstetric complications. This may be due to a favourable effect of risperidone on the prefrontal cortex dysfunction mediating these deficits.     

Added ondansetron for stable schizophrenia: a double blind, placebo controlled trial

It is well documented that 5-hydroxytryptamine3 (5-HT3) receptors are involved in the pathogenesis of schizophrenia and cognitive impairment. The purpose of this study was to assess the efficacy of ondansetron, a 5-HT3 receptor antagonist as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments. This investigation was a 12-week, double blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments. All participants met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive ondansetron (8 mg/day) or the placebo in addition to risperidone. Clinical psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a cognitive battery. Patients were assessed at baseline and after 8, and 12 weeks after the medication started. The PANSS scores and cognitive performance were used as the outcome measures. The ondansetron group had significantly greater improvement in the negative symptoms, general psychopathological symptoms and PANSS total scores over the trial. Administration of ondansetron significantly improved visual memory based on improvement on visual reproduction, visual paired associate and figural memory sub tests of Wechsler Memory Scale--Revised. The present study indicates ondansetron as potential adjunctive treatment strategy for chronic schizophrenia particularly for negative symptoms and cognitive impairments.     

Risperidone treatment of schizophrenia: improvement in psychopathology and neuropsychological tests

The aim of the study was to assess the effects of short-term risperidone treatment on schizophrenic symptoms and on neuropsychological frontal tests, and to find an association between the improvements in these two kinds of domains. Twenty-two schizophrenic patients treated with risperidone (2-6 mg/day) for 4 weeks were studied. Treatment with risperidone resulted in a significant decrease in the intensity of schizophrenic symptoms and in an improvement in all neuropsychological tests applied. A robust correlation was obtained between the amelioration of negative symptoms and improvements in many neuropsychological tests, specifically with amelioration in the Wisconsin Card Sorting Test (WCST), perseverative errors. Some correlation was also found with the improvement of positive symptoms, specifically with amelioration in the WCST, completed categories. The results may suggest a common neurobiological substrate of negative and cognitive symptoms, reflected in prefrontal cortex pathology and in therapeutic response to atypical antipsychotics.     

吸烟对利培酮治疗首发精神分裂症疗效、认知功能的影响

目的探讨吸烟对利培酮治疗首发精神分裂症的疗效和认知功能的影响。方法选择符合美国精神障碍诊断与统计手册第4版（DSM-IV）诊断标准的首发精神分裂症住院患者90例,其中吸烟患者27例,非吸烟患者63例,均使用利培酮治疗。详细收集临床资料,使用住院患者烟草使用状态调查表对患者吸烟状况进行详细调查,使用阳性和阴性症状量表（PANSS）评定基线时及治疗12周末的临床症状;威斯康星卡片分类（WCST）、重复性神经心理测查系统（RBANS）对患者在基线时及治疗12周末进行认知功能的检测,分别对吸烟组和非吸烟组的患者治疗前、后临床症状和认知功能变化值进行比较。结果基线时吸烟组患者PANSS总分（91.3±20.9）vs.（80.6±17.2）、阴性症状量表分（20.7±8.6）vs.（17.4±6.3）、一般精神病理症状量表分（43.4±12.3）vs.（38.2±10.8）均高于非吸烟组（均P〈0.05）;非吸烟组的正确应答数高于吸烟组（50.6±18.2）vs.（42.2±14.3）,P〈0.05,而错误应答数低于吸烟组（75.5±21.9）vs.（85.3±15.8）,P〈0.05。治疗12周末,吸烟组患者阴性症状减分值为（12.2±10.4）,非吸烟组（6.1±5.8）两组比较有显著性差异（t=2.7,P〈0.05）;吸烟组患者WCST中完成测查总应答数、错误应答数以及学习到学会的改善值显著高于非吸烟组,差异有统计学意义（t分别为-2.2、-2.1、2.0;P均〈0.05）;RBANS总分及各分量表分的增分值在两组之间差异不显著,无统计学意义（P均〉0.05）。结论吸烟患者临床症状、认知功能受损程度重于非吸烟患者;但是吸烟患者阴性症状、认知功能在治疗后的改善明显好于非吸烟患者。     

利培酮与氯丙嗪对精神分裂症认知功能的影响

目的：比较利培酮和氯丙嗪对首发精神分裂症患者认知功能的影响。方法：将符合入组标准的首发精神分裂症62例随机分为利培酮组与氯丙嗪组,分别进行8周系统治疗,用阳性与阴性症状量表（PANSS）、韦氏成人智力量表（WAIS－RC）、数字划销试验（CT）和临床记忆量表（CMS）进行检查,评估其疗效和对认知功能的影响。结果：脱落3例,59例患者在8周治疗后PANSS总分明显下降,但两组之间差异无显著性。利培酮组的WAIS－CT、CMS总分均明显高于氯丙嗪组,差异有显著性。结论：利培酮对首发精神分裂症患者认知功能的影响明显好于氯丙嗪。     

首发精神分裂症的认知功能与阴,阳性症状和抗精神病药物效应的关系

目的 探讨首发精神分裂症认知功能与阴、阳性症状和抗精神病药物效应的关系。方法 对７８例精神分裂症患者给予氯丙嗪或氯氮平治疗,于治疗前及治疗１２周末各作一次Ｗｉｓｃｏｎｓｉｎ卡片分类测验（ＷＣＳＴ）、韦氏成人智力量表（ＷＡＩＳＲ）、韦氏记忆量表（ＷＭＳ）、语言流利性测验等。另外,４５例正常人也做了上述测验。结果 首发精神分裂症患者存在广泛的认知功能障碍,上述则查结果均较正常对照组差,尤以ＷＣＳＴ明显     

Study of positive and negative feedback sensitivity in psychosis using the Wisconsin Card Sorting Test

BackgroundSchizophrenia involves marked motivational and learning deficits that may reflect abnormalities in reward processing. The purpose of this study was to examine positive and negative feedback sensitivity in schizophrenia using computational modeling derived from the Wisconsin Card Sorting Test (WCST). We also aimed to explore feedback sensitivity in a sample with bipolar disorder.MethodsEighty-three individuals with schizophrenia and 27 with bipolar disorder were included. Demographic, clinical and cognitive outcomes, together with the WCST, were considered in both samples. Computational modeling was performed using the R syntax to calculate 3 parameters based on trial-by-trial execution on the WCST: reward sensitivity (R), punishment sensitivity (P), and choice consistency (D). The associations between outcome variables and the parameters were investigated.ResultsPositive and negative sensitivity showed deficits, but P parameter was clearly diminished in schizophrenia. Cognitive variables, age, and symptoms were associated with R, P, and D parameters in schizophrenia. The sample with bipolar disorder would show cognitive deficits and feedback abnormalities to a lesser extent than individuals with schizophrenia.ConclusionNegative feedback sensitivity demonstrated greater deficit in both samples. Idiosyncratic cognitive requirements in the WCST might introduce confusion when supposing model-free reinforcement learning. Negative symptoms of schizophrenia were related to lower feedback sensitivity and less goal-directed patterns of choice.     

利培酮与氯氮平治疗首发精神分裂症对认知功能的影响

目的 比较利培酮和氯氮平对首发精神分裂症患者认知功能的影响。方法 将符合入组标准的首发精神分裂症患者77例随机分为利培酮组与氯氮平组,分别进行8周系统治疗,用阳性与阴性症状量表(PANSS)、韦氏成人智力量表(WAIS-RC)、数字划销试验(CT)和临床记忆量表(CMS)进行检查,评估其疗效和对认知功能的影响。结果 脱落4例,73例患者在8周治疗后PANSS总分明显下降(P<0.01),两组之间差异无显著性(P>0.05)。利培酮组的WAIS-RC、CT、CMS总分均明显高于氯氮平组,差异有显著性(P<0.05～0.01)。结论 利培酮对首发精神分裂症患者认知功能的影响明显好于氯氮平。