精神分裂症患者与其健康同胞的注意和执行功能障碍的对照研究

目的　探讨精神分裂症患者及其健康同胞的注意、工作记忆 /执行功能的特点。方法对 5 0例精神分裂症患者 (患者组 )及其健康同胞 5 0名 (同胞组 ) ,以及 4 5名正常对照者 (正常对照组 )采用威斯康星卡片分类测验 (WCST)和持续操作测验 (CPT) ,评估注意、工作记忆 /执行功能。结果　(1)在WCST中 ,患者组及其同胞组的总测验次数 (分别为 83 4± 2 3 2和 74 1± 2 4 6 )、持续错误数 (分别为 2 5 8± 11 7和 2 2 8± 10 7)、随机错误数 (33 4± 19 2和 2 5 9± 17 1)均高于正常对照组 (分别为6 0 0± 2 1 6、14 8± 8 3和 18 1± 16 0 ;P <0 0 1)。 (2 )在CPT中 ,患者组的评分 [(2 8 4± 4 0 )分 ]低于同胞组 [(30 4± 2 3)分 ]和正常对照组 [(30 9± 2 8)分 ],而同胞组与正常对照组的差异无显著性(P >0 0 5 )。(3)患者组及其同胞组发生执行功能障碍 (分别为 2 9例和 2 5例 )和注意缺陷 (分别为 2 2例和 7例 )的例数均多于正常对照组 (分别为 9例和 4例 ;P <0 0 1) ,其中有工作记忆 /执行功能缺陷的精神分裂症患者 ,其同胞出现这一缺陷的比率 (6 6 % )高于无缺陷的精神分裂症患者的同胞 (2 8% )。(4)WCST中的持续错误数与文化程度呈负相关 (r =- 0 32 ,P <0 0 1) ,CPT与性别 (r=- 0 2     

Executive control of working memory in schizophrenia

There is considerable evidence that working memory impairment is a common feature of schizophrenia. The present study assessed working memory and executive function in 54 participants with schizophrenia, and a group of 54 normal controls matched to the patients on age, gender and estimated premorbid IQ, using traditional and newer measures of executive function and two dual tasks-Telephone Search with Counting and the Memory Span and Tracking Task. Results indicated that participants with schizophrenia were significantly impaired on all standardised measures of executive function with the exception of a composite measure of the Trail Making Test. Results for the dual task measures demonstrated that while the participants with schizophrenia were unimpaired on immediate digit span recall over a 2-min period, they recalled fewer digit strings and performed more poorly on a tracking task (box-crossing task) compared with controls. In addition, participants with schizophrenia performed more poorly on the tracking task when they were required to simultaneously recall digits strings than when they performed this task alone. Contrary to expectation, results of the telephone search task under dual conditions were not significantly different between groups. These results may reflect the insufficient complexity of the tone-counting task as an interference task. Overall, the present study showed that participants with schizophrenia appear to have a restricted impairment of their working memory system that is evident in tasks in which the visuospatial sketchpad slave system requires central executive control.     

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test

The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophrenia-specific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.     

Declarative memory and WCST-64 performance in subjects with schizophrenia and healthy controls

The Wisconsin Card Sorting Test (WCST) is a set-switching task used extensively to study impaired executive functioning in schizophrenia. Declarative memory deficits have also been associated with schizophrenia and may affect WCST performance because continued correct responding depends on remembering the outcome of previous responses. This study examined whether performance in visual and verbal declarative memory tasks were associated with WCST performance. Subjects comprised 30 patients with schizophrenia or schizoaffective disorder (SCZ) and 30 demographically matched healthy controls (CON) who were tested on the WCST, the Benton Visual Retention Test (BVRT), the California Verbal Learning Test (CVLT), and the Continuous Performance Test (CPT). SCZ subjects showed significant correlations between visual and verbal declarative memory and performance on the WCST-64 that were in the hypothesized direction such that worse memory performance was associated with worse performance on the WCST. CON subjects did not show a significant relationship between visual or verbal memory and WCST-64 performance. Fisher's r to z transformations indicated that the associations between declarative memory and WCST-64 performance in the SCZ subjects differed significantly from those of CON subjects. The findings suggest that interpretations of WCST-64 scores for subjects with schizophrenia should be considered in light of their declarative memory functioning.     

Comparative effects of risperidone and olanzapine on cognition in elderly patients with schizophrenia or schizoaffective disorder

OBJECTIVE: To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder. METHOD: One hundred seventy-six elderly inpatients and outpatients with schizophrenia or schizoaffective disorder were enrolled in this multicenter, double-blind trial. After their antipsychotic medications were tapered for 1 week, patients were randomly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks. Performance on the Continuous Performance Test (CPT), Serial Verbal Learning Test (SVLT), TMT (Trail Making Test) Parts A and B, Wisconsin Card Sorting Test (WCST), and Verbal Fluency Examinations (VFE) was assessed at baseline and at end point. RESULTS: Patients in the risperidone group had improved scores on at least one test of attention, memory, executive function, and verbal fluency, and those in the olanzapine group had improved scores on at least one test of attention and memory function. Scores on the TMT Part B, WCST total errors (executive function domain), and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group. No significant differences in change scores between the two groups were found. Higher baseline scores on each test predicted more improvement at endpoint. CONCLUSIONS: Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder. Consistent with research in younger populations, these improvements occur in aspects of cognitive functioning related to functional outcome.     

Cognitive deficits in early-onset schizophrenia spectrum patients and their non-psychotic siblings: a comparison with ADHD

BACKGROUND: Previous research has shown cognitive deficits in patients with schizophrenia spectrum disorders in the areas of executive function, verbal memory and attention. Subtle deficits have been shown in healthy first-degree relatives of patients, suggesting that they may be trait markers. The specificity of these markers for schizophrenia compared with another neurodevelopmental disorder, Attention Deficit Hyperactivity Disorder (ADHD) has not been reliably established. METHODS: The Rey Auditory Verbal Learning Test (RAVLT), Hayling Sentence Completion Test (HSCT), FAS Test of orthographic verbal fluency (FAS) and Continuous Performance Test-Identical Pairs (CPT-IP) were administered to adolescent schizophrenia spectrum patients (SZ; n=30), adolescent siblings of schizophrenia spectrum patients (SZ-SIB; n=36), healthy control participants (HC; n=72); a neurodevelopmental comparison group of adolescents with ADHD (n=27). RESULTS: The SZ group were impaired on all measures. The SZ-SIB group were impaired on IQ, immediate recall (RAVLT), target sensitivity (CPT-IP), response initiation (HSCT); error rates for the FAS and HSCT. There were no significant differences between the SZ-SIB and ADHD groups on individual measures of cognitive function. Principal Components Analysis revealed four factors on which further analyses were conducted. The SZ-SIB and ADHD groups showed different profiles of impairment on components related to response initiation and sustained attention/vigilance when each was compared with the HC group. CONCLUSIONS: Deficits in intellectual function, verbal memory and response initiation/inhibition were found in the SZ-SIB group indicating that these are markers of risk for schizophrenia. Subtle differences in profiles of impairment in the SZ-SIB and ADHD groups on composite measures of attention and response initiation require further investigation.     

Spatial working memory performance in patients with schizoaffective psychosis versus schizophrenia: a tale of two disorders?

We explored the relationship between schizophrenia and schizoaffective disorder by comparing the two patient groups in terms of their performance on measures of executive functioning (spatial working memory and Wisconsin Card Sorting Test). Patients with schizophrenia (N=34) and those with schizoaffective disorder (N=23) performed significantly poorer than community controls (N=30). However, the schizoaffective and schizophrenia groups did not differ from each other in terms of working memory accuracy or mean response latencies. Similarly, the two patient groups did not differ in terms of the number of categories achieved or number of perseverative errors on the Wisconsin Card Sorting Test. Among the patients, working memory accuracy was associated with number of WCST perseverative errors and number of categories achieved, though working memory performance was not associated with number of WCST nonperseverative errors. These findings indicate that both schizophrenia and schizoaffective disorder are associated with executive functioning deficits. The findings are discussed in the context of the ongoing debate regarding the conceptualization of schizoaffective disorder.     

精神分裂症认知功能损害与病程的关系

目的：探讨精神分裂症认知功能损害的程度与病程关系。方法;分别用韦氏记忆测验,数字划销测验和威斯康星卡片分类测验评估27例急性精神分裂症病人和31例慢性精神分裂症病人的记忆、注意和执行功能。结果：注意损害随病程的延长而加重,记忆和执行功能损害与病程无关。     

Schizophrenic subjects show deficient inhibition but intact task switching on saccadic tasks.

BACKGROUND: Schizophrenic patients have executive function deficits, presumably on the basis of prefrontal cortex dysfunction. Although they consistently show impaired inhibition, the evidence of a task switching deficit is less consistent and is often based on performance of neuropsychological tests that require several cognitive processes (e.g., the Wisconsin Card Sort Test [WCST]). We investigated inhibition and task switching using saccadic tasks to determine whether schizophrenic patients have selective impairments of these executive functions. METHODS: Sixteen normal and 21 schizophrenic subjects performed blocks of randomly mixed prosaccade and antisaccade trials. This gave rise to four trial types: prosaccades and antisaccades that were either repeated or switched. Response accuracy and latency were measured. Schizophrenic subjects also performed the WCST. RESULTS: Schizophrenic subjects showed abnormal antisaccade and WCST performance. In contrast, task switching was normal and unrelated to either antisaccade or WCST performance. CONCLUSIONS: The finding of intact task switching performance that is unrelated to other measures of executive function demonstrates selective rather than general impairments of executive functions in schizophrenia. The findings also suggest that abnormal WCST performance is unlikely to be a consequence of deficient task switching. We hypothesize that inhibition and task switching are mediated by distinct neural networks, only one of which is dysfunctional in schizophrenia.     

The relationships of positive and negative symptoms with neuropsychological functioning and their ability to predict verbal memory in psychotic major depression

Neuropsychological functioning, in relation to positive and negative symptoms in psychotic major depression (PMD), has not been as thoroughly studied as it has been in schizophrenia. Thus, the current study investigated the associations between positive and negative symptoms with cognitive functioning, with an emphasis on verbal memory in PMD. Attention, working memory, and the executive functioning domains were analyzed among 49 PMD participants. Positive symptoms did not correlate significantly with any measures of verbal memory but did correlate with one measure of attention, working memory, and executive functioning. Negative symptoms correlated significantly with two California Verbal Learning Test-II (CVLT-II) measures of verbal memory and three measures of executive function. Hierarchical regressions were conducted to determine if negative symptoms could predict verbal memory performance after controlling for depression. Of the two verbal memory measures, negative symptoms significantly explained additional variance for CVLT Recognition, but not for CVLT Trials 1-5 total score. Our results provide some evidence that, consistent with the schizophrenia literature, negative symptoms contributed more to verbal memory deficits in PMD than positive symptoms, regardless of depression severity.     

Dimensions of working memory dysfunction in schizophrenia

The aim of this study was to investigate the underlying structure of eight working memory tests used to assess prefrontal dysfunction in schizophrenia research [Letter-Number Span (LNS), Digit-Symbol Test (DST), Trail-Making Test B (TMT-B), Delayed Response Task (DRT) for spatial working memory, Subject Ordered Pointing Task (SOPT), Dual Tasking (DUAL), Continuous Performance Test (CPT)-Identical Pairs, Wisconsin Card Sorting Test (WCST)]. Sixty-six patients with schizophrenia showed significant working memory performance deficits in all tests when compared with 45 healthy controls. Performance was not systematically related to psychopathology. When differences in IQ were controlled, working memory deficits remained stable except in the WCST. Principal components analyses yielded three components for healthy controls: a comparator function of the central executive defined by a comparison of working memory content with information from the environment, an allocation of attentional resources function, and a maximum storage capacity function. The comparator and maximum storage functions could be replicated in the schizophrenia sample. However, the allocation function did not emerge as an independent component and was replaced by a component defined by the WCST. These findings suggest that working memory is not a unitary concept but rather should be conceptually differentiated as functions of transient storage/active rehearsal capacity and central executive manipulation supporting a previous suggestion proposed by Perry et al. [Schizophr. Bull. 27 (2001) 157].     

Self-monitoring enhances Wisconsin Card Sorting Test performance in patients with schizophrenia: performance is improved by simply asking patients to verbalize their sorting strategy.

Patients with schizophrenia have Wisconsin Card Sorting Test (WCST) deficits, which are commonly interpreted as reflecting frontal cortex-based executive dysfunction. One means of assessing the refractoriness of frontal-executive impairment is to utilize a training or modification strategy to improve WCST performance. In this study, 73 patients with schizophrenia were assigned to 1 of 2 groups. Group 1 received the standard WCST instructions for 64 cards (Condition 1). For the second 64-card deck, the patients were asked to verbalize the reason that they placed the card where they did after each sort (Condition 2). Group 2 received this modified instruction 1st (Condition 1) and then the standard instructions for the second deck (Condition 2). A group of normal comparison participants was also tested using standard instructions alone. Group 2 committed significantly fewer perseverative responses than did Group 1. Furthermore, there was no significant difference between Group 2 (Condition 1) and the normal participants. Group 1's performance improved when patients were exposed to the modified instructions (Condition 2). Additionally, poor premorbid factors and disorganized symptoms were associated with decreased benefit from the modified instructions across both groups. Cumulatively, these data suggest that a simple instruction may enhance executive function and impact WCST performance in patients with schizophrenia.     

Relationship of affect recognition with psychopathology and cognitive performance in schizophrenia.

The purpose of the present study was to explore the relationship between emotion perception and both psychopathology and cognitive functioning in a group of Greek patients with schizophrenia. Thirty-five patients with schizophrenia were assessed with computerized tests of emotion perception, using visual faces (Kinney's Affect Matching Test, KAMT), prosody (Affective Prosody Test, APT), and visual everyday scenarios (Fantie's Cartoon Test, FCT), as well as a facial recognition test (Kinney's Identity Matching Test, KIMT). The patients were also evaluated with the symptoms dimensions derived from the PANSS (positive, negative, cognitive, depression, and excitement) and a battery of neuropsychological tests measuring executive functions, attention, working memory, verbal and visual memory, visuospatial ability, and visual scanning/psychomotor speed. The three emotion perception and face recognition tests correlated significantly with each other. The KAMT was significantly related to the cognitive symptoms dimension of the PANSS and executive functions. The FCT was significantly related to level of education and attention. Finally, the APT was significantly related to the cognitive symptoms dimension, executive functions, and attention. Our findings regarding the significant relationships of affect perception, both facial and vocal, as well as in everyday scenarios, with several cognitive abilities support the notion that deficits in decoding affective information in schizophrenia could be attributed to impairment in more basic neurocognitive domains.     

Wisconsin Card Sorting Test deficits in schizotypic individuals

The present study investigates executive functioning in schizotypic college students and control subjects using the Wisconsin Card Sorting Test (WCST). Inhibitory control and working memory, two aspects of executive functioning, were examined in deviantly high scorers on the Perceptual Aberration and Magical Ideation Scales (n=97), high scorers on the revised Social Anhedonia Scale (n=58), and in control subjects (n=104). The schizotypic groups displayed significantly more perseverative errors and achieved fewer categories than the control group. The two schizotypic groups did not differ from each other. We identified a subset of schizotypic individuals who also produced clinically deviant WCST profiles. The findings support the hypothesis that executive function deficits may precede the onset of schizophrenia and related illnesses.     

Educational level and age influence spatial working memory and Wisconsin Card Sorting Test performance differently: a controlled study in schizophrenic patients

The influence of educational level and age on executive function, as evaluated by the Wisconsin Card Sorting Test (WCST), and 'working memory,' as evaluated by means of a visual-manual delayed-response task, has been investigated in 25 schizophrenic patients and 35 healthy controls matched for age. Different patterns of correlations between educational level, age and cognitive variables were seen for the 'working memory' task but not for the WCST. No significant correlations between the WCST and the 'working memory' task indexes have been observed. Based on multivariate analyses, poor performance of schizophrenic patients on working memory and executive function tasks was observed; after covarying for the educational level, group differences were no longer significant for executive functions, but the difference in 'working memory' performance persisted. The implications of sociodemographic variables as well as the role of statistical manipulation are evaluated and their differential impact on 'working memory' and executive functions is proposed in further support of these neurocognitive constructs that may be dissociable.     

Cognitive functioning related to quality of life in schizophrenia

The present study compared the cognitive function of patients with schizophrenia to that of healthy subjects, and investigated the relationships between cognitive function and quality of life (QOL). Participants consisted of 53 patients meeting DSM-IV criteria for schizophrenia and 31 normal controls. All participants completed a neuropsychological test battery assessing executive function, verbal memory, and social knowledge. QOL was rated using the Schizophrenia Quality of Life Scale. Patients with schizophrenia showed lower performance across various cognitive measures of memory, including the Sentence Memory Test, the Verbal Learning Test, and the Script Test, as well as the Rule Shift Cards Test of executive function. Multiple regression analyses were used to evaluate the neuropsychological measures and clinical symptoms to predict QOL. The QOL total score, the social initiative score or the empathy score were significantly predicted by the Script or/and the Sentence Memory. Neuropsychological functioning was unrelated to most QOL scores in the presence of clinical symptoms, while ability of empathy in the QOL was predicted by performance of the Sentence Memory Test. These results demonstrated patients with schizophrenia have deficits in executive function, memory and learning, and social knowledge, and that social knowledge and memory are related to QOL. Thus, in patients with schizophrenia, deficits in social knowledge appear to be associated with current QOL in general, and specifically with the capacity for empathy and social initiative.     

Effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on executive function in schizophrenia

BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with both overall schizophrenia risk and severity of negative symptoms. This study examined whether schizophrenia patients homozygous for the risk allele (T/T) exhibit greater impairment in executive function, and determined the extent to which MTHFR's effects on negative symptoms underlie this relationship. METHODS: 200 outpatients with chronic schizophrenia were evaluated with the Verbal Fluency Test (VFT), Wisconsin Card Sort Test (WCST), and California Verbal Learning Test (CVLT). Performance was stratified by MTHFR C667T genotype. Path analysis determined the extent to which MTHFR effects on negative symptoms mediated the relationship between genotype and cognitive measures. RESULTS: T/T subjects exhibited significantly greater deficits on the VFT and had more difficulty achieving the first category on the WCST. Genotype groups did not differ in CVLT performance. C677T effects on negative symptoms contributed to, but did not fully account for, genotype effects on VFT. Negative symptoms did not mediate WCST performance. CONCLUSIONS: MTHFR C677T genotype contributes to certain executive function deficits in schizophrenia. These deficits remained significant when taking into account mediating effects of negative symptoms. Although the intermediate mechanisms for C677T effects remain uncertain, these results suggest that MTHFR-related cognitive impairment and negative symptoms reflect differing neural substrates.     

A comparison of remediation techniques on the Wisconsin Card Sorting Test in schizophrenia

A wealth of evidence has revealed that deficits on a commonly used measure of executive-function, the Wisconsin Card Sorting Test (WCST), can be improved through a variety of methods of instruction in patients with schizophrenia. Relatively little is known however, which of these remediation methods produce strongest and most durable effects and whether these effects generalize to other, untrained executive-function measures. Two of the most commonly studied methods for remediation on the WCST, step-by-step didactic instruction on the task and utilization of self-monitoring strategies, have both been shown to improve WCST performance, yet have never been directly compared. Thirty-four participants with schizophrenia were randomly assigned to one of three experimental conditions: Condition A consisted of didactic training which incorporated a detailed account of changing sorting principles throughout the test; Condition B consisted of a self-monitoring strategy that required that participants verbalize their strategies out loud after each card sort; Condition C was a non-trained control group that received the same outcome assessments as the two training groups at identical time intervals without intervening training. Patients were assessed with the WCST and two other executive-function tests immediately prior to training, immediately after training and at a 1-month follow-up. Results revealed: (1) participants assigned to the didactic and self-monitoring conditions made significant gains on the WCST relative to a no-intervention control condition; (2) the effects of self-monitoring, but not didactic training, were evident at a one-month follow-up; and (3) only participants assigned to the self-monitoring condition showed generalization to a second, non-trained measure of executive-function. The significance of these results for implementation of strategies for comprehensive and sustained programs of remediation are discussed.     

Generalization of training effects in schizophrenia

The primary goal of this study was to investigate transfer of training (generalization) in patients with schizophrenia. We randomly assigned 33 schizophrenia subjects to one of three conditions: training on the Wisconsin Card Sort Test (WCST-T), training on the Halstead Category Test (CAT-T), or no training (No-T). The WCST and CAT were administered to all subjects at baseline. Subjects in the WCST-T and CAT-T groups then received training on the respective test, while the No-T group received additional untrained trials. All participants were subsequently retested on the WCST and CAT, and completed a brief neuropsychological battery. As hypothesized, the WCST-T and CAT-T groups exhibited large improvements on the trained test and moderate improvement on the untrained test, while the No-T group failed to show improvement on either test. These results suggest that the training paradigm did produce generalization, and that the changes were not due to practice effects. The extent of generalization across both training groups was strongly associated with neuropsychological test performance (Spearman's rho=0.56, P<0.05). The implications of these findings for rehabilitation programs were discussed, and recommendations were made for future research.     

Learning proficiency on the Wisconsin Card Sorting Test in people with serious mental illness: what are the cognitive characteristics of good learners?

Although it is widely accepted that schizophrenia and other serious mental illnesses (SMI) are associated with neurocognitive difficulties, there is great variability in neurocognitive functioning across individuals. In recent years, a growing number of schizophrenia studies have utilized the concept of learning potential to explore individual variation in cognition. Learning potential refers to the ability to benefit from instruction and is measured by assessing test performance before and after training. The present study was intended to explore the cognitive characteristics associated with learning potential in people with serious mental illness. Sixty individuals with schizophrenia, bipolar or major (unipolar) depression completed a learning potential assessment using the Wisconsin Card Sorting Test (WCST) and a battery of standard cognitive measures. Based on established criteria for WCST learner subgroups, participants were categorized as high achievers, learners or non-retainers. There were several significant cognitive differences among the three learner subgroups. Most notably, individuals who were categorized as learners on the WCST showed significantly better verbal and working memory compared to non-retainers. Secondary analyses revealed that the three SMI diagnostic groups (depression, bipolar, schizophrenia) were similar in learning potential and did not differ on any of the standard cognitive measures. This study provides support for learning potential classification in schizophrenia as well as other serious mental illnesses, and indicates that learning potential may specifically be related to verbal and working memory abilities.