Wisconsin Card Sorting Test deficits in chronic paranoid schizophrenia. Evidence for a relatively discrete subgroup?

Some, although not all, researchers have reported dramatically increased numbers of perseverative responses on the Wisconsin Card Sorting Test (WCST) in schizophrenic patients compared to normal comparison subjects. The current study was designed to further explore the nature of possible WCST deficits in a group of paranoid schizophrenic patients compared to normal and psychiatric comparison subjects. In the current study, schizophrenic patients had significantly greater numbers of perserverative responses on the WCST than the comparison groups. The sample of patients with schizophrenia appeared to be characterized by a non-Gaussian distribution of perseverative responses on the WCST. WCST-impaired and WCST-nonimpaired schizophrenic subgroups were compared on cognitive and symptom measures, and increased perseverative responding was associated with negative symptoms, slowed reaction time, and more hospitalizations. While additional research is necessary to further investigate hypotheses of frontal versus generalized brain dysfunction in schizophrenic patients, WCST impairment seems to be present in a clinically meaningful subgroup of paranoid schizophrenic patients.     

50岁以上精神分裂症患者的认知特征

目的：探讨50岁以上精神分裂症患者的认知损害特征及其影响因素。方法：对60例50岁以上精神分裂症患者和40例正常人进行了威斯康星卡片分类测验（WCST）、韦氏成人智力量表（WAIS－R）、韦氏记忆量表（WMS）、语言流利性测验（LF）、手指敲击测验（FTT）、简明精神病评定量表（BPRS）及阴性症状评定量表（SANS）等测查。结果：患者组的所有认知测查结果均较正常人显著减退,且年龄、病程、阴性症状及亚型对患者认知功能有显著影响。结论：年龄较大、病程较长、阴性症状较重及非偏执型的精神分裂症患者认知缺损严重。     

Schizophrenia and performance on the Wisconsin Card Sorting Test (WCST): deficits and rehabilitation]

In recent years, there has been a sustained interest in the so-called "frontal hypothesis" of schizophrenia: the idea that clinical symptoms and cognitive deficits characteristic of schizophrenia might be explained by defective function of the frontal lobes. Several studies have attempted to test this hypothesis by examining the performance of schizophrenic subjects on the Wisconsin Card Sorting Test (WCST), a neuropsychological evaluation widely believed to reflect the functional capacity of frontal lobes. A typical finding is that schizophrenic patients demonstrate a tendency to perseverate in producing an inappropriate response in spite of negative feedback. This perseverative tendency resembles the perseveration often seen in patients with frontal brain damage. This article proposes a critical examination of the available evidence linking frontal deficits with schizophrenia via the WCST. As we will show, in most of these studies, only a relatively small number of the available measures on the WCST are made, and consequently many interesting cognitive capacities in schizophrenic subjects have not been adequately examined with this test. These "non-classical" measures will be described and critically examined with respect to their pertinence for further work on schizophrenic subjects. Of particular interest are the "failure to maintain set", which measures cognitive instability, "conceptual responses", which can indicate a certain conceptual capacity even in subjects who show perseveration, and "learning to learn", which can demonstrate a capacity to profit from experience on the test. A second objective will be to critically examine the evidence concerning the capacity of schizophrenic patients to improve their performance on the WCST. To the extent that performance on the WCST reflects the functional level of cognitive capacities important for everyday life, any capacity in schizophrenic patients to improve their performance could have important implications for therapeutic intervention and re-education.     

The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia

OBJECTIVE: Cognitive function and regional cerebral blood flow (rCBF) were studied in negative symptom profile schizophrenic patients by using WCST and SPECT. METHODS: Twenty-one schizophrenic patients who matched the criteria of Andreason's negative symptom profile received SPECT and WCST, and then were treated with clozapine for 8 consecutive weeks. There were 28 and 12 normal subjects as the control groups of WCST and SPECT, respectively. RESULTS: Compared with controls, significantly poorer performance on total trials of category (TT), persevering errors (PE), and non-persevering errors (NPE) of WCST were found in schizophrenia (p < 0.05). The total score of the scale for assessment negative symptoms (SANS) was significantly related with poor TT (r = 0.45, p < 0.01) and PE performance (r = 0.45, p < 0.01). The poor TT, PE, and NPE tasks of WCST and SANS scores in the negative schizophrenic patients were significantly improved through clozapine treatment (p < 0.05). The schizophrenic patients had a significantly lower rCBF in bilateral frontal and temporal lobes and lower change rate of rCBF in bilateral frontal lobes during WCST compared to normal controls (p < 0.05). CONCLUSIONS: Negative symptom profile schizophrenia has cognitive deficits and lower rCBF in bilateral frontal and temporal lobes, which suggests that negative symptom profile schizophrenic patients have hypofrontality. Clozapine can improve negative symptoms and improve cognitive dysfunction, although it cannot improve reduced rCBF in the frontal lobes.     

A study of visual and auditory verbal working memory in schizophrenic patients compared to healthy subjects

Impaired working memory (WM) performance is considered as a central feature of schizophrenia. Divided into two components, verbal and spatial, WM has been shown to involve frontal and parietal regions. Verbal WM can be tested either visually or aurally. The present study aimed to test schizophrenic patients in both visual and auditory verbal WM in order to assess a possible distinct pattern of alteration of these two modalities. Twenty-four schizophrenic patients and 24 healthy controls were compared with 2-back continuous visual and auditory verbal WM testing. Both groups were also tested on a neuropsychological battery including Wisconsin Card Sorting Test (WCST). Schizophrenic patients were less efficient in both verbal WM tests. When taking age and educational level as covariates and both WM modalities as dependent variables, there was no differential effect of modalities across groups. In further exploratory analyses, partial correlations brought association between verbal WM and psychosocial adaptation, WCST and length of illness. These results suggest a similar pattern of alteration of both modalities of verbal WM in schizophrenic patients. The implications of this finding are discussed. Received: 16 February 1999 / Accepted: 20 December 1999     

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.     

Processing of context information in schizophrenia: relation to clinical symptoms and WCST performance

Failure in contextual information processing has been hypothesized as being the single function responsible for several impairments in cognitive tasks and symptoms, through an involvement of the prefrontal cortex, in patients with schizophrenia. A variant of the Continuous Performance Test (CPT) designed specifically to elicit deficits in the processing of contextual information has been administered to 20 schizophrenic patients and 20 healthy controls. The relation to Wisconsin Card Sorting Test (WCST), relatively specific to prefrontal damage and executive dysfunctioning, and clinical status by using scales for the assessment of positive, negative symptoms and outcome has been investigated. The data show that multi-episode schizophrenic patients manifest inability to use contextual information to inhibit habitual response to an ambiguous stimulus and to maintain information across delay, without a general attention deficit. We also found a relationship between contextual reasoning and WCST unique errors, hallucinations, formal thought disorders, and outcome evaluation. Our results further support the hypothesis that the deficit of contextual reasoning could account for cognitive impairments and symptoms of patients with schizophrenia.     

Learning potential on the WCST in schizophrenia is related to the neuronal integrity of the anterior cingulate cortex as measured by proton magnetic resonance spectroscopy

BACKGROUND: In recent years, schizophrenia has increasingly been recognized as a neurocognitive disorder, which has led to a growing literature on cognitive rehabilitation, and suggested several potential enhancements to cognitive function. For instance, it has been shown that executive functioning deficits as measured by the Wisconsin Card Sorting Test (WCST) can be modified in a subgroup of schizophrenic patients. The neurobiological basis of cognitive remediation has not been elucidated so far, although structural, functional and metabolic abnormalities of the prefrontal cortex have been associated with cognitive impairment. METHODS: In this study, learning potential was investigated in 43 schizophrenic patients and 37 age- and education-matched healthy controls, using a dynamic version of the WCST, which integrates instructions and feedback into the testing procedure. Performance was related to cerebral metabolism, assessed by single-voxel proton magnetic resonance spectroscopy of the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC). RESULTS: N-acetylaspartate (NAA), a marker of neuronal integrity, was significantly reduced in the DLPFC of schizophrenic patients as compared to the healthy control group. The level of NAA in the DLPFC positively correlated with performance in the dynamic WCST in healthy subjects, whereas in schizophrenic patients a significant correlation was observed between NAA and glutamate/glutamine in the ACC and learning potential. CONCLUSION: These data imply a relationship between neuronal plasticity as assessed by learning potential and NAA levels of the prefrontal cortex in schizophrenic patients and healthy subjects, and suggest the involvement of differential neuronal networks in learning for schizophrenic patients compared to healthy controls.     

Cognitive flexibility and its electrophysiological correlates in Gilles de la Tourette syndrome

Motor symptoms in Gilles de la Tourette syndrome (GTS) have been related to changes in frontostriatal brain networks. These changes may also give rise to alterations in cognitive flexibility. However, conclusive evidence for altered cognitive flexibility in patients with GTS is still lacking. Here, we meta-analyzed data from 20 neuropsychological studies that investigated cognitive flexibility in GTS using the Wisconsin Card Sorting Test (WCST). Results revealed medium-sized GTS-related performance deficits, which were significantly modulated by age: Whilst being substantial in children and adolescents with GTS, WCST deficits seem to dissolve in adult patients with GTS. This age-related normalization of WCST performance might result from the compensatory recruitment of cognitive control in adult patients with GTS. We addressed this possibility by examining neural correlates of proactive and reactive cognitive control in an event-related potential (ERP) study. We analyzed cue- and target-locked ERPs from 23 adult patients with GTS and 26 matched controls who completed a computerized version of the WCST. Compared to controls, patients with GTS showed a marked increase in parietal cue-locked P3 activity, indicating enhanced proactive cognitive control. We conclude that the additional recruitment of proactive cognitive control might ensure flexible cognitive functioning in adult patients with GTS.     

The concept of working memory in schizophrenia: current evidence and future perspectives

Working memory (WM) deficits are core symptoms of cognitive impairment in schizophrenia. The psychological concept of WM offers a theoretical and empirical framework for the investigation of perceptual and attentional dysfunction as well as of deficits of higher cognitive functions in schizophrenia. From a theoretical perspective, schizophrenic psychopathology and cognitive dysfunction can be both integrated and experimentally validated within the concept of WM-impairment. In the last years investigation of WM has been a major issue in neuropsychiatric research, not least because of the association of prefrontal cortex and WM-function. The advent of functional imaging techniques, e. g. functional magnetic resonance imaging (fmri) has additionally contributed in generating neurobiological WM-models. Regarding the neuronal basis of WM-deficits in schizophrenia, prefrontal cortex dysfunction has been of major interest. This review provides a short overview on the concept of WM and its relevance for cognitive psychology, discussing both recent behavioral and functional neuroimaging evidence on WM-dysfunction in schizophrenia.     

Relationship of good and poor Wisconsin Card Sorting Test performance to illness duration in schizophrenia: a cross-sectional analysis

The authors investigated whether schizophrenic patients with good and poor performance on the Wisconsin Card Sorting Test (WCST) showed cognitive modifications related to duration of illness. Of the 154 patients evaluated with the WCST, 56 subjects had normal or mildly impaired performance and 98 showed impairment on the basis of the number of categories achieved (0-3 categories = poor performance). These subsamples were then cross-sectionally divided into three subsamples depending on length of illness (< 5 years, 6-10 years, > 10 years). The inclusion of 69 healthy controls allowed the effect of age to be taken into account. The schizophrenic group as a whole and the group of poor performers did not show differences in any of the WCST indices related to length of illness. Good performers instead showed improvement on the intermediate length-of-illness group (6-10 years of illness), and then decline in the third one (> 10 years). Good performers only showed a positive significant correlation between age, age at onset, educational level and successful WCST performance. Results for the poor performers support the hypothesis of no progressive 'deteriorating' course of schizophrenia, while good performers show an unstable pattern of cognitive functions. These data support the hypothesis that cognitive deficits associated with schizophrenia cannot be considered a unitary trait, but emerge along different hypothetical trajectories.     

精神分裂症患者基础及认知激活状态局部脑血流的研究

目的 探讨精神分裂症患者基础及认知激活状态局部脑血流量(rCBF)特点及精神分裂症症状与rCBF之间的关系。方法 患者组为49例未用过抗精神病药治疗的精神分裂患者,对照组为26名正常人。以阳性及阴性症状量表（PANSS）等量表评定患者组疾病严重程度,用双日法进行基础及认知激活状态单光子发射计算机断层扫描（SPECT）脑显像,以威斯康星卡片分类试验（ WCST）为认知激活工具。结果 患者组基础状态时左颞叶外侧部及左右颞叶后下部rCBF比值明显高于对照组（P＝0.050,0.002及0.001)。认知激活状态时与基础状态时比较,对照组左额叶外侧中部及右枕叶上部的血流灌注明显增加（ P＝0.001及0.033);患者组各感兴趣区（region of interest,ROI）血流灌注无明显变化。PANSS阳性量表及阳性症状量靛（SAPS）评分与左颞叶外侧部、右颞枕部、右颞叶后上部、右枕叶上部、右顶叶中部及左右顶叶等ROI的rCBF比值呈正相关。结论 精神分裂症患者可能存在潜在的额叶功能低下,阳性症状的严重程度与一些ROI的血流灌注量有关。     

Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia.

BACKGROUND: Schizophrenic patients show deficits in working memory (WM) and inhibition of prepotent responses. We examined brain activity while subjects performed tasks that placed demands on WM and overriding prepotent response tendencies, testing predictions that both processes engage overlapping prefrontal cortical (PFC) regions and that schizophrenic patients show reduced PFC activity and performance deficits reflecting both processes. METHODS: Functional magnetic resonance imaging data were acquired while 16 schizophrenic and 15 healthy subjects performed the N-Back task that varied WM load and a version of the AX-CPT that required overriding a prepotent response tendency. RESULTS: Both tasks engaged overlapping cortical networks (e.g., bilateral dorsolateral PFC, Broca's area, parietal cortex). Increased WM load monotonically increased activity; preparation to override a prepotent response produced greater and more enduring activity. Group differences on each task emerged in a right dorsolateral PFC region: schizophrenic subjects showed lesser magnitude increases under conditions of high WM and prepotent response override demands, with concomitant performance impairments. CONCLUSIONS: Schizophrenic patients exhibit PFC-mediated deficits in WM and preparation to override prepotent responses. Findings are consistent with the operation of a single underlying PFC-mediated cognitive control mechanism and with physiologic dysfunction of the dorsolateral PFC in schizophrenic patients reflecting impairments in this mechanism.     

精神分裂症患者认知功能与精神症状相关性研究

目的：探讨精神分裂症患者认知功能与精神症状的相关性。方法：对40例精神分裂症患者于治疗前、治疗12周末分别进行韦氏成人智力量表（WAIS-R）、韦氏记忆量表（WMS）、H—R神经心理成套测验（HRB）中的连线测验A、威斯康星卡片分类测验（WCST）及言语流利性测验及简明精神病评定量表（BPRS）评定。结果：治疗前焦虑抑郁因子分与总记忆商数（MQ）分显著相关,迟滞因子分与WCST完成类别数、智力显著相关;治疗12周末焦虑抑郁因子分与总智商（IQ）显著相关,迟滞因子分与WCST持续反应数、言语IQ、操作IQ显著相关,猜疑因子分与WCST持续反应数显著相关。结论：精神分裂症患者部分认知功能与精神症状显著相关。     

Tower of Hanoi and WCST performance in schizophrenia: problem-solving capacity and clinical correlates.

We administered a computerized version of WCST, a well established test, sensitive to executive function deficits in schizophrenia that involves many features of cognitive processing, and of Tower of Hanoi, a test that may offer cognitive challenges more specifically related to planning and sequencing, to 28 schizophrenic patients and 28 matched controls to examine a worthwhile question regarding the relative ability of these two tasks to differentiate schizophrenia and normal groups as well as exploring the relationship of these two instruments to clinical variables. The schizophrenic patients performed significantly worse than normal subjects both on Tower of Hanoi test and on WCST. The discriminant analysis identified in a multivariate way a pattern of indexes that differentiate the two groups. This pattern, characterized by specific indexes of WCST and TOH, could suggest the existence of a common underlying factor that determines the cognitive impairment in problem-solving of schizophrenics. These findings and the relationship with positive and negative symptoms have been discussed in the light of the model of the impairment in the internal representation of context information.     

Cognitive flexibility in neurological disorders: Cognitive components and event-related potentials

Performance deficits on the Wisconsin Card Sorting Test (WCST) in patients with prefrontal cortex (PFC) lesions are traditionally interpreted as evidence for a role of the PFC in cognitive flexibility. However, WCST deficits do not occur exclusively after PFC lesions, but also in various neurological and psychiatric disorders. We propose a multi-component approach that can accommodate this pattern of omnipresent WCST deficits: the WCST is not a pure test of cognitive flexibility, but relies on the effective functioning of multiple dissociable cognitive components. Our review of recent efforts to decompose WCST performance deficits supports this view by revealing that WCST deficits in different neurological disorders can be attributed to alterations in different components. Frontoparietal changes underlying impaired set shifting seem to give rise to WCST deficits in patients with amyotrophic lateral sclerosis, whereas the WCST deficits associated with primary dystonia and Parkinson’s disease are rather related to frontostriatal changes underlying deficient rule inference. Clinical implications of these findings and of a multi-component view of WCST performance are discussed.     

Cognitive remediation therapy (CRT) for young early onset patients with schizophrenia: an exploratory randomized controlled trial

BACKGROUND: Schizophrenia with an onset in adolescence is known to be associated with a poorer outcome and cognitive difficulties. These impairments have an impact on quality of life and represent treatment targets. Cognitive remediation therapy (CRT) attempts to improve cognitive deficits by teaching information processing strategies through guided mental exercises. The objective of this study is to evaluate the efficacy of CRT in alleviating cognitive deficits compared to treatment as usual and explore the mediating and moderating effects of cognitive improvement. METHOD: Single-blind randomized controlled trial with two groups, one receiving CRT (N21) and the other standard care (N19) assessed at baseline, 3 months (post therapy) and follow-up (3 months post therapy). Participants were recruited from specialist inpatient and community mental health services and were young patients with recent onset schizophrenia (average age of 18) and evidence of cognitive and social behavioural difficulties. The intervention was individual cognitive remediation therapy delivered over a period of 3 months with at least three sessions per week. The main outcome measures were cognition (memory, cognitive flexibility and planning) and secondary outcomes (symptoms, social contacts and self-esteem). RESULTS: Compared to standard care, CRT produced significant additional improvements in cognitive flexibility as measured by the Wisconsin Card Sort Test (WCST). Therapy moderated the effects of improved planning ability on symptoms such that improvements only had a beneficial effect when they were achieved in the context of CRT. Improvements in cognition in all domains had a direct effect on social functioning and improvements in WCST had a direct effect on overall symptom improvement. CONCLUSIONS: Cognitive remediation therapy can contribute to the improvement in WCST even in adolescents. The changes in cognitive outcomes also contributed to improvements in functioning either directly or solely in the context of CRT. Evidence of the mediator and moderator effects of cognitive changes should lead to more effective therapy development.     

Visuospatial context processing in untreated schizophrenic patients and relation to disorganization syndrome

AIM: Previous studies on schizophrenia have suggested that context-processing disturbances were one of the core cognitive deficits present in schizophrenia. Schizophrenic patients have a failure either of inhibition strategy and maintenance of visuospatial information (25) in condition of contextual interference. In the present study, we explored the performances of untreated schizophrenic patients with 2 tasks exploring detection and long term retention of complex visual features and field dependence-independence tasks were selected. These abilities involve temporary maintenance of visuospatial information and executive functioning of visual working memory system. Several studies have shown that cognitive deficit may depend on schizophrenic symptomatology. However results remain controversial in determining the specific influence of negative and positive symptomatologies as well as clinical disorganization. Our goal was to explore the processing of spatial context and its relation to disorganized syndrome. This study was approved by the local ethic committee. METHODOLOGY: Thirty-six schizophrenic patients were included according to DSM IV criteria (19 neuroleptic na?ve, 17 unmedicated patients during more than 3 months). Thirty-six healthy controls were matched to patients for age, gender and level of education. Absence of axis 1 pathology was attested for controls with SCID-NP. Current symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) (14). Clinical disorganisation was evaluated with the disorganisation score established upon a factorial analysis of PANSS by Lepine and Lan?on. Items selected to distinguish the disorganised group were abstraction, disorganization, orientation, and attention. PROCEDURE: Two tasks of embedded figures were administered individually to patients and controls. The Faverge task (Research of Figures-RF) (10) evaluates the ability to recognize the target from spatial complex geometrical figures. The Group Embedded Figure Task (GEFT - Oltman) assesses the detection and maintenance of visual target and its recognition within a complex figure. Performance between patients and controls were compared with the Student T test. The comparison of two clinical subgroups of disorganized and low disorganized patients and control group was performed with an ANOVA. Tuckey test was used for pairwise comparisons. RESULTS: We defined two subgroups of patients, disorganized patients (subscore 12, n=17) and low disorganized patients (subscore<12, n=19). Theses 2 subgroups were similar for age and level of education. Concerning the two tasks, there was no significant difference between schizophrenic patients and normal controls. The comparison between subgroups of disorganized and low disorganized patients, for RF task, showed a decrease of correct answers with disorganized patients (p<0.05). For GEFT task, disorganized patients had a decrease of correct answers p<0.01) and more errors (p<0.01) and omissions (p<0.05). The low disorganized patients exhibited for the two tests comparable performance to controls. The disorganized patients had a decrease of right answers (p<0.05) and more errors (p<0.05) than controls for GEFT task and no significant difference for RF. However, with IQ (evaluated with an abstract reasoning test) introduced as covariate, only correct answers for GEFT task remain significant (p<0.05). DISCUSSION: The weak performance of disorganized schizophrenic patients for two tasks RF and GEFT showed that treatment of visuospatial information was impaired in the first perceptive phase of selection and in the organization of information (RF), especially with the maintenance of visual information in memory (GEFT). By contrast, low disorganized patients demonstrated a correct analytic treatment of elementary processing and visuospatial working memory. CONCLUSION: The severity of disorganization influences the visuospatial context processing and visuospatial working memory. These results show the heterogeneity of cognitive functioning regarding to schizophrenic symptomatologies. This difficulty could be related to a problem of central executive functioning in the visuospatial component of working memory, possibly mediated by the dysfunction of dorsolateral prefrontal cortex.     

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。