Are neuropsychological deficits trait markers in OCD?

OBJECTIVE: Neuropsychological deficits are potential endophenotype markers. In obsessive-compulsive disorder (OCD), there is impairment in executive functions and nonverbal memory. However, studies have largely examined neuropsychological functioning in patients during the symptomatic phase. The state independent nature of neuropsychological deficits in OCD is not established. For neuropsychological deficits to be endophenotype markers, they have to be state-independent. We compared neuropsychological functions in recovered OCD patients with matched healthy controls. METHOD: We assessed 30 recovered DSM-IV OCD patients without any concurrent comorbidity or lifetime history of schizophrenia, bipolar disorder, tics and alcohol/substance abuse and 30 healthy controls individually matched for age, sex and education. They were assessed on different neuropsychological dimensions: attention, executive function, memory and intelligence. For between-group comparisons, we employed univariate analyses, and to identify neuropsychological variables that differentiate cases and controls, we used backward conditional logistic regression for matched case-control design. RESULTS: Patients in the recovered phase of the illness had significant deficits in tests of set-shifting ability, alternation, response inhibition and nonverbal memory but had intact performance in other tests. In the logistic regression, scores on the Wisconsin Card Sorting Test 'categories completed' and the Rey's Complex Fig. Test 'delayed recall' were significant after controlling for the possible confounding effects of age and education. There was no correlation between illness-related variables and neuropsychological deficits. CONCLUSIONS: Deficits in certain executive functions and nonverbal memory are possibly state independent. Neuropsychological deficits are possibly candidate endophenotype markers for OCD and may help clarify genetic contributions. Future studies should evaluate unaffected siblings to establish deficits are endophenotype markers. Prospective studies with serial measurements of cognitive deficits are also needed to assess whether these deficits are cumulative with the progression of illness.     

Quality of life and cognitive dysfunction in people with schizophrenia

The main purpose of the present study was to examine the relationship between quality of life (QOL) and cognitive dysfunction in schizophrenia. Subjects were 61 stabilized outpatients. Quality of life and cognitive function were assessed using the Quality of Life Scale (QLS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). The BACS composite score and the BACS Verbal memory score were positively correlated with the QLS total score and two subscales. The BACS Attention and speed of information processing score had positive correlation with the QLS total and all the subscales scores. The PANSS Positive and Negative syndrome scores also had significant correlations with the QLS total score and all of the subscales. In addition, the CDSS score was negatively correlated with the QLS total score and some of the subscales. Stepwise regression analysis showed that the BACS Attention and speed of information processing score was an independent predictor of the QLS total score but it was less associated with the QLS than the PANSS Negative syndrome score and the CDSS score. The results suggest that negative and depressive symptoms are important factors on patients' QOL and also support the view that cognitive performance provides a determinant of QOL in patients with schizophrenia.     

An unblinded comparison of the clinical and cognitive effects of switching from first-generation antipsychotics to aripiprazole, perospirone or olanzapine in patients with chronic schizophrenia

The objective of this study, the effect of aripiprazole on clinical symptoms and cognitive function in patients with chronic schizophrenia was compared to that of perospirone and olanzapine. The subjects were 31 patients, they were diagnosed with schizophrenia on the basis of the criteria of the DSM-IV. Clinical symptoms were assessed using Brief Psychiatric Rating Scale (BPRS), and cognitive function was assessed using the Wisconsin Card Sorting Test (Keio Version: KWCST) and the St. Marianna University School of Medicine's Computerized Memory Test (STM-COMET) as executive function and memory/attention function tests at baseline and 8 weeks after switching. As a result, comparison of the BPRS mean total score revealed no significant difference between aripiprazole and the other medications. Aripiprazole resulted in significant changes in the number of categories achieved (CA) and difficulty maintaining set (DMS) compared to olanzapine at the second level of the KWCST. Comparison thus revealed no difference in clinical effect between aripiprazole and the other medications, but might suggest possible differences between aripiprazole and olanzapine in the profiles of the improvement effects on executive function, memory, and attention function.     

精神分裂症首次发病患者及其健康同胞认知功能的比较研究

目的 比较精神分裂症首次发病患者与健康同胞及正常对照认知功能的差异,探讨精神分裂症在认知功能领域的内表型.方法 采用目前常用的范畴流畅测验(CFT)、数字符号编码测验(DSCT)、连线测验(TMT)、韦克斯勒记忆量表第3版(WMS-Ⅲ)空间广度测验(WMS-ⅢSST)、霍普金斯词汇学习测验-修订版(HVLT-R)、简易视觉空间记忆测验-修订版(BVMT-R)、定步调听觉连续加法测验(PASAT)和威斯康星卡片分类测验-64(WCST-64)对92例精神分裂症首次发病患者(患者组)、56例健康同胞(同胞组)和62名健康对照者(对照组)的认知功能进行检测.结果 (1)患者组所有神经心理测验成绩均差于对照组,差异有统计学意义(P＜0.01).(2)同胞组的CFT、DSCT、TMT、HVLT-R即刻记忆和延迟记忆、BVMT-R即刻记忆、PASAT、WCST-64持续错误数、持续反应数和完成分类数的测验成绩差于对照组,差异有统计学意义(P＜0.05).(3)患者组与同胞组的CFT、WCST-64中的持续错误数、持续反应数和完成分类数测验成绩分别为(18.40±12.12)分比( 18.86±5.19)分、(16.48±8.19)分比(14.80±5.86)分、(18.76±10.91)分比(16.86 ±7.73)分、(1.33±2.81)分比(1.63±1.36)分,2组比较差异无统计学意义(P＞0.05),其他神经心理测验成绩比较,患者组差于同胞组,差异有统计学意义(P＜0.05).结论 精神分裂症首次发病患者存在处理速度、工作记忆、言语记忆、空间记忆、注意警觉和执行功能广泛性的认知功能损害,精神分裂症健康同胞存在处理速度、言语记忆、视觉记忆、注意警觉、执行功能的认知缺陷;语义流畅性功能和执行功能可能是精神分裂症的潜在内表型.     

Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.     

Tone duration mismatch negativity deficits predict impairment of executive function in schizophrenia

Impairment in mismatch negativity (MMN) potentials is a robust finding in schizophrenia. There are few studies which examined the correlation between MMN deficits and neuropsychological performances. The purpose of this study was to investigate the relationship between deficits of tone duration MMN and various neuropsychological measures in schizophrenic patients (n=23). The results demonstrated a significant correlation between low MMN amplitude and poor performances of executive function in Wisconsin Card Sorting Test, Stroop Test and Trail Making Test. Our finding suggests MMN deficits in schizophrenia predict deficits of executive function and might reflect ongoing functional abnormality of fronto-temporal interaction.     

Neuropsychological function in subjects with psychotic and affective disorders. Relationship to diagnostic category and duration of illness.

OBJECTIVE: To explore the links between neuropsychological performance, diagnostic category and duration of illness in subjects with psychotic and affective disorders. METHODS: Memory and executive abilities were tested in consecutively admitted patients with schizophrenia (N = 20), other non-schizophrenic psychotic disorders (N = 29), bipolar disorder (N = 33) and major depression (N = 19). RESULTS: Subjects with schizophrenia had poorer global memory performances than subjects with major depression, and poorer delayed verbal memory abilities than those from the other three diagnostic groups. Executive abilities explored by the Stroop test and the Wisconsin Card Sorting Test did not differ between diagnostic groups. Neuropsychological performances were not influenced by previous duration of illness. CONCLUSION: Memory deficits are the most discriminatory cognitive features between subjects with schizophrenia and those with other psychotic or mood disorders. The fact that cognitive deficits are static whatever the diagnostic group indirectly suggests that they may have a neurodevelopmental origin in subjects with schizophrenia, but perhaps also in subjects with other psychotic and mood disorders.     

精神分裂症认知功能评测量表与韦氏成人智力量表及韦氏记忆量表的相关性研究

目的对精神分裂症认知功能评测量表（SCoRS）、韦氏成人智力量表（WAIS—RC）和韦氏记忆量表（WMS）作相关分析并评估SCoRS在国内的适用性。方法对60例精神分裂症患者用SCoRS及wAIS—RC和wMS进行测评。结果相关分析显示SCoRS自评分、知情者评分、评定者评分各因子及总分与WAIS—RC评分的总智商、言语智商、操作在智商均呈显著相关性；SCoRS自评分、知情者评分、评定者评分各因子及总分与WMS评分的总记忆商数及10个分测验均呈显著相关性。结论SCoRS可以对精神分裂症患者的记忆及执行功能作出有力评估，能较好反映患者认知功能及生活功能状态，且简便易行，有较好适用性。     

Executive function and memory in posttraumatic stress disorder: a study of Bosnian war veterans.

The present study assessed neuropsychological functions related to attention, executive function and everyday memory in a group of men with a diagnosis of combat-related posttraumatic stress disorder (PTSD). Twenty Bosnian male combat veterans with a diagnosis of PTSD were tested using the Sustained Attention to Response Task, the Hayling Sentence Completion Test, the Trail Making Test, Rivermead Behavioral Memory Test and Wechsler Adult Intelligence Scale (verbal scales). Their performance was compared with age- and IQ-matched male war veterans with no PTSD. The study disclosed pervasive cognitive impairments with large effect sizes pertaining to attention, working memory, executive function, and memory. The effects did not appear to be attributable to alcohol abuse, loss of consciousness, or educational level. We speculate that, in the present group of combat veterans, PTSD was associated with dysfunction of a higher-level attentional resource which in turn affected the activity in other systems concerned with memory and thought.     

Brief assessment of cognition in schizophrenia: validation of the Japanese version

This preliminary study was performed to test the reliability and validity of the Brief Assessment of Cognition in Schizophrenia (BACS) as an assessment tool in a Japanese-language version (BACS-J). The subjects for the present study were 30 outpatients with chronic schizophrenia. Each subject gave written informed consent to participate in the research. Cronbach's alpha for the BACS-J was 0.77. The BACS-J composite score was significantly correlated with all primary measures of BACS-J (verbal memory, working memory, motor speed, verbal fluency, attention, and executive function). All BACS-J primary measures and the composite score were significantly correlated between two assessments. The mean score of the Digit Sequencing Task and composite score on the second assessment were significantly larger than those on the first assessment. All BACS-J primary measures except the Symbol Coding Task were significantly correlated with relevant standard neurocognitive tests. Also, the BACS-J composite score was significantly correlated with all standard neurocognitive tests except the Continuous Performance Test. A principal components analysis with varimax rotation resulted in a three-factor solution (executive function and memory; motor speed and general cognitive functions; and working memory). This preliminary study indicates that the BACS-J is a reliable and practical scale to evaluate cognitive function.     

Cognitive endophenotypes in OCD: A study of unaffected siblings of probands with familial OCD

Background

Impairments in executive functions and non-verbal memory are considered potential endophenotype markers of obsessive–compulsive disorder (OCD). For the neuropsychological deficits to be considered endophenotypes, they should be demonstrable in unaffected family members.

Aim

To compare the neuropsychological performance in unaffected siblings of probands with familial OCD with that of individually matched healthy controls.

Methods

Twenty-five unaffected siblings of OCD probands with familial OCD, and 25 individually matched healthy controls were assessed with tests of attention, executive function, memory and intelligence.

Results

Unaffected siblings showed significant deficits in tests of decision making and behavioural reversal i.e., the Iowa Gambling Task (IGT) and the Delayed Alternation Test (DAT) respectively, but performed adequately in other tests.

Conclusions

Our study suggests that the deficits in decision making and behavioural reversal could be potential endophenotypes in OCD. These deficits are consistent with the proposed neurobiological model of OCD involving the orbitofrontal cortex. Future studies could couple cognitive and imaging strategies to identify neurocognitive endophenotypes in homogenous samples of OCD.     

首发精神分裂症利培酮治疗前后认知功能的比较研究

目的探讨首发精神分裂症患者利培酮治疗前后认知功能的变化。方法采用认知评估工具连线测验、简单视觉空间记忆测验（BVMT-R）、WMS-III空间广度测验、霍普金斯词语学习测验（HVLT-R）、定步调听觉连续加法测验（PASAT）和威斯康星卡片分类测验（WCST-64）对经利培酮治疗8周前后的89例首发精神分裂症患者和62例健康对照者进行神经心理测试。结果首发精神分裂症患者治疗前的神经心理测验成绩显著差于治疗后和健康对照组（P〈0.05）;经利培酮治疗8周后达到临床痊愈标准患者的神经心理测验成绩除WMS-III空间广度测验外,其它大部分测验测验成绩仍显著差于健康对照组（P〈0.05）。结论首发精神分裂症患者存在处理速度、工作记忆、言语记忆、空间记忆、注意警觉和执行功能广泛的认知功能损害,利培酮治疗可部分改善认知缺陷,但精神症状达到临床痊愈的患者仍然存在多个领域认知缺陷,提示认知缺陷是精神分裂症的内表型。     

The differential impact of executive attention dysfunction on episodic memory in obsessive-compulsive disorder patients with checking symptoms vs. those with washing symptoms

Neuropsychological studies of obsessive-compulsive disorder (OCD) have pointed to memory and attention deficits among its sufferers, but these reports have largely ignored the possibility that cognitive disturbances may vary across OCD clinical subtypes, or that their interactions may differ between subtypes. The purpose of the present study was to determine whether "checkers" and "washers" demonstrate differences in their memory and executive attention function. Fifty-three outpatients with primary DSM-IV diagnosis of OCD with typical checking (n=27) or washing (n=26) rituals participated in the study. Patients were administered the Wechsler Memory Scale-Revised and a comprehensive neuropsychological battery to assess executive attention function. Various neuropsychological tests were then subjected to factor analysis. Neuropsychological test results and obtained factor scores were compared between "washers" and "checkers". Effects of these factor scores on memory by OCD subtypes were examined. No significant difference in terms of demographic and clinical variables was found between the two groups. Checkers displayed performance deficits on Stroop test, Trail Making Test, GO/NO GO test (commission errors) and category fluency. Three factors, inhibition, cognitive flexibility, and multi-tasking, were obtained. Statistically significant differences were observed between the two groups on the inhibition and the cognitive flexibility scores, but not on the general memory or the multi-tasking score. There was a statistically significant interaction between groups and the inhibition score. Only among "checkers", a significant correlation was noted between the inhibition factor and the general memory, while no such correlation was observed among "washers". Among "checkers", poor general memory was related to inhibition deficits.     

Neurocognitive,clinical and functional correlates of subjective quality of life in Asian outpatients with schizophrenia

Quality of life (QOL) impairment is evident in patients with schizophrenia and is increasingly recognised as an important evaluation criterion of treatment outcome. Hence, this study aimed to identify the neurocognitive, clinical and functional parameters associated with subjective QOL in patients with schizophrenia within an Asian context, and specifically in an outpatient setting. This study was conducted on 83 outpatients with DSM-IV diagnosis of schizophrenia, and 47 age- and gender-matched healthy controls. All participants were administered with the World Health Organisation Quality of Life Assessment-Brief Form (WHOQOL-BREF) and Brief Assessment of Cognition in Schizophrenia (BACS), to measure quality of life and cognitive function respectively. Patients were also assessed for severity of psychopathology, as well as level of psychosocial functioning, using the Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) rating scales respectively. Specific psychopathology (greater severity of PANSS negative symptoms, general psychopathology subscale scores), cognitive deficits (working and verbal memories), and lower GAF scores were correlated with poorer QOL in patients. Multivariate analyses revealed that younger age, being single and lower level of psychosocial functioning were associated with poorer QOL but level of psychosocial functioning did not appear to mediate the effects of symptoms and neurocognitive deficits on QOL. Overall, this study highlighted the need for clinicians to pay more attention to these clinical, neurocognitive and functional parameters and their integrative relationships with QOL in order to optimise the treatment outcomes of patients with schizophrenia.     

Relationship between psychopathology and cognitive functioning in schizophrenia

The purpose of this study was to delineate the relationship between positive, negative, cognitive, depressive, and excitement symptom dimensions of schizophrenia and cognitive functioning. Fifty-eight patients with schizophrenia (DSM-IV criteria) were assessed using the Positive and Negative Syndrome Scale (PANSS) and a battery of neuropsychological tests (executive function/abstraction, verbal and spatial working memory, verbal and nonverbal memory/learning, attention, visuospatial ability, and psychomotor speed). The cognitive symptom dimension correlated with executive functions, attention, verbal memory, and spatial ability. Severity of the negative symptom dimension was related to impairment in the structure of the semantic knowledge system, verbal memory, and auditory attention. In contrast, severity of the positive symptom dimension correlated only with impairment in the structure of the semantic knowledge system, and psychomotor speed. Finally, severity of the depressive and excitement symptom dimension was not associated with cognition. Correlations between symptom dimensions and cognitive measures were at best modest. Severity of cognitive and negative symptoms was mainly correlated with deficits on executive functions, semantic memory, and verbal memory, while positive symptoms only with semantic memory. These correlations were modest, suggesting that psychopathology and cognitive deficits in schizophrenia are caused, at least partially, by distinct pathophysiological processes.     

Trail Making Test Errors and Executive Function in Schizophrenia and Depression

The Trail Making Test (TMT) frequently is used as a measure of executive cognitive function. However, traditional use of test completion time as the primary outcome score does not give the more detailed information on cognitive processes that analysis of test-taking errors may provide. The present study compared TMT performance of three groups: patients with schizophrenia, patients with major depression, and healthy control participants (n = 30 for each group). Three operationally defined error types were examined: (a) tracking, (b) perseverative, and (c) proximity. Although both patient groups were slower than the healthy control group, only the schizophrenia group made significantly more errors, particularly tracking errors, suggesting a greater degree of cognitive disorganization. Within-group analysis of a larger group of schizophrenia patients (n = 84) revealed that TMT time was most strongly associated with the Withdrawal-Retardation factor of the Brief Psychiatric Rating scale. In contrast, TMT errors were most strongly associated with the Conceptual Disorganization factor. Comparisons of TMT scores and other cognitive tests showed moderate to high associations with tests of working memory, psychomotor speed, and executive function. Stepwise regression analysis revealed an independent association between Digit Cancellation and Part B Time, indicating a unique contribution of visuomotor scanning to performance. In contrast, Part B errors were uniquely associated with the Verbal Series Attention Test and the Token Test, tests of mental tracking and executive-mediated working memory, respectively. These findings demonstrate the utility of TMT error analysis in revealing cognitive deficits not traditionally captured using completion time as the sole outcome variable.     

Neuropsychological outcomes after Gamma Knife radiosurgery for mesial temporal lobe epilepsy: a prospective multicenter study

Purpose: To assess outcomes of language, verbal memory, cognitive efficiency and mental flexibility, mood, and quality of life (QOL) in a prospective, multicenter pilot study of Gamma Knife radiosurgery (RS) for mesial temporal lobe epilepsy (MTLE). Methods: RS, randomized to 20 Gy or 24 Gy comprising 5.5–7.5 ml at the 50% isodose volume, was performed on mesial temporal structures of patients with unilateral MTLE. Neuropsychological evaluations were performed at preoperative baseline, and mean change scores were described at 12 and 24 months postoperatively. QOL data were also available at 36 months. Key Findings: Thirty patients were treated and 26 were available for the final 24‐month neuropsychological evaluation. Language (Boston Naming Test), verbal memory (California Verbal Learning Test and Logical Memory subtest of the Wechsler Memory Scale‐Revised), cognitive efficiency and mental flexibility (Trail Making Test), and mood (Beck Depression Inventory) did not differ from baseline. QOL scores improved at 24 and 36 months, with those patients attaining seizure remission by month 24s accounting for the majority of the improvement. Significance: The serial changes in cognitive outcomes, mood, and QOL are unremarkable following RS for MTLE. RS may provide an alternative to open surgery, especially in those patients at risk of cognitive impairment or who desire a noninvasive alternative to open surgery.     

Effects of tapering of long-term benzodiazepines on cognitive function in patients with schizophrenia receiving a second-generation antipsychotic

Background

The high use of long-term benzodiazepines (BZDs) with second-generation antipsychotics (SGAs) has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual reduction or discontinuation of daytime BZD use on cognitive function and quality of life (QOL) in patients with chronic schizophrenia receiving an SGA.

Methods

Thirty schizophrenic patients who had received an SGA with concomitant BZDs for at least 3 months were enrolled. Before and 4 weeks after tapering of daytime BZDs, the Brief Assessment of Cognition in Schizophrenia Japanese-language version (BACS-J) and the Schizophrenia Quality of Life Scale Japanese-language version (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare for practice effects on the BACS-J, 10 patients with chronic schizophrenia were assessed without tapering BZDs.

Results

BZDs were reduced or discontinued safely in most patients, and no emergent withdrawal symptoms were observed. Significant improvements were shown in verbal memory, working memory, and composite score, as measured by the BACS-J without practice effects. In addition, the motivation/energy score on the SQLS-J, the negative symptoms and total scores on the PANSS significantly improved after tapering BZDs.

Conclusion

Reduction or discontinuation of long-term daytime use of BZDs may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects.     

Specific cognitive deficits are common in children with Duchenne muscular dystrophy

A neuropsychological assessment was conducted to study cognition, with emphasis on memory, information processing/learning ability, and executive functions in boys with Duchenne muscular dystrophy (DMD). A group of 20 boys with DMD, aged 7 to 14 years (mean age 9 years 5 months, SD 2 years 2 months), was contrasted with 17 normally developing age-matched comparison individuals, using specific neuropsychological tests (Block Span, Digit Span, Story Recall, Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Spatial Learning Test, Verbal Fluency, Trail Making Test, Tower of London, Memory for Faces, and Raven's Coloured Progressive Matrices). The DMD group performed significantly worse on all aspects of memory, learning, and executive functions. There was no significant difference in general intellectual ability between the two groups. Analyses of group differences indicate that problems in short-term memory are the most apparent, suggesting specific cognitive deficits. The differences between the groups were similar for both verbal-auditory and visuospatial tests, thus contradicting the idea that cognitive deficits are related to type of stimulus presented. It is concluded from this study that short-term memory deficits might play a critical role in the cognitive impairment and intellectual development seen in those with DMD.     

Enhancement of executive functioning skills: an additional tier in the treatment of schizophrenia

Schizophrenia is viewed by most as having a neuropsychological component, with deficits primarily occurring in the areas of attention/concentration, memory, and executive functioning. These deficits often contribute to difficulties in everyday living and social functioning. The purpose of this study is to examine the efficacy of cognitive rehabilitation methods, typically utilized by brain-injured patients, to improve the executive functioning skills of patients with schizophrenia spectrum disorders. While this pilot study is limited in terms of sample size, results suggest that the addition of cognitive rehabilitation to the comprehensive treatment of schizophrenia could be beneficial in enhancing daily living skills.