Neuropsychological impairments in schizophrenia: Integration of performance-based and brain imaging findings

Until recently, the dominant view was that schizophrenia patients have limited, if any, neuropsychological impairments, and those that are observed are only secondary to the florid symptoms of the disorder. This view has dramatically changed. This review integrates recent evidence demonstrating the severity and profile of neuropsychological impairments in schizophrenia. We present quantitative evaluation of the literature demonstrating that the most severe impairments are apparent in episodic memory and executive control processes, evident on a background of a generalized cognitive deficit. The neuropsychological impairments potentially represent genetic liability to the disorder, as similar, yet milder, impairments are evident in schizophrenia patients even before the onset of psychotic symptoms, as well as in the nonpsychotic relatives of schizophrenia patients. Corresponding cognitive neuroimaging literature on executive functions, episodic memory, and working memory in schizophrenia documenting abnormalities in frontal and medial temporal lobes is summarized, and current models integrating neuropsychological and neuroimaging data are discussed.     

Episodic Memory in Schizophrenia

Episodic memory impairments in individuals with schizophrenia have been well documented in the literature. However, despite the abundance of findings, constituent cognitive, neural, behavioral, and genetic components of the deficits continue to elude full characterization. This review provides a characterization of these deficits by organizing findings within three frameworks of interest: 1) neuroanatomical; 2) genetic; and 3) behavioral. Within each approach, evidence from imaging studies as well as behavioral studies is examined. The hope is that by synthesizing the cognitive science paradigms, molecular genetic neurophysiological findings, and computational algorithms applied to medial temporal lobe subregions, we will be able to expand our understanding of the types of compromises in episodic memory systems of individuals with schizophrenia.     

Turning it Upside Down: Areas of Preserved Cognitive Function in Schizophrenia

Patients with schizophrenia demonstrate marked impairments on most clinical neuropsychological tests. These findings suggest that patients suffer from a generalized form of cognitive impairment, with little evidence of spared performance documented in several large meta-analytic reviews of the clinical literature. In contrast, we review evidence for relative sparing of aspects of attention, procedural memory, and emotional processing observed in studies that have employed experimental approaches adapted from the cognitive and affective neuroscience literature. These islands of preserved performance suggest that the cognitive deficits in schizophrenia are not as general as they appear to be when assayed with clinical neuropsychological methods. The apparent contradiction in findings across methods may offer important clues about the nature of cognitive impairment in schizophrenia. The documentation of preserved cognitive function in schizophrenia may serve to sharpen hypotheses about the biological mechanisms that are implicated in the illness.     

生物运动及其在社会认知障碍研究中的应用

人类对生物运动具有较强的视觉敏感性,即使在视觉线索有限的情况下,仍能提取其中的社会性信息。本研究系统梳理了当前生物运动视知觉实验研究涉及的各类社会性信息,并归纳分析社会认知缺陷与生物运动视知觉加工之间的内在联系,以期促进对生物运动视知觉加工心理机制问题的深入探讨     

Pharmacological Cognitive Enhancement in Schizophrenia

Cognitive impairments in schizophrenia are common and severe. These impairments are also related to functional disability in schizophrenia. As a result, efforts are underway to enhance cognition in schizophrenia through a variety of pharmacological mechanisms. As part of this effort, a designated research design has been developed for this process, through an extensive consensus and validation effort. This paper reviews the methods for pharmacological cognitive enhancement, as well as previous results of efforts in the pharmacological domains. These domains include cholinergic, noradrenergic, serotonergic, glutamatergic, and GABA-ergic mechanisms. While previous results have not been particularly encouraging, there are many challenges that need to be overcome and many of the reasons for past failures may be due to resolvable issues. It is likely that this will be an area of research that will be developing extensively over the next decade and expanding to other conditions as well.     

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early‐onset schizophrenia patients

Cognitive deficits in several domains have been demonstrated in early‐onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early‐onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual‐construction, aspects of visual and verbal memory, and executive functions in chronic, early‐onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early‐onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual‐construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early‐onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms     

Stress‐related exhaustion disorder – clinical manifestation of burnout? A review of assessment methods,sleep impairments,cognitive disturbances,and neuro‐biological and physiological changes in clinical burnout

The aim of this paper was to provide an overview of the literature on clinically significant burnout, focusing on its assessment, associations with sleep disturbances, cognitive impairments, as well as neurobiological and physiological correlates. Fifty‐nine English language articles and six book chapters were included. The results indicate that exhaustion disorder (ED), as described in the Swedish version of the International Classification of Diseases, seems to be the most valid clinical equivalent of burnout. The data supports the notion that sleep impairments are causative and maintaining factors for this condition. Patients with clinical burnout/ED suffer from cognitive impairments in the areas of memory and executive functioning. The studies on neuro‐biological mechanisms have reported functional uncoupling of networks relating the limbic system to the pre‐frontal cortex, and decreased volumes of structures within the basal ganglia. Although there is a growing body of literature on the physiological correlates of clinical burnout/ED, there is to date no biomarker for this condition. More studies on the role of sleep disturbances, cognitive impairments, and neurobiological and physiological correlates in clinical burnout/ED are warranted.     

Potential noradrenergic targets for cognitive enhancement in schizophrenia

Substantial evidence suggests that alterations in noradrenergic function contribute to the cognitive impairments of schizophrenia. Activation of post-junctional alpha 2a-adrenergic receptors in the prefrontal cortex by the alpha 2a-selective agonist guanfacine has demonstrated some preliminary benefit in subjects with schizophrenia treated with atypical antipsychotics. alpha 1-adrenergic receptor activity may be less important in mediating the cognitive impairments of schizophrenia. beta-adrenergic receptors may serve as another potential target for cognitive remediation in schizophrenia. However, the potential increase in memory consolidation in schizophrenia patients produced by beta-adrenergic agonists may be outweighed by the impairment in cognitive flexibility and executive functioning produced by beta-adrenergic agonists. Finally, norepinephrine reuptake inhibitors, such as atomoxetine, hold promise as potential cognitive enhancers in schizophrenia because of their ability to indirectly but selectively increase extracellular dopamine concentrations in the prefrontal cortex.     

CANTAB explicit memory is less impaired in addicted schizophrenia patients

It has been suggested that in order to sustain the lifestyle of substance abuse, addicted schizophrenia patients would have less negative symptoms, better social skills, and less cognitive impairments. Mounting evidence supports the first two assumptions, but data lack regarding cognition in dual diagnosis schizophrenia. Seventy-six schizophrenia outpatients (DSM-IV) were divided into two groups: with (n = 44) and without (n = 32) a substance use disorder. Motor speed and visuo-spatial explicit memory were investigated using CANTAB. As expected, dual diagnosis patients showed a better cognitive performance. Our results suggest either that substance abuse relieves the cognitive deficits of schizophrenia or that the patients with less cognitive deficits are more prone to substance abuse.     

A systematic review of the association between attributional bias/interpersonal style,and violence in schizophrenia/psychosis

Despite the widely recognized link between schizophrenia and violence, the illness-specific factors underlying that association remain unclear. A body of work has implicated deficits in social cognition, consistently seen in schizophrenia, that may mediate the risk of violence. Two specific areas of interest are attributional bias and interpersonal style. We conducted a systematic literature search using EMBASE, Scopus, Ovid Medline, PsycINFO and Science Direct databases with search terms relating to attributional bias, interpersonal style and violence/aggression in schizophrenia. Eleven studies were identified, six related specifically to attributional bias and five to interpersonal style. Results suggest an association between hostile and externalizing attribution biases, and violence in schizophrenia. Furthermore, hostile, dominant, and coercive interpersonal styles are also frequently associated with violence in schizophrenia. An interaction between cognitive impairments and underlying personality traits, as well as other co-morbid or illness factors, is proposed to likely underpin associations with violence in schizophrenia. Conclusions are limited by methodological constraints. The field would benefit from consistent definitions of violence, and a more systematic approach to cognitive assessment. Furthermore, studies with more homogeneous samples; and longitudinal designs are warranted in order to gain a better understanding of causation with regard to illness factors specific to schizophrenia.     

Impaired conditional task performance in a high schizotypy population: relation to cognitive deficits

Cognitive impairments in schizophrenia have been characterized as reflecting a core deficit in the maintenance or use of task-setting cues to mediate appropriate ongoing behaviour. This analysis suggests that cognitive deficits in schizophrenia will be particularly evident when different task-setting cues dictate when different responses are required by the same stimuli. One simple task in which task-setting cues are required is a biconditional discrimination. Here we examined the performance of participants with high and low schizotypy scores (Mason, Claridge, & Jackson, 1995) on a biconditional discrimination and an otherwise equivalent, control discrimination that did not require the use of task-setting cues. Participants scoring highly on the Introvertive Anhedonia subscale (which has been allied to the negative and cognitive symptoms of schizophrenia) performed poorly on the biconditional, but not on the control, discrimination. No other subscales demonstrated a significant influence on either biconditional or control performance.     

Neuropsychological profile and neuroimaging in patients with 22Q11.2 Deletion Syndrome: a review.

22q11.2 Deletion Syndrome is associated with cognitive, behavioural, and psychiatric problems and is known to affect brain structure. Recently, 22q11.2 Deletion Syndrome has been proposed as a disease model for a genetic subtype of schizophrenia. In this paper we discuss the currently available literature on neurocognitive functioning and brain anatomy in patients with 22q11.2 Deletion Syndrome, and how this contributes to our understanding of the neurobiology of schizophrenia. Research on cognitive functioning in 22q11.2 Deletion Syndrome patients suggests a specific cognitive profile with impairments on arithmetical, visuo-spatial, and executive tasks and relatively preserved language skills. Prominent findings of neuroimaging studies in 22q11.2 Deletion Syndrome patients are: reduction of overall brain volume, midline defects, structural alterations of cerebellum and frontal lobe, white matter abnormalities, and decreased grey matter volumes in parietal and temporal areas. We describe how brain abnormalities in patients with 22q11.2 Deletion Syndrome may contribute to the understanding of the clinical syndrome including cognitive impairments, psychotic symptoms, and social and communication problems.     

Cognitive impairments and disordered speech in schizophrenia: thought disorder, disorganization, and communication failure perspectives

This article posits that basic cognitive impairments in schizophrenia are more highly related to speech disorder measured as communication failures than speech disorder measured as thought disorder or disorganization. The author tested 47 schizophrenia patients and 36 control participants for sustained attention, sequencing, and conceptual sequencing ability. Their speech was also rated for communication failures, thought disorder, and conceptual disorganization. Attention and sequencing impairments, examined hierarchically, explained a substantial 38% of the variance in the communication measure of speech disorder but little of the variance in formal thought disorder or conceptual disorganization. The author concludes that (a) impairments in attention and sequencing abilities contribute substantially to schizophrenic communication failures, and (b) it is important to consider lower level cognitive "3rd variables" when examining higher level cognitive associates of speech disorder.     

Understanding the executive functioning heterogeneity in schizophrenia

Schizophrenia is characterized by heterogeneous brain abnormalities involving cerebral regions implied in the executive functioning. The dysexecutive syndrome is one of the most prominent and functionally cognitive features of schizophrenia. Nevertheless, it is not clear to what extend executive deficits are heterogeneous in schizophrenia patients. Furthermore, it is still unknown if the executive impairments observed in schizophrenia are better characterized as specific or as reflecting generalized cognitive factors. The four executive processes (i.e. updating, inhibition, shifting and divided attention) described in Miyake et al.'s (2000) theoretical model were examined in 62 individuals with schizophrenia and 49 healthy controls. At group level, impairments in all four executive processes confirmed the marked impairment in executive functioning in patients with schizophrenia. Statistical analysis indicated that executive performances in schizophrenia patients were more heterogeneous than in healthy controls. Compared with standardized norms, 94% of patients exhibited impairment in at least one of the executive tasks. Twenty-one percent of patients exhibited impairment in one executive task, 27% in two tasks, 23% in three executive tasks and 23% exhibited impairments in the four executive tasks. Six percent of patients had normal executive profile. Regression analysis indicated that only premorbid intellectual quotient and a general slowing in processing speed predicted the executive dysfunction severity. Executive functioning was not affected by age, duration of illness, psychotic status, or by antipsychotic dosage. Our results emphasize the heterogeneity of the dysexecutive syndrome in schizophrenia when individual profile analysis is considered, and extend the view that individual cognitive differences in schizophrenia are largely underlined by general cognitive factors such as intellectual level and general processing speed.     

Deficits on the Continuous Performance Test within the schizophrenia spectrum and the mediating effects of family history of schizophrenia

Individuals with schizophrenia spectrum personality disorders (SSPD) and schizophrenia show similar cognitive impairments. The authors examined the contributions of SSPD symptoms and familial risk for schizophrenia to impairments on the Continuous Performance Test--Identical Pairs Version. Participants included 103 schizophrenia patients, 66 first-degree relatives (29 SSPD), and 103 community controls (26 SSPD) screened for family history of psychosis. Patients and SSPD relatives performed significantly worse than non-SSPD relatives and SSPD and non-SSPD community controls. No differences in performance were observed among non-SSPD relatives and SSPD and non-SSPD community controls. Results suggest a continuum in which risk for schizophrenia-related cognitive impairments is highest among patients and SSPD relatives, intermediate among non-SSPD relatives, and lowest among SSPD and non-SSPD community controls. Results suggest that SSPD in the absence of a family history of psychosis may be a phenocopy.     

执行功能与精神分裂症

执行功能障碍是精神分裂症最重要的认知功能障碍,与精神分裂症其它方面的障碍有着密不可分的关系。文章在相关的认知神经心理学和临床研究的基础上,分别综述了精神分裂症执行功能障碍的特点、研究方法、相关脑机制,执行功能与注意、记忆等一般认知功能间的关系,执行功能与精神症状间的联系及其在诊断、康复、判断预后方面的作用等。对精神分裂症执行功能障碍的认识有助于更深入地理解其病因机制,并有利于临床评价与防治     

Exploring Predictors of Outcome in the Psychosis Prodrome: Implications for Early Identification and Intervention

Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth.     

Neuropsychology,genetic liability,and psychotic symptoms in those at high risk of schizophrenia

Neuropsychological assessments were compared among individuals at enhanced genetic risk of schizophrenia (n = 157) and controls (n = 34). The relationship between cognitive impairments and the presence of psychotic symptoms and measures of genetic risk was explored in the high-risk subjects. Neuropsychological differences were identified in many areas of function and were not accounted for by the presence of psychotic symptoms. Genetic liability was not associated with neuropsychological performance or with psychotic symptoms, but exploratory analysis showed some tests were associated with both liability measures. These results suggest that what is inherited is not the disorder itself but a state of vulnerability manifested by neuropsychological impairment, occurring in many more individuals than are predicted to develop the disorder.     

Optimizing treatment of schizophrenia. Enhancing affective/cognitive and depressive functioning

Recognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patient in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments.     

内表型方法在精神疾病研究中的应用

精神疾病在很大程度上受到遗传的影响,而对疾病的遗传学研究却没有得到一致的结论,内表型正是在这一背景下提出。内表型是可以通过生化测试或显微镜检查发现的内在的表现型,即内表型不是很明显的、外在的而是微观的、内在的,内表型比疾病的外在表现更接近疾病的生物学基础,更少受到外在因素的影响,因而通过内表型来研究疾病的遗传基因有着显著的优势。现有的精神疾病诊断和分类标准都是以临床症状和行为描述为基础的,缺少生物学基础,基于内表型的分析对建立疾病的诊断和分类的生物学基础是非常重要的。内表型可以是神经生理的,生物化学的,神经解剖的,认知的,神经心理学的测量。作为内表型需要满足与疾病共同存在,可遗传,状态独立,在家庭中和疾病共分离,在病人未发病亲属中比一般人群的比率要高等标准。该文在介绍了内表型的概念,说明了内表型的原理,优点与用处,以及作为内表型需要满足的标准之后,进而以几种常见的精神疾病（多动症、精神分裂症、抑郁症）为例说明了目前认知内表型研究的进展,其中反应抑制和工作记忆可以作为多动症的内表型,注意、言语记忆和工作记忆可以作为精神分裂症和抑郁症的内表型,文章回顾了它们作为内表型所满足的标准的相关文献。最后对内表型的研究做出了展望