The antisaccade task as a research tool in psychopathology: a critical review

The antisaccade task is a measure of volitional control of behavior sensitive to fronto-striatal dysfunction. Here we outline important issues concerning antisaccade methodology, consider recent evidence of the cognitive processes and neural mechanisms involved in task performance, and review how the task has been applied to study psychopathology. We conclude that the task yields reliable and sensitive measures of the processes involved in resolving the conflict between volitional and reflexive behavioral responses, a key cognitive deficit relevant to a number of neuropsychiatric conditions. Additionally, antisaccade deficits may reflect genetic liability for schizophrenia. Finally, the ease and accuracy with which the task can be administered, combined with its sensitivity to fronto-striatal dysfunction and the availability of suitable control conditions, may make it a useful benchmark tool for studies of potential cognitive enhancers.     

Animal models of behavioral dysfunctions: basic concepts and classifications, and an evaluation strategy

In behavioral neurosciences, such as neurobiology and biopsychology, animal models make it possible to investigate brain-behavior relations, with the aim of gaining insight into normal and abnormal human behavior and its underlying neuronal and neuroendocrinological processes. Different types of animal models of behavioral dysfunctions are reviewed in this article. In order to determine the precise criteria that an animal model should fulfill, experts from different fields must define the desired characteristics of that model at the neuropathologic and behavioral level. The list of characteristics depends on the purpose of the model. The phenotype-abnormal behavior or behavioral dysfunctions-has to be translated into testable measures in animal experiments. It is essential to standardize rearing, housing, and testing conditions, and to evaluate the reliability, validity (primarily predictive and construct validity), and biological or clinical relevance of putative animal models of human behavioral dysfunctions. This evaluation, guided by a systematic strategy, is central to the development of a model. The necessity of animal models and the responsible use of animals in research are discussed briefly.     

Reelin down-regulation in mice and psychosis endophenotypes

Reelin, a large glycoprotein secreted by telencephalic GABAergic neurons, plays an important role in neuronal guidance embryonically and in synaptic plasticity postnatally. The reeler heterozygous mouse (+/rl) appears superficially normal but has been of interest as an animal model for psychosis since the discovery that reelin is 50% down-regulated in postmortem psychotic brain. Brain abnormalities in +/rl are similar to psychotic brain and include a reduction in glutamic acid de carboxylase 67 (GAD₆₇), dendritic arbors and spine density in cortex and hippocampus, and abnormalities in synaptic function including long-term potentiation (LTP). In spite of these abnormalities, behavioral abnormalities in +/rl are subtle and controversial. Recent findings indicate that the reelin (RELN) and GAD₆₇ promoters are hypermethylated in GABAergic neurons of psychotic postmortem brain and that DNA methyltransferase 1 (DNMT1) is up-regulated. Hypermethlyation of RELN and GAD₆₇ promoters can be induced by treating mice with methionine, and these mice display brain and behavioral abnormalities similar to +/rl. Thus, an animal model that combines genetic heterozygocity with epigenesis holds promise for understanding the role of Reelin down-regulation in psychosis     

The error-related negativity (ERN) and psychopathology: toward an endophenotype

The ERN is a negative deflection in the event-related potential that peaks approximately 50 ms after the commission of an error. The ERN is thought to reflect early error-processing activity of the anterior cingulate cortex (ACC). First, we review current functional, neurobiological, and developmental data on the ERN. Next, the ERN is discussed in terms of three psychiatric disorders characterized by abnormal response monitoring: anxiety disorders, depression, and substance abuse. These data indicate that increased and decreased error-related brain activity is associated with the internalizing and externalizing dimensions of psychopathology, respectively. Recent data further suggest that abnormal error-processing indexed by the ERN indexes trait- but not state-related symptoms, especially related to anxiety. Overall, these data point to utility of ERN in studying risk for psychiatric disorders, and are discussed in terms of the endophenotype construct.     

APOE-ε4 associates with hippocampal volume,learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Introduction

Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored.

首发精神分裂症及其健康同胞神经心理功能的比较

目的:探讨首发精神分裂症患者及其健康同胞神经心理功能差异。方法:采用范畴流利测验、连线测验(TMT)、数字符号编码测验和Stoop测验对在92例首发精神分裂症患者、56例健康同胞及62例健康对照者进行测评。结果:首发精神分裂症患者及其健康同胞所有神经心理测验成绩均差于健康对照组(P<0.05)。与健康同胞组比较,首发精神分裂症患者组除范畴流利测验外,其他神经心理测验成绩差异均有统计学意义(P<0.05)。结论:首发精神分裂症患者及其健康同胞存在认知损害,语义流畅性功能可能是精神分裂症的潜在内表型。     

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.