与精神分裂症相关的认知障碍:从病理生理学到治疗。

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI:10.1146/annurev-pharmtox-051921-093250
Daniel C Javitt
{"title":"与精神分裂症相关的认知障碍:从病理生理学到治疗。","authors":"Daniel C Javitt","doi":"10.1146/annurev-pharmtox-051921-093250","DOIUrl":null,"url":null,"abstract":"<p><p>Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction to higher-order impairments. At the neurochemical level, acute administration of <i>N</i>-methyl-d-aspartate receptor (NMDAR) antagonists reproduces the pattern of neurocognitive dysfunction associated with schizophrenia, encouraging the development of treatments targeted at both NMDAR and its interactome. At the local-circuit level, an auditory neurophysiological measure, mismatch negativity, has emerged both as a veridical index of NMDAR dysfunction and excitatory/inhibitory imbalance in schizophrenia and as a critical biomarker for early-stage translational drug development. Although no compounds have yet been approved for treatment of cognitive impairment associated with schizophrenia, several candidates are showing promise in early-phase testing.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"119-141"},"PeriodicalIF":11.2000,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"11","resultStr":"{\"title\":\"Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment.\",\"authors\":\"Daniel C Javitt\",\"doi\":\"10.1146/annurev-pharmtox-051921-093250\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction to higher-order impairments. At the neurochemical level, acute administration of <i>N</i>-methyl-d-aspartate receptor (NMDAR) antagonists reproduces the pattern of neurocognitive dysfunction associated with schizophrenia, encouraging the development of treatments targeted at both NMDAR and its interactome. At the local-circuit level, an auditory neurophysiological measure, mismatch negativity, has emerged both as a veridical index of NMDAR dysfunction and excitatory/inhibitory imbalance in schizophrenia and as a critical biomarker for early-stage translational drug development. Although no compounds have yet been approved for treatment of cognitive impairment associated with schizophrenia, several candidates are showing promise in early-phase testing.</p>\",\"PeriodicalId\":8057,\"journal\":{\"name\":\"Annual review of pharmacology and toxicology\",\"volume\":\"63 \",\"pages\":\"119-141\"},\"PeriodicalIF\":11.2000,\"publicationDate\":\"2023-01-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"11\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual review of pharmacology and toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-pharmtox-051921-093250\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of pharmacology and toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-pharmtox-051921-093250","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 11

摘要

认知障碍是精神分裂症的核心特征,也是导致功能不良的主要因素。评估精神分裂症患者认知功能障碍的方法现已得到很好的确立。此外,近年来越来越多的人认识到社会认知障碍在驱动功能结果中的额外作用,以及感觉水平障碍对高阶障碍的贡献。在神经化学水平上,急性给药n -甲基-d-天冬氨酸受体(NMDAR)拮抗剂再现了与精神分裂症相关的神经认知功能障碍模式,鼓励了针对NMDAR及其相互作用组的治疗方法的发展。在局部回路水平上,一种听觉神经生理学测量,失配负性,已经成为精神分裂症NMDAR功能障碍和兴奋/抑制失衡的真实指标,也是早期翻译药物开发的关键生物标志物。虽然目前还没有化合物被批准用于治疗与精神分裂症相关的认知障碍,但一些候选药物在早期测试中显示出希望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment.

Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction to higher-order impairments. At the neurochemical level, acute administration of N-methyl-d-aspartate receptor (NMDAR) antagonists reproduces the pattern of neurocognitive dysfunction associated with schizophrenia, encouraging the development of treatments targeted at both NMDAR and its interactome. At the local-circuit level, an auditory neurophysiological measure, mismatch negativity, has emerged both as a veridical index of NMDAR dysfunction and excitatory/inhibitory imbalance in schizophrenia and as a critical biomarker for early-stage translational drug development. Although no compounds have yet been approved for treatment of cognitive impairment associated with schizophrenia, several candidates are showing promise in early-phase testing.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
期刊最新文献
How Biologics Have Changed the Drug Discovery Landscape. Inhibitors of Intracellular RyR2 Calcium Release Channels as Therapeutic Agents in Arrhythmogenic Heart Diseases. Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics. Evolving Approaches for Pharmacological Therapy of Obesity. Genetically Enriched Clinical Trials for Precision Development of Noncancer Therapeutics: A Scoping Review.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1