Emerging principles of altered neural circuitry in schizophrenia
Emerging principles of altered neural circuitry in schizophrenia
复制标题
DOI：
10.1016/s0165-0173(99)00041-7
复制
发表时间：
2000-03-01
影响因子：
--
通讯作者：
Benes, FM
中科院分区：
文献类型：
--
作者：
Benes, FM
本文概述了最近的微观研究，这些研究试图定义死后精神分裂症大脑中边缘回路如何改变。讨论围绕几个基本问题进行，这些问题涉及前扣带皮层和海马结构内部和之间的互连方式，以及谷氨酸、GABA 和多巴胺系统可能有助于这种疾病的病理生理学。这些问题的答案可用于得出有关精神分裂症电路变化的几个结论：1）精神分裂症不是一种“典型”的退行性疾病，而是一种兴奋性毒性可能导致神经元病理学的疾病，无论是否发生细胞死亡； 2）三个或更多神经递质系统可以在单个微电路内同时改变； 3) 每个发射机系统可能会在多个区域显示电路变化，但这种变化可能因地区而异； 4) 精神分裂症的病理生理学可能涉及给定区域内固有电路（微电路）的“错误接线”，但网络内两个或多个区域（宏电路）之间的互连水平也可能存在显着变化； 5) 虽然一些微观发现似乎选择性地存在于精神分裂症中，并且与该疾病的易感基因有关，但其他一些发现也可能存在于双相情感障碍患者中； 6) 尽管在精神分裂症和双相情感障碍中看到的一些电路变化似乎与抗精神病药暴露有关，但大多数并非如此，并且可能反映了非特定环境因素的影响，例如产前和/或产后压力； 7) 边缘系统内宏观和微电路水平的正常产后变化可能是青春期精神分裂症发作的“触发因素”。总而言之，这些新兴原理可以为未来精神分裂症大脑的尸检研究提供一个框架。 (C) 2000 Elsevier Science B.V. 保留所有权利。
This paper presents an overview of recent microscopic studies that have sought to define how limbic circuitry may be altered in postmortem schizophrenic brain, The discussion is organized around several basic questions regarding the manner in which interconnections within and between the anterior cingulate cortex and hippocampal formation and involving the glutamate, GABA and dopamine systems may contribute to the pathophysiology of this disorder. The answers to these questions are used to derive several conclusions regarding circuitry changes in schizophrenia: 1) Schizophrenia is not a 'typical' degenerative disorder, but rather it is one in which excitotoxicity may contribute to neuronal pathology, whether or not cell death occurs; 2) Three or more neurotransmitter systems may be simultaneously altered within a single microcircuit; 3) Each transmitter system may show circuitry changes in more than one region, but such changes may vary on a region-by-region basis; 4) The pathophysiology of schizophrenia may involve 'mis-wirings' in intrinsic circuits (microcircuitry) within a given region, but significant changes are probably also present at the level of interconnections between two or more regions within a network (macrocircuitry); 5) While some microscopic findings appear to be selectively present in schizophrenia and be related to a susceptibility gene for this disorder, others may also be present in patients with bipolar disorder; 6) Although some of the circuitry changes seen in schizophrenia and bipolar disorder seem to be associated with neuroleptic exposure, most are not and may reflect the influence of non-specific environmental factors such as pre- and/or postnatal stress; 7) Normal postnatal changes at the level of both macro- and microcircuitry within the limbic system may serve as 'triggers' for the onset of schizophrenia during adolescence. Taken together, these emerging principles can provide a framework for future postmortem studies of schizophrenic brain. (C) 2000 Elsevier Science B.V. All rights reserved.