Prenatal ontogeny as a susceptibility period for cortical GABA neuron disturbances in schizophrenia.
Prenatal ontogeny as a susceptibility period for cortical GABA neuron disturbances in schizophrenia.
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DOI：
10.1016/j.neuroscience.2013.06.008
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发表时间：
2013-09-17
期刊：
影响因子：
3.3
通讯作者：
Lewis DA
中科院分区：
文献类型：
--
作者：
Volk DW;Lewis DA
精神分裂症患者的认知缺陷与前额皮质GABA神经元的紊乱有关。此外，精神分裂症的认知缺陷早在精神病发作之前就出现了，据报道，在儿童早期甚至在生命的第一年就出现了。综上所述，这些数据提出了以下问题：精神分裂症患者产生前额叶GABA神经元异常的疾病过程是否在产前就开始了，并破坏了皮质GABA神经元的个体发育？在这里，我们通过考虑妊娠期间发生的遗传和/或环境损害启动一个致病过程来解决这个问题，该过程改变了皮质GABA神经元的个体发育，并产生GABA神经元异常的模式，从而导致认知困难，在精神分裂症中可见。首先，我们回顾了来自死后人类脑组织研究的现有证据，这些证据描述了前额叶GABA神经元某些亚群的变化，这些变化为精神分裂症的产前起源提供了线索。其次，我们回顾了最近发现的转录因子、细胞因子受体和其他发育调节因子，这些调节因子控制着前额叶GABA神经元不同亚群的产生、迁移、规范、成熟和存活。第三，我们讨论了最近的研究表明，这些个体发生因素在精神分裂症的前额叶皮层中表达改变。第四，我们讨论了母胎环境干扰的潜在作用，如母体免疫激活在GABA神经元功能障碍的发展中。最后，我们提出了在未来的研究中需要回答的关键问题，以进一步研究GABA神经元个体发生改变在精神分裂症发病机制中的作用。
Cognitive deficits in schizophrenia have been linked to disturbances in GABA neurons in the prefrontal cortex. Furthermore, cognitive deficits in schizophrenia appear well before the onset of psychosis and have been reported to be present during early childhood and even during the first year of life. Taken together, these data raise the following question: Does the disease process that produces abnormalities in prefrontal GABA neurons in schizophrenia begin prenatally and disrupt the ontogeny of cortical GABA neurons? Here, we address this question through a consideration of evidence that genetic and/or environmental insults that occur during gestation initiate a pathogenetic process that alters cortical GABA neuron ontogeny and produces the pattern of GABA neuron abnormalities, and consequently cognitive difficulties, seen in schizophrenia. First, we review available evidence from postmortem human brain tissue studies characterizing alterations in certain subpopulations of prefrontal GABA neuron that provide clues to a prenatal origin in schizophrenia. Second, we review recent discoveries of transcription factors, cytokine receptors, and other developmental regulators that govern the birth, migration, specification, maturation, and survival of different subpopulations of prefrontal GABA neurons. Third, we discuss recent studies demonstrating altered expression of these ontogenetic factors in the prefrontal cortex in schizophrenia. Fourth, we discuss the potential role of disturbances in the maternal-fetal environment such as maternal immune activation in the development of GABA neuron dysfunction. Finally, we propose critical questions that need to be answered in future research to further investigate the role of altered GABA neuron ontogeny in the pathogenesis of schizophrenia.
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影响因子：
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作者：
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