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首页> 外文期刊>Neuron >Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments
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Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments

机译：抑郁症的连接改变：GABA和谷氨酸神经递质缺乏和逆转新的治疗方法

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摘要

The mechanisms underlying the pathophysiology and treatment of depression and stress-related disorders remain unclear, but studies in depressed patients and rodent models are beginning to yield promising insights. These studies demonstrate that depression and chronic stress exposure cause atrophy of neurons in cortical and limbic brain regions implicated in depression, and brain imaging studies demonstrate altered connectivity and network function in the brains of depressed patients. Studies of the neurobiological basis of the these alterations have focused on both the principle, excitatory glutamate neurons, as well as inhibitory GABA interneurons. They demonstrate structural, functional, and neurochemical deficits in both major neuronal types that could lead to degradation of signal integrity in cortical and hippocampal regions. The molecular mechanisms underlying these changes have not been identified but are thought to be related to stress induced excitotoxic effects in combination with elevated adrenal glucocorticoids and inflammatory cytokines as well as other environmental factors. Transcriptomic studies are beginning to demonstrate important sex differences and, together with genomic studies, are starting to reveal mechanistic domains of overlap and uniqueness with regards to risk and pathophysiological mechanisms with schizophrenia and bipolar disorder. These studies also implicate GABA and glutamate dysfunction as well as immunologic mechanisms. While current antidepressants have significant time lag and efficacy limitations, new rapid-acting agents that target the glutamate and GABA systems address these issues and offer superior therapeutic interventions for this widespread and debilitating disorder.
机译：抑郁症病理生理学和治疗抑郁和压力相关疾病的机制仍然尚不清楚，但抑郁症患者和啮齿动物模型的研究开始产生有前途的见解。这些研究表明，抑郁和慢性应激暴露导致皮质和肢体脑区中神经元的萎缩以及脑成像研究中的脑成像研究表明了抑郁症患者大脑中的改变的连接和网络功能。这些改变的神经能源基础的研究专注于原理，兴奋性谷氨酸神经元以及抑制性GABA中间核。它们展示了两种主要神经元类型中的结构，功能和神经化学缺陷，这可能导致皮质和海马区域中信号完整性降低。尚未确定这些变化的分子机制，但被认为与升高的肾上腺素糖皮质激素和炎症细胞因子以及其他环境因素组合有关。转录组研究开始表现出重要的性别差异，与基因组研究一起开始揭示与精神分裂症和双相障碍的风险和病理生理机制的重叠和唯一性的机械结构域。这些研究还涉及加巴和谷氨酸功能障碍以及免疫机制。虽然目前的抗抑郁药具有显着的时间滞后和功效限制，但靶向谷氨酸和GABA系统的新型快速作用剂解决了这些问题，并为这一普遍和衰弱的疾病提供了卓越的治疗干预措施。

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  • 来源
    《Neuron》 |2019年第1期|共16页
  • 作者

    Duman Ronald S.; Sanacora Gerard; Krystal John H.;

  • 作者单位

    Yale Univ Sch Med Dept Psychiat 34 Pk St New Haven CT 06508 USA;

    Yale Univ Sch Med Dept Psychiat 34 Pk St New Haven CT 06508 USA;

    Yale Univ Sch Med Dept Psychiat 34 Pk St New Haven CT 06508 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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