Glutamate in schizophrenia: Neurodevelopmental perspectives and drug development
Glutamate in schizophrenia: Neurodevelopmental perspectives and drug development
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DOI：
10.1016/j.schres.2020.09.013
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发表时间：
2020-09-01
影响因子：
4.5
通讯作者：
McGuire, Philip
中科院分区：
文献类型：
--
作者：
Egerton, Alice;Grace, Anthony A.;McGuire, Philip
对可能导致精神分裂症发作的神经生物学过程的研究越来越重视神经系统和大脑发育。临床前研究表明，神经发育，遗传和环境因素有助于神经元功能障碍和精神分裂症相关的表型。临床研究表明，脑谷氨酸水平的改变可能存在于精神病发作之前，并与临床高危人群的结局有关。精神病发作后，谷氨酸功能障碍也可能与抗精神病药物的反应程度和临床结局有关。这些发现支持正在进行的开发针对谷氨酸系统的药理学干预措施的努力，并可能表明谷氨酸能化合物在特定的患者亚组或疾病阶段可能更有效。在这篇综述中，我们认为更新谷氨酸假说的精神分裂症，从神经发育的角度来看，通过审查最近的临床前和临床证据，并讨论新的治疗方法的潜在影响。(C)2020年，任作家。由爱思唯尔公司出版
Research into the neurobiological processes that may lead to the onset of schizophrenia places growing emphasis on the glutamatergic system and brain development. Preclinical studies have shown that neurodevelopmental, genetic, and environmental factors contribute to glutamatergic dysfunction and schizophrenia-related phenotypes. Clinical research has suggested that altered brain glutamate levels may be present before the onset of psychosis and relate to outcome in those at clinical high risk. After psychosis onset, glutamate dysfunction may also relate to the degree of antipsychotic response and clinical outcome. These findings support ongoing efforts to develop pharmacological interventions that target the glutamate system and could suggest that glutamatergic compounds may be more effective in specific patient subgroups or illness stages. In this review, we consider the updated glutamate hypothesis of schizophrenia, from a neurodevelopmental perspective, by reviewing recent preclinical and clinical evidence, and discuss the potential implications for novel therapeutics. (C) 2020 The Authors. Published by Elsevier B.V.