Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
Schizophr Res. 2020 Sep;223:59-70. doi: 10.1016/j.schres.2020.09.013. Epub 2020 Oct 16.
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.
研究可能导致精神分裂症发作的神经生物学过程越来越强调谷氨酸能系统和大脑发育。临床前研究表明，神经发育、遗传和环境因素导致谷氨酸能功能障碍和与精神分裂症相关的表型。临床研究表明，在精神病发作之前，大脑谷氨酸水平可能发生改变，并且与处于临床高风险的患者的结局相关。精神病发作后，谷氨酸功能障碍也可能与抗精神病药物反应和临床结局的程度有关。这些发现支持正在进行的开发靶向谷氨酸系统的药物干预的努力，并且可能表明谷氨酸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，我们从神经发育的角度考虑了精神分裂症的更新谷氨酸假说，通过回顾最近的临床前和临床证据，讨论了对新型治疗方法的潜在影响。
