Heckers Stephan, Konradi Christine
Department of Psychiatry, Vanderbilt University, 1601 23rd Avenue South, Room 3060, Nashville, TN 37212, United States.
Department of Pharmacology, Vanderbilt University, Nashville, TN 37212, USA.
Schizophr Res. 2015 Sep;167(1-3):4-11. doi: 10.1016/j.schres.2014.09.041. Epub 2014 Oct 18.
Schizophrenia is associated with abnormalities of hippocampal structure and function. Neuroimaging studies have shown that the hippocampus is hyperactive in schizophrenia. Here we explore GABAergic mechanisms of this hippocampal hyperactivity. The initial evidence for GABAergic abnormalities of the hippocampus in schizophrenia came from post-mortem studies of interneuron number, protein expression, and gene expression. These studies revealed marked decreases in gene and protein expression of somatostatin-positive and parvalbumin-positive interneurons, and indicated reduced interneuron numbers. Animal studies of decreased parvalbumin and NMDA-receptor function have shown that selective abnormalities of hippocampal interneurons mimic some of the cognitive deficits and clinical features of schizophrenia. The post-mortem and animal studies are consistent with the neuroimaging finding of increased hippocampal activity in schizophrenia, which can explain some of the psychotic symptoms and cognitive deficits. Taken together, these findings may guide the development of biomarkers and the development of new treatments for psychosis.
精神分裂症与海马体结构和功能异常有关。神经影像学研究表明，精神分裂症患者的海马体过度活跃。在此，我们探讨这种海马体过度活跃的γ-氨基丁酸能机制。精神分裂症中海马体γ-氨基丁酸能异常的初步证据来自对中间神经元数量、蛋白质表达和基因表达的尸检研究。这些研究显示，生长抑素阳性和小白蛋白阳性中间神经元的基因和蛋白质表达显著降低，并表明中间神经元数量减少。关于小白蛋白和N-甲基-D-天冬氨酸受体功能降低的动物研究表明，海马体中间神经元的选择性异常模拟了精神分裂症的一些认知缺陷和临床特征。尸检和动物研究与精神分裂症中海马体活动增加的神经影像学发现一致，这可以解释一些精神病症状和认知缺陷。综上所述，这些发现可能会为生物标志物的开发和精神病新疗法的开发提供指导。
