Brain glutamine metabolism in schizophrenia

项目摘要/摘要 精神分裂症是一种致残性精神障碍，影响大约1%的人口，而且 给社会带来了巨大的负担。虽然抗精神病药物通常能有效地控制 精神分裂症的阳性症状、持续的阴性症状和认知障碍 严重的发病率和功能障碍。 越来越多的证据表明，多种因素可能与老年痴呆症患者的认知障碍有关。 精神分裂症，包括大脑固有的疾病，行为并存，长期服用抗精神病药物， 以及系统性因素。先前使用磁共振波谱(MRS)的研究表明 慢性精神分裂症患者脑谷氨酰胺(Gln)水平升高，呈负相关 与认知表现相关。然而，谷氨酰胺升高的潜在机制尚不清楚；它 可能与谷氨酰胺代谢改变和/或血氨水平亚临床升高有关。 这项初步研究的目的是探索大脑谷氨酰胺和血氨水平的关系，两者都是 在精神分裂症患者和对照组中。这些因素与认知的关系 功能将通过详细的神经心理测试进行评估。将使用高场(7T)MRS，因为它 与低场强下进行的MRS相比，可提供更准确的脑谷氨酸氨基转移酶估计。 对精神分裂症患者谷氨酸氨基转移酶改变与认知缺陷之间关系的更好理解可能 在动物模型中使用反向转换方法为未来的机械学研究提供信息，并最终指导 精神分裂症的新治疗干预措施。

Project Summary/Abstract Schizophrenia is a disabling psychiatric disorder that affects approximately 1% of the population, and which places an enormous burden on society. While antipsychotic medications are usually effective at controlling the positive symptoms of schizophrenia, persistent negative symptoms and deficits in cognition contribute to significant morbidity and functional impairment. There is increasing evidence that multiple factors may be associated with cognitive deficits in patients with schizophrenia, including both those intrinsic to the brain, behavioral comorbidities, long-term antipsychotic use, as well as systemic factors. Prior studies using magnetic resonance spectroscopy (MRS) have indicated that brain glutamine (Gln) levels are elevated in patients with chronic schizophrenia, and which are negatively correlated with cognitive performance. The underlying mechanism of Gln elevation is unknown, however; it may be related to altered Gln metabolism and/or subclinical increases in blood ammonia levels. The goal of this pilot study is to probe the relationship between brain Gln and blood ammonia levels, both in patients with schizophrenia and control subjects. The relationship between these factors and cognitive function will be evaluated using detailed neuropsychological testing. High-field (7T) MRS will be used, since it provides more accurate estimation of brain Gln compared to MRS performed at lower field strengths. Improved understanding of the relationship between altered Gln and cognitive deficits in schizophrenia may inform future mechanistic studies using back-translational approaches in animal models, and ultimately guide novel therapeutic interventions in schizophrenia.