Brain glutamine metabolism in schizophrenia

精神分裂症的脑谷氨酰胺代谢

• 批准号: 10467055
• 负责人: PETER B BARKER
• 金额: $ 20.34万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10467055
• 关键词: Affect; Ammonia; Animal Model; Anterior; Antipsychotic Agents; Attention; Back; Behavioral; Biochemical; Biochemical Markers; Biochemistry; Blood; Blood - brain barrier anatomy; Brain; Brain Chemistry; Brain region; Chronic; Chronic Schizophrenia; Clinic; Clinical; Cognition; Cognitive deficits; Development; Disease; Evolution; Exhibits; Functional disorder; Future; General Population; Glutamates; Glutamine; Goals; Health; Hepatic Encephalopathy; Hippocampus (Brain); Impaired cognition; Intelligence; Lead; Life; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Memory; Mental disorders; Metabolic; Metabolism; Monitor; Morbidity - disease rate; Neuraxis; Neuropsychological Tests; Pathogenesis; Patients; Peripheral; Pharmaceutical Preparations; Pilot Projects; Population; Prefrontal Cortex; Protons; Psychoses; Reporting; Research Proposals; Resolution; Schizophrenia; Short-Term Memory; Societies; Symptoms; Testing; Thalamic structure; Uncertainty; Urea cycle disorders; Verbal Learning; cingulate cortex; cognitive function; cognitive performance; comorbidity; effective therapy; executive function; functional disability; functional status; improved; interest; magnetic field; neurochemistry; neuroimaging; novel strategies; novel therapeutic intervention; translational approach; treatment response

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.

项目总结/摘要 精神分裂症是一种致残性精神疾病，影响约1%的人口， 给社会带来了巨大的负担。虽然抗精神病药物通常能有效控制 精神分裂症的阳性症状，持续的阴性症状和认知缺陷有助于 严重的发病率和功能障碍。 有越来越多的证据表明，多种因素可能与认知功能障碍患者 精神分裂症，包括大脑固有的精神分裂症，行为共病，长期使用抗精神病药物， 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， 与认知表现相关。然而，谷氨酰胺升高的潜在机制尚不清楚， 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讨脑谷氨酰胺和血氨水平之间的关系， 在精神分裂症患者和对照组中。这些因素与认知的关系 将使用详细的神经心理学测试来评估功能。将使用高场（7 T）MRS，因为它 与在较低场强下进行的MRS相比，提供了更准确的脑Gln估计。 对谷氨酰胺改变与精神分裂症认知缺陷之间关系的进一步理解可能 为未来在动物模型中使用反向翻译方法的机制研究提供信息，并最终指导 精神分裂症的新治疗干预。