Functional MR of the Effects of D-Serine

D-丝氨酸作用的功能 MR

• 批准号: 8074009
• 负责人: JOSEPH T. COYLE
• 金额: $ 24.85万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8074009
• 关键词: Agonist; Brain; Clinical Trials; Collaborations; Data; Enrollment; Face; Functional Magnetic Resonance Imaging; Glycine; Grant; Hippocampus (Brain); Image; Learning; Magnetic Resonance Spectroscopy; Measurement; Measures; Mediating; Memory; Methods; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; N-acetylaspartate; N-acetylaspartylglutamate; Neurobehavioral Manifestations; Occipital lobe; Patients; Performance; Protocols documentation; Protons; Relative (related person); Reporting; Resolution; Schizophrenia; Serine; Signal Transduction; Site; Spectrum Analysis; Task Performances; Temporal Lobe; Testing; Water; Work; analog; blood oxygenation level dependent response; improved; in vivo; placebo controlled study; relational memory; virtual; way finding

This project will test the hypothesis that schizophrenia is associated with NMDA hypofunction by examining in-vivo brain data acquired through the combined use of proton magnetic resonance spectroscopy (MRS) and BOLD functional magnetic resonance imaging (fMRI). We propose to measure proton metabolite concentrations, including N-acetyl-aspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), in temporal and prefrontal cortical regions in schizophrenic patients and healthy controls. MRS data will be acquired on a 4T scanner with newly developed methods that provide improved resolution of peaks and signal components within the proton spectrum, thus improving interpretability of NAA measurements, as well as extending MRS capabilities to include quantification of NAAG. The quantification of these metabolites is relevant for the main hypothesis of the center grant as work from our group has reported reduced NAA in temporal cortex bilaterally. Further, NAAG has been implicated in NMDA hypofunction. At present in-vivo measurements of these metabolites, have not been concurrently characterized in schizophrenia. Moreover, it has been shown that NMDA receptors in the hippocampus are essential for spatial learning and that pharmacological blockade of NMDA receptors impairs spatial navigation. Therefore, as an exploratory endpoint, we propose to acquire fMRI data on a 3Tscanner during the completion of a virtual analogue of a spatial navigation task, the water maze, to assess spatial memory performance. We will also acquire fMRI data during a transitive inference task to assess relational memory, and during a facial recall challenge, tasks previously shown to be mediated by the hippocampus. Finally, in collaboration with Dr. Don Goff (Clinical Trials Section), we will enroll 60 schizophrenic patients into a placebo-controlled trial of D-serine, an agonist at the glycine site on the NMDA receptor. Patients will be imaged with the MRS/fMRI protocols described above to examine the effects of D-serine treatment on spatial and relational memory performance, BOLD activation and NAA and NAAG concentrations.

本项目将通过检查来验证精神分裂症与NMDA功能低下相关的假设