Ultra-high field GluCEST MRI and MRS in youth at risk for psychosis

超高场 GluCEST MRI 和 MRS 在有精神病风险的青少年中的应用

• 批准号: 10574595
• 负责人: DAVID R ROALF
• 金额: $ 73.8万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-10 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574595
• 关键词: Acceleration; Adolescence; Adolescent; Adolescent Behavior; Age; Anterior; Antipsychotic Agents; Area; Axon; Biological; Brain; Chemicals; Choline; Clinical; Cognitive deficits; Complement; Corpus Callosum; Creatine; Data; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease Progression; Dopamine; Etiology; Exhibits; Functional disorder; Funding; Glutamate Receptor; Glutamates; Glutamine; Glutathione; Health; Human; Image; Impairment; Individual; Learning; Link; Machine Learning; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurable; Measures; Medial; Memory; Motor; N-Methylaspartate; Neurons; Neurotransmitters; Parietal Lobe; Patients; Pattern; Pharmaceutical Preparations; Play; Prefrontal Cortex; Production; Protons; Psychiatry; Psychoses; Puberty; Public Health; Research; Risk; Role; Sampling; Schizophrenia; Science; Sensory; Societies; Source; Structural defect; Structure; Symptoms; Synapses; System; Techniques; Time; Work; Youth; clinical high risk for psychosis; cohort; cost; diagnostic value; early psychosis; effective therapy; emerging adult; frontal lobe; gamma-Aminobutyric Acid; in vivo; in vivo monitoring; innovation; longitudinal design; multilevel analysis; neurochemistry; neurodevelopment; neuroinflammation; neuropsychiatric disorder; neurotransmission; nonhuman primate; novel; novel imaging technique; precision medicine; psychosis risk; recruit; trend; white matter

ABSTRACT: Psychosis commonly develops in adolescence or early adulthood. Malfunctioning neurotransmitter systems, such as glutamate, are implicated in the disease progression of psychosis. Changes in brain glutamate in psychosis likely have several sources, as such, many frontline antipsychotic medications indirectly target the glutamate system and alleviate clinical symptoms. Unfortunately, monitoring in vivo alterations of the glutamate system within the brain are spatially limited by traditional magnetic resonance techniques. But, recently a novel 7T MRI technique (GluCEST) has shown that brain glutamate levels are lower across the brain in youth on the psychosis spectrum and patients with schizophrenia as compared to typically developing youth. Here, we propose to extend this novel work to directly measure glutamate within the brain of patients at risk for developing psychosis. Thus, this proposal is motivated by the need to better understand associations of brain neurochemistry, structure and function in both normal development and during early psychosis. In this study, we seek to 1) compare measures of glutamatergic development across the cortex in a cohort of typically developing (TD) youth, those at-clinical high-risk for psychosis (CHR) and individuals with frank psychosis (PSY); 2) associate changes in brain glutamate with age- and diagnosis- related structural network changes in those at risk for developing psychosis; and 3) to establish comparison data of glutamate measures at 7T MRI (1HMRS vs. GluCEST). We will recruit and follow 35 TD, CHR and PSY over the 5-year funding period. Imaging data will be acquired at 7T and analyses will leverage recent advances in network science and machine learning. We believe this innovative approach can significantly advance our understanding of the etiology of glutamate hypofunction in psychosis and provide advances to precision medicine in psychiatry. Through the proposed multi-level analysis, this innovative research will provide a substantial advance in our understanding of the neurodevelopmental substrates of psychosis.

摘要：精神病通常在青春期或成年早期发展。故障 神经递质系统（例如谷氨酸）与精神病的疾病进展有关。更改 在脑谷氨酸中，精神病中的谷氨酸可能有多种来源，因此，许多前线抗精神病药物 间接靶向谷氨酸系统并减轻临床症状。不幸的是，监视体内 大脑内谷氨酸系统的改变在空间上受到传统磁共振的限制 技术。但是，最近一种新型的7T MRI技术（Glucest）表明脑谷氨酸水平是 与精神病谱和精神分裂症患者相比 通常发展青年。在这里，我们建议扩展这项新颖的工作，以直接测量谷氨酸 患有精神病风险的患者大脑。因此，这一建议是由于需要更好的动机 了解脑神经化学，正常发育和功能的关联 在早期精神病期间。在这项研究中，我们寻求1）比较整个谷氨酸能发育的措施 在典型发展（TD）青年队列中的皮质，精神病和精神病的高风险（CHR）和 患有弗兰克精神病的人（PSY）； 2）将脑谷氨酸的变化与年龄和诊断 - 相关的结构网络发生了患有精神病风险的人的变化； 3）建立比较 7T MRI（1HMRS与Glucest）的谷氨酸量度数据。我们将招募并关注35 TD，CHR和PSY 在5年的资金期间。成像数据将以7T获取，分析将利用最近的进步 在网络科学和机器学习中。我们认为，这种创新的方法可以大大推动我们的 理解精神病中谷氨酸性功能障碍的病因，并提供精确的进步 精神病学医学。通过拟议的多层次分析，这项创新的研究将提供 我们对精神病的神经发育底物的理解实质性进步。