CEREBRAL 18FDG UPTAKE FOLLOWING HYDROCORTISONE IN PTSD

PTSD 患者使用氢化可的松后大脑 18FDG 的摄取

• 批准号: 6185367
• 负责人: Robert A Grossman
• 金额: $ 15.49万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185367
• 关键词: brain metabolism; clinical research; cortisol; dexamethasone; glucocorticoids; hippocampus; human subject; hypothalamic pituitary adrenal axis; magnetic resonance imaging; memory; neuropsychological tests; positron emission tomography; posttraumatic stress disorder

DESCRIPTION (Adapted from Applicant's Abstract): Dr. Robert Grossman received his M.D. from the Mount Sinai School of Medicine, was a resident at Cornell New York Hospital-Westchester Division, completed an NIMH sponsored research fellowship in the neurobiology of trauma and personality, and has been an Assistant Professor of Psychiatry since July, 1996. Over the past 4 years he has been engaged in research of glucocorticoid and serotonin function in post traumatic stress disorder (PTSD) and borderline personality disorder with his mentors Rachel Yehuda, Ph.D. and Larry Siever, M.D. He has recently begun preliminary work in quantitative hippocampal neuroimaging in trauma-related disorders with Monte Buchsbaum M.D. Dr. Grossman's immediate career goals are to devote at least 75% of his time over the next five years to further conceptual and technical training in eruoendocrinology, structural, functional, and metabolic neuroimaging, and neuropsychological assessment of cognitive function. His intensive training program will include: 1) formal postgraduate coursework; 2) supervision and interaction with mentors, collaborators and scientific advisors; and 3) conduct of original research. Dr. Grossman's long-term career goals are to establish himself as an independent investigator within an academic psychiatry program in the area of central glucocorticoid-mediated effects on hippocampal volume and functioning. Two major findings in the field of PTSD research have been hypothalamic-pituitary-adrenal (HPA) axis alterations and smaller hippocampal volumes. Preclinical studies suggest that central glucocorticoid-mediated effects may be associated with these hippocampal abnormalities. In addition, the hippocampus is an important region (both structural and functionally) intimately involved in declarative memory. Dr. Grossman's broad aims are to investigate these relationships in PTSD. Dr. Grossmans's specific aims are to measure and correlates: 1) central glucocorticoid sensitivity utilizing a placebo-controlled hydrocortisone challenge followed by 18-FDG uptake and PET scanning; 2) peripheral HPA axis measures of cortisol negative feedback sensitivity to dexamethasone and plasma lymphocyte glucocorticoid receptors; 3) hippocampal volume using MRI; 4) neuropsychological deficits at baseline; and 5) alternations in declarative memory function following a hydrocortisone/placebo challenge. Subject groups will include PTSD subjects, traumatized subjects without PTSD, and health nontraumatized subjects. Animal studies have found flucocorticoid-mediated effects to include both hippocampal cell atrophy and death. These models have also demonstrated that particular interactions can prevent or reverse hippocampal atrophy. The results of these studies will likely have broad and important implications for the neuroscience's, and treatment implications in PTSD patients and perhaps other populations with HPA axis alterations and hippocampal findings such as Suching's disease, Alzheimer's disorder, and recurrent major depression.

描述（改编自申请人摘要）：Robert Grossman博士收到 医学博士学位来自西奈山医学院，是康奈尔大学的一名住院医生。 约克医院-威彻斯特分部，完成了NIMH赞助的研究 在创伤和人格的神经生物学奖学金，并一直是一个 自1996年7月起担任精神病学助理教授。在过去的四年里，他 长期从事糖皮质激素和5-羟色胺在脑卒中后的作用研究 创伤性应激障碍（PTSD）和边缘型人格障碍， 导师Rachel Yehuda博士和Larry Siever，医学博士他最近开始 创伤相关海马定量神经成像的初步研究 Monte Buchsbaum M.D. 格罗斯曼博士的近期职业目标是投入至少75%的时间 在未来五年内，进一步加强概念和技术培训， 神经内分泌学、结构、功能和代谢神经影像学，以及 认知功能的神经心理学评估。他的强化训练 计划将包括：1）正式的研究生课程; 2）监督和 与导师、合作者和科学顾问的互动;以及3）开展 原创研究。格罗斯曼博士的长期职业目标是建立 作为一名独立的精神病学研究者， 中枢糖皮质激素介导的对海马体积的影响区域， 功能 PTSD研究领域的两个主要发现是， 下丘脑-垂体-肾上腺（HPA）轴改变和海马 卷临床前研究表明，中枢糖皮质激素介导的 影响可能与这些海马异常有关。此外，本发明还提供了一种方法， 海马是一个重要的区域（结构和功能） 与陈述性记忆密切相关格罗斯曼博士的主要目标是 研究创伤后应激障碍中的这些关系 Grossmans博士的具体目标是测量和关联：1）中心 使用安慰剂对照氢化可的松的糖皮质激素敏感性 激发后18-FDG摄取和PET扫描; 2）外周HPA轴 测量皮质醇对地塞米松和血浆的负反馈敏感性 淋巴细胞糖皮质激素受体; 3）使用MRI的海马体积; 4） 基线时的神经心理学缺陷;和5）陈述性 氢化可的松/安慰剂激发后的记忆功能。受试者组 将包括创伤后应激障碍受试者，没有创伤后应激障碍的创伤受试者，以及健康 没有受过创伤的实验对象 动物研究发现，氟皮质激素介导的效应包括 海马细胞萎缩和死亡。这些模型还表明， 特定的相互作用可以防止或逆转海马萎缩。结果 这些研究可能会对未来的发展产生广泛而重要的影响。 神经科学的，和治疗的影响，创伤后应激障碍患者，也许其他 HPA轴改变和海马发现的人群， 苏青氏病，老年痴呆症和复发性抑郁症。