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: 6391404
• 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/6391404
• 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(改编自申请者摘要)：罗伯特·格罗斯曼博士 他的医学博士毕业于西奈山医学院，是康奈尔大学的住院医生 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方面的研究成果，并一直是 1996年7月起任精神病学助理教授。在过去的4年里，他 从事岗位糖皮质激素和5-羟色胺功能的研究 创伤应激障碍(PTSD)与HIS的边缘人格障碍 导师雷切尔·耶胡达博士和拉里·西弗医学博士，他最近开始 创伤相关海马神经定量成像的初步研究 蒙特巴克斯鲍姆医学博士的疾病。 格罗斯曼博士近期的职业目标是将至少75%的时间 在未来五年内，进一步开展概念和技术培训 神经内分泌学、结构、功能和代谢神经成像，以及 认知功能的神经心理学评估。他的高强度训练 课程将包括：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)进行 原创研究的成果。格罗斯曼博士的长期职业目标是建立 他是一个精神病学学术项目的独立调查员 中枢糖皮质激素对大鼠海马区体积和功能的影响 功能正常。 创伤后应激障碍研究领域的两个主要发现是 下丘脑-垂体-肾上腺(HPA)轴改变与海马体缩小 音量。临床前研究表明，中枢糖皮质激素介导的 这些效应可能与这些海马区的异常有关。此外, 海马体是一个重要的区域(无论是结构上还是功能上) 与陈述性记忆密切相关。格罗斯曼博士的广泛目标是 在创伤后应激障碍中调查这些关系。 格罗斯曼斯博士的具体目标是衡量和关联：1)中心 使用安慰剂控制的氢化可的松对糖皮质激素的敏感性 挑战之后是18-FDG摄取和PET扫描；2)外周HPA轴 皮质醇对地塞米松和血浆负反馈敏感性的测定 淋巴细胞糖皮质激素受体；3)MRI测量海马区体积；4) 基线时的神经心理缺陷；5)陈述中的交替 氢化可的松/安慰剂挑战后的记忆功能。课题组 将包括创伤后应激障碍受试者、无创伤后应激障碍受试者和健康受试者 没有精神创伤的受试者。 动物研究发现，氟皮质激素介导的效应包括这两种 海马区细胞萎缩和死亡。这些模型也证明了 特定的相互作用可以防止或逆转海马体萎缩。结果是 这些研究中的每一项都可能对 神经科学对创伤后应激障碍患者和其他患者的治疗意义 有HPA轴改变和海马区表现的人群，如 苏金氏病、阿尔茨海默氏症和复发性重度抑郁症。