DRUG SENSITIVITY IN ELDERLY PSYCHIATRIC PATIENTS

描述(改编自申请人的摘要)：本申请提出 伊恩·A·库克，医学博士，获得临床科学家发展导师奖。这个 目标是使他能够在因素方面追求一个新的研究方向 影响老年人对药物的敏感性增加。该奖项将 允许库克博士获得新的技能和专门知识来支持这项工作(A) 库克博士将把他的技能应用于定量神经成像和 定量脑电(QEEG)研究血脑屏障的关系 儿童脑白质对药物敏感性的变化及功能 老年人。他的具体目标是(1)考察两者之间的联系 增加药物敏感性和WMC，(2)检查特异性的作用 载脂蛋白E(Apo E)基因型别对药物敏感性的影响； 应用药物探针输注诱发的脑电改变检查 钻井液选择性渗透性的变化。他将测试 以下假设：1.药理探针法将是一种有效的 体内评估血脑屏障功能的技术2.白细胞的存在 将与血脑屏障通透性的增加(大量 WMC将与对药物探针的高渗透性相关)； 3.载脂蛋白E基因将改变wmc的影响；携带e3/3的个体 基因型和小WMC对药物的渗透性最低 虽然e4/4基因型和大量WMC将具有最高的， 其他州为中等渗透率。4.一种模式可以将这些组合在一起 允许预测探头渗透率的WMC和apo E因子 方法和相关的药物敏感性。 他的三个阶段的项目将用一个药理探针来评估血脑屏障的功能 在受试者中：59名老年对照组，5名已知 血脑屏障中断。探针分子穿过血脑屏障进入大脑 将通过qEEG测量大脑功能的变化来检测。这些数据 将与MRI确定的WMC体积相关，并与 临床出现的药物敏感性增加与额外的 在获奖期间获得的技能和经验，库克博士将 做好准备进行独立和合作的调查，以 扩大他的教学角色，发挥基础科学和 科室内的临床研究。

DESCRIPTION (Adapted from applicant's abstract): This application proposes Ian A. Cook, M.D., for a Mentored Clinical Scientist Development Award. The goal is to enable him to pursue a new research direction in factors influencing increased drug sensitivity in the elderly. The Award will permit Dr. Cook to acquire new skills and expertise to support this work (a) in Dr. Cook will apply his skills in quantitative neuroimaging and in quantitative electroencephalography (QEEG) to study the relationship of BBB function and cerebral white matter changes (WMC) to drug sensitivity in the elderly. His specific aims are (1) to examine the association between increased drug sensitivity and WMC, (2) to examine the role of specific apolipoprotein E (apo E) genotypes in modifying drug sensitivity, and (3) to use EEG changes induced by infusion of pharmacologic probes to examine alteration in the selective permeability of the BBB. He will test the following hypotheses: 1. the pharmacologic probe method will be a valid technique for in vivo assessment of BBB function 2. the presence of WMC will be associated with an increase in BBB permeability (large amounts of WMC will be associated with high permeability to the pharmacologic probes); 3. the apo E genotype will modify the impact of WMC; individuals with e3/3 genotype and little WMC will have the lowest permeability to pharmacologic probes while e4/4 genotype and large amounts of WMC will have the highest, and other states intermediate permeability. 4. A mode can combine these WMC and apo E factors to permit prediction of permeability to the probe method and associated sensitivity to drug effects. His three-phase project will assess BBB function with a pharmacologic probe in a total of 64 subjects: 59 elderly control subjects, and 5 with known BBB disruption. Entry of the probe molecule across the BBB into the brain will be detected by changes in QEEG measures of brain function. These data will be correlated with MRI-determined volumes of WMC, and compared with the clinical occurrence of increased medication sensitivity With the additional skills and experience acquired during the Award period, Dr. Cook will be well prepared to undertake independent and collaborative investigations, to expand his teaching roles, and to play a role in bridging basic science and clinical research within the Department.