DRUG SENSITIVITY IN ELDERLY PSYCHIATRIC PATIENTS

描述（改编自申请人摘要）：本申请提出 伊恩·A库克，医学博士，临床科学家发展指导奖 的 他的目标是使他能够在因素方面追求新的研究方向， 影响老年人药物敏感性的增加。 该奖项将 允许库克博士获得新的技能和专业知识，以支持这项工作（a） 库克博士将运用他在定量神经成像和 定量脑电图（QEEG）研究血脑屏障（BBB） 功能和大脑白色物质变化（WMC）对药物敏感性的影响 老人 他的具体目标是：（1）检查 增加药物敏感性和WMC，（2）检查特异性 载脂蛋白E（apo E）基因型改变药物敏感性，和（3） 使用药物探针输注引起的EEG变化来检查 BBB的选择性渗透性的改变。 他将测试 以下假设：1. 药理学探测方法将是一种有效的 用于体内评估BBB功能技术2. 妇女运动的存在 将与BBB渗透性的增加（大量的 WMC将与药理学探针的高渗透性相关）; 3. 载脂蛋白E基因型将改变WMC的影响;具有e3/3的个体 基因型和小WMC将具有最低的药物渗透性， 而e4/4基因型和大量的WMC将具有最高的， 和其它状态的中间磁导率。 4. 一种模式可以将这些联合收割机 WMC和载脂蛋白E因子，用于预测探针的渗透性 方法和对药物作用的相关敏感性。 他的三阶段项目将用药理学探针评估BBB功能 在总共64名受试者中：59名老年对照受试者和5名已知 BBB中断。 探针分子穿过BBB进入大脑 将通过定量脑电图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 增加药物敏感性的临床发生 在奖励期间获得的技能和经验，库克博士将 做好充分准备进行独立和合作调查， 扩大他的教学作用，并发挥桥梁作用，基础科学和 在部门内进行临床研究。

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.