PLATELET LSD BINDING & 5HT UPTAKE IN DEPRESSION

这项拟议的工作评估了六个具体的假设 血小板5-羟色胺摄取与血浆5-羟色胺的关系 与重度抑郁症的临床病程有关。这项研究 利用纵向设计跟踪60名患者 开始使用去甲替林治疗，并评估其在 血小板5-羟色胺配基动力学与其临床相关性 抗抑郁剂反应。 在这项提案中，测量血小板的新技术 以LSD为配基的5-羟色胺2受体结合 与先前建立的运动学特征的方法 血小板5-羟色胺摄取和丙咪嗪结合。 这项工作是基于我们自己生成的试验数据 实验室，这表明这些措施可能潜在地 检测患者对三环类药物的个体5-羟色胺反应 抗抑郁药，缓解后抑郁症患者的复发 退出药物治疗是可以预见的。 拟议的对患者的仔细评估将完成四项工作 一些事情。首先，血小板5-羟色胺摄取将作为一种生物测定进行测试 考察亲和常数(Km)可以 说明去甲替林的最小有效剂量。第二，我们 将扩展我们之前的横断面发现，记录了 无毒抑郁症患者的血小板5-羟色胺摄取功能障碍 患者，并检查成功的治疗反应是否 与纠正5羟色胺容量下降有关 摄取和丙咪嗪结合。第三，项目将结合 新开发的LSD绑定技术用于测量 血小板上5-羟色胺(5HT2)受体用于寻找慢性 与抗抑郁药起效相关的适应性变化 回应。第四，为了利用我们的未来 与患者接触，我们会用这些方法收集 关于这些措施的效用的初步信息 预测对治疗有反应的患者的疾病复发 去甲替林治疗。 这项研究的设计建立在NIMH的资源- 圣地亚哥VAMC资助临床研究中心(CRC) 作为患者识别、治疗和随访的一种方法。 拟议的五年研究计划将使预期的、 对必要的时间长度和数量进行纵向研究 不同抗抑郁药反应分类的受试者 结果。

The proposed work evaluates six specific hypotheses examining the relationship between platelet serotonin (5HT) uptake and binding and the clinical course of major depression. The study utilizes a longitudinal design to follow 60 patients who are initiating therapy with nortriptyline and evaluated for changes in platelet serotonin ligand kinetics associated with their clinical antidepressant response. In this proposal, new techniques for measurement of platelet serotonin2 receptor binding, using LSD as a ligand, are combined with previously established methods for kinetically characterizing platelet serotonin uptake and imipramine binding. The work is based on pilot data generated from our own laboratory, which indicates that these measures may potentially assay a patient's individual serotonin response to tricyclic antidepressants, and that relapses in remitted depressed patients withdrawing from medication can be predicted. The proposed careful evaluations of the patients will do four things. First, platelet 5HT uptake will be tested as a bioassay to examine the possibility that the affinity constant (Km) may indicate a minimum effective dose of nortriptyline. Second, we will extend our prior cross-sectional findings that documented disturbances of platelet 5HT uptake in drug-free depressed patients, and examine whether a successful treatment response is associated with a correction of the decreased capacity for 5HT uptake and imipramine binding. Third, the project will combine newly developed LSD binding techniques for measurement of serotonin (5HT2) receptors on platelets to search for chronic adaptive changes associated with the onset of antidepressant response. Fourth, in order to take advantage of our future contact with the patients, we will use these methods to gather preliminary information on the utility of these measures to predict recurrences of illness in patients who have responded to nortriptyline treatment. The design of the study builds on the resources of the NIMH- funded Clinical Research Center (CRC) at the San Diego VAMC as a method for patient identification, treatment and followup. The proposed five-year research plan will enable prospective, longitudinal study for a necessary length of time and number of subjects for classification of the different antidepressant response outcomes.