PLATELET LSD BINDING & 5HT UPTAKE IN DEPRESSION

拟议的工作评估六个具体的假设， 血小板5-羟色胺（5-HT）摄取与 绑定和抑郁症的临床过程。 研究 采用纵向设计随访60例患者， 开始用去甲替林治疗，并评估 血小板5-羟色胺配体动力学与其临床 抗抑郁反应 在这项建议中，新的技术，测量血小板 使用LSD作为配体的降钙素2受体结合， 用以前建立的动力学表征方法 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的试验数据产生的。 实验室，这表明这些措施可能会 测定病人对三环类抗生素的血清素反应 抗抑郁药，缓解抑郁症患者复发， 可以预测药物的退出。 对病人的仔细评估将做四个方面的工作。 东西 首先，将对血小板5 HT摄取进行生物测定， 研究亲和常数（Km）可能 表示去甲替林最小有效剂量。 二是 将扩展我们先前的横截面研究结果， 无药抑郁症患者血小板5-HT摄取障碍 患者，并检查是否成功的治疗反应， 与5 HT能力降低的校正相关 摄取和丙咪嗪结合。 三是项目将联合收割机 新开发的LSD结合技术，用于测量 5-羟色胺（5-HT 2）受体在血小板上寻找慢性 与抗抑郁药起效相关的适应性变化 反应 第四，为了利用我们的未来， 与患者接触，我们将使用这些方法收集 关于这些措施的效用的初步资料， 预测对治疗有反应的患者的疾病复发 去甲替林治疗 该研究的设计建立在NIMH的资源基础上， 圣地亚哥VAMC的临床研究中心（CRC） 作为患者识别、治疗和随访的方法。 拟议的五年研究计划将使未来， 纵向研究的必要长度的时间和数量 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.