MONOAMINE RECEPTOR SENSITIVITY AND ANTIDEPRESSANT DRUGS

这项研究计划将集中在5羟色胺（5 HT）在 抑郁症的发病机制及抗抑郁药的作用机制 ADT治疗。低色氨酸（TRP）饮食和缺乏TRP的氨基酸 酸性饮料（D-TFD）已被开发并用于评估的作用， 5 HT在抑郁症中的作用。在ADT缓解的患者中， D-TFD 8小时内抑郁症状增加， 24-48小时恢复正常。这强调了完整的 收缩前5 HT功能对ADT疗效的影响。大约50%的 抑郁症患者停止服药后， 抑郁症状与D-TFD D-TFD产生5-HT功能变化的特异性将 通过评估血浆TRP快速补充的效果进行评价 与IV TRP输注，并通过比较D-TFD与 缺乏其他氨基酸的饮料。D-TFD将提供给 恢复的患者停止治疗，看看它是否是一个标志， 特质在D-TFD之前7天锂处理作为D-TFD治疗的效果。 保护免受D-TFD对其他缺乏的饮料的影响 个氨基酸D-TFD将用于停止治疗的恢复患者 看看它是状态还是特征的标志7天的影响 在D-TFD之前进行锂处理，以防止其影响 将对接受ADT治疗的缓解患者进行评估。锂将与 安慰剂作为治疗用于维持抑郁症的改善 停药时接受D-TFD的患者的症状。更好地 了解5-HT在神经内分泌调节中的作用 抑郁症的异常，研究将在恒河猴中进行 使用5 HT受体敏感性的测量和神经内分泌的测量， 类似于患者的调节。D-TFD对 这些措施将与对氯苯丙氨酸，一种药物， 已知会损害5 HT合成。 这些研究将有助于阐明突触前5-HT功能在 抑郁症的发病机制及治疗。

This research program will focus on the role of serotonin (5HT) in the pathogenesis of depression and mechanism of action of antidepressant treatment (ADT). A low tryptophan (TRP) diet and a TRP deficient amino acid drink (D-TFD) has been developed and used to evaluate the role of 5HT function in depression. In patients remitted on ADT, there is a rapid increase in depressive symptoms within 8 hours of the D-TFD which return to normal by 24-48 hours. This emphasizes the importance of intact presynpatic 5HT function for the efficacy of ADT. Approximately 50% of depressed patients off medication have a 1 to 4 day improvement in depressive symptoms with the D-TFD. The specificity of the D-TFD for producing changes in 5HT function will be evaluated by assessing the effects of rapid repletion of plasma TRP with a IV TRP infusion and by comparing the effects of the D-TFD to drinks deficient in other amino acids. The D-TFD will be given to recovered patients off treatment to see if it is a marker for state or trait. The effects of 7 days lithium treatment prior to the D-TFD as a protection against its effects of the D-TFD to drinks deficient in other amino acids. The D-TFD will be given to recovered patients off treatment to see if it is a marker for state or trait. The effects of 7 days lithium treatment prior to the D-TFD as a protection against its effects in remitted patients on ADT will be assessed. Lithium will be compared to placebo as a treatment to be used to maintain improvement in depressive symptoms of patients receiving the D-TFD while off medication. To better understand the role of 5HT function in the modulation of neuroendocrine abnormalities in depression, studies will be conducted in Rhesus monkeys using measures of 5HT receptor sensitivity and measures of neuroendocrine regulation similar to those made in patients. The effects of the D-TFD on these measures will be compared to parachlorophenylalanine, a drug that is known to impair 5HT synthesis. These studies will help clarify the role of presynaptic 5HT function in the pathogenesis and treatment of depression.