MONOAMINE RECEPTOR SENSITIVITY AND ANTIDEPRESSANT DRUGS

这项研究计划将重点放在5-羟色胺(5-羟色胺)在 抑郁症的发病机制及抗抑郁剂的作用机制 治疗(ADT)。低色氨酸(Trp)饮食和色氨酸缺乏 酸性饮料(D-TFD)已被开发并用于评估 5-羟色胺在抑郁症中的作用。在接受ADT缓解的患者中，有一个快速的 抑郁症状在D-TFD恢复后8小时内增加 在24-48小时内恢复正常。这强调了完好无损的重要性。 突触前5-羟色胺功能对于ADT的疗效。约50%的 抑郁症患者停药后1至4天内 D-TFD的抑郁症状。 D-TFD引起5-羟色胺功能改变的特异性将 通过评估血浆色氨酸快速补充的效果进行评估 通过静脉输注色氨酸和比较D-TFD的效果 缺乏其他氨基酸的饮料。D-TFD将提供给 康复者停止治疗，看看它是状态还是 特质。D-TFD术前7天锂离子治疗的疗效观察 D-TFD对缺乏其他营养成分的饮料的保护作用 氨基酸。D-TFD将用于治疗后康复的患者 看看它是否是状态或特征的标记。7天的影响 D-TFD前的锂治疗对其影响的保护作用 在缓解的患者中，将对ADT进行评估。锂将被比作 安慰剂作为一种治疗方法用于维持抑郁症的改善 停药期间接受D-TFD治疗的患者的症状。为了更好地 了解5-羟色胺功能在神经内分泌调节中的作用 抑郁症的异常，将在恒河猴身上进行研究 5-羟色胺受体敏感性测定和神经内分泌测定的应用 类似于在病人身上制定的规则。D-TFD对心脏功能的影响 这些措施将与对氯苯丙氨酸进行比较，后者是一种 已知会损害5-羟色胺的合成。 这些研究将有助于阐明突触前5-羟色胺功能在 抑郁症的发病机制和治疗。

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.