TRYPTOPHAN DEPLETION AND CSF MONOAMINE METABOLITES

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Plasma tryptophan (TRP) depletion is increasingly being used by many investigators as a research tool for determining the role of brain serotonin (5-HT) function in a variety of psychiatric disorders because of its simplicity, safety, and robust behavioral effects observed in some patient groups. However no study to date has shown that this technique actually alters brain 5-HT metabolites in humans. This study will determine the cerebrospinal fluid (CSF) monoamine metabolite response to TRP depletion in 12 remitted depressed patients who have been symptom-free, and medication-free for a period of at least 3 months, and 12 age-gender matched healthy controls. It is anticipated that remitted depressed subjects will experience a relapse of depressive symptoms during TRP depletion, but not the healthy controls. After initial screening, informed consent, and baseline assessment, 12 patients meeting DSM-IV criteria for a past major depressive episode, and HAM-D score greater than or equal to 9, and 12 age-gender matched subjects without personal or family history of mental disorders will undergo testing. TRP depletion and control testing will be administered in a placebo-controlled, double-blind, randomized, cross-over design. This includes 2 three-day tests 1 week apart. On one test the subjects will receive 103 gm, TRP-free, 15-amino acid drink (TRP depletion) and on the other test a 105 gm, TRP-supplemented 16-amino acid drink (control). Plasma free and total TRP levels, large neutral amino acid levels, and behavioral ratings will be obtained prior to and five hours after ingestion of each amino acid drink. The primary aim of this project is to determine if TRP depletion causes a decrease of CSF 5-HIAA but not in HVA and MHPG, and to determine which plasma measure of TRP depletion best correlate with CSF 5-HIAA. Additionally this project will allow us to obtain preliminary data on the relationship of change in mood during TRP depletion to CSF 5-HIAA. This study will provide essential data on which to interpret the relevance of plasma TRP depletion to 5-HT function in humans. Preliminary data regarding the relationship of CSF 5-HIAA to depressive response to TRP depletion will serve as a basis for future investigations by Dr. Moreno.