We review here the rapid tryptophan depletion (RTD) methodology and its controversial association with depressive relapse. RTD has been used over the past decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans and to probe the role of the central serotonin system in a variety of psychiatric conditions. Its current popularity was stimulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) KEY WORDS : 5-HT; Serotonin; Tryptophan-free drink; Major depressionSerotonin (5-hydroxy-tryptamine, or 5-HT) is involved in many physiologic and behavioral systems and clinical disease states. Much of the information available on the function of serotonin comes from pharmacological agents which mimic or amplify endogenous serotonergic neurotransmission, such as serotonin agonists or SSRIs. Historically, methods to functionally deplete serotonin have been problematic. Even previous approaches that have been moderately successful in experimental animals -such as the 5-HT synthesis inhibitor, parachloro-phenylalanine (PCPA); the neurotoxin 5-6-dihydroxy-tryptamine; or various lesions to the serotonergic raphe nuclei of the brainstem -have been non-specific, rife with secondary effects, or clearly inapplicable to humans (e.g., Engelman et al. 1967;Koella et al. 1968;Jouvet et al. 1967). The advent of rapid tryptophan depletion (RTD) as a method to deplete central serotonin has been met with enthusiasm because of its reversibil- NO . 6 ity, its relative lack of side effects, and its merit in elucidating the pathophysiology of various psychiatric conditions. This paper reviews the RTD methodology and its reported ability to induce a depressive relapse in euthymic patients, and other physiological and clinical effects. RAPID TRYPTOPHAN DEPLETION Availability of Tryptophan and Serotonin SynthesisRTD is based on the current understanding of the 5-HT biosynthetic pathway, in which the first step is generally considered to be the rate-limiting one. The first step entails the hydroxylation of the amino acid TRP (by the enzyme TRP hydroxylase, or TRP-H) into the intermediate product 5-hydroxy-tryptophan, or 5-HTP. 5-HTP is then decarboxylated into 5-HT. Under normal conditions, TRP-H is about 50% saturated with TRP. Increasing or decreasing the availability of TRP correlates highly with the amount of 5-HT produced (e.g., Lin et al. 1969;Schaechter and Wurtman 1990). Because the body cannot synthesize TRP, reducing dietary intake of TRP reduces TRP levels in plasma and diminishes its transport from plasma into the brain.In humans, TRP depletion is accomplished by consuming a TRP-free amino acid drink (e.g., Delgado et al. 1990;Biggio et al. 1974). This drink contains 15 amino acids in the same proportion as in human milk, except that TRP, aspartic acid, and glutamic acid are omitted (see Table 1). Within a matter of hours (4 to 12), plasma TRP declines to 10-50% of baseline levels (Delgado et al. 1990(Delgado et al. , 199...

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Background:In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs.

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Introduction: Torsion of the gallbladder is a rare condition that most commonly affects the elderly. Pre-operative diagnosis is the exception rather than the rule. Any delay in treatment can be fatal as the gallbladder may rupture, leading to biliary peritonitis.