Specificity of the tryptophan depletion method

Klaassen, Tim; Riedel, Wim J.; Deutz, N.E.P.; Someren, A. van; Praag, H. M. van

doi:10.1007/s002130050835

Cited by 73 publications

(46 citation statements)

References 33 publications

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“…Given that these amino acids are present in the same amounts in TRP-free and TRP-containing preparations, and that sham depletion techniques have measurable effects only rarely, the discrepancy between the effects seen with TRP-free and TRP-containing challenges therefore cannot be accounted for by simply having taken in a huge bolus of amino acids. In support of this, Klaassen et al (1999a) depleted healthy subjects either of TRP or lysine, using a similar preparation. Unlike RTD, rapid lysine depletion provoked no measurable mood or memory effects.…”

Section: Are There Non-serotonergic Explanations For the Effects Of Rtd?mentioning

confidence: 76%

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

Moore

Landolt

Seifritz

et al. 2000

Neuropsychopharmacology

184

121

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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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Section: Are There Non-serotonergic Explanations For the Effects Of Rtd?mentioning

confidence: 76%

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

Moore

Landolt

Seifritz

et al. 2000

Neuropsychopharmacology

184

121

View full text Add to dashboard Cite

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“…For example, a growing body of literature has demonstrated that tryptophan depletion is associated with decrements in cognition in samples of healthy controls (Evers et al 2005;Klaassen et al 1999;Murphy et al 2002). One study showed that manipulation of tryptophan levels in abstinent MDMA users is associated with altered performance on a memory test (Curran and Verheyden 2003).…”

Section: Discussionmentioning

confidence: 99%

MDMA use and neurocognition: a meta-analytic review

et al. 2006

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Rationale To determine the association between MDMA misuse and neurocognition using meta-analysis. Objective Separate analyses were conducted based on two sets of inclusion/exclusion criteria. A relatively stringent set required that the subjects be matched on important moderator variables, whereas the other did not. The study participants' performance in the following neurocognitive domains was reviewed: attention/concentration, verbal and nonverbal learning and memory, psychomotor speed and executive systems functioning. Results In the 11 studies meeting the relatively stringent inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Similarly, in the 23 studies meeting the relatively lenient inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Small to medium effect sizes were generally observed. A comparison of the effect sizes across the two sets of analyses did not reveal significant differences. Conclusions The findings from this review reveal that MDMA use is associated with neurocognitive deficits. The implications of these findings are discussed.

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“…The clinical and physiological consequences of ATD can be followed over a period of several hours. After the intervention, tryptophan levels quickly return to normal upon return to a normal diet (Klaassen et al, 1999b).…”

Section: Amino-acid Mixturesmentioning

confidence: 99%

“…The preparation and composition of the amino-acid mixture was the same as described by Klaassen et al (1999b) and Riedel et al (1999) In the active condition, 3 g/100 g tryptophan was left out. Apart from the amino acids, the mixture contained 63 g carbohydrates and 33 g fat in order to dissolve the amino acids and provide caloric value.…”

Section: Amino-acid Mixturesmentioning

confidence: 99%

The Serotonergic Hypothesis for Depression in Parkinson's Disease: an Experimental Approach

Leentjens

Scholtissen

Vreeling

et al. 2005

Neuropsychopharmacol

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The serotonergic hypothesis for depression in Parkinson's disease (PD) states that the reduced cerebral serotonergic activity that occurs in PD constitutes a biological risk factor for depression. The aim of our study was to assess the serotonergic hypothesis of depression in PD patients using an experimental approach. In a double-blind, randomized order, placebo-controlled crossover design, the response on the Profile of Mood States (POMS) questionnaire to acute tryptophan depletion (ATD) was studied in 15 PD nondepressed patients and 15 control subjects, without a prior personal or family history of depression. PD patients had lower (worse) baseline scores on the sadness, fatigue and vigor subscales of the POMS, in both ATD and the placebo condition, but not on the tension and anger subscales. There was however neither a significe between group effect, nor significe within-group effect due to ATD. We could find no evidence of a specific serotonergic vulnerability of PD patients for depression. Therefore, our results do not support the serotonergic hypothesis for depression in PD.

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Specificity of the tryptophan depletion method

Cited by 73 publications

References 33 publications

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

MDMA use and neurocognition: a meta-analytic review

The Serotonergic Hypothesis for Depression in Parkinson's Disease: an Experimental Approach

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