Mood-Lowering Effect of Tryptophan Depletion

Benkelfat, Chawki; Ellenbogen, Mark A.; Dean, Peggy; Palmour, Roberta M.; Young, Simon N.

doi:10.1001/archpsyc.1994.03950090019003

Cited by 311 publications

(61 citation statements)

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“…Clarifying studies have found that increased susceptibility to mood effects occurs in healthy subjects at genetic risk for depression (27), in women (28) and in remitted subjects with major depressive disorder -whether receiving medication (29) or not receiving medication (30). The probability of TD-induced mood symptoms is highest in remitted patients with a major depressive disorder and in those who are treated with selective SSRIs (31).…”

Section: Tryptophan Depletion (Td) Studiesmentioning

confidence: 99%

Mood effects of the amino acids tryptophan and tyrosine

Parker

Brotchie

2011

Acta Psychiatr Scand

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Parker G, Brotchie H. Mood effects of the amino acids tryptophan and tyrosine.Objective: Reflecting increased scientific interest in any nutritional contribution to the onset and treatment of mood disorders, we overview research into two neurotransmitter precursors – the amino acids tryptophan and tyrosine – particularly examining whether any deficiency increases risk to depression and whether those amino acids have any antidepressant properties.Method: The theoretical relevance of the two amino acids was overviewed by considering published risk and intervention studies, technical papers and reviews.Results: There is some limited evidence, suggesting that depressed patients, especially those with a melancholic depression, have decreased tryptophan levels. Whether such findings reflect a causal contribution or are a consequence of a depressed state remains an open question. There is a small database supporting tryptophan preparations as benefitting depressed mood states. There is no clear evidence as to whether tyrosine deficiency contributes to depression, while the only randomized double‐blind study examining tyrosine supplementation did not show antidepressant benefit.Conclusion: Acute tryptophan depletion continues to provide a research tool for investigating the relevance of serotonin to depression onset. There is limited evidence that tryptophan loading is effective as a treatment for depression through its action of increasing serotonin production. Most clinical studies are dated, involve small sample sizes and/or were not placebo controlled. The development of the new serotonin reuptake inhibitor drugs seemingly signalled an end to pursuing such means of promoting increased serotonin as a treatment for depression. The evidence for tyrosine loading promoting catecholamine production as a possible treatment for depression appears even less promising, and depletion studies less informative.

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Section: Tryptophan Depletion (Td) Studiesmentioning

confidence: 99%

Mood effects of the amino acids tryptophan and tyrosine

Parker

Brotchie

2011

Acta Psychiatr Scand

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“…The latter hypothesis for a causal role of 5-HT in MDD has often been dismissed over the years, because of a lack of consistency of observations on a decrease of 5-HT concentrations in post-mortem brain samples, and the fact that acute tryptophan depletion does not produce depression in healthy controls, tryptophan being the essential amino acid precursor of 5-HT [6]. Nevertheless, in unaffected individuals with a family history of depression, mild dysphoric symptoms can be triggered by this acute 5-HT-lowering challenge [7]. One can thus wonder whether a prolonged 5-HT lowering might not lead to MDD.…”

Section: Introductionmentioning

confidence: 99%

Serotonin and beyond: therapeutics for major depression

Blier

Mansari

2013

Phil. Trans. R. Soc. B

215

136

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The serotonin (5-HT, 5-hydroxytryptamine) system has been implicated in the pathogenesis of major depressive disorder (MDD). The case for its contribution to the therapeutic efficacy of a wide variety of antidepressant treatments is, however, much stronger. All antidepressant strategies have been shown to enhance 5-HT transmission in the brain of laboratory animals. Catecholamines, norepinephrine (NE) and dopamine (DA) can also play a pivotal role in the mechanism of action of certain antidepressant strategies. The enhancement of 5-HT transmission by selective serotonin reuptake inhibitors, which leads to a dampening of the activity of NE and DA neurons, may account in part for the low remission rate achieved with these medications and/or the residuals symptoms after remission is achieved. The functional connectivity between the 5-HT, NE and DA systems can be used to understand the mechanism of action of a wide variety of augmentation strategies in treatment-resistant MDD. Proof-of-concept studies have shown that antidepressant medications with complementary mechanisms of action on monoaminergic systems can double the remission rate achieved in a trial of standard duration. Novel approaches are also being used to treat MDD, which also appear to involve the monoaminergic system(s) to a varying extent.

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“…Second, ATD induces a transient reappearance of depressive symptoms in patients under treatment with antidepressants (13). Moreover, ATD also produces a mild lowering of mood in normal subjects with a family history of depression (14). It is therefore of interest to determine the degree of reduction in serotonin synthesis associated with changes in mood.…”

mentioning

confidence: 99%

Differences between males and females in rates of serotonin synthesis in human brain

Nishizawa

Benkelfat²,

Young³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

823

587

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Rates of serotonin synthesis were measured in the human brain using positron emission tomography. The sensitivity of the method is indicated by the fact that measurements are possible even after a substantial lowering of synthesis induced by acute tryptophan depletion. Unlike serotonin levels in human brain, which vary greatly in different brain areas, rates of synthesis of the indolamine are rather uniform throughout the brain. The mean rate of synthesis in normal males was found to be 52% higher than in normal females; this marked difference may be a factor relevant to the lower incidence of major unipolar depression in males. Low brain serotonin (5-HT) levels or function have been implicated in various types of psychopathology, including depression, suicide, aggression, anxiety, and bulimia (for reviews see refs. 1-3). Until recently, the principal methods for studying serotonin metabolism in human brain were determination of the metabolite of serotonin 5-hydroxyindole-3-acetic acid (5-HIAA) in cerebrospinal fluid (CSF) and postmortem measurements of brain serotonin and 5-HIAA. Both methods have limitations. In particular, neither provides a direct measure of serotonin synthesis in the living brain. Recently, a method for measuring serotonin synthesis in the brain of living mammals has been developed (4-5) and tested successfully in dogs (6). The method uses positron emission tomography (PET) and ␣-[11 C]methyl-L-tryptophan as a tracer. The tracer is converted in part to ␣-[11 C]methylserotonin, which accumulates in serotonin neurons, because it is not a substrate for monoamine oxidase and does not cross the bloodbrain barrier.We report here in vivo measurements of serotonin synthesis in the brain of healthy volunteers. Both male and female subjects were studied because CSF studies suggest that the rate of brain serotonin metabolism is higher in females than in males (7-8), and because the incidence of major unipolar depression is higher in women (9). We measured rates of serotonin synthesis under two conditions: at baseline and after acute tryptophan depletion (ATD). For ATD, subjects ingest a tryptophan-free mixture of all the essential amino acids. This induces protein synthesis, which incorporates body stores of free tryptophan into protein, thus reducing the level of this amino acid in tissues, including brain (10). Because tryptophan is the precursor of serotonin, its reduction is thought to lower the rate of serotonin synthesis in brain (11-12). ATD was used in the present study for several reasons. First, low serotonin levels have been proposed to relate to various types of psychopathology (for reviews see refs. 1-3), so any useful method of in vivo measurements of the serotonin synthesis rate must have a demonstrated capability for measuring low rates of serotonin synthesis. Second, ATD induces a transient reappearance of depressive symptoms in patients under treatment with antidepressants (13). Moreover, ATD also produces a mild lowering of mood in normal subjects with a family history of de...

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Mood-Lowering Effect of Tryptophan Depletion

Cited by 311 publications

References 50 publications

Mood effects of the amino acids tryptophan and tyrosine

Mood effects of the amino acids tryptophan and tyrosine

Serotonin and beyond: therapeutics for major depression

Differences between males and females in rates of serotonin synthesis in human brain

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