Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet

Biggio, Giovanni; Fadda, F; Fanni, Patrizia; Tagliamonte, A.; Gessa, Gian Luigi

doi:10.1016/0024-3205(74)90440-8

Cited by 256 publications

(154 citation statements)

References 9 publications

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“…364 ATD lowers plasma TRP 365 and alters 5-HT synthesis, metabolism, and release. 366 Brain 5-HT levels are temporarily lowered 367,368 and there is a decrease in brain 5-HT synthesis, 109 CSF 5-HT 369 and 5-HIAA concentrations. 366,370,371 Nishizawa et al 109 studied the effects of ATD on 5-HT synthesis and found that the rates of 5-HT synthesis were reduced by ATD by a factor of about 9.5 in men and a factor of about 40 in women.…”

Section: Depletion/atdmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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Section: Depletion/atdmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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“…Rapid depletion of plasma tryptophan levels by administration of a tryptophan-free amino acid drink (TFD) depletes central 5-HT levels (Biggio et al 1974;Moja et al 1988). See Moore et al (2000) for a recent review of the TFD literature.…”

Section: Serotonin Has Been Implicated In Both Sleep and Mood Regulatmentioning

confidence: 99%

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Evans

Golshan

Kelsoe

et al. 2002

Neuropsychopharmacology

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Serotonin has been implicated in both sleep and mood regulation. When central serotonin was depleted with a tryptophan-free amino acid drink (TFD),Serotonin (5-hydroxytryptamine; 5-HT) has long been implicated in the pathophysiology of depression as well as in the sleep and mood abnormalities associated with depression (Maes and Meltzer 1995). Specifically, deficiencies in 5-HT levels or in cellular responses to 5-HT neurotransmission are thought to be involved in depression. In support of this idea, deficiencies in 5-HT neurotransmission in various projections from the raphe nucleus can at least partially explain many of the common abnormalities seen in depression such as a depressed mood, decreased interest and pleasure, decreased appetite, and insomnia (Stahl 2000). Also commonly seen in depression are reduced rapid eye -Colin 1982;McCarley 1982;Jones 1991;Luebke et al. 1992).The rate of 5-HT synthesis is limited by the availability of its amino acid precursor, tryptophan. Rapid depletion of plasma tryptophan levels by administration of a tryptophan-free amino acid drink (TFD) depletes central 5-HT levels (Biggio et al. 1974;Moja et al. 1988). See Moore et al. (2000) for a recent review of the TFD literature.Consistent with the hypothesis that 5-HT inhibits REM sleep, Bhatti et al. (1998) found that a TFD decreased REM latency and increased REM% in normal male subjects. Voderholzer et al. (1998) found a significant increase in RD in 12 healthy subjects after TFD administration but saw no other significant REM changes. A study by Moore et al. (1998) found reduced RL and stage 2 percent (S2%) and increased REM% and RD after TFD administration in fully remitted depression patients on selective serotonin reuptake inhibitors (SSRIs). Additionally, in four patients treated with the monoamine oxidase inhibitor (MAOI), phenelzine, Landolt et al. (2000) showed increased REM time and REM% after TFD administration.With regard to mood, TFD studies have had mixed results when tested in normal subjects. One TFD study showed normal males having significantly increased scores on a depression scale, the Multiple Affect Adjective Checklist (MAACL), after TFD administration (Young et al. 1985). Benkelfat et al. (1994) also found decreased mood on the Profile of Mood States (POMS) in six out of 20 of his healthy male subjects with a multigenerational history of affective disorder. Additionally, Klaassen et al. (1999) found that TFD administration lowered mood in both subjects with and without a family history of affective disorders with the mood changes being significantly more evident in those with a family history. Ellenbogen et al. (1996) showed that healthy female subjects had significantly lower scores after a TFD on four of six scales on the bipolar form of the POMS including the depression scale. However, Ellenbogen et al. (1999) showed that normal females with a multi-generational family history of major affective disorders had no lowering of mood in response to a TFD. Quintin et al. (2001) showed a decline in mood as m...

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“…First, decline in plasma Trp occurs because the Trpdeficient amino acid mixture promotes synthesis of new proteins. Trp incorporated into protein comes from blood and tissue pools, and therefore its concentration in plasma and brain falls (Biggio et al 1974;Gessa et al Stancampiano et al 1997). Magnetoencephalography (MEG) is a method for the measurement of extracranial magnetic fields produced by ionic current flow generated mainly by cortical pyramidal cells.…”

mentioning

confidence: 99%

“…First, decline in plasma Trp occurs because the Trpdeficient amino acid mixture promotes synthesis of new proteins. Trp incorporated into protein comes from blood and tissue pools, and therefore its concentration in plasma and brain falls (Biggio et al 1974;Gessa et al 1975). Second, all large neutral amino acids (LNAA) compete for the same carrier system that transport them across the blood-brain barrier (Oldendorf 1973).…”

mentioning

confidence: 99%

Serotonin Modulates Early Cortical Auditory Processing in Healthy Subjects. Evidence from MEG with Acute Tryptophan Depletion

Kähkönen

Ahveninen

Pennanen

et al. 2002

Neuropsychopharmacology

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We studied the effects of acute tryptophan depletion (ATD) on early cortical auditory processing. Middle-latency auditory evoked fields (MAEF) were investigated in 14 healthy subjects after 5 h of ATD or control mixture ingestion in a randomized, double-blinded, controlled crossover design study. MAEFs to monaural click stimuli (0.1-ms duration) were recorded with a 122-channel neuromagnetometer. Total plasma tryptophan (Trp),Low brain serotonin (5-HT) levels and function have been implicated in various psychopathologies including depression and anxiety. Acute tryptophan depletion (ATD) is a dietary intervention that rapidly lowers plasma tryptophan (Trp) and alters 5-HT synthesis, metabolism, and release in animals and humans (Young et al. 1985;Nishizawa et al. 1997;Stancampiano et al. 1997;Carpenter et al. 1998). It involves the administration of an amino acid mixture that lacks Trp, the amino acid precursor of serotonin. The effect of ATD on 5-HT synthesis and metabolism is twofold (Young et al. 1985). First, decline in plasma Trp occurs because the Trpdeficient amino acid mixture promotes synthesis of new proteins. Trp incorporated into protein comes from blood and tissue pools, and therefore its concentration in plasma and brain falls (Biggio et al. 1974;Gessa et al. Stancampiano et al. 1997). Magnetoencephalography (MEG) is a method for the measurement of extracranial magnetic fields produced by ionic current flow generated mainly by cortical pyramidal cells. MEG is a non-invasive method for functional brain studies with temporal resolution as high as electroencephalography (EEG), but with more accurate source localization . Because of cortical folding in the Sylvian fissure, MEG is ideally suited for the localization and measurement of supratemporal auditory cortical activity .Auditory evoked magnetic potentials (AEP) and fields (AEF), which allow the investigation underlying auditory processing, can be obtained by averaging EEG or MEG epochs time-locked to the presentation of auditory stimuli. The earliest cortical AEFs, the middlelatency AEFs (MAEFs), occur at about 20-70 ms from stimulus onset. The MAEFs are composed of several distinct deflections, with Pam peaking at approximately 30 ms and Nbm at about 45 ms.There is evidence to suggest that serotonergic activity may modulate auditory evoked potentials (Hegerl and Juckel 1993;Juckel et al. 1997;Dierks et al. 1999) and background EEG frequencies (Knott et al. 1999). The sound intensity dependence of auditory N1/P2 amplitude has been suggested to be a specific indicator of serotonin function (Hegerl and Juckel 1993;Juckel et al. 1997). Reduced serotonin function leads to higher intensity dependence of N1/P2 amplitude and vice versa. However, Dierks et al. (1999) were not able to confirm these findings using ATD in healthy subjects. In contract, this study showed that ATD decreases the intensity dependence of N1/P2 amplitudes. In the recent ATD study using a 52-g amino acid challenge, Hughes et al. (2000) found no changes in auditory N1, P2, or P3 ampl...

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Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet

Cited by 256 publications

References 9 publications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Serotonin Modulates Early Cortical Auditory Processing in Healthy Subjects. Evidence from MEG with Acute Tryptophan Depletion

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