Tryptophan Depletion During Continuous CSF Sampling in Healthy Human Subjects

Carpenter, MW; Anderson, George M.; Pelton, M.D Gregory H.; Gudin, M.D Jeffrey A.; Kirwin, M.D Paul D.S.; Price, Marjorie; Heninger, M.D George R.; McDougle, M

doi:10.1016/s0893-133x(97)00198-x

Cited by 283 publications

(257 citation statements)

References 44 publications

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“…Furthermore, decreases of such a magnitude have been shown to significantly affect brain serotonin synthesis (Moja et al, 1988;Nishizawa et al, 1997), CSF concentrations of serotonin metabolites (Carpenter et al, 1998;Williams et al, 1999), and serotonin-dependent cognitive processes (Sambeth et al, 2007). Following ATD we observed impairments in sensorimotor gating, as evidenced by a reduction in PPI.…”

Section: Serotonin Depletionmentioning

confidence: 81%

“…Participants were seated in a comfortable chair, approximately 60 cm from a computer screen, tested for hearing, and given instructions for each test paradigm. The 5-h latency period was chosen to coincide with the timing of the maximal pharmacokinetic and physiological effects of monoamine depletion, as determined in the previous research (Carpenter et al, 1998;Harrison et al, 2004;Harmer et al, 2001;Leyton et al, 2000;Matrenza et al, 2004;McTavish et al, 1999a;Moja et al, 1988;Mehta et al, 2005;Nathan et al, 2004;Nishizawa et al, 1997;Sambeth et al, 2007;Williams et al, 1999). Upon conclusion of the testing procedure, participants were provided with high-protein snacks to replenish their amino-acid levels.…”

Section: Methodsmentioning

confidence: 99%

“…On the basis of acute precursor restrictions, endogenous neurotransmitter release is reduced through an ingested suspension of amino acids that lack certain neurotransmitter precursors. In humans, acute tryptophan depletion (ATD) has been shown to acutely decrease concentrations of serotonin and its metabolites (Carpenter et al, 1998;Moja et al, 1988;Nishizawa et al, 1997;Williams et al, 1999), and has been shown to consistently impair serotonin-dependent processes such as memory consolidation and learning Sambeth et al, 2007). Using this method, serotonin depletion was found to decrease PPI in healthy humans (Phillips et al, 2000a).…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

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Schizophrenia is associated with impairments of sensorimotor and sensory gating as measured by prepulse inhibition (PPI) of the acoustic startle response and P50 suppression of the auditory event-related potential respectively. While serotonin and dopamine play an important role in the pathophysiology and treatment of schizophrenia, their role in modulating PPI and P50 suppression in humans is yet to be fully clarified. To further explore the role of serotonin and dopamine in PPI and P50 suppression, we examined the effects of acute tryptophan depletion (to decrease serotonin) and acute tyrosine/phenylalanine depletion (to decrease dopamine) on PPI and P50 suppression in healthy human participants. In addition, we also examined for the first time, the effects of simultaneous serotonin and dopamine depletion (ie combined monoamine depletion) on PPI and P50 suppression. The study was a double-blind, placebo-controlled cross-over design in which 16 healthy male participants completed the PPI and P50 paradigms under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/ phenylalanine/tryptophan depletion (combined monoamine depletion). Selective depletion of dopamine had no significant effect on either PPI or P50 suppression, whereas selective serotonin depletion significantly disrupted PPI, but not P50 suppression. Finally, the simultaneous depletion of both serotonin and dopamine resulted in significant reduction of both PPI and P50 suppression. We suggest these results can be explained by theories relating to optimal levels of monoaminergic neurotransmission and synergistic interactions between serotonergic and dopaminergic systems for normal 'gating' function. These findings suggest that a dysfunction in both serotonin and dopamine neurotransmission may, in part, be responsible for the gating deficits observed in schizophrenia, and their normalization following administration of atypical antipsychotic drugs.

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Section: Serotonin Depletionmentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

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“…5 brain regions (Nishizawa et al 1997). Furthermore ATD has been shown to decrease the concentration of 5-HIAA, the principal metabolite of serotonin in cerebrospinal fluid in normal volunteers, by over 30% (Carpenter et al 1998;Williams et al 1999). There is evidence from animal and human studies that an amino acid drink deficient in tyrosine (Tyr) can interfere with central catecholamine function in a way similar to the effects of ATD in humans (Moja et al 1996;Harmer et al 2001).…”

Section: Resultsmentioning

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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“…Here, we test this hypothesis by investigating the effects of ATD, a well-known procedure to reduce central nervous system 5-HT (Nishizawa et al, 1997;Carpenter et al, 1998), on performance of an observational learning paradigm that allowed the independent assessment of reward and punishment prediction. Reward-and punishment-prediction trials were matched in terms of response inhibition demands, and learning demands were maximized by repeatedly reversing contingencies at unpredictable intervals.…”

Section: Introductionmentioning

confidence: 99%

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Cools

Robinson

Sahakian

2007

Neuropsychopharmacol

152

154

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Central serotonin (5-HT) has been implicated in emotional and behavioral control processes for many decades, but its precise contribution is not well understood. We used the acute tryptophan depletion procedure in young healthy volunteers to test the hypothesis that central 5-HT is critical for predicting punishment. An observational reversal-learning task was employed that provided separate measures of punishment and reward prediction. Under baseline, subjects made more prediction errors for punishmentassociated stimuli than for reward-associated stimuli. This bias was abolished after central 5-HT depletion, which enhanced the ability to predict punishment while not affecting reward prediction. The selective potentiation of punishment prediction concurs with recent theorizing, suggesting that central 5-HT carries a prediction error for future punishment, but not for future reward (Daw et al, 2002). Furthermore, the finding highlights the importance of central 5-HT in resilience to adversity and may have implications for a variety of neuropsychiatric disorders including depression and anxiety.

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Tryptophan Depletion During Continuous CSF Sampling in Healthy Human Subjects

Cited by 283 publications

References 44 publications

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

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

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

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