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Psychopharmacology (Berl). 2011 Jun;215(4):739-48. doi: 10.1007/s00213-011-2177-8. Epub 2011 Feb 19.

Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers.

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  • 1Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. a.colasanti@imperial.ac.uk

Abstract

RATIONALE:

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges.

OBJECTIVES:

Using a high-dose carbon dioxide (CO(2)) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO(2)-induced panic response in healthy volunteers.

METHODS:

Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO(2) inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO(2).

RESULTS:

CO(2)-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p < 0.05). In the separate-group analysis, ΔVAAS scores were positively correlated to the ratio Trp:ΣLNAA after treatment (r = 0.39; p < 0.05).

CONCLUSIONS:

The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects.

PMID:
21336580
[PubMed - indexed for MEDLINE]
PMCID:
PMC3102203
Free PMC Article
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