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

Colasanti A, Esquivel G, den Boer E, Horlings A, Dandachi A, Oostwegel JL, van Donkelaar EL, Griez EJ, Schruers K - Psychopharmacology (Berl.) (2011)

Bottom Line: CO(2)-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p < 0.05).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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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VAAS scores for fear/discomfort at 0, 1.5, 3, 4.5 h after treatment, and after CO2 inhalation, across treatment conditions. Acute tryptohan depletion (ATD), balanced condition (BAL), acute tryptophan loading (ATL); change in VAAS scores was significantly lower in ATD compared to BAL and ATL (time X condition interaction: p < 0.05)
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Fig2: VAAS scores for fear/discomfort at 0, 1.5, 3, 4.5 h after treatment, and after CO2 inhalation, across treatment conditions. Acute tryptohan depletion (ATD), balanced condition (BAL), acute tryptophan loading (ATL); change in VAAS scores was significantly lower in ATD compared to BAL and ATL (time X condition interaction: p < 0.05)

Mentions: VAAS scores (fear/discomfort) between conditions at different time points, are presented in Fig. 2. There were no significant differences in VAAS scores at T0, T1, T2, and T3 between conditions. No effect of GBM administration per se was observed on VAAS scores, as no significant difference was found between any of pre-CO2 challenge time points (T3, T2, T1) and T0 in any condition. CO2 inhalation was followed by an increase in VAAS scores in all the conditions (F = 57.49; p < 0.0001). A significant time X condition interaction was found, indicating that ΔVAAS scores were significantly lower in ATD compared to BAL and ATL (33.89 ± 26.18 vs 43.78 ± 25.5 and 44.17 ± 23.88, respectively; F = 5.79 and F = 6.58, p < 0.05). No significant differences were found between BAL and ATL conditions. The findings remained identical after controlling for gender and no effects of time X gender X condition interaction have been found.Fig. 2


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

Colasanti A, Esquivel G, den Boer E, Horlings A, Dandachi A, Oostwegel JL, van Donkelaar EL, Griez EJ, Schruers K - Psychopharmacology (Berl.) (2011)

VAAS scores for fear/discomfort at 0, 1.5, 3, 4.5 h after treatment, and after CO2 inhalation, across treatment conditions. Acute tryptohan depletion (ATD), balanced condition (BAL), acute tryptophan loading (ATL); change in VAAS scores was significantly lower in ATD compared to BAL and ATL (time X condition interaction: p < 0.05)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102203&req=5

Fig2: VAAS scores for fear/discomfort at 0, 1.5, 3, 4.5 h after treatment, and after CO2 inhalation, across treatment conditions. Acute tryptohan depletion (ATD), balanced condition (BAL), acute tryptophan loading (ATL); change in VAAS scores was significantly lower in ATD compared to BAL and ATL (time X condition interaction: p < 0.05)
Mentions: VAAS scores (fear/discomfort) between conditions at different time points, are presented in Fig. 2. There were no significant differences in VAAS scores at T0, T1, T2, and T3 between conditions. No effect of GBM administration per se was observed on VAAS scores, as no significant difference was found between any of pre-CO2 challenge time points (T3, T2, T1) and T0 in any condition. CO2 inhalation was followed by an increase in VAAS scores in all the conditions (F = 57.49; p < 0.0001). A significant time X condition interaction was found, indicating that ΔVAAS scores were significantly lower in ATD compared to BAL and ATL (33.89 ± 26.18 vs 43.78 ± 25.5 and 44.17 ± 23.88, respectively; F = 5.79 and F = 6.58, p < 0.05). No significant differences were found between BAL and ATL conditions. The findings remained identical after controlling for gender and no effects of time X gender X condition interaction have been found.Fig. 2

Bottom Line: CO(2)-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p < 0.05).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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

Show MeSH
Related in: MedlinePlus