title: Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.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
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colasanti
authors.forename: Gabriel
authors.initials: G
authors.lastname: Esquivel
authors.forename: Erik
authors.initials: E
authors.lastname: den Boer
authors.forename: Annerieke
authors.initials: A
authors.lastname: Horlings
authors.forename: Abdul
authors.initials: A
authors.lastname: Dandachi
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Oostwegel
authors.forename: Eva L
authors.initials: EL
authors.lastname: van Donkelaar
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Griez
authors.forename: Koen
authors.initials: K
authors.lastname: Schruers
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency; D002245:Carbon Dioxide; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000097:blood / Q000139:chemically induced / Q000523:psychology*; D008297:Male; D016584:Panic Disorder / Q000097:blood / Q000517:prevention & control* / Q000523:psychology; D011581:Psychological Tests; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism; D014364:Tryptophan / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency*
chemical_list: D000596:Amino Acids; D002245:Carbon Dioxide; D012701:Serotonin; D014364:Tryptophan