title: Characterization of a 7% carbon dioxide (CO2) inhalation paradigm to evoke anxiety symptoms in healthy subjects.
abstract: The present study is aimed at characterizing the carbon dioxide (CO2) procedure in healthy subjects to achieve reliable provocation of anxiety symptoms. Thirty healthy subjects inhaled in single-blind both compressed air and 7% CO2 mixture. Panic Symptom List (PSLIII-R), Visual Analogue Scale-Anxiety (VAS-A), State Anxiety Inventory (STAI-Y/1), respiratory parameters and skin conductance were measured. 'Responders' were classified depending on PSLIII-R scores after CO2. Twelve out of the 21 'responders' performed a second test to assess test-retest repeatability. In 21 subjects Delta%VAS-A (45.4 +/- 32.1) and PSLIII-R (pre-test 2.3 +/-2.1, post-test 17.5 +/- 8.2) but not STAI-Y/1, significantly increased during CO2 inhalation. Respiratory Rate, Minute Volume, end-Tidal CO2 and skin conductance rose in 'responders'. Repeatability was studied with Bland-Altman plots, revealing mean difference between tests close to 0 for both Delta%VAS-A and PSLIII-R. Among physiologic parameters, end-Tidal CO2 and Respiratory Rate showed good repeatability, with a within-subject CV of 9.2% and 6%, respectively. The challenge produced measurable response in healthy subjects. Good test-retest repeatability was observed in 'responders'. These data indicate that the test can be suitable for testing putative anti-panic or anxiolytic drugs in clinical studies using a within subject, crossover design.
authors.affiliation: Psychiatry Centre of Excellence for Drug Discovery, Medical Research Centre, GlaxoSmithKline, Verona, Italy. stezanone@libero.it
authors.forename: Stefano Zanone
authors.initials: SZ
authors.lastname: Poma
authors.forename: Stefano
authors.initials: S
authors.lastname: Milleri
authors.forename: Lisa
authors.initials: L
authors.lastname: Squassante
authors.forename: Gianluca
authors.initials: G
authors.lastname: Nucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Bani
authors.forename: Giulia I
authors.initials: GI
authors.lastname: Perini
authors.forename: Emilio
authors.initials: E
authors.lastname: Merlo-Pich
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology*; D002245:Carbon Dioxide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D011594:Psychometrics / Q000379:methods; D012372:ROC Curve; D015203:Reproducibility of Results; D012119:Respiration / Q000187:drug effects; D016037:Single-Blind Method; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors
chemical_list: D002245:Carbon Dioxide