title: The four-dimensional stress test: psychological, sympathetic-adrenal-medullary, parasympathetic and hypothalamic-pituitary-adrenal responses following inhalation of 35% CO2.
abstract: BACKGROUND
  Hypercapnia is a threat to homeostasis and results in neuroendocrine, autonomic and anxiogenic responses. The inhalation of carbon dioxide (CO2) may, therefore, provide a good paradigm for exploring the pathways by which stress can lead to increased susceptibility to ill-health through physiological and psychological stress reactivity. The current study was designed, therefore, to assess the psychological and physiological responses to the inhalation of CO2.
  
  
  METHODS
  Healthy participants (N = 24) inhaled a single vital capacity breath of a mixture of CO2 (35%) and oxygen (65%). Blood pressure and heart rate were recorded for 5 min before and after the test and blood and saliva samples were taken immediately before and 2, 10, 20 and 30 min post-inhalation for the measurement of noradrenaline, salivary and serum cortisol and salivary alpha amylase. In addition, psychosomatic symptoms were recorded immediately before and after the test. The same protocol was repeated 4-6 weeks later at the same time of day.
  
  
  RESULTS
  A single inhalation of CO2 increased blood pressure, noradrenaline, salivary alpha amylase and psychosomatic symptoms, but decreased heart rate at both testing sessions. Analyses of salivary cortisol data revealed that 70% of the sample could be reliably classified as either responders (i.e. demonstrated a post-CO2 cortisol increase) or non-responders (i.e. responded with a decrease or no change in cortisol following CO2) at both test sessions. Responders also perceived the test to be more aversive than non-responders.
  
  
  CONCLUSIONS
  Inhalation of 35% CO2 reliably stimulated the key mechanisms involved in the human stress response. The inter-individual differences in the reactivity of the hypothalamic-pituitary-adrenal axis were also related to differences in the perception of the test.
authors.affiliation: MRC Health Services Research Collaboration, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, UK. mark.wetherell@bristol.ac.uk
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wetherell
authors.forename: Anna L
authors.initials: AL
authors.lastname: Crown
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: Jeremy N V
authors.initials: JN
authors.lastname: Miles
authors.forename: Joey
authors.initials: J
authors.lastname: Kaye
authors.forename: Kavita
authors.initials: K
authors.lastname: Vedhara
mesh_terms: D000280:Administration, Inhalation; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006935:Hypercapnia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D012463:Saliva / Q000378:metabolism; D018709:Statistics, Nonparametric; D013312:Stress, Physiological / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology; D013315:Stress, Psychological / Q000139:chemically induced / Q000378:metabolism*; D000516:alpha-Amylases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002245:Carbon Dioxide; D000516:alpha-Amylases; D006854:Hydrocortisone; D009638:Norepinephrine