Does a laboratory-based CO2 challenge induce a hypothalamic-pituitary-adrenal (HPA) axis stress response in healthy adults?

A methodological limitation to studying hypothalamic-pituitary-adrenal (HPA) axis functioning is that there are few laboratory-based tasks that consistently induce a stress response. Moreover, most tasks use a socially-evaluative approach to eliciting a stress response. The aim of the current study was to test whether a CO2 inhalation challenge (originally designed to induce panic symptoms) produces a robust HPA-axis stress response. Forty-eight adults (mean age = 25.6; 69% women; 73% white) were recruited from a local university in the mid-southern part of the United States. Participants were asked to complete a 35% CO2 inhalation challenge. Six saliva samples were collected to measure cortisol responses to the task (a pre-stress baseline sample followed by 5 post-stress samples). Linear mixed effects modeling was used to examine whether there was a significant increase in cortisol following the challenge. There was substantial between-subjects variability in cortisol responses to the challenge. That said, the mean group cortisol response indicated that participants experienced an increase in cortisol 15-30 minutes post-challenge and a subsequent decrease in cortisol 45-60 minutes post-challenge (linear effect, b=0.007, p<0.001; quadratic effect, b=-0.0001, p<0.001). On average, there was a 53% increase in cortisol from baseline and nearly two-thirds of participants had at least a 45% increase in cortisol. The data suggest that a CO2 inhalation challenge can be used to induce a cortisol stress response among healthy participants and offers an alternative laboratory-based task that does not rely on socially-evaluative cues to induce stress.