Hypothalamic-pituitary-adrenal (HPA) axis stress response to a laboratory-based 10 % CO2 challenge in healthy adults

Authors

• Harrison Dickens, University of Arkansas-FayettevilleFollow
• L. Riley Gournay-Berman, University of Arkansas, Fayetteville
• Morgan Hill, University of Arkansas, Fayetteville
• Mikayla Danielle Marie Joslin, University of Arkansas-FayettevilleFollow
• Jamie Walker, University of Arkansas, Fayetteville
• Anastasia Makhanova, University of Arkansas, FayettevilleFollow
• Ellen Leen-Feldner, University of Arkansas, FayettevilleFollow
• Ivan Vargas, University of Arkansas, FayettevilleFollow

Document Type

Article

Publication Date

2-2026

Keywords

HPA-axis, CO (2) challenge, Stress reactivity, Sex differences, Hormonal contraceptives

Abstract

Background: Acute stress reactivity has been implicated in a wide range of physical and psychological disorders. Most literature has focused on laboratory paradigms that elicit neuroendocrine responses via socially evaluative stress. While shown to be effective at eliciting stress responses, these socially evaluative paradigms may only tap into a narrow range of stressors. Carbon dioxide (CO2) inhalation challenges have been shown to reliably elicit panic-relevant symptoms in healthy populations but evidence on the ability to elicit a neuroendocrine response is limited. Methods: The current secondary analysis sought to examine the magnitude of neuroendocrine, sympathetic, and emotional response to a 5-minute, 10 % CO2-enriched air inhalation task in healthy volunteers. Seventy-five healthy adults (M-age: 27.2, 53.3 % female) completed the laboratory procedure. Results: Results from mixed effects growth curve models found a significant linear (b = 0.006, df = 367, p < 0.001) and quadratic effect (b = -0.0001, df = 293, p < 0.001) of the challenge on salivary cortisol. The majority of the sample (57.3 %) experienced at least a 50 % increase in salivary cortisol from baseline. Women displayed a more blunted cortisol response than men (b = -0.00007, df = 293, p < 0.001). Hormonal contraceptive users, relative to naturally cycling women, also had a more blunted reactivity slope. Both heart rate and perceived fear also increased significantly in response to the task. Conclusions: Findings from the current study suggest that the CO2 protocol employed in the current study can elicit meaningful neuroendocrine, sympathetic, and emotional responses.

Comments

Web of Science

Elsevier

Citation

Harrison Dickens, L. Riley Gournay-Berman, Morgan Hill, Mikayla D.M. Joslin, Jamie Walker, Anastasia Makhanova, Ellen Leen-Feldner, Ivan Vargas, Hypothalamic-pituitary-adrenal (HPA) axis stress response to a laboratory-based 10 % CO2 challenge in healthy adults, Psychoneuroendocrinology, Volume 184, 2026, 107712, ISSN 0306-4530, https://doi.org/10.1016/j.psyneuen.2025.107712.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.