A mathematical model of the HPA axis demonstrates bifurcations under varying stress and systemic conditions
- 1Department of Electrical and Computer Engineering, University of Western Macedonia, 50131 Kozani, Greece
Abstract
In this study, we develop a mathematical model of the hypothalamic pituitary adrenal (HPA) axis and systematically investigate the model complexity required to reproduce observed hormone dynamics. The model is fitted to ACTH and cortisol measurements from five healthy volunteers reported in the literature. We show that simultaneous reproduction of both hormone profiles requires a delay differential equation model with at least five state variables among the model architectures considered. Following fitting the volunteer data, we investigate the response of the model to sustained stress using bifurcation analysis. The coupled system exhibits bifurcations over a range of stress intensities. This analysis reveals bifurcations whose critical stress thresholds depend strongly on the modulatory state of the system. These results provide a mathematical framework for investigating transitions between physiological and dysregulated HPA axis dynamics, which may be related to states of health and disease.
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BibTeX
@misc{violaris2026mathematical,
title = {{A mathematical model of the HPA axis demonstrates bifurcations under varying stress and systemic conditions}},
author = {I. G. Violaris and D. Pinotsis and M. Tsipouras and K. Kalafatakis},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.757338},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757338v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A mathematical model of the HPA axis demonstrates bifurcations under varying stress and systemic conditions
AU - I. G. Violaris
AU - D. Pinotsis
AU - M. Tsipouras
AU - K. Kalafatakis
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.757338
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.757338v1
AB - In this study, we develop a mathematical model of the hypothalamic pituitary adrenal (HPA) axis and systematically investigate the model complexity required to reproduce observed hormone dynamics. The model is fitted to ACTH and cortisol measurements from five healthy volunteers reported in the literature. We show that simultaneous reproduction of both hormone profiles requires a delay differential equation model with at least five state variables among the model architectures considered. Following fitting the volunteer data, we investigate the response of the model to sustained stress using bifurcation analysis. The coupled system exhibits bifurcations over a range of stress intensities. This analysis reveals bifurcations whose critical stress thresholds depend strongly on the modulatory state of the system. These results provide a mathematical framework for investigating transitions between physiological and dysregulated HPA axis dynamics, which may be related to states of health and disease.
ER -