Sedghamiz, Hooman, Morris, Matthew, Craddock, Travis J A et al. · BMC systems biology · 2018 · DOI
This study created a simple computer model to understand how the body's stress-response system (the HPA axis) works and how it can get stuck in unhealthy patterns in conditions like ME/CFS. The researchers found that stress may push this system into a low-cortisol state and keep it there, and that certain treatments might help restore normal daily rhythms. The model worked better and required less data than previous complex models.
HPA axis dysfunction is a hallmark of both Gulf War Illness and ME/CFS, yet traditional models require extensive data that is rarely available in clinical settings. This parsimonious discrete modeling approach offers a new framework to understand how the stress-response system becomes dysregulated and could guide identification of therapeutic targets to restore normal cortisol rhythms in ME/CFS patients.
This is a theoretical modeling study and does not prove that stress directly causes the HPA axis to shift to low-cortisol states in ME/CFS patients. The model predictions require experimental validation in human or animal studies before clinical applications can be established. The work does not provide evidence about the cause of HPA axis dysregulation or whether the proposed interventions would work in actual patients.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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Primary citation
Sedghamiz, Hooman, Morris, Matthew, Craddock, Travis J A, Whitley, Darrell, & Broderick, Gordon (2018). High-fidelity discrete modeling of the HPA axis: a study of regulatory plasticity in biology.. BMC systems biology. https://doi.org/10.1186/s12918-018-0599-1
BibTeX
@article{mecfsatlas-sedghamiz-2018-high-fidelity,
author = {Sedghamiz, Hooman and Morris, Matthew and Craddock, Travis J A and Whitley, Darrell and Broderick, Gordon},
title = {High-fidelity discrete modeling of the HPA axis: a study of regulatory plasticity in biology.},
journal = {BMC systems biology},
year = {2018},
doi = {10.1186/s12918-018-0599-1},
note = {PubMed: 30016990},
url = {https://www.mecfsatlas.com/evidence/sedghamiz-2018-high-fidelity},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/sedghamiz-2018-high-fidelity
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