Milrad, Sara F, Hall, Daniel L, Jutagir, Devika R et al. · International journal of psychophysiology : official journal of the International Organization of Psychophysiology · 2018 · DOI
This study examined how depression, stress hormone levels, and inflammation connect in ME/CFS patients. Researchers found that people with ME/CFS who had higher evening cortisol (a stress hormone) levels also had more depression and higher levels of inflammatory markers in their blood. The results suggest that depression, hormones, and the immune system may be interconnected in ME/CFS, though more research is needed to understand which causes which.
Understanding how depression, stress hormones, and inflammation interact in ME/CFS could help explain why these symptoms cluster together and may inform treatment strategies targeting multiple biological systems simultaneously. This research bridges psychological and immunological aspects of ME/CFS, supporting a biopsychosocial approach rather than viewing these as separate problems.
This cross-sectional design cannot establish causation—it shows associations only, not whether depression causes elevated cortisol, cortisol causes depression, or whether both are caused by another factor. The study does not prove that the observed hormonal and inflammatory patterns are unique to ME/CFS or that they directly cause the fatigue characteristic of the illness. Time-lagged longitudinal data would be needed to determine the temporal sequence and causal directionality of these relationships.
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Milrad, Sara F, Hall, Daniel L, Jutagir, Devika R, Lattie, Emily G, Czaja, Sara J, Perdomo, Dolores M, et al. (2018). Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model.. International journal of psychophysiology : official journal of the International Organization of Psychophysiology. https://doi.org/10.1016/j.ijpsycho.2017.09.009
BibTeX
@article{mecfsatlas-milrad-2018-depression-evening,
author = {Milrad, Sara F and Hall, Daniel L and Jutagir, Devika R and Lattie, Emily G and Czaja, Sara J and Perdomo, Dolores M and Fletcher, Mary Ann and Klimas, Nancy and Antoni, Michael H},
title = {Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model.},
journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology},
year = {2018},
doi = {10.1016/j.ijpsycho.2017.09.009},
note = {PubMed: 28918107},
url = {https://www.mecfsatlas.com/evidence/milrad-2018-depression-evening},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/milrad-2018-depression-evening
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