Jones, James F · Psychoneuroendocrinology · 2008 · DOI
This paper proposes that ME/CFS and post-infection fatigue may develop when the brain's ability to sense and respond to the body becomes stuck in a protective 'sickness mode' even after the infection has cleared. Rather than being a true ongoing disease, the authors suggest it may be an altered state where the brain continues to trigger immune and stress responses as if the body is still fighting an infection, causing ongoing fatigue and other symptoms.
This conceptual framework offers an important bridge between biological and psychological perspectives on ME/CFS, proposing that brain-immune dysregulation rather than purely peripheral immune dysfunction or psychiatric pathology could explain persistent post-infection fatigue. Understanding the brain's role in perpetuating symptoms could redirect research toward novel imaging and challenge-based diagnostic tools and open new therapeutic avenues targeting neural-immune signaling.
This is a theoretical paper with no empirical data; it does not prove that interoceptive dysfunction causes ME/CFS or that functional brain imaging will identify meaningful biomarkers. The paper does not establish whether the proposed 'altered self state' is distinct from other biological mechanisms of ME/CFS, nor does it demonstrate that targeted interventions based on this model will be clinically effective.
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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