Masuda, A, Nozoe, S I, Matsuyama, T et al. · Psychosomatic medicine · 1994 · DOI
This study compared immune system function and psychological stress levels in three groups: healthy people, those with chronic fatigue (but not ME/CFS), and patients with ME/CFS. All three groups showed differences in how stressed they felt, their activity levels, and how well their immune cells (specifically natural killer cells) worked. Importantly, the chronic fatigue group fell somewhere between healthy people and ME/CFS patients in terms of both psychological stress and immune function.
This study suggests that chronic fatigue without ME/CFS diagnosis may represent an early or prodromal state, with some individuals progressing to full ME/CFS. The identification of specific immune markers (NK cell activity, CD16+/CD56+ cells) alongside psychological and behavioral patterns could help identify who is at risk of developing ME/CFS, potentially enabling early intervention.
This study does not prove that low NK cell activity causes ME/CFS or chronic fatigue, only that the two are associated. The small sample size and cross-sectional design cannot establish causation or confirm whether the immune changes are primary drivers of the condition or secondary consequences. The observation of three intermediate cases developing CFS is suggestive but not definitive proof of disease progression.
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
Masuda, A, Nozoe, S I, Matsuyama, T, & Tanaka, H (1994). Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome.. Psychosomatic medicine. https://doi.org/10.1097/00006842-199411000-00006
BibTeX
@article{mecfsatlas-masuda-1994-psychobehavioral-immunological,
author = {Masuda, A and Nozoe, S I and Matsuyama, T and Tanaka, H},
title = {Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome.},
journal = {Psychosomatic medicine},
year = {1994},
doi = {10.1097/00006842-199411000-00006},
note = {PubMed: 7871106},
url = {https://www.mecfsatlas.com/evidence/masuda-1994-psychobehavioral-immunological},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/masuda-1994-psychobehavioral-immunological
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