Smesam, Hasan Najah, Qazmooz, Hasan Abbas, Khayoon, Sinan Qayes et al. · Journal of personalized medicine · 2022 · DOI
This study looked at 118 people with rheumatoid arthritis (RA, an autoimmune disease affecting joints) and 50 healthy people to understand why RA patients often experience depression, anxiety, and fatigue. Researchers measured immune system markers and psychological symptoms, finding that about 70% of these mental and fatigue symptoms could be explained by the same immune system problems that cause RA itself.
This work is relevant to ME/CFS research because it demonstrates that chronic inflammatory and autoimmune conditions can produce depression, anxiety, and fatigue through shared immune-inflammatory mechanisms rather than psychological factors alone. Understanding these shared pathways may help explain why ME/CFS frequently co-occurs with mood and anxiety symptoms and could support biomarker-driven approaches to diagnosis and treatment.
This study does not prove causation—the cross-sectional design means researchers measured immune markers and symptoms at a single time point, so they cannot establish that immune dysregulation directly causes depression and fatigue. The study focuses on RA specifically and does not directly measure ME/CFS patients, so findings may not fully generalize to ME/CFS populations. Correlation between markers and symptoms does not exclude other contributing mechanisms, such as cytokine-induced pain or metabolic dysfunction.
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
Smesam, Hasan Najah, Qazmooz, Hasan Abbas, Khayoon, Sinan Qayes, Almulla, Abbas F, Al-Hakeim, Hussein Kadhem, & Maes, Michael (2022). Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis.. Journal of personalized medicine. https://doi.org/10.3390/jpm12030476
BibTeX
@article{mecfsatlas-smesam-2022-pathway-phenotypes,
author = {Smesam, Hasan Najah and Qazmooz, Hasan Abbas and Khayoon, Sinan Qayes and Almulla, Abbas F and Al-Hakeim, Hussein Kadhem and Maes, Michael},
title = {Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis.},
journal = {Journal of personalized medicine},
year = {2022},
doi = {10.3390/jpm12030476},
note = {PubMed: 35330475},
url = {https://www.mecfsatlas.com/evidence/smesam-2022-pathway-phenotypes},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/smesam-2022-pathway-phenotypes
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