Al-Hakeim, Hussein Kadhem, Al-Naqeeb, Tabarek Hadi, Almulla, Abbas F et al. · Journal of affective disorders · 2023 · DOI
This study examined whether brain and nerve damage markers in the blood are connected to depression symptoms and other physical complaints. Researchers measured several proteins in the blood of people with depression and compared them to healthy controls, finding that markers of brain cell and nerve damage—along with inflammation and insulin resistance—together explained about 61% of the severity of depression, anxiety, fatigue, and physical symptoms.
For ME/CFS patients, this work is relevant because ME/CFS shares significant overlap with depression and anxiety, and both conditions involve fatigue, physical symptoms, and potential neuro-immune dysfunction. Understanding whether peripheral markers of neuronal and glial damage contribute to the constellation of depressive and somatic symptoms may illuminate shared pathophysiological mechanisms and guide future diagnostic or therapeutic approaches in post-viral and chronic fatigue conditions.
This cross-sectional study cannot prove causality—it cannot determine whether elevated neuroaxis biomarkers cause depressive symptoms or whether the depressive state elevates these biomarkers. The study is conducted in MDD patients and does not directly test whether these mechanisms apply to ME/CFS. Association does not imply that targeting these biomarkers will improve symptoms.
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
Al-Hakeim, Hussein Kadhem, Al-Naqeeb, Tabarek Hadi, Almulla, Abbas F, & Maes, Michael (2023). The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium.. Journal of affective disorders. https://doi.org/10.1016/j.jad.2023.03.072
BibTeX
@article{mecfsatlas-al-hakeim-2023-physio-affective,
author = {Al-Hakeim, Hussein Kadhem and Al-Naqeeb, Tabarek Hadi and Almulla, Abbas F and Maes, Michael},
title = {The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium.},
journal = {Journal of affective disorders},
year = {2023},
doi = {10.1016/j.jad.2023.03.072},
note = {PubMed: 36996718},
url = {https://www.mecfsatlas.com/evidence/al-hakeim-2023-physio-affective},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/al-hakeim-2023-physio-affective
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