van der Schaaf, Marieke E, De Lange, Floris P, Schmits, Iris C et al. · Biological psychiatry · 2017 · DOI
This study examined brain structure in 89 women with ME/CFS using brain imaging. Researchers found that the amount of pain a patient experiences—not fatigue—was the strongest predictor of changes in a specific brain region called the dorsolateral prefrontal cortex. People with more pain showed smaller brain volume and lower levels of brain chemicals in this region, even after accounting for fatigue, depression, and physical activity.
This finding challenges the assumption that fatigue drives brain changes in ME/CFS and highlights pain as an important neurobiological feature deserving research focus. Understanding that pain—rather than fatigue alone—correlates with specific brain alterations may help researchers develop targeted interventions and improve how we conceptualize ME/CFS heterogeneity.
This study does not establish causation—it cannot determine whether pain causes the brain changes, brain changes cause pain, or whether both result from an underlying mechanism. The cross-sectional design prevents conclusions about whether these brain alterations develop before, during, or after pain onset. Additionally, findings are limited to women and may not generalize to men with ME/CFS.
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
van der Schaaf, Marieke E, De Lange, Floris P, Schmits, Iris C, Geurts, Dirk E M, Roelofs, Karin, van der Meer, Jos W M, et al. (2017). Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome.. Biological psychiatry. https://doi.org/10.1016/j.biopsych.2016.07.016
BibTeX
@article{mecfsatlas-van-der-schaaf-2017-prefrontal-structure,
author = {van der Schaaf, Marieke E and De Lange, Floris P and Schmits, Iris C and Geurts, Dirk E M and Roelofs, Karin and van der Meer, Jos W M and Toni, Ivan and Knoop, Hans},
title = {Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome.},
journal = {Biological psychiatry},
year = {2017},
doi = {10.1016/j.biopsych.2016.07.016},
note = {PubMed: 27817843},
url = {https://www.mecfsatlas.com/evidence/van-der-schaaf-2017-prefrontal-structure},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/van-der-schaaf-2017-prefrontal-structure
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