Sulheim, Dag, Fagermoen, Even, Winger, Anette et al. · JAMA pediatrics · 2014 · DOI
This study looked at whether adolescents with ME/CFS have overactive stress response systems in their bodies and whether a medication called clonidine could help. Researchers found that young people with ME/CFS did have higher levels of stress chemicals and signs of body inflammation compared to healthy teens, but the medication did not improve their condition and actually reduced their physical activity. The study suggests that the overactive stress response may be the body's attempt to cope with ME/CFS rather than the root cause.
This study provides objective evidence of specific biological abnormalities in adolescent ME/CFS—sympathetic hyperactivity, inflammation, and HPA axis dysfunction—validating a physiological basis for the condition. The unexpected finding that sympathetic inhibition worsens activity suggests current treatment approaches targeting these pathways may be counterproductive and informs future therapeutic strategies.
The study does not prove that sympathetic hyperactivity causes ME/CFS; these abnormalities may be secondary responses to an underlying pathology. A single failed pharmacological trial does not rule out the involvement of the sympathetic nervous system in disease pathogenesis. The findings are limited to adolescents and may not generalize to adult populations.
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
Sulheim, Dag, Fagermoen, Even, Winger, Anette, Andersen, Anders Mikal, Godang, Kristin, Müller, Fredrik, et al. (2014). Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial.. JAMA pediatrics. https://doi.org/10.1001/jamapediatrics.2013.4647
BibTeX
@article{mecfsatlas-sulheim-2014-disease-mechanisms,
author = {Sulheim, Dag and Fagermoen, Even and Winger, Anette and Andersen, Anders Mikal and Godang, Kristin and Müller, Fredrik and Rowe, Peter C and Saul, J Philip and Skovlund, Eva and Øie, Merete Glenne and Wyller, Vegard Bruun},
title = {Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial.},
journal = {JAMA pediatrics},
year = {2014},
doi = {10.1001/jamapediatrics.2013.4647},
note = {PubMed: 24493300},
url = {https://www.mecfsatlas.com/evidence/sulheim-2014-disease-mechanisms},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/sulheim-2014-disease-mechanisms
Contribute
Private, reviewed by a human. Not a public comment thread.