Staines, Donald R, Brenu, Ekua W, Marshall-Gradisnik, Sonya · Neuropsychiatric disease and treatment · 2009
This paper proposes that ME/CFS, along with MS, Parkinson's disease, and ALS, may involve immune system problems affecting the protective barriers around the brain and spinal cord. Specifically, the authors suggest that certain signaling molecules called PACAP and VIP, which normally help maintain these barriers, may become targets of autoimmune attack. They propose that a class of drugs called phosphodiesterase inhibitors might help restore normal function by boosting protective immune responses.
This paper offers a testable immunological hypothesis for why ME/CFS involves neurological and psychiatric symptoms—specifically, barrier dysfunction and dysregulated immune tolerance. If validated, it could redirect research toward biomarkers (autoantibodies against PACAP/VIP receptors) and identify a new class of therapeutic targets (phosphodiesterase inhibitors) with preclinical support.
This study does not prove that PACAP or VIP autoimmunity occurs in ME/CFS patients, nor does it provide evidence that phosphodiesterase inhibitors improve ME/CFS outcomes. It is a theoretical framework without human clinical data, immunological assays, or treatment trials. The proposed mechanisms remain speculative and require empirical validation in ME/CFS cohorts.
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
Staines, Donald R, Brenu, Ekua W, & Marshall-Gradisnik, Sonya (2009). Postulated vasoactive neuropeptide immunopathology affecting the blood-brain/blood-spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment?. Neuropsychiatric disease and treatment. https://pubmed.ncbi.nlm.nih.gov/19557103/
BibTeX
@article{mecfsatlas-staines-2009-postulated-vasoactive,
author = {Staines, Donald R and Brenu, Ekua W and Marshall-Gradisnik, Sonya},
title = {Postulated vasoactive neuropeptide immunopathology affecting the blood-brain/blood-spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment?},
journal = {Neuropsychiatric disease and treatment},
year = {2009},
note = {PubMed: 19557103},
url = {https://www.mecfsatlas.com/evidence/staines-2009-postulated-vasoactive},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/staines-2009-postulated-vasoactive
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