ME/CFS Biomarkers Explained
What the Science Says About Immune, Autonomic, and Energy Dysfunction
By a therapist who spends a lot of time listening to chronically ill, neurodivergent, and medically complex humans. Who in an effort to support them spends a lot of time reading medical journals so you don’t have to. I am not a doctor, and this is not medical advice. Please see disclaimer at the end of the blog post.
What Research Shows About ME/CFS Biomarkers and Biological Dysfunction
A large 2023 systematic review in BMC Medicine analyzed 101 studies looking at biological markers in ME/CFS.¹
There is no single diagnostic test yet.
But there is clear evidence of real, measurable biological dysfunction across multiple systems.
Researchers repeatedly found differences in:
The immune system
Cellular signaling (especially calcium signaling)
Inflammatory regulation
Energy metabolism
The autonomic nervous system
Blood flow and vascular function
Brain signaling
Not one system. Many systems.
Immune Dysfunction in ME/CFS: Natural Killer Cells and Immune Regulation
One of the most consistent findings is reduced natural killer (NK) cell function. These cells help regulate immune response to stress and infection.
This does not look like classic autoimmune disease. It looks more like immune dysregulation—a system that doesn’t respond efficiently under strain.
Cellular Signaling and Inflammation in ME/CFS
Several studies point to disruptions in calcium and receptor signaling pathways, including TRP ion channels. These pathways affect immune response, energy production, and autonomic balance.
Inflammatory markers are inconsistent—some elevated, some reduced. The pattern suggests instability rather than simple "high inflammation."
This is important. It moves the conversation away from "it’s just inflammation" and toward "the signaling networks are out of sync."
Mitochondrial Function and Energy Metabolism in ME/CFS
Mitochondria in ME/CFS appear stressed—not structurally broken, but less efficient when demand increases.
This helps explain post‑exertional malaise (PEM): symptoms that worsen after physical, cognitive, or emotional effort.
Autonomic Nervous System Dysfunction and Blood Flow Problems in ME/CFS
Research consistently shows autonomic differences, including:
Altered heart‑rate variability
Slower heart‑rate recovery
Orthostatic intolerance
There are also signs of reduced endothelial function, meaning blood vessels may not regulate oxygen delivery efficiently.
When signaling instability affects autonomics and blood flow, exertion becomes harder to recover from. PEM appears to reflect a systems‑level recovery failure, not simple fatigue.
Why ME/CFS Biomarkers Vary: Understanding Network Illness and Biological Heterogeneity
In complex “network illnesses” like ME/CFS, variability is expected. Immune signaling, autonomics, metabolism, and brain function constantly interact.
Different patients may show different dominant abnormalities depending on genetics, infection history, hormones, and illness duration.
The absence of one universal lab marker does not invalidate the illness. It reflects the reality of interconnected biological systems.
Why Therapists Should Understand ME/CFS: Mental Health Implications and Clinical Considerations
ME/CFS symptoms can look like depression, avoidance, or low motivation. But post‑exertional crashes, cognitive slowing, and autonomic instability are physiological.
Clients who cancel after a productive session may not be resistant. They may be in a crash.
Homework non‑completion may reflect cognitive stamina limits—not ambivalence.
Therapy may need pacing, shorter sessions, reduced cognitive load, and careful trauma processing.
Depression and anxiety, when present, are often secondary to loss, invalidation, and chronic stress—not the cause of the illness.
Understanding the biology helps therapists avoid harm.
What ME/CFS Research Does Not Support: Myths About Exercise and Psychiatric Causes
ME/CFS as a primary psychiatric disorder
Forced or graded exercise as a cure
The idea that symptoms persist because of beliefs or lack of effort
Final Thoughts on ME/CFS, Biology, and Validation
The science is clear: ME/CFS is a multisystem biological condition. Medicine may not yet have a single test, but the dysfunction is measurable.
For many people, simply hearing that the body’s signaling, autonomic, and immune systems are involved—not their character—can be deeply validating.
You were never imagining it.
Reference
Maksoud R, Magawa C, Eaton‑Fitch N, Thapaliya K, Marshall‑Gradisnik S. Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review. BMC Medicine. 2023;21:189. doi:10.1186/s12916‑023‑02893‑9.
IMPORTANT DISCLAIMER
I am not a medical doctor. This post is not medical advice. It is educational information based on peer‑reviewed journal articles, summarized with the assistance of AI technology. Any medical decisions should be made with your qualified healthcare provider.