ME/CFS Is Not Static
What the Science Tells Us About Timing, the Immune System, and Why Early Treatment Matters
By Aimee Mills-Viscovich, LICSW
By a friendly, very human therapist who 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 the disclaimer at the end of the blog post.
“Your Labs are Normal.”
If you live with ME/CFS—or love someone who does—you’ve probably heard some version of this before:
“Your labs are normal.”
“There’s no clear biomarker.”
“We don’t really know what’s going on.”
That uncertainty can feel invalidating, frustrating, and exhausting. Fortunately, scientists have continued to study conditions like ME/CFS, and the science has been moving forward—quietly, carefully, and with increasing clarity.
One of the most important shifts in ME/CFS research over the past decade is this idea: ME/CFS is not one static condition. It changes over time—especially in the immune system. And that is a very important discovery in itself.
The Study That Changed How Many Clinicians Think About ME/CFS
In 2015, a large, well-designed study published in Science Advances looked at immune signaling molecules (cytokines) in nearly 300 people with ME/CFS and compared them to healthy controls¹.
What made this study different was one crucial decision:
The researchers separated participants by how long they had been ill.
Early ME/CFS: ≤3 years since onset
Long-duration ME/CFS: >3 years
That single choice explained why so many earlier studies seemed contradictory.
What the Found
In the first three years of ME/CFS:
The immune system looks like it’s on high alert.
Many pro-inflammatory cytokines are elevated
Many anti-inflammatory cytokines are also elevated
Immune signaling networks are disorganized, not smoothly regulated
One immune signal—interferon-gamma (IFN-γ)—stands out as especially strong
This pattern suggests immune activation with poor regulation—not a simple explanation of “too much inflammation.”
After three years (long-duration ME/CFS):
The picture changes.
Many of the same immune markers are now lower than normal
This suggests immune exhaustion or burnout
The immune system may no longer respond normally to stress, infection, or exertion
In other words, the immune system looks very different later in the illness than it does early on¹.
What Is Interferon-Gamma?
Interferon-gamma (IFN-γ) is a powerful immune signal. When it stays elevated for too long, it can have significant downstream effects.
Research shows IFN-γ activates something called the kynurenine pathway, which:
Diverts tryptophan away from making serotonin and melatonin
Increases quinolinic acid, a compound that overstimulates NMDA (glutamate) receptors in the brain²³
This pathway has been linked to:
Cognitive fog
Slowed thinking
Mood changes
Sleep disruption
Sensory overload
All of which are common symptoms in ME/CFS.
The Big Takeaway: Timing Matters
One of the most important conclusions from this research is this:
Immune abnormalities in ME/CFS correlate more strongly with how long someone has been ill than with how severe their symptoms are.
That means:
Early ME/CFS may represent a biological window where immune-targeted interventions might be more feasible (under medical supervision)
Later ME/CFS likely requires a very different approach, focused on stabilization rather than immune “fixing”¹
This helps explain why:
“Anti-inflammatory” treatments often don’t help
Immune-boosting strategies can backfire
Exercise-based approaches can worsen symptoms
What this means for treatment:
This study does not test treatments, But it does give us a framework for future studies, along with answering some questions about the discrepancies found when treating and researching this condition.
What treatments align with the science:
Early pacing and energy protection (to avoid PEM)
Avoiding immune over-activation (“pushing through” pain or fatigue)
Supporting nervous system regulation
Recognizing that early and late ME/CFS are not biologically identical
What the science cautions against:
One-size-fits-all protocols
Blanket immune stimulation
Aggressive exercise as treatment
Assuming ME/CFS is purely psychological
A Therapist’s Closing Thoughts
As a clinician who works with people managing chronic illness, trauma, and neurodivergence, I want to say this plainly:
ME/CFS is real. It is biological. And it deserves stage-specific, compassionate care. It can cause long-term disability and may worsen with improper treatment or misdiagnosis.
This research doesn’t magically fix everything—but it does something powerful:
It gives language, structure, and legitimacy to what patients have been reporting for decades, and that matters. If you have a client who has been diagnosed with ME/CFS or presents with symptoms consistent with ME/CFS, educate yourself so that you can support them in the ways that they need you to. Giving a client the wrong advice or support, regardless of your intent, can have serious consequences.
Reference
Hornig M, Montoya JG, Klimas NG, et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Science Advances. 2015;1(1):e1400121.
Miller AH, Haroon E, Raison CL, Felger JC. Cytokine targets in the brain: Impact on neurotransmitters and neurocircuits. Depression and Anxiety. 2013.
Myint AM, Kim YK. Network beyond IDO in psychiatric disorders: Revisiting neurodegeneration hypothesis. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2014.
IMPORTANT DISCLAIMER
I am not a medical doctor. This blog is not medical advice. Nothing here should be used to diagnose, treat, or replace care from a licensed medical provider.
What follows is an educational summary of peer-reviewed scientific research, written to help people better understand what researchers are learning about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). This post was created with the assistance of AI technology and reviewed for accuracy and clarity.
If you have ME/CFS or think you might, please work with a qualified medical professional.