Is Chronic Fatigue Syndrome Just All In Our Heads?

Over the last few years, a body of research has grown looking into the nature of chronic fatigue syndrome (CFS) –– in particular, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disorder defined by several consistently recurring symptoms: tiredness despite not doing unusually strenuous activity; that is not relieved by a consistent sleep schedule; and then is either causing thinking or memory problems and/or symptoms becoming more severe when standing – a condition itself known as orthostatic intolerance. The degrees to which people suffer from CFS often vary – there are severe cases, but no cases known to bring about lifelong suffering. However, in seeking its answers, medical science has been looking for objective measures in order to diagnose the problem beyond the patient’s complaint.

A recent study conducted by the National Institutes of Health (NIH) has studied a more diverse group of test subjects than ever before, while working with extensive biological measurements of individuals living with CFS than any past research has covered. With the help of immune testing, brain scans, and other tools, the research team investigated abnormalities that could drive the patients’ typical health complaints – problems that include crushing fatigue or brain fog. Let’s take a closer look at their findings and what they mean going forward.

What did we already know about chronic fatigue syndrome?

In those who suffer from chronic fatigue syndrome, there exist underlying abnormalities in various parts of the body: The brain, primarily – but also the immune system and the way in which the body generates energy: the cardiovascular system. Even the microbiome, the bacterial population that reside in the gut, are thought to play a role. These abnormalities have already been documented in much of the literature we have: thousands of papers published since the 1980s.

Who participated in the NIH study?

Published in February by the journal Nature Communications, this minute NIH study compared individuals who had developed the chronic fatigue syndrome following some type of infection against an equally sized control group of healthy individuals.

Those who had CFS had all been in perfect health prior to coming down with symptoms that appeared to be reminiscent of a simple “flu” virus: a sore throat, coughing and sneezing, achy muscles, and low energy. Unlike any previous bouts they may have had with flu-like illnesses, they saw no signs of recovery. What often cleared up in a matter of weeks, progressed for years. All of the test subjects in the CFS group reported suffering from debilitating levels of fatigue that required bed rest, as well as difficulty with thinking and problem solving, and notably, their symptoms flared up after participating in physically demanding exercise or mentally complex tasks. Some had symptoms so severe that they had become either bedridden or homebound.

All of the study participants resided for a week at the NIH facility, located just outside of Washington, DC. Every day, they were given different tests. The assiduous testing is the primary strength for this new study.

What are the biggest takeaways from this study?

The new study has three significant key findings, among them is a new important discovery.

First of all, as has been confirmed true in most previous literature, the NIH research team saw evidence that the patients’ immune systems were chronically activated. It appears as though the immune system is engaged in perpetual war against invasive pathogens  — but one where it could never fully triumph by simply developing the right antibodies and need to constantly fight.

In addition, the new study revealed that an area of the brain we already know is crucial to perceiving that we’re tired but pushes us to persevere anyway – that is, he right temporal-parietal area — was not functioning at normal levels. Typically, when a healthy individual is asked to perform a physically or mentally strenuous task, that right temporal-parietal lobe of the brain will light up in an MRI brain scan. However, for the patient with CFS, it only lit up dimly when they were asked to exert themselves.

Although earlier experiments had recorded a number of other brain abnormalities in CFS, this particular discovery was new. A deficiency in this region would make it considerably more difficult for a person with CFS to do demanding cognitive or physical tasks, the team documented. While the CFS patient feels tired and wishes to be doing the tasks they once felt were meaningful, working a steady job or going for a long walk, their own brain makes a steady fight against them trying to do it.

Finally, in the patients’ spinal fluid, researchers found that the levels of brain chemicals known as neurotransmitters – as well as markers of inflammation (a typical immune response) were different in their test subjects with CFS when compared against the control group of healthy individuals.  Spinal fluid surrounds and insulates the brain and therefore reflects its chemistry.

What else can this study tell us?

There are a number of other interesting findings that the NIH brought to light in their new study. The team documented an array of significant differences between men and women with CFS when they made their biological measurements. This data will inevitably pave the way for larger studies in the future to verify gender-based differences, and also help determine what it is that shapes these differences.

The team also cites that there was no difference between either people with CFS or the healthy comparison group in the degree to which they experienced psychiatric disorders — either ones they are currently being treated for, or episodes in their past. That means that the symptoms of CFS were not attributable to other psychological causes.

So is chronic fatigue syndrome really all about the brain?

The NIH team ultimately concluded that chronic fatigue syndrome is primarily a brain disorder, one that could potentially be activated by chronic activation of the immune system and potential changes in the gut microbiome. This is also consistent with the data found in much of the previous studies.

The increasing recognition of abnormalities that involve the brain, as well as chronic activation (and even exhaustion) of one’s  immune system, as well as changes within the gut’s microbiome are altering the conceptions we have of what defines CFS –– at least if the causes are viral in nature – and this is the start to discovering and improving any potential treatments.

For one example, the NIH team learned that there are immune system cells that become exhausted by dwelling in a continuous state of activation. These exhausted cells are not as efficient as their healthy counterparts are when it comes to eliminating infections. The NIH researchers suggest that a group of drugs known as immune checkpoint inhibitors can work to strengthen any exhausted cells.

So how much can we be sure about?

The drawback to the study is that they measured a small number of people: 17 individuals with varying degrees of ME/CFS alongside 21 healthy persons of the same age and sex, who functioned as the control group. Unfortunately, the study also had to be paused before it could accept more applicants as it overlapped with the onset of the COVID-19 pandemic.

This means that their study does not contain a significant deal of statistical power and could have also failed to take notice of some abnormalities that may have played out over a longer time span. That is the ultimate shortcoming of the NIH study.

In Conclusion

This new study by the NIH succeeds thousands of previously published scientific studies carried out over the last four decades. Like the previous research, it also indicates that people who have ME/CFS exhibit measurable abnormalities in the brain, their immune systems, energy metabolisms, blood vessels, and even bacteria that live in the gut – an area of science that is also being studied more heavily.

What accounts for all of these abnormalities to appear? Are they reinforcing each other, creating spiraling cycles that lead the patient to long-term illness? In what way do they contribute to the debilitating symptoms we use to define the illness? We aren’t yet sure of the answer. What we do understand is that a significant number of people suffer every year and that the illness currently afflicts millions of people in the United States. The only way we can be sure of a cure is by continuing studies like the latest work from NIH that further probe into the disease’s symptoms. Focusing on the systematic changes over time will lead ways to effectively manage and treat ME/CFS.

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