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Chronic fatigue syndrome (CFS) –– or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), to be specific ––  is an illness defined by a group of symptoms. Yet medical science always seeks objective measures that go beyond the symptoms people report.

A new study from the National Institutes of Health (NIH) has performed more diverse and extensive biological measurements of people experiencing CFS than any previous research. Using immune testing, brain scans, and other tools, the researchers looked for abnormalities that might drive health complaints like crushing fatigue and brain fog. Let’s dig into what they found and what it means.

What was already known about chronic fatigue syndrome?

In people with chronic fatigue syndrome, there are underlying abnormalities in many parts of the body: The brain. The immune system. The way the body generates energy. Blood vessels. Even in the microbiome, the bacteria that live in the gut. These abnormalities have been reported in thousands of published studies over the past 40 years.

Who participated in the NIH study?

Published in February in Nature Communications, this small NIH study compared people who developed chronic fatigue syndrome after having some kind of infection with a healthy control group.

Those with CFS had been perfectly healthy before coming down with what seemed like just a simple “flu”: sore throat, coughing, aching muscles, and poor energy. However, unlike their experiences with past flulike illnesses, they did not recover. For years, they were left with debilitating fatigue, difficulty thinking, a flare-up of symptoms after exerting themselves physically or mentally, and other symptoms. Some were so debilitated that they were bedridden or homebound.

All the participants spent a week at the NIH, located outside of Washington, DC. Each day they received different tests. The extensive testing is the great strength of this latest study.

What are three important findings from the study?

The study had three key findings, including one important new discovery.

First, as was true in many previous studies, the NIH team found evidence of chronic activation of the immune system. It seemed as if the immune system was engaged in a long war against a foreign microbe — a war it could not completely win and therefore had to keep fighting.

Second, the study found that a part of the brain known to be important in perceiving fatigue and encouraging effort — the right temporal-parietal area — was not functioning normally. Normally, when healthy people are asked to exert themselves physically or mentally, that area of the brain lights up during an MRI. However, in the people with CFS it lit up only dimly when they were asked to exert themselves.

While earlier research had identified many other brain abnormalities, this one was new. And this particular change makes it more difficult for people with CFS to exert themselves physically or mentally, the team concluded. It makes any effort like trying to swim against a current.

Third, in the spinal fluid, levels of various brain chemicals called neurotransmitters and markers of inflammation differed in people with CFS compared with the healthy comparison group. The spinal fluid surrounds the brain and reflects the chemistry of the brain.

What else did study show?

There are some other interesting findings in this study. The team found significant differences in many biological measurements between men and women with chronic fatigue syndrome. This surely will lead to larger studies to verify these gender-based differences, and to determine what causes them.

There was no difference between people with CFS and the healthy comparison group in the frequency of psychiatric disorders — currently, or in the past. That is, the symptoms of the illness could not be attributed to psychological causes.

Is chronic fatigue syndrome all in the brain?

The NIH team concluded that chronic fatigue syndrome is primarily a disorder of the brain, perhaps brought on by chronic immune activation and changes in the gut microbiome. This is consistent with the results of many previous studies.

The growing recognition of abnormalities involving the brain, chronic activation (and exhaustion) of the immune system, and of alterations in the gut microbiome are transforming our conception of CFS –– at least when caused by a virus. And this could help inform potential treatments.

For example, the NIH team found that some immune system cells are exhausted by their chronic state of activation. Exhausted cells don’t do as good a job at eliminating infections. The NIH team suggests that a class of drugs called immune checkpoint inhibitors may help strengthen the exhausted cells.

What are the limitations of the study?

The number of people who were studied was small: 17 people with ME/CFS and 21 healthy people of the same age and sex, who served as a comparison group. Unfortunately, the study had to be stopped before it had enrolled more people, due to the COVID-19 pandemic.

That means that the study did not have a great deal of statistical power and could have failed to detect some abnormalities. That is the weakness of the study.

The bottom line

This latest study from the NIH joins thousands of previously published scientific studies over the past 40 years. Like previous research, it also finds that people with ME/CFS have measurable abnormalities of the brain, the immune system, energy metabolism, the blood vessels, and bacteria that live in the gut.

What causes all of these different abnormalities? Do they reinforce each other, producing spiraling cycles that lead to chronic illness? How do they lead to the debilitating symptoms of the illness? We don’t yet know. What we do know is that people are suffering and that this illness is afflicting millions of Americans. The only sure way to a cure is studies like this one that identify what is going wrong in the body. Targeting those changes can point the way to effective treatments.

About the Author

Anthony L. Komaroff, MD, Editor in Chief, Harvard Health Letter

Dr. Anthony L. Komaroff is the Steven P. Simcox/Patrick A. Clifford/James H. Higby Professor of Medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital in Boston, and editor in chief of the Harvard … See Full Bio View all posts by Anthony L. Komaroff, MD

Are online gambling and sports betting new to your area? Are gambling advertisements catching your eye? Have you noticed sports and news shows covering the spread? Recent changes in laws have made gambling widely accessible, and its popularity has soared.

Occasional bets are rarely an issue. But uncontrolled gambling can lead to financial, psychological, physical, and social consequences, some of which are extreme. Understanding whether gambling is becoming a problem in your life can help you head off the worst of these issues and refocus on having more meaning, happiness, and psychological richness in your life. Gambling screening is a good first step.

Can you screen yourself for problem gambling?

Yes. Screening yourself is easy. The Brief Biosocial Gambling Screen (note: automatic download) is a validated way to screen for gambling disorder. It has three yes-or-no questions. Ask yourself:

• During the past 12 months, have you become restless, irritable, or anxious when trying to stop/cut down on gambling?
• During the past 12 months, have you tried to keep your family or friends from knowing how much you gambled?
• During the past 12 months, did you have such financial trouble as a result of your gambling that you had to get help with living expenses from family, friends, or welfare?

What do your answers mean?

Answering yes to any one of these questions suggests that you are at higher risk for experiencing gambling disorder. Put simply, this is an addiction to gambling. Like other expressions of addiction, for gambling this includes loss of control, craving, and continuing despite bad consequences. Unique to gambling, it also often means chasing your losses.

A yes doesn’t mean that you are definitely experiencing a problem with gambling. But it might be valuable for you to seek a more in-depth assessment of your gambling behavior. To find an organization or person qualified to help, ask a health care provider, your local department of public health, or an advocacy group like the National Council on Problem Gambling.

Are you ready for change?

Your readiness to change a behavior matters when deciding the best first steps for making a change. If someone asks you whether you want to change your gambling, what would you say?

Depending on your answer, you might seek out different solutions. What’s most important initially is choosing a solution that feels like the right fit for you.

What if you don’t feel ready to change? If you haven’t thought about your gambling or only occasionally think about changing your gambling, you might explore lower intensity actions. For example, you could

• read more about how gambling could create a problem for you
• listen to stories of those who have lived experience with gambling disorder.

If you are committed to making a change or are already trying to change, you might seek out more engaging resources and strategies to support those decisions, like attending self-help groups or participating in treatment.

Read on for more details on choices you might make.

What options for change are available if you want to continue gambling?

If you want to keep gambling in some way, you might want to stick to lower-risk gambling guidelines:

• gamble no more than 1% of household income
• gamble no more than four days per month
• avoid regularly gambling at more than two types of games, such as playing the lottery and betting on sports.

Other ways to reduce your risk of gambling harm include:

• Plan ahead and set your own personal limits.
• Keep your entertainment budget in mind if you decide to gamble.
• Consider leaving credit cards and debit cards at home and use cash instead.
• Schedule other activities directly after your gambling to create a time limit.
• Limit your use of alcohol and other drugs if you decide to gamble.

What are easy first steps toward reducing or stopping gambling?

If you’re just starting to think about change, consider learning more about gambling, problem gambling, and ways to change from

• blogs, like The BASIS
• books like Change Your Gambling, Change Your Life
• podcasts like After Gambling, All-In, and Fall In, which offer expert interviews, personal recovery stories, and more.

Some YouTube clips demystify gambling, such as how slot machines work, the limits of skill and knowledge in gambling, and how gambling can become an addiction. These sources might help you think about your own gambling in new ways, potentially identifying behaviors that you need to change.

What are some slightly more active steps toward change?

If you’re looking for a slightly more active approach, you can consider engaging in traditional self-help experiences such as helplines and chatlines or Gamblers Anonymous.

Another option is self-help workbooks. Your First Step to Change is a popular workbook that provides information about problem gambling, self-screening exercises for gambling and related conditions like anxiety and depression, and change exercises to get started. A clinical trial of this resource suggested that users were more likely than others to report having recently abstained from gambling.

Watch out for gambling misinformation

As you investigate options, keep in mind that the quality of information available can vary and may even include misinformation. Misinformation is incorrect or misleading information. Research suggests that some common types of gambling misinformation might reinforce harmful beliefs or risky behaviors.

For example, some gambling books, websites, and other resources exaggerate your likelihood of winning, highlight win and loss streaks as important (especially for chance-based games like slots), and suggest ways to change your luck to gain an edge. These misleading ideas can help you to believe you’re more likely to win than you actually are, and set you up for failure.

The bottom line

Taking a simple self-screening test can start you on a journey toward better gambling-related health. Keep in mind that change can take time and won’t necessarily be a straight path.

If you take a step toward change and then a step back, nothing is stopping you from taking a step forward again. Talking with a care provider and getting a comprehensive assessment can help you understand whether formal treatment for gambling is a promising option for you.

About the Author

Debi LaPlante, PhD, Contributor

Dr. Debi LaPlante is director of the division on addiction at the Cambridge Health Alliance, and an associate professor of psychiatry at Harvard Medical School. She joined the division in 2001 and is involved with its … See Full Bio View all posts by Debi LaPlante, PhD