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ME/CFS Appears to Be a Disease Affecting the Basal Ganglia & Dopamine Metabolism

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A new study led by CDC investigator Elizabeth Unger, MD, PhD, with collaborators at Emory University, Atlanta, and the University of Modena and Reggio Emilia, Italy, has identified unique responses in the brain’s basal ganglia that suggest an association between a biologic functional response and chronic fatigue syndrome (ME/CFS).

In a paper presented April 24 at the Experimental Biology conference in San Diego,(1) the team reports that:

• Patients with ME/CFS have decreased activation in response to reward of an area of the brain known as the basal ganglia. (Ganglia are bundles of neurons providing relay points and interconnections. The basal ganglia are a constellation of interconnected areas deep in the brain. They appear to be associated with many functions, from motor activity and motivation/perceived reward to learning and habit encoding, and apparently with addictive disorders, OCD, and ADHD.)
• Problems with the basal ganglia tend to involve fatigue.

• The extent of the lowered activation in the ME/CFS patients’ basal ganglia is associated with the individual patient’s measured levels of physical and mental fatigue. (Less activation, more severe fatigue.)

How the Study Came About

Dr. Unger (chief of the CDC’s Viral Diseases Branch) says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue.

Interferons are proteins that cells make to trigger immune defenses in response to pathogens such as viruses, and tumor cells. They ‘interfere’ with viral replication within host cells and activate immune cells.

Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy.

Similar Symptoms

Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Dr. Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

• The researchers recruited 18 patients with chronic fatigue syndrome (ME/CFS), as well as 41 healthy volunteers with no symptoms of ME/CFS.

• Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward.

• The participants were each told that they’d win a small amount of money if they correctly guessed whether a preselected card was red or black. After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands. This is considered a good test, as perceptions of winning or losing normally evoke strong activations of the basal ganglia.

More Muted Reaction to Stimulus = More Fatigue

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. (Stimulating activities can normally produce ‘razzle-dazzle’ activity in the basal ganglia, says one leading researcher.)

When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient’s fatigue was tightly tied with the change in brain activity between winning and losing.

Those with the most fatigue had the smallest change in brain activity.

Dopamine Dysfunction Involved; Inflammation Possible Cause

These findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome, Dr. Unger says.

“Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness,” she says. “They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.”

The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future.

• Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. (Parkinson’s disease, for example, is a movement disorder known to be tied to the death of dopamine-producing neurons in the basal ganglia.)

• And in turn, the researchers speculate the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.

These results shed some important light on the riddle of ME/CFS – information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.


* The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC); Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia.

They discussed an abstract of their study – entitled “Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue” – on April 24 at the Experimental Biology Conference 2012 in San Diego.

The abstract is sponsored by the American Society for Investigative Pathology (ASIP).

Based on a Federation of American Societies for Experimental Biology (FASB) news release, Apr 24, 2012

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15 thoughts on “ME/CFS Appears to Be a Disease Affecting the Basal Ganglia & Dopamine Metabolism”

  1. slowdreamer says:

    For some reason this doesn’t get me excited..I would think that being depressed would have the same lack of reward excitement i.e. past caring.
    By using the term biological markers I feel we are getting some pretty low level research…bit like green wash.
    yrs in grumpiness

    1. blacksnake says:

      Dears yrs in grumpiness,

      If there is any excitement with this its maybe more with the “who” than the “what”. Nice to see the CDC come up with some serious work. After the years of drivel.


    2. Laehcar says:

      I’ve been saying this for years now, that CFS and fibromyalgia are both caused by problems with dopamine metabolism.

      “After centuries of disrespect and scorn, no one questions the validity of Parkinson’s disease today. It is ironic that the same neurotransmitter, dopamine, appears to play a control role in another enigma: fibromyalgia.”

      “The modern history of Parkinson’s disease began with the discovery that individuals with this condition had lost the ability to manufacture adequate amounts of dopamine in an area of the central brain called the BASAL GANGLIA.”

      From Parkinson’s Disease To Fibromyalgia


    3. aliaus says:

      recently I was on Champix (Australia) I think it might be Chantix in the US. If I understand correctly it effects your dopamine so you dont enjoy a cigarette as much. Over recent years there has been a lot of discussion about low dose naltrexone for fibro. If you dont know this works to reduce the enjoyment for alcohol and drugs. I have just been looking up the on naltrexone and cannot find if it is relative to dopamine, but it does affect some receptors. If anyone can give me further details I would be very grateful, If what I understand is correct it could be why I have seen so much good feedback on Low dose naltrexone. I agree it sound like they could be onto something with the dopamine connection.

  2. Laehcar says:

    This probably helps explain why so many of us have a problem with post-exertional fatigue after exercise. A person with an adequate amount of the neurotransmitter dopamine will benefit from exercise by allowing the brain to make “pain-killing”, “feel-good” endorphins. However, if you are depleted in dopamine (running on empty), which I suspect many people who suffer from ME/CFS are, no amount of exercise will help alleviate the symptoms. In fact, it could make the illness much worse by causing a “flare” or “crash”. If you are lacking in dopamine and your body has lost the ability to restore dopamine levels in the brain exercise, stress, alcohol etc., anything that eats up your small reserve will cause more fatigue, “flu-like-symptoms”, pain etc. Dopamine can act like a brake and without it the immune system becomes hyper-responsive making you feel like you have a terrible flu, or hangover.

  3. Laehcar says:

    Many people have described CFS like having a terrible hangover or flu. CFS sounds and feels a lot like, what people experience, who are going through opiate/drug/alcohol withdrawal, except it’s 24/7. The deficiency of dopamine/endorphins produces the syndrome of intense suffering known as withdrawal. Flu like symptoms; feelings of malaise; joint/muscle pain; problems regulating body temperature; anxiety; agitation; insomnia; nausea; irritable bowel are signs and symptoms of botconditions. And, since I believe that CFS is linked to dopamine/endorphin depletion (much like Parkinson’s Disease) and an inability to restore sufficient levels of these neurotranmitters in the brain, anything that causes a further depletion (exercise, stress, aspartame etc) will only make CFS worse (running on empty). That is why it is so important for people with CFS to pace themselves, or they will find themselves crashing (no dopamine/endorphins; no brake).

    1. windwsprer says:

      Yes both seem to be missing. Wish I could exercise; I’m pretty physical by nature, but it hurts too much even on leva-dopa. Let’s see more research in these areas.

  4. ex-cfs says:

    Increasingly, research has seemed to point to dopamine (especially certain types of dopamine) as part of the problem in CFS. In fact, it may be a central part and causative for some of the lingering problems.

    Interestingly, the CDC found in their genetic research that a Parkinson’s gene was improperly regulated (forget if it was up-or down-regulated). They noted that this did not mean that those with CFS had the abnormal gene leading to Parkinson’s Disease. They did not know why the normal Parkinson’s gene was abnormally regulated. This study seems to add another piece to that puzzle.

    I have noted in my family, and some researchers have discussed with me their contention that several illnesses, especially CFS, fibro, ADD/ADHD, and autism may be related in families. These might include a number of illnesses in which dopamine irregularities have been implicated such as:

    o Alcoholism (in relatives, those with CFS generally become alcohol intolerant)– I have not seen studies with links between alcoholism and CFS, but in my multigenerational family we have it along with CFS and ADHD, so I wondered if dopamine dysfunction might be a link

    o ADD or ADHD (also even if not diagnosed with ADD/ADHD or having family members with it, many with CFS were highly energetic and active, though not abnormally so, before illness)– brain fog seems like ADD sometimes and some researchers have noted a family connection — some similar supplements help with both, especially those that assist calming neurotransmitters and good fat balance

    o Autism (in the family, may be a link to ADD/ADHD and CFS, sometimes autism and ADD/ADHD diagnoses are intermingled in the same person, one becoming the other)– some researchers have noticed a possible family connection, and others implicate systemic candida as a possible cause in common

    The way the study was done also leads me to wonder about whether the same findings would be found in cases of “learned helplessness” and whether this is a consequence of having such a disabling and disheartening illness like CFS, especially when few believe you are really ill, and doctors often offer little hope to get better. I would like to see those with “learned helplessness” from non-illness causes tested with a similar test to see how similar their reactions are. Then someone could do a causal study to see whether dopamine dysfunction can cause “learned helplessness” or whether “learned helplessness” comes after CFS or other causes of inability to extricate oneself from a bad situation, and perhaps damages the basal ganglia, much as excessive cortisol from chronic high stress damages the hippocampus and other brain structures.

    I think this will prove to be an important study that can open more doors, with more questions than answers initially. But at least it proves one more biological indication that we’re not making this all up!

  5. sagallagherwarden says:

    Interestingly and sadly, I believe there is a genetic link to CFS/Parkinsons/ADHD,etc. I have CFS, my 2 cousins said they had it; but not any longer. One of the same cousin ended up with Parkinsons in her 70’s. Also another cousin, Male, had a Parkinsons related disease Nuclear ???Palsy(Very rare and very awful.) Also, 3 other individuals in my family, have ADD and/or ADHD. I do believe that CFS is a a combination of a neurological/physiological/biological/chronic stress related (anxiety/depression)illness.

    Does anyone out there know of any research or meds to increase dopamine production when or before it gets depleted–bec. that’s what limits the lives (mine included)of so many people–can’t even do simplest things–how debilitating it is! Yet, it’s very difficult to explain to others, especially if one looks fine.

    1. windwsprer says:

      Fava beans. Seriously. An alternative MD suggested this to me. You could also try the amino acid precursor to dopamine but be very careful everything is a balance and you might create something worse – well added to your misery, anyway. Best bet is a doctor who uses alternative therapies to regulate how much. Good luck to you and hang in there; it may take years but it does usually ease off some.

    2. knackers says:

      You still there?

  6. elusoria says:

    For many years now, I’ve thought that ME/CFS had something to do with dopamine. My grandfather suffered from severe Parkinson’s for a long time. It ultimately took his life. At the beginning of my own illness, I had several Parkinson’s-type symptoms. Enough that the doctors were concerned when they heard my family history. Another recent federal study at a NJ dental/medical practice showed that ME/CFS had some overlapping spinal fluid proteins with Parkinson’s. This is the news I’ve been waiting to hear. For the first time in years, I’m really heartened by the results of a study. It sounds like there are other ME/CFS patients who also previously suspected dopamine as a culprit. Hadn’t heard of any other dopamine studies. If the commenters above could come back and leave some links, I’d be very appreciative. Or any doctors who are treating ME/CFS patients with dopamine related drugs or supplements.

  7. windwsprer says:

    This makes sense to me. I had a severe 7 year bout of ME/CFS with convulsions, central pain syndrome and photophobia that still bothers me (to a lesser degree)27 years later. I developed paresthesias that were overwhelming along with the pain. Coincidentally, I worked at CDC (through Emory) in 1986 when I suddenly was knocked flat. When I had actual sleep I dreamed about being knocked in the head one way or another and having brain damage. I was diagnosed with Parkinson’s 6 years ago based on some movement problems and intense central pain. I have mainly balance issues. I have felt like walking in my sleep since ’86. Dopamine boost does help pain and balance but the unrelenting fatigue is now being called Parkinson’s inertia. I have been on the same starting dose for over 6 years. Maybe I have a bunch of unconnected conditions? (I didn’t mention the fibromyalgia that was present since early childhood because after CFS I swore I would never complain about it again. Actually, I can’t distinguish it from the rest anymore.)

  8. windwsprer says:

    Right on. They have tried the other 3 major neurotansmitters but not dopamine. GABA does help some. Are they afraid dopamine may make us feel good? Maybe normal people but good luck with us. Normal would be fantastic. I suppose lack of studies has a lot to do with it.

  9. prohealthnelg says:

    Dopamine or, more likely, problems with processing dopamine is now my primary suspect for my Chronic Fatigue Syndrome. I’ll tell you why – this certainly isn’t a fully formed scientific theory, but it adds up for me now. The light bulb went off when I recently had a negative reaction to a medication, Nuvilgil, that was similar to what I experienced with my first big, debilitating crash and similar to withdrawal symptoms I had experienced from antidepressants. I’ve taken Nuvigil sporadically for a few months. Sporadically because I find it very strong and was only using it every once in awhile to give an extra boost when I thought I would need it. But recently, I began using it every day, only about 1/8 of the full tablet. What I noticed was a sharp uptick in energy, mental and physical that lasted about a week, a reduction in energy the next week, a flatlining if you will, a complete crash with lack of energy and increased pain the next week, and finally, severe pain that was obviously withdrawal symptoms after not taking it for 1-2 days. So basically a very quick cycle of up, then down, then way down. Rewind back a few years when all of this began. I went to a sleep doctor and was diagnosed with sleep apnea. I had been under a lot of stress from work and life and had gone an extended period of time with only sleeping 3 or 4 hours a night. When a CPAP machine didn’t seem to cure my tiredness, the doctor prescribed Wellbutrin and Provigil, medications that both work on dopamine. Instead of getting better, I was getting worse. I then went to a psychiatrist and tried med after med to try to address the fatigue and pain. Nothing worked and eventually I had the big crash which let to be not being able to work and fully function or even take care of myself. What I now believe happened is that my dopamine receptors were already malfunctioning or burned out because of the stress and lack of sleep and the medication that was meant to help by increasing dopamine backfired because my body was already overwhelmed by too much and couldn’t process it. I don’t think my problem was/is not enough dopamine, it’s that my body can’t process it correctly. So my question is what happens to the dopamine or other neurotransmitters that cannot be processed? I think it may be treating it like a virus and would explain an immune system that is constantly in overdrive. I read someone said it was something like being in state of withdrawal from drugs 24/7 , and I thought that’s it! It is like being in detox/withdrawal constantly and I think the body is doing something with the excess dopamine, etc. that cannot be processed normally by properly working dopamine receptors. I would love for someone to comment on this, because after years of dealing with this horrible condition, I think it comes close to explaining it for me. Thanks.

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