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Serotonin and CFS

serotonin chronic fatigueA recent PubMed article talks about the serotonin system being over-active in CFS patients. It states that genetic abnormalities were found in serotonin receptors of patients. They were all located in the same receptor subtype (5-HT receptor subtype HTR2A).
Another article dated 2001, says that researchers found evidence of increased serotonergic activity and elevated levels of a serotonin metabolites in patients. It also says that certain treatments that increased serotonin turnover rates, like NADH, led to an improvement in symptoms.

I was wondering if there was a connection between the overactive serotonin system and the HPA axis.

I know that in people that are depressed, there is chronic overactivity of the HPA axis (in most cases). This increase in HPA activity leads to a decrease in the activity of serotonin. In CFS, it seems to be complete opposite.

Maybe the reduced activity of the HPA axis leads to an oversensitivity of serotonin receptors, or vice versa. But which is the cause and which is the symptom?

Also there is some evidence that the immune system, the serotonin system, and the HPA axis may all be interacting with each other.

Could a viral infection kick off the disease by interacting with the immune system, which then could effect the serotonin levels and the HPA axis?


Could a malfunctioning HPA axis lead to increased serotonin activity and decreased immunity? Causing viruses to re-emerge and cause symptoms of CFS.

This could explain why so many causes are implicated in CFS. The interaction and balances of these systems can be disrupted in many different ways. It would be incredibly difficult for a doctor to find the root cause.

In the CDC’s genetic studies of CFS, there was found to be malfunctioning genes on the glucocorticoid receptor, the serotonin [receptor], and tryptophan hydroxylase.

The glucocorticoid receptor senses how much cortisol is in the body and is part of a feedback loop that helps the body determine how much cortisol to produce.

Tryptophan Hydroxylase directly controls the levels of serotonin in the boy, and the serotonin receptors control how the body interacts with the serotonin.

Just thinking about how these complicated systems interact, it is easy to see why CFS symptoms vary so greatly between patients. And how many different causes can bring about the same disease.

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4 Responses to “Serotonin and CFS”

  1. Amy says:

    Aha! Interesting! After an extremely stressful year and a wide variety of symptoms that fit CFS (some that have been off and on for years) I was put on an SSRI and ended up in the ER with a mild case of serotonin syndrome. This info would seem to fit my situation. I have low memory and processing speed, a history of allergies that seemingly came out of no where, weird viral infections, skin conditions, weird headaches, fainting, dizziness…and more recently TMJ and SI joint problems, tics, spasms, balance problems, high white blood cell count, high glucose levels, extreme fatigue and fuzziness even while taking concerta. Please post if you have any history of serotonin syndrome and CFS. I want to learn more…My health has gone straight down the toilet during the last 9 months.

  2. Ivar J Tonisson says:

    I have been suffering from excercise induced Serotonin
    Syndrome and CFS for 29 years.Regular excercise leads
    to horrible symptoms:high blood pressure,a terrible
    headache,profuse sweating,itching skin etc. .When I
    try to excerise I can stop antidepressants after awhile , because I will beome euforic anyway just before the headaches set in accompained by
    uncontrolable diarrhea.
    Naturally , at that stage I will stop excercising ,and a few days later most irritating symptons are down.Two weeks later I am fine , in the sense that the Serotonin Syndrome symptons are totally gone , but all my pre-excercise symptons are back :severe fatigue , deep depression without antidepressants (which I am luckily able to take again),muscle pain etc.Ampligen was very effective against the main symptons of CFS but has no effect at all against the excercise induced Serotonin Syndrome.Kytril ,however,quickly removes those symptoms as long as its effect lasts.It is a medicine to prevent nausea when patients undergo chemotherapy for cancer etc..Kytril is a powerful anti-serotonin agent with side effects that makes it unsuitable for long time use.Therefore , I can only take it occasionally e.g.,when I want to participate in a scientific conference.
    When I was treated for CFS by Ampligen in Belgium 10 years ago by Dr Kenny Demeirleir he had nothing to offer against the noncentral -but very common-symptoms of CFS connected with digestive tract problems in my case chronic but controlable diarrrhea (naturally provided I did not excercise).Now Dr Demeirleir recommends megadoses of the right kind of Pro-Biotics taken on an empty stomach every Morning during 12 Months for CFS digestive problems.
    I have now folloed his regiment almost 3 months . I have noticed now that I begin to tolerate very moderate regular excercise like taking my puppy for regular short walks.Futhermore,I am happy to notice -quite paradoxically but understandablely after 29 years ot excercise induced Serotonin Syndrome -that I am still dead tired.
    Ivar J Tonisson ,PhD

  3. tania selth says:

    Ive got CFS/ME. A couple of years ago a doctor called an ambulance and had me taken to the main cities hospital as he was worried I had serotonin syndrome, due to the symptoms I had.

    After a night stay there, I was released the next day. Neurologists confused over my symptoms which they ended up putting down to my CFS/ME and dismissing the idea of serotonin syndrome.

    All i know is that I dont do at all well on SSRI drugs. I also get scary bad reaction after being on St John Wort for a couple of weeks.

  4. John Currin says:

    I am becoming convinced that excessive serotonin is involved in CFS symptoms. I have suspected this for years, but have failed to convince any of my doctors-yet. I was originally diagnosed with narcolepsy over 10 years ago, and the usual stimulant meds (adderall, etc.) were somewhat effective for a while. Like many of you, I am EXTREMELY sensitive to any serotonin-increasing meds (SSRI’s, SNRI’s) and get serotonin syndrome symptoms from miniscule doses. I have tried probably 40 or so meds over the years, with very little help. The only thing that I have found to help are opiates and small doses of Xyrem during the day- both of which are classified as CNS depressants- but when I take them it is like flipping a switch, and all of my symptoms go away for a short while. But trying to get a Dr. to understand this and prescribe them to stimulate me (wake me up, get my brain working, etc) is next to impossible. Next on my list of things to try are cyproheptadine (Serotonin antagonist) and Oxytocin. Good luck to the rest of you

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