Table of ContentsView AllTable of ContentsGeneticsInfectionsImmune SystemHormones and the CNSChemicals/ToxinsYour SexFrequently Asked QuestionsNext in Chronic Fatigue Syndrome GuideHow Chronic Fatigue Syndrome Is Diagnosed
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Frequently Asked Questions
Next in Chronic Fatigue Syndrome Guide
The causes ofchronic fatigue syndrome(ME/CFS) are unclear. Despite extensive research, experts haven’t been able to pin the disease on any one factor, and some believe the condition could result from multiple factors coming together under the right conditions. These factors may include:
Not everyone with chronic fatigue syndrome has all of these factors. They likely have a combination of them that, for some reason, has led to the condition, which is more common in women than men.
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People may be genetically predisposed to ME/CFS—in other words, they’re likely to get it if enough triggers come together. For example, someone who’s predisposed and is going through a stressful time and is then exposed to a particular toxin may develop ME/CFS, while someone in the same scenario but with a different genetic makeup would not.
Research is trying to identify the genes that could be responsible. Some has focused on the genes involved in thehypothalamic-pituitary-adrenal(HPA) axisand the sympathetic nervous system. The HPA axis controls your sleep, response to stress, and depression. There may be genetic abnormalities in people with ME/CFS that influence immune function, cellular communication, and the ways your cells get energy.
Many of the signs andsymptoms of chronic fatigue syndromeare similar to those of a lingering viral illness, so research has focused on the possibility of a viral or infectious cause. An infectious trigger is also suspected because many ME/CFS cases start suddenly after a flu-like condition.
Each of these viruses often shows few symptoms in humans, but those who have more severe symptoms are more likely to develop chronic fatigue syndrome symptoms.
Other infections that have been suspected and studied include HHV-6, Lyme disease, andenterovirus. However, none of these infections has been shown tocauseME/CFS.
Researchers have examined three infection-related theories, though none has been proven:
People with ME/CFS may have higher levels of antibodies to some infection-causing organisms and show signs of chronic immune system activity, suggesting the body is fighting an infection. Some researchers even theorize that changes in normally harmless bacteria in the intestine may play a role in the development of chronic fatigue syndrome.
However, some evidence seems to run counter to the viral cause theory. ME/CFS doesn’t appear to spread through direct contact, people with it don’t seem to be contagious, and—in spite of well-designed studies—researchers have not been able to link chronic fatigue syndrome with any specific infections. For example, there was a great deal of excitement over a study finding a newly discovered retrovirus, XMRV, in ME/CFS patients. However,later studiesdid not confirm the results; it could be that the original study was flawed due to contamination of the samples.
Chronic fatigue syndrome appears to have some features in common withautoimmune diseasessuch aslupusormultiple sclerosis, in which the immune system mistakenly attacks healthy parts of the body. One theory is that allergies, stress, and infection may combine to deplete a chemical calledadenosine triphosphate(ATP), which stores energy in cells. Some ME/CFS patients show evidence of decreased ATP production.
Irregularities may be seen in the immune systems of people with chronic fatigue syndrome, but researchers have not found a consistent pattern of abnormalities. Among the most common areallergiesand an overactive immune system.
The immune system produces many chemicals that are collectively calledcytokines. These act on immune cells to regulate their behavior in many ways. Some ME/CFS patients have high levels of these chemicals, which scientists theorize could cause symptoms of chronic fatigue, including exhaustion and muscle aches.
Changes can also be seen in the function of a couple of types of immune cells in people with ME/CFS. T-cells are active in both producing and calming the immune response. Some people with this syndrome show abnormal T-cell activation, while others do not. Natural killer (NK) cells are immune system cells that help the body fight infection. Low-functioning NK cells are seen in people with chronic fatigue syndrome, and it appears that the worse the functioning of these cells, the more severe the illness. Research is ongoing to find the specific mechanism that could lead to impairment of these cells.
Neurotransmitter Changes
Neurotransmitters are chemicals that communicate messages between nerve cells in your brain and throughout your body. Each bodily function, thought, and emotion is linked to the operations of specific neurotransmitters. When the activity of a particular one is too high or too low, things can start to malfunction. Some people with ME/CFS have abnormal levels of certain important neurotransmitters (serotoninanddopamine). It could also be that there is enough present but the receptors for them are not working properly. Researchers are working to explain the role these abnormalities play in chronic fatigue syndrome.
Stress Hormone Deficiencies
The level of the stress hormone cortisol tends to be low in ME/CFS patients. Some theorize this could make it hard to deal with stress, either physical (such as infection or exertion) or mental. Cortisol levels are not diagnostic for the condition and replacement helps some, but not all, chronic fatigue patients.
Disturbed Circadian Rhythms
Psychological Factors
Researchers believe your psychological makeup, personality, and social situation can impact whether you’ll develop ME/CFS, but they don’t yet fully understand the complex relationship between these factors. While they are probably not primary causes of chronic fatigue syndrome, they’re likely to play a role in making you susceptible.
Note that ME/CFS is not considered a primarily psychological illness, nor does having it mean someone is psychologically “weak” or unable to cope with things. While it is sometimes linked to clinical depression,chronic fatigue syndrome is a distinct condition.
In some, chronic fatigue and pain are associated with exposure to various chemicals and environmental toxins. These can include solvents, pesticides, or heavy metals. However, because most people have been exposed to these types of chemicals at some point, it’s difficult to track down which ones might be causing problems.
A condition calledmultiple chemical sensitivity(MCS) causes many of the same symptoms as ME/CFS, and the two are believed to beoverlapping conditions.
Two to four times as many women arediagnosed with ME/CFSas are men.Any cause, if discovered, would need to account for this difference. There are sexual differences in hormones, brain chemistry, immune system function, inflammation, and genetics:
There could also be a bias in diagnosis. Men might not seek medical attention for their symptoms due to perceived social pressure to “tough things out,” among other reasons. Healthcare providers may also have a bias that ME/CFS is a female disease and be less likely to consider the diagnosis for men with the symptoms.
As research continues, there may be a breakthrough in identifying the cause and risk factors for ME/CFS. In the meantime, if you feel yoursymptomsalign with chronic fatigue syndrome, advocate for yourself and work with your healthcare provider to get to the bottom of them.
While myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) isn’t necessarily hereditary, there can be a genetic component that predisposes some people to develop it. Scientists are still working to identify the specific genes involved, but some research suggests that genetic abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, which manages the stress response, could be a factor.
According to the CDC, one in 10 people who get the above infections will developsymptoms of ME/CFS.
Yes, some studies have pinpointed that emotionalstressor childhood trauma specifically is a risk factor for developing ME/CFS.Additionally, levels of the stress hormone cortisol tend to be lower in people with ME/CFS, suggesting that the way they process and manage stress may be altered.
Surgery, trauma, and intense stress can cause anME/CFS flare-up, but there may not always be an obvious trigger. In some cases, it could be everyday activities such as taking a shower or running errands that can cause a crash.
How Chronic Fatigue Syndrome Is Diagnosed
16 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Centers for Disease Control and Prevention.Myalgic encephalomyelitis/chronic fatigue syndrome: Possible causes.Schlauch KA, Khaiboullina SF, De meirleir KL, et al.Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome. Transl Psychiatry. 2016;6:e730. doi:10.1038/tp.2015.208Tomas C, Newton J, Watson S.A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.ISRN Neurosci. 2013;2013:784520. doi:10.1155/2013/784520Newberry F, Hsieh SY, Wileman T, Carding SR.Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?Clin Sci. 2018;132(5):523-542. doi:10.1042/CS20171330Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P.Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.PLoS ONE. 2018;13(2):e0192817. doi:10.1371/journal.pone.0192817Montoya JG, Holmes TH, Anderson JN, et al.Cytokine signature associated with disease severity in chronic fatigue syndrome patients.Proc Natl Acad Sci USA. 2017;114(34):E7150-E7158. doi:10.1073/pnas.1710519114Cliff JM, King EC, Lee JS, et al.Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Immunol. 2019;10:796. doi:10.3389/fimmu.2019.00796Hardcastle SL, Brenu EW, Johnston S, et al.Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). BMC Immunol. 2015;16:35. doi:10.1186/s12865-015-0101-4Glassford JA.The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Physiol. 2017;8:88. doi:10.3389/fphys.2017.00088Jackson ML, Bruck D.Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review.J Clin Sleep Med. 2012;8(6):719-28. doi:10.5664/jcsm.2276Comorbid Conditions | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | CDC. Centers for Disease Control and Prevention.Pacini S, Fiore MG, Magherini S, et al.Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Med Hypotheses. 2012;79(3):403-7. doi:10.1016/j.mehy.2012.06.007Chronic fatigue syndrome. womenshealth.gov.Chu L, Valencia IJ, Garvert DW, Montoya JG.Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Pediatr. 2019;7:12. doi:10.3389/fped.2019.00012Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC.Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction.Arch Gen Psychiatry.2009;66(1):72–80. doi:10.1001/archgenpsychiatry.2008.508Centers for Disease Control and Prevention.Symptoms of ME/CFS.Additional ReadingCenters for Disease Control and Prevention.Possible Causes. https://www.cdc.gov/me-cfs/about/possible-causes.html.Gluckman S.Chronic Fatigue Syndrome. Merck Manual. https://www.merckmanuals.com/home/special-subjects/chronic-fatigue-syndrome/chronic-fatigue-syndrome#.Simmons G, Glynn SA, Komaroff AL, et al.Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-laboratory Study.Science. 2011;334(6057):814-817. doi:10.1126/science.1213841.
16 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Centers for Disease Control and Prevention.Myalgic encephalomyelitis/chronic fatigue syndrome: Possible causes.Schlauch KA, Khaiboullina SF, De meirleir KL, et al.Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome. Transl Psychiatry. 2016;6:e730. doi:10.1038/tp.2015.208Tomas C, Newton J, Watson S.A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.ISRN Neurosci. 2013;2013:784520. doi:10.1155/2013/784520Newberry F, Hsieh SY, Wileman T, Carding SR.Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?Clin Sci. 2018;132(5):523-542. doi:10.1042/CS20171330Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P.Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.PLoS ONE. 2018;13(2):e0192817. doi:10.1371/journal.pone.0192817Montoya JG, Holmes TH, Anderson JN, et al.Cytokine signature associated with disease severity in chronic fatigue syndrome patients.Proc Natl Acad Sci USA. 2017;114(34):E7150-E7158. doi:10.1073/pnas.1710519114Cliff JM, King EC, Lee JS, et al.Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Immunol. 2019;10:796. doi:10.3389/fimmu.2019.00796Hardcastle SL, Brenu EW, Johnston S, et al.Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). BMC Immunol. 2015;16:35. doi:10.1186/s12865-015-0101-4Glassford JA.The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Physiol. 2017;8:88. doi:10.3389/fphys.2017.00088Jackson ML, Bruck D.Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review.J Clin Sleep Med. 2012;8(6):719-28. doi:10.5664/jcsm.2276Comorbid Conditions | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | CDC. Centers for Disease Control and Prevention.Pacini S, Fiore MG, Magherini S, et al.Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Med Hypotheses. 2012;79(3):403-7. doi:10.1016/j.mehy.2012.06.007Chronic fatigue syndrome. womenshealth.gov.Chu L, Valencia IJ, Garvert DW, Montoya JG.Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Pediatr. 2019;7:12. doi:10.3389/fped.2019.00012Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC.Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction.Arch Gen Psychiatry.2009;66(1):72–80. doi:10.1001/archgenpsychiatry.2008.508Centers for Disease Control and Prevention.Symptoms of ME/CFS.Additional ReadingCenters for Disease Control and Prevention.Possible Causes. https://www.cdc.gov/me-cfs/about/possible-causes.html.Gluckman S.Chronic Fatigue Syndrome. Merck Manual. https://www.merckmanuals.com/home/special-subjects/chronic-fatigue-syndrome/chronic-fatigue-syndrome#.Simmons G, Glynn SA, Komaroff AL, et al.Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-laboratory Study.Science. 2011;334(6057):814-817. doi:10.1126/science.1213841.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Centers for Disease Control and Prevention.Myalgic encephalomyelitis/chronic fatigue syndrome: Possible causes.Schlauch KA, Khaiboullina SF, De meirleir KL, et al.Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome. Transl Psychiatry. 2016;6:e730. doi:10.1038/tp.2015.208Tomas C, Newton J, Watson S.A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.ISRN Neurosci. 2013;2013:784520. doi:10.1155/2013/784520Newberry F, Hsieh SY, Wileman T, Carding SR.Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?Clin Sci. 2018;132(5):523-542. doi:10.1042/CS20171330Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P.Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.PLoS ONE. 2018;13(2):e0192817. doi:10.1371/journal.pone.0192817Montoya JG, Holmes TH, Anderson JN, et al.Cytokine signature associated with disease severity in chronic fatigue syndrome patients.Proc Natl Acad Sci USA. 2017;114(34):E7150-E7158. doi:10.1073/pnas.1710519114Cliff JM, King EC, Lee JS, et al.Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Immunol. 2019;10:796. doi:10.3389/fimmu.2019.00796Hardcastle SL, Brenu EW, Johnston S, et al.Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). BMC Immunol. 2015;16:35. doi:10.1186/s12865-015-0101-4Glassford JA.The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Physiol. 2017;8:88. doi:10.3389/fphys.2017.00088Jackson ML, Bruck D.Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review.J Clin Sleep Med. 2012;8(6):719-28. doi:10.5664/jcsm.2276Comorbid Conditions | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | CDC. Centers for Disease Control and Prevention.Pacini S, Fiore MG, Magherini S, et al.Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Med Hypotheses. 2012;79(3):403-7. doi:10.1016/j.mehy.2012.06.007Chronic fatigue syndrome. womenshealth.gov.Chu L, Valencia IJ, Garvert DW, Montoya JG.Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Pediatr. 2019;7:12. doi:10.3389/fped.2019.00012Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC.Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction.Arch Gen Psychiatry.2009;66(1):72–80. doi:10.1001/archgenpsychiatry.2008.508Centers for Disease Control and Prevention.Symptoms of ME/CFS.
Centers for Disease Control and Prevention.Myalgic encephalomyelitis/chronic fatigue syndrome: Possible causes.
Schlauch KA, Khaiboullina SF, De meirleir KL, et al.Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome. Transl Psychiatry. 2016;6:e730. doi:10.1038/tp.2015.208
Tomas C, Newton J, Watson S.A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.ISRN Neurosci. 2013;2013:784520. doi:10.1155/2013/784520
Newberry F, Hsieh SY, Wileman T, Carding SR.Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?Clin Sci. 2018;132(5):523-542. doi:10.1042/CS20171330
Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P.Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.PLoS ONE. 2018;13(2):e0192817. doi:10.1371/journal.pone.0192817
Montoya JG, Holmes TH, Anderson JN, et al.Cytokine signature associated with disease severity in chronic fatigue syndrome patients.Proc Natl Acad Sci USA. 2017;114(34):E7150-E7158. doi:10.1073/pnas.1710519114
Cliff JM, King EC, Lee JS, et al.Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Immunol. 2019;10:796. doi:10.3389/fimmu.2019.00796
Hardcastle SL, Brenu EW, Johnston S, et al.Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). BMC Immunol. 2015;16:35. doi:10.1186/s12865-015-0101-4
Glassford JA.The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Physiol. 2017;8:88. doi:10.3389/fphys.2017.00088
Jackson ML, Bruck D.Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review.J Clin Sleep Med. 2012;8(6):719-28. doi:10.5664/jcsm.2276
Comorbid Conditions | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | CDC. Centers for Disease Control and Prevention.
Pacini S, Fiore MG, Magherini S, et al.Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Med Hypotheses. 2012;79(3):403-7. doi:10.1016/j.mehy.2012.06.007
Chronic fatigue syndrome. womenshealth.gov.
Chu L, Valencia IJ, Garvert DW, Montoya JG.Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Pediatr. 2019;7:12. doi:10.3389/fped.2019.00012
Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC.Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction.Arch Gen Psychiatry.2009;66(1):72–80. doi:10.1001/archgenpsychiatry.2008.508
Centers for Disease Control and Prevention.Symptoms of ME/CFS.
Centers for Disease Control and Prevention.Possible Causes. https://www.cdc.gov/me-cfs/about/possible-causes.html.Gluckman S.Chronic Fatigue Syndrome. Merck Manual. https://www.merckmanuals.com/home/special-subjects/chronic-fatigue-syndrome/chronic-fatigue-syndrome#.Simmons G, Glynn SA, Komaroff AL, et al.Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-laboratory Study.Science. 2011;334(6057):814-817. doi:10.1126/science.1213841.
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