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Autism spectrum disorder

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

Autism spectrum disorder (ASD) is a developmental disorder, meaning it affects how an individual develops mentally and physically. As of 2020, the CDC estimates 1 in 36 children have an autism diagnosis.[1]

Causes[edit | edit source]

A 2017 Swedish study suggests autism is 83% heritable.[2] In other words, most cases of autism are caused by genes inherited from one's parents. There are up to 1,000 genes that can potentially be involved in developing autism.[3]

Some prenatal environmental triggers are also linked with autism, including (but not limited to):

  • Prenatal infection with viruses such as measles and rubella. It's unclear whether a fetus' development changes due to direct interference from the virus or influence from the mother's activated immune system.[4]
  • Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).[5]
  • Maternal exposure to traffic-related air pollution. More specifically, mothers living within 309 meters (~3.5 football fields) of a freeway during the third trimester are more likely to have autistic babies.[6]

It's important to note that environmental triggers generally do not cause autism by themselves.[7] Rather, they cause changes that are thought to overlap with a child's pre-existing genetic risk factors - tipping the scales, so to speak.

There is little to no evidence that individuals can develop autism after birth.[8] Research repeatedly demonstrates no connection between autism and childhood vaccination.[9]

Similarities to ME/CFS[edit | edit source]

Symptoms[edit | edit source]

People with autism can develop many of the same symptoms as ME/CFS, including:[10]

Cellular Metabolism[edit | edit source]

Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.

Topic Summary ME/CFS ASD
Lactate Levels People with ME/CFD and autism both have high lactate levels in the blood. However, the conditions for high lactate levels differ. Lactate levels rise after exercise.[12] A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM.[13]


Some autistic kids have high lactate levels at rest.[14][15]
mtDNA Mutations in mitochondrial DNA (mtDNA) can cause fatigue. This issue is much more prevalent in autism than ME/CFS. A large, multi-national study found mutations in mtDNA are not any more common in the ME/CFS population than in the general public.[16]


Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.[17] The most common genes involved are:
  • 3397A>G (complex I)
  • 4295A>G (tRNA)
  • 3243A>G MELAS × 2, POLG × 2, LHON × 2
  • 3243A>G × 2
  • G8363A (tRNA)
  • G10406A (tRNA)



Mitochondrial dysfunction in skeletal muscle Both conditions have mitochondrial dysfunction in skeletal muscle. The dysfunction in ME/CFS seems to be more structural. Meanwhile, the dysfunction in autism is more related to a part of cellular respiration called the electron transport chain (ETC). ETC has 5 stages called complexes, labeled I through V. Within ME/CFS patients, the subsarcolemmal mitochondria have fewer cristae (folds), which may affect the production of certain chemicals.[18] Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and glucose transport.[19]

There aren't significant changes in complex I-IV in the ETC.[18][20]



In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.[21] The type of abnormality wasn't listed.


The same study found 65% of participants had a defect in the first part of ETC, called complex I. The middle stage, complex III, was affected in 20% of patients.[21] Smaller studies have had similar findings.[22]

Mitochondrial dysfunction in lymphocytes Research suggests both ME/CFS and ASD individuals may have altered ETC processes in their immune cells. In certain people, it seems Complex V is underactive, while other parts of the ETC process become hyperactive to compensate. Lymphoblastoid cell lines (LCLs) are actively replicating B cells cultured outside the body. The LCLs derived from ME/CFS patients have an inefficient Complex V. It seems as though the rest of the ETC is constantly upregulated to compensate. Yet when extra ATP is needed, such as during exercise, the mitochondria can't deliver because they're already working at full capacity.[23] Within LCLs derived from autistic people, mitochondria are more vulnerable to oxidative stress. This seems to be driven by alterations to glutathione metabolism.[24] The study authors believe these changes are related to overactivity in Complex IV found in a previous study.[25]

A 2010 study looked at peripheral blood lymphocytes, which are immune cells taken directly from the blood. Six out of 10 patients had low activity in Complex I. Four of those six also had deficiencies in Complex V.[26]


Autistic Burnout[edit | edit source]

Autistic Burnout Symptoms[edit | edit source]

Autistic burnout is a phenomenon characterized by:[27]

  • Severe exhaustion: Physical and mental fatigue can impact employment, relationships, and self-care. Similar to post-exertional malaise, the fatigue can worsen after straining oneself mentally or physically. However, physical triggers generally involve sensory sensitivities rather than exercise.
  • Reduced tolerance to stimulus: Individuals may be more sensitive to noise, light, and other sensory stimuli. They may also have more trouble regulating their emotions than they used to. Some may grow extremely dependent on routines in order to self-regulate.
  • Loss of skills: Individuals may have difficulty with executive functions like following plans and making decisions. They also may have trouble speaking or remembering common vocabulary. These skills can often return after the burnout episode, but not always to the level they were before.
Autistic Burnout Diagnosis[edit | edit source]

The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.[28] Some research may also call it "autistic regression."[29] However, neither of these names are an official diagnosis.

There is no official test for autistic burnout. However, a 2024 study found the AASPIRE Autistic Burnout Measure (ABM) is a valid measure of autistic burnout.[30] (Validity means the test accurately captures the concept it claims to measure.)

While some symptoms of autistic burnout do overlap with depression criteria, the two conditions are distinct. Autistic people experiencing burnout can still experience the full range of emotions and find joy in special interests. While low mood is common, it's not the defining feature of burnout. Similar to post-exertional malaise, rest is considered the primary method of recovery for an autistic burnout episode. [31]

Notable studies[edit | edit source]

  • 2024 - A genome-wide association study suggests autism has a "shared genetic architecture" with fatigue, multi-site pain, and IBS. However, it's too early to say whether there is a causal relationship.[32]
  • 2024 - Children with autistic traits are 78% more likely to have chronic disabling fatigue by the time they reach 18. The link between autism and fatigue held true even when researchers controlled for depressive symptoms. The study authors said this link was likely mediated by higher levels of the inflammatory cytokine IL-6.
  • 2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more central sensitivity syndromes (CSS). These included fibromyalgia, ME/CFS, IBS, restless leg syndrome, and temperomandibular joint disorder. In addition, 60% of participants met the clinical cut-off for a CSS on the Central Sensitization Inventory.
  • 2018 - Patients with chronic fatigue syndrome do not score higher on the Autism Spectrum Quotient (a test measuring autistic traits) than healthy controls.[10] (Abstract)

References[edit | edit source]

  1. ↑ CDC (July 19, 2024). "Data and Statistics on Autism Spectrum Disorder". Autism Spectrum Disorder (ASD). Retrieved January 25, 2025.
  2. ↑ Sandin, Sven; Lichtenstein, Paul; Kuja-Halkola, Ralf; Hultman, Christina; Larsson, Henrik; Reichenberg, Abraham (September 26, 2017). "The Heritability of Autism Spectrum Disorder". JAMA. 318 (12): 1182–1184. doi:10.1001/jama.2017.12141. ISSN 0098-7484. PMC 5818813. PMID 28973605.
  3. ↑ Chen, Jason; Penagarikano, Olga; Belgard, T. Grant; Swarup, Vivek; Geschwind, Daniel (2015). "The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology". Annual Reviews. 10: 111–144.
  4. ↑ Shuid, Ahmad Naqib; Jayusman, Putri Ayu; Shuid, Nazrun; Ismail, Juriza; Kamal Nor, Norazlin; Mohamed, Isa Naina (March 10, 2021). "Association between Viral Infections and Risk of Autistic Disorder: An Overview". International Journal of Environmental Research and Public Health. 18 (6): 2817. doi:10.3390/ijerph18062817. ISSN 1661-7827. PMC 7999368. PMID 33802042.
  5. ↑ Brown, Alan S.; Cheslack-Postava, Keely; Rantakokko, Panu; Kiviranta, Hannu; Hinkka-Yli-Salomäki, Susanna; McKeague, Ian W.; Surcel, Heljä-Marja; Sourander, Andre (November 1, 2018). "Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort". The American Journal of Psychiatry. 175 (11): 1094–1101. doi:10.1176/appi.ajp.2018.17101129. ISSN 1535-7228. PMC 6377859. PMID 30111184.
  6. ↑ Volk, Heather E.; Hertz-Picciotto, Irva; Delwiche, Lora; Lurmann, Fred; McConnell, Rob (2011-06). "Residential proximity to freeways and autism in the CHARGE study". Environmental Health Perspectives. 119 (6): 873–877. doi:10.1289/ehp.1002835. ISSN 1552-9924. PMC 3114825. PMID 21156395. Check date values in: |date= (help)
  7. ↑ "Autism". National Institute of Environmental Health Sciences. Retrieved January 25, 2025.
  8. ↑ "Is Autism Genetic?". UCLA Medical School. April 10, 2024. Retrieved January 26, 2025.
  9. ↑ Gabis, Lydia; Attia, Odelia; Goldman, Mia; Barak, Noy; Tefera, Paula; Shefer, Shahar (January 2022). "The myth of vaccination and autism spectrum". European Journal of Paediatric Neurology. 36: 151–158.
  10. ↑ Jump up to: 10.0 10.1 Bileviciute Ljungar, Indre; Maroti, Daniel; Bejerot, Susanne (2018), "Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder", Scandinavian Journal of Psychology
  11. ↑ Madra, Moneek; Ringel, Roey; Margolis, Kara G. (2020-7). "Gastrointestinal issues and Autism Spectrum Disorder". Child and adolescent psychiatric clinics of North America. 29 (3): 501–513. doi:10.1016/j.chc.2020.02.005. ISSN 1056-4993. PMC 8608248. PMID 32471598. Check date values in: |date= (help)
  12. ↑ Lien, Katarina; Johansen, Bjørn; Veierød, Marit B.; Haslestad, Annicke S.; Bøhn, Siv K.; Melsom, Morten N.; Kardel, Kristin R.; Iversen, Per O. (2019-06). "Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome". Physiological Reports. 7 (11): e14138. doi:10.14814/phy2.14138. ISSN 2051-817X. PMC 6546966. PMID 31161646. Check date values in: |date= (help)
  13. ↑ Ghali, Alaa; Lacout, Carole; Ghali, Maria; Gury, Aline; Beucher, Anne-Berengere; Lozac’h, Pierre; Lavigne, Christian; Urbanski, Geoffrey (December 11, 2019). "Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome". Scientific Reports. 9 (1): 18817. doi:10.1038/s41598-019-55473-4. ISSN 2045-2322.
  14. ↑ Weissman, Jacqueline R.; Kelley, Richard I.; Bauman, Margaret L.; Cohen, Bruce H.; Murray, Katherine F.; Mitchell, Rebecca L.; Kern, Rebecca L.; Natowicz, Marvin R. (November 26, 2008). "Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis". PLOS ONE. 3 (11): e3815. doi:10.1371/journal.pone.0003815. ISSN 1932-6203.
  15. ↑ Oliveira, G; Diogo, L; Grazina, M; Garcia, P (February 13, 2007). "Mitochondrial dysfunction in autism spectrum disorders: a population-based study". Developmental Medicine and Child Neurology. 47 (3): 185–189.
  16. ↑ Venter, Marianne; Tomas, Cara; Pienaar, Ilse S.; Strassheim, Victoria; Erasmus, Elardus; Ng, Wan-Fai; Howell, Neil; Newton, Julia L.; Van der Westhuizen, Francois H.; Elson, Joanna L. (February 27, 2019). "MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants". Scientific Reports. 9: 2914. doi:10.1038/s41598-019-39060-1. ISSN 2045-2322. PMC 6393470. PMID 30814539.
  17. ↑ Rossignol, D A; Frye, R E (2012-03). "Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis". Molecular Psychiatry. 17 (3): 290–314. doi:10.1038/mp.2010.136. ISSN 1359-4184. PMC 3285768. PMID 21263444. Check date values in: |date= (help)
  18. ↑ Jump up to: 18.0 18.1 Bizjak, Daniel Alexander; Ohmayer, Birgit; Buhl, Jasmine Leonike; Schneider, Elisabeth Marion; Walther, Paul; Calzia, Enrico; Jerg, Achim; Matits, Lynn; Steinacker, Jürgen Michael (January 30, 2024). "Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome". International Journal of Molecular Sciences. 25 (3): 1675. doi:10.3390/ijms25031675. ISSN 1422-0067. PMID 38338957.
  19. ↑ Ritov, Vladimir; Menshikova, Elizabeth; He, Jing; Ferrell, Robert (January 1, 2005). "Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes". Diabetes. 54 (1): 8–14.
  20. ↑ Tomas, Cara; Brown, Audrey E.; Newton, Julia L.; Elson, Joanna L. (2019). "Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types". PeerJ. 7: e6500. doi:10.7717/peerj.6500. ISSN 2167-8359. PMC 6398432. PMID 30847260.
  21. ↑ Jump up to: 21.0 21.1 Weissman, Jacqueline R.; Kelley, Richard I.; Bauman, Margaret L.; Cohen, Bruce H.; Murray, Katherine F.; Mitchell, Rebecca L.; Kern, Rebecca L.; Natowicz, Marvin R. (November 26, 2008). "Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis". PLOS ONE. 3 (11): e3815. doi:10.1371/journal.pone.0003815. ISSN 1932-6203.
  22. ↑ Griffiths, Keren; Levy, Richard (May 29, 2017). "Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms". Oxidative Medicine and Cellular Longevity.
  23. ↑ Missailidis, Daniel; Annesley, Sarah J.; Allan, Claire Y.; Sanislav, Oana; Lidbury, Brett A.; Lewis, Donald P.; Fisher, Paul R. (February 6, 2020). "An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients". International Journal of Molecular Sciences. 21 (3): 1074. doi:10.3390/ijms21031074. ISSN 1422-0067. PMC 7036826. PMID 32041178.
  24. ↑ Rose, S.; Frye, R. E.; Slattery, J.; Wynne, R.; Tippett, M.; Melnyk, S.; James, S. J. (2014-04). "Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines". Translational Psychiatry. 4 (4): e377–e377. doi:10.1038/tp.2014.15. ISSN 2158-3188. Check date values in: |date= (help)
  25. ↑ Frye, Richard E.; Naviaux, Robert K. (2011-12). "Autistic disorder with complex IV overactivity: A new mitochondrial syndrome". Journal of Pediatric Neurology. 09 (4): 427–434. doi:10.3233/JPN-2011-0507. ISSN 1304-2580. Check date values in: |date= (help)
  26. ↑ Giulivi, Cecilia; Zhang, Yi-Fan; Omanska-Klusek, Alicja; Ross-Inta, Catherine; Wong, Sarah; Hertz-Picciotto, Irva; Tassone, Flora; Pessah, Isaac N. (December 1, 2010). "Mitochondrial Dysfunction in Autism". JAMA : the journal of the American Medical Association. 304 (21): 2389–2396. doi:10.1001/jama.2010.1706. ISSN 0098-7484. PMC 3915058. PMID 21119085.
  27. ↑ Raymaker, Dora M.; Teo, Alan R.; Steckler, Nicole A.; Lentz, Brandy; Scharer, Mirah; Delos Santos, Austin; Kapp, Steven K.; Hunter, Morrigan; Joyce, Andee; Nicolaidis, Christina (June 1, 2020). ""Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew": Defining Autistic Burnout". Autism in Adulthood. 2 (2): 132–143. doi:10.1089/aut.2019.0079. ISSN 2573-9581. PMC 7313636. PMID 32851204.
  28. ↑ Mantzalas, Jane; Richdale, Amanda L.; Adikari, Achini; Lowe, Jennifer; Dissanayake, Cheryl (March 1, 2022). "What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms". Autism in Adulthood: Challenges and Management. 4 (1): 52–65. doi:10.1089/aut.2021.0021. ISSN 2573-9581. PMC 8992925. PMID 36605565.
  29. ↑ Tan, Christine; Frewer, Veronica; Cox, Georgina; Williams, Katrina; Ure, Alexandra (2021-03). "Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update". Autism Research: Official Journal of the International Society for Autism Research. 14 (3): 582–598. doi:10.1002/aur.2463. ISSN 1939-3806. PMID 33491292. Check date values in: |date= (help)
  30. ↑ Mantzalas, Jane; Richdale, Amanda; Li, Xia; Dissanayake, Cheryl (Apr, 25, 2024). "Measuring and validating autistic burnout". Autism Research. 17 (7): 1417–1449. Check date values in: |date= (help)
  31. ↑ Higgins, Julianne; Arnold, Samuel; Weise, Janelle; Pellicano, Elizabeth; Trollor, Jullian (June 4, 2021). "Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout". Autism. 25 (8).
  32. ↑ Li, Yiran; Xie, Tian; Vos, Melissa; Snieder, Harold; Hartman, Catharina A. (November 23, 2024). "Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue". Translational Psychiatry. 14 (1): 1–9. doi:10.1038/s41398-024-03184-4. ISSN 2158-3188. PMC 11585586. PMID 39580447.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

See Centers for Disease Control and Prevention.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

See post-exertional malaise.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

an organism's complete set of DNA, including all of its genes[1]

genome an organism's complete set of DNA, including all of its genes

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

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