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Autism spectrum disorder

2026-08-13T05:10:16Z

Galimatias:I added another study suggesting an additional genetic link between autism and ME/CFS

'''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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==

====== Symptoms ======
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

====== Genes Related to Neuron Function ======
A 2025 preprint study linked ME/CFS to dysfunction in genes that control synaptic function (e.g., [[Synaptic Ras GTPase Activating Protein 1|SYNGAP1]]).<ref>{{Cite web|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC12047926|title=Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis|last=Zhang|first=Sai|last2=Jahanbani|first2=Fereshteh|date=2025-04-16|website=pmc.ncbi.nlm.nih.gov|language=en|doi=10.1101/2025.04.15.25325899|access-date=2025-08-03|last3=Chander|first3=Varuna|last4=Kjellberg|first4=Martin|last5=Liu|first5=Menghui|last6=Glass|first6=Katherine A.|last7=Iu|first7=David S.|last8=Ahmed|first8=Faraz|last9=Li|first9=Han}}</ref> Mutations in these genes affect how your brain cells communicate. Prior research has also linked these genes to differences in autistic brain development.<ref>{{Cite journal|title=SYNGAP1: Mind the Gap|date=2016-02-15|url=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00032/full|journal=Frontiers in Cellular Neuroscience|volume=10|last=Nallathambi|first=Jeyabalan,|last2=P.|first2=Clement, James|language=English|doi=10.3389/fncel.2016.00032/full|issn=1662-5102}}</ref>

Another 2025 study found a link between ME/CFS susceptibility and the variants of the neurodevelopment genes NBPF1, NBPF10, and NBPF16.<ref>{{Cite journal|title=Neurodevelopment Genes Encoding Olduvai Domains Link Myalgic Encephalomyelitis to Neuropsychiatric Disorders|url=https://www.mdpi.com/2075-4418/15/12/1542|journal=diagnostics|last=Arcos-Burgos|first=Mauricio|doi=10.3390/diagnostics15121542}}</ref> These genes all encode the Olduvai domain, a section of proteins that repeats multiple times in human DNA. Research has shown people with autism tend to have with a higher than average number of Olduvai domain copies, and people with schizophrenia tend to have fewer copies.<ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/30764650/|title=pubmed.ncbi.nlm.nih.gov|website=pubmed.ncbi.nlm.nih.gov|access-date=2026-08-13}}</ref>

====== Cellular Metabolism ======
Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.
{| class="wikitable"
|'''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.<ref>{{Cite journal|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|date=2019-06|url=https://pubmed.ncbi.nlm.nih.gov/31161646/|journal=Physiological Reports|volume=7|issue=11|pages=e14138|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|doi=10.14814/phy2.14138|pmc=6546966|pmid=31161646|issn=2051-817X}}</ref> A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM'''.<ref>{{Cite journal|title=Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome|date=2019-12-11|url=https://www.nature.com/articles/s41598-019-55473-4|journal=Scientific Reports|volume=9|issue=1|pages=18817|last=Ghali|first=Alaa|last2=Lacout|first2=Carole|last3=Ghali|first3=Maria|last4=Gury|first4=Aline|last5=Beucher|first5=Anne-Berengere|last6=Lozac’h|first6=Pierre|last7=Lavigne|first7=Christian|last8=Urbanski|first8=Geoffrey|language=en|doi=10.1038/s41598-019-55473-4|issn=2045-2322}}</ref>'''

|Some autistic kids have high lactate levels at rest.<ref>{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref><ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a population-based study|date=Feb 13, 2007|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2005.tb01113.x|journal=Developmental Medicine and Child Neurology|volume=47|issue=3|pages=185-189|last=Oliveira|first=G|last2=Diogo|first2=L|last3=Grazina|first3=M|last4=Garcia|first4=P}}</ref>

|-
|'''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.<ref>{{Cite journal|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|date=2019-02-27|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393470/|journal=Scientific Reports|volume=9|pages=2914|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|last10=Elson|first10=Joanna L.|doi=10.1038/s41598-019-39060-1|pmc=6393470|pmid=30814539|issn=2045-2322}}</ref>

|Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.<ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis|date=2012-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285768/|journal=Molecular Psychiatry|volume=17|issue=3|pages=290–314|last=Rossignol|first=D A|last2=Frye|first2=R E|doi=10.1038/mp.2010.136|pmc=3285768|pmid=21263444|issn=1359-4184}}</ref> 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.<ref name=":2">{{Cite journal|title=Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome|date=2024-01-30|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855807/|journal=International Journal of Molecular Sciences|volume=25|issue=3|pages=1675|last=Bizjak|first=Daniel Alexander|last2=Ohmayer|first2=Birgit|last3=Buhl|first3=Jasmine Leonike|last4=Schneider|first4=Elisabeth Marion|last5=Walther|first5=Paul|last6=Calzia|first6=Enrico|last7=Jerg|first7=Achim|last8=Matits|first8=Lynn|last9=Steinacker|first9=Jürgen Michael|doi=10.3390/ijms25031675|pmid=38338957|issn=1422-0067}}</ref> Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and [[glucose]] transport.<ref>{{Cite journal|title=Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes|date=Jan 1, 2005|url=https://diabetesjournals.org/diabetes/article/54/1/8/14686/Deficiency-of-Subsarcolemmal-Mitochondria-in|journal=Diabetes|volume=54|issue=1|pages=8-14|last=Ritov|first=Vladimir|last2=Menshikova|first2=Elizabeth|last3=He|first3=Jing|last4=Ferrell|first4=Robert}}</ref>

There aren't significant changes in complex I-IV in the ETC.<ref name=":2" /><ref>{{Cite journal|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|date=2019|url=https://pubmed.ncbi.nlm.nih.gov/30847260/|journal=PeerJ|volume=7|pages=e6500|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|doi=10.7717/peerj.6500|pmc=6398432|pmid=30847260|issn=2167-8359}}</ref>

|In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.<ref name=":3">{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref> 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.<ref name=":3" /> Smaller studies have had similar findings.<ref>{{Cite journal|title=Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms|date=May 29, 2017|url=https://onlinelibrary.wiley.com/doi/10.1155/2017/4314025|journal=Oxidative Medicine and Cellular Longevity|last=Griffiths|first=Keren|last2=Levy|first2=Richard}}</ref>
|-
|'''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 cell|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.<ref>{{Cite journal|title=An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients|date=2020-02-06|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036826/|journal=International Journal of Molecular Sciences|volume=21|issue=3|pages=1074|last=Missailidis|first=Daniel|last2=Annesley|first2=Sarah J.|last3=Allan|first3=Claire Y.|last4=Sanislav|first4=Oana|last5=Lidbury|first5=Brett A.|last6=Lewis|first6=Donald P.|last7=Fisher|first7=Paul R.|doi=10.3390/ijms21031074|pmc=7036826|pmid=32041178|issn=1422-0067}}</ref>
|Within LCLs derived from autistic people, mitochondria are more vulnerable to [[oxidative stress]]. This seems to be driven by alterations to [[glutathione]] metabolism.<ref>{{Cite journal|title=Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines|date=2014-04|url=https://www.nature.com/articles/tp201415|journal=Translational Psychiatry|volume=4|issue=4|pages=e377–e377|last=Rose|first=S.|last2=Frye|first2=R. E.|last3=Slattery|first3=J.|last4=Wynne|first4=R.|last5=Tippett|first5=M.|last6=Melnyk|first6=S.|last7=James|first7=S. J.|language=en|doi=10.1038/tp.2014.15|issn=2158-3188}}</ref> The study authors believe these changes are related to overactivity in Complex IV found in a previous study.<ref>{{Cite journal|title=Autistic disorder with complex IV overactivity: A new mitochondrial syndrome|date=2011-12|url=http://www.thieme-connect.de/DOI/DOI?10.3233/JPN-2011-0507|journal=Journal of Pediatric Neurology|volume=09|issue=4|pages=427–434|last=Frye|first=Richard E.|last2=Naviaux|first2=Robert K.|language=en|doi=10.3233/JPN-2011-0507|issn=1304-2580}}</ref>
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.<ref>{{Cite journal|title=Mitochondrial Dysfunction in Autism|date=2010-12-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915058/|journal=JAMA : the journal of the American Medical Association|volume=304|issue=21|pages=2389–2396|last=Giulivi|first=Cecilia|last2=Zhang|first2=Yi-Fan|last3=Omanska-Klusek|first3=Alicja|last4=Ross-Inta|first4=Catherine|last5=Wong|first5=Sarah|last6=Hertz-Picciotto|first6=Irva|last7=Tassone|first7=Flora|last8=Pessah|first8=Isaac N.|doi=10.1001/jama.2010.1706|pmc=3915058|pmid=21119085|issn=0098-7484}}</ref>

|}

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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. <ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Autism spectrum disorder

2025-08-03T03:02:10Z

Galimatias:added new genetic findings from a preprint study

'''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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==

====== Symptoms ======
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

====== Genes Related to Neuron Function ======
A 2025 preprint study linked ME/CFS to dysfunction in genes that control synaptic function (e.g., ''SYNGAP1'').<ref>{{Cite web|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC12047926|title=Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis|last=Zhang|first=Sai|last2=Jahanbani|first2=Fereshteh|date=2025-04-16|website=pmc.ncbi.nlm.nih.gov|language=en|doi=10.1101/2025.04.15.25325899|access-date=2025-08-03|last3=Chander|first3=Varuna|last4=Kjellberg|first4=Martin|last5=Liu|first5=Menghui|last6=Glass|first6=Katherine A.|last7=Iu|first7=David S.|last8=Ahmed|first8=Faraz|last9=Li|first9=Han}}</ref> Mutations in these genes affect how your brain cells communicate. Prior research has also linked these genes to differences in autistic brain development.<ref>{{Cite journal|title=SYNGAP1: Mind the Gap|date=2016-02-15|url=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00032/full|journal=Frontiers in Cellular Neuroscience|volume=10|last=Nallathambi|first=Jeyabalan,|last2=P.|first2=Clement, James|language=English|doi=10.3389/fncel.2016.00032/full|issn=1662-5102}}</ref>

====== Cellular Metabolism ======
Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.
{| class="wikitable"
|'''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.<ref>{{Cite journal|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|date=2019-06|url=https://pubmed.ncbi.nlm.nih.gov/31161646/|journal=Physiological Reports|volume=7|issue=11|pages=e14138|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|doi=10.14814/phy2.14138|pmc=6546966|pmid=31161646|issn=2051-817X}}</ref> A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM'''.<ref>{{Cite journal|title=Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome|date=2019-12-11|url=https://www.nature.com/articles/s41598-019-55473-4|journal=Scientific Reports|volume=9|issue=1|pages=18817|last=Ghali|first=Alaa|last2=Lacout|first2=Carole|last3=Ghali|first3=Maria|last4=Gury|first4=Aline|last5=Beucher|first5=Anne-Berengere|last6=Lozac’h|first6=Pierre|last7=Lavigne|first7=Christian|last8=Urbanski|first8=Geoffrey|language=en|doi=10.1038/s41598-019-55473-4|issn=2045-2322}}</ref>'''

|Some autistic kids have high lactate levels at rest.<ref>{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref><ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a population-based study|date=Feb 13, 2007|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2005.tb01113.x|journal=Developmental Medicine and Child Neurology|volume=47|issue=3|pages=185-189|last=Oliveira|first=G|last2=Diogo|first2=L|last3=Grazina|first3=M|last4=Garcia|first4=P}}</ref>

|-
|'''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.<ref>{{Cite journal|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|date=2019-02-27|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393470/|journal=Scientific Reports|volume=9|pages=2914|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|last10=Elson|first10=Joanna L.|doi=10.1038/s41598-019-39060-1|pmc=6393470|pmid=30814539|issn=2045-2322}}</ref>

|Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.<ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis|date=2012-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285768/|journal=Molecular Psychiatry|volume=17|issue=3|pages=290–314|last=Rossignol|first=D A|last2=Frye|first2=R E|doi=10.1038/mp.2010.136|pmc=3285768|pmid=21263444|issn=1359-4184}}</ref> 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.<ref name=":2">{{Cite journal|title=Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome|date=2024-01-30|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855807/|journal=International Journal of Molecular Sciences|volume=25|issue=3|pages=1675|last=Bizjak|first=Daniel Alexander|last2=Ohmayer|first2=Birgit|last3=Buhl|first3=Jasmine Leonike|last4=Schneider|first4=Elisabeth Marion|last5=Walther|first5=Paul|last6=Calzia|first6=Enrico|last7=Jerg|first7=Achim|last8=Matits|first8=Lynn|last9=Steinacker|first9=Jürgen Michael|doi=10.3390/ijms25031675|pmid=38338957|issn=1422-0067}}</ref> Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and [[glucose]] transport.<ref>{{Cite journal|title=Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes|date=Jan 1, 2005|url=https://diabetesjournals.org/diabetes/article/54/1/8/14686/Deficiency-of-Subsarcolemmal-Mitochondria-in|journal=Diabetes|volume=54|issue=1|pages=8-14|last=Ritov|first=Vladimir|last2=Menshikova|first2=Elizabeth|last3=He|first3=Jing|last4=Ferrell|first4=Robert}}</ref>

There aren't significant changes in complex I-IV in the ETC.<ref name=":2" /><ref>{{Cite journal|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|date=2019|url=https://pubmed.ncbi.nlm.nih.gov/30847260/|journal=PeerJ|volume=7|pages=e6500|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|doi=10.7717/peerj.6500|pmc=6398432|pmid=30847260|issn=2167-8359}}</ref>

|In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.<ref name=":3">{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref> 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.<ref name=":3" /> Smaller studies have had similar findings.<ref>{{Cite journal|title=Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms|date=May 29, 2017|url=https://onlinelibrary.wiley.com/doi/10.1155/2017/4314025|journal=Oxidative Medicine and Cellular Longevity|last=Griffiths|first=Keren|last2=Levy|first2=Richard}}</ref>
|-
|'''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 cell|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.<ref>{{Cite journal|title=An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients|date=2020-02-06|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036826/|journal=International Journal of Molecular Sciences|volume=21|issue=3|pages=1074|last=Missailidis|first=Daniel|last2=Annesley|first2=Sarah J.|last3=Allan|first3=Claire Y.|last4=Sanislav|first4=Oana|last5=Lidbury|first5=Brett A.|last6=Lewis|first6=Donald P.|last7=Fisher|first7=Paul R.|doi=10.3390/ijms21031074|pmc=7036826|pmid=32041178|issn=1422-0067}}</ref>
|Within LCLs derived from autistic people, mitochondria are more vulnerable to [[oxidative stress]]. This seems to be driven by alterations to [[glutathione]] metabolism.<ref>{{Cite journal|title=Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines|date=2014-04|url=https://www.nature.com/articles/tp201415|journal=Translational Psychiatry|volume=4|issue=4|pages=e377–e377|last=Rose|first=S.|last2=Frye|first2=R. E.|last3=Slattery|first3=J.|last4=Wynne|first4=R.|last5=Tippett|first5=M.|last6=Melnyk|first6=S.|last7=James|first7=S. J.|language=en|doi=10.1038/tp.2014.15|issn=2158-3188}}</ref> The study authors believe these changes are related to overactivity in Complex IV found in a previous study.<ref>{{Cite journal|title=Autistic disorder with complex IV overactivity: A new mitochondrial syndrome|date=2011-12|url=http://www.thieme-connect.de/DOI/DOI?10.3233/JPN-2011-0507|journal=Journal of Pediatric Neurology|volume=09|issue=4|pages=427–434|last=Frye|first=Richard E.|last2=Naviaux|first2=Robert K.|language=en|doi=10.3233/JPN-2011-0507|issn=1304-2580}}</ref>
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.<ref>{{Cite journal|title=Mitochondrial Dysfunction in Autism|date=2010-12-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915058/|journal=JAMA : the journal of the American Medical Association|volume=304|issue=21|pages=2389–2396|last=Giulivi|first=Cecilia|last2=Zhang|first2=Yi-Fan|last3=Omanska-Klusek|first3=Alicja|last4=Ross-Inta|first4=Catherine|last5=Wong|first5=Sarah|last6=Hertz-Picciotto|first6=Irva|last7=Tassone|first7=Flora|last8=Pessah|first8=Isaac N.|doi=10.1001/jama.2010.1706|pmc=3915058|pmid=21119085|issn=0098-7484}}</ref>

|}

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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. <ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Female predominant diseases

2025-05-28T23:24:05Z

Galimatias:/* List of diseases */ added more statistics

Many [[Immune system|immunological]] and [[Nervous system|neurological]] diseases disproportionately affect women.

== Epidemiology ==

==== Autoimmune Disease ====
Roughly 80% of patients with [[autoimmune disease]] are women.<ref name="Fairweather2004">{{Cite journal | title = Women and Autoimmune Diseases1 | date =Nov 2004| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328995/|journal=Emerging Infectious Diseases|volume=10|issue=11 | pages = 2005–2011 | last = Fairweather | first = DeLisa | author-link = | last2 = Rose | first2 = Noel R. | authorlink2 = |doi=10.3201/eid1011.040367|pmc=3328995|pmid=15550215|access-date=|issn=1080-6040|quote=|via=}}</ref> In other words, women have four times the risk of developing an autoimmune disease than men.<ref>{{Cite journal|title=Why women have more autoimmune diseases than men: An evolutionary perspective|date=2020-12|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC7980266/|journal=Evolutionary Applications|volume=14|issue=3|pages=629–633|last=Kronzer|first=Vanessa L.|last2=Bridges|first2=Stanley Louis|last3=Davis|first3=John M.|language=en|doi=10.1111/eva.13167|issn=1752-4571}}</ref>

(The terms "woman" and "man" refer to assigned sex at birth. Research shows gender-affirming hormone therapy does not affect an individual's risk of developing autoimmune disease. So trans women have similar risks as cisgender men, and trans men have similar risks as cisgender women.<ref>{{Cite journal|title=SAT416 The Incidence Of Autoimmune Disease In Transgender People After Initiation Of Gender-Affirming Hormone Therapy|date=2023-10|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10554423/#:~:text=Conclusion%20The%20risk%20of%20developing,risk%20of%20developing%20autoimmune%20diseases.|journal=Journal of the Endocrine Society|volume=7|issue=Supplement_1|last=Wiepjes|first=Chantal|last2=Heijer|first2=Martin Den|language=en|doi=10.1210/jendso/bvad114.2087|issn=2472-1972}}</ref>)

== Mechanisms ==

=== Immune system ===
'''Summary of sex differences in innate and adaptive immune responses'''<ref name="Klein2016">{{Cite journal | title = Sex differences in immune responses | date = Oct 2016| url = https://www.nature.com/articles/nri.2016.90|journal=Nature Reviews. Immunology|volume=16|issue=10 | pages = 626–638 | last = Klein | first = Sabra L. | author-link = | last2 = Flanagan | first2 = Katie L. | authorlink2 = |doi=10.1038/nri.2016.90|pmc=|pmid=27546235|access-date=|issn=1474-1741|quote=|via=}}</ref>
{| class="wikitable mw-collapsible mw-collapsed"
!Immune component
!Characteristic
!In Females (relative to males)
|-
|'''Innate immune system'''
|
|
|-
|[[Toll-like receptor]] (TLR) pathways
|[[TLR pathway]] gene expression
|Higher
|-
|
|[[Toll-like receptor 7|TLR7]] expression
|Higher
|-
|
|[[Interleukin 10]] (IL10) production by [[Toll-like receptor 9|TLR9]]-stimulated [[peripheral blood mononuclear cell]]
|Lower
|-
|[[antigen-presenting cell]]s (APCs)
|APC efficiency
|Higher
|-
|[[Dendritic cell]]s
|[[Toll-like receptor 7|TLR7]] activity
|Higher
|-
|[[Macrophage]]s
|[[Toll-like receptor 4|TLR4]] expression
|Lower
|-
|
|Activation
|Higher
|-
|
|[[Phagocytic capacity]]
|Higher
|-
|
|Pro-inflammatory [[cytokine]] production
|Lower
|-
|
|[[Interleukin 10|IL10]] production
|Higher
|-
|[[Neutrophil|Neutrophils]]
|[[Phagocytic capacity]]
|Higher
|-
|
|[[Toll-like receptor|TLR]] expression
|Lower
|-
|[[Natural killer cell|Natural killer cells]]
|NK cell numbers
|Lower
|-
|'''Adaptive immune system'''
|
|
|-
|[[Thymus]]
|Size of thymus
|Smaller
|-
|[[T cell]]s
|[[CD4]] T cell counts
|Higher
|-
|
|[[CD4]]/[[CD8]] T cell ratio
|Higher
|-
|
|[[CD8]] T cell counts
|Lower
|-
|
|Number of activated T cells
|Higher
|-
|
|[[T cell]] proliferation
|Higher
|-
|
|[[Cytotoxic T cell]]
|Increased activity
|-
|
|[[Th1]] versus [[Th2]] cell bias
|Th2 cell bias in females, Th1 cell bias in males
|-
|
|[[Regulatory T cell]] numbers
|Lower
|-
|[[B cell]]
|B cell numbers
|Increased
|-
| [[Immunoglobulin]]s
| Antibody production
|Higher
|}

=== Hormones ===
Women with these diseases may experiencing a worsening of symptoms at specific points in their [[menstrual cycle]], particularly just before or around their periods.<ref name="Zierau2012">{{Cite journal | title = Role of female sex hormones, estradiol and progesterone, in mast cell behavior | date = 2012-06-19| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/|journal=Frontiers in Immunology|volume=3 | pages = 169 | last = Zierau | first = Oliver | last2 = Zenclussen | first2 = Ana C. | last3 = Jensen | first3 = Federico|doi=10.3389/fimmu.2012.00169|pmc=3377947|pmid=22723800|issn=1664-3224}}</ref> [[Estradiol]] and [[progesterone]] induce [[mast cell]] maturation and degranulation,<ref name="Zierau2012" /> which may contribute to the symptoms of a wide range of allergic and mast cell-mediated diseases.

=== Genetics ===

== Diseases ==

=== Asthma ===
In humans, a much higher [[asthma]] prevalence was found in women at reproductive age as compared to men. Serum levels of [[estradiol]] and [[progesterone]] have been directly correlated with the clinical and functional features of asthma. Around 30–40% of women with asthma experience a worsening of symptoms near their period. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma.<ref name="Zierau2012" />

== Social impact ==

=== Treatment options ===

=== Research funding ===

=== Stigma ===
Men and women with these diseases are at risk of [[Stigma|stigmatization]], dismissal, minimization and [[psychologization]] of their symptoms.<ref name="Goudsmit1993">{{Cite journal | journal = Health Psychology Update | url =https://books.google.co.uk/books?hl=en&lr=&id=E1afUMVG0VEC&oi=fnd&pg=PA7 | title = All in her mind! Stereotypic views and the psychologisation of women's illness | last = Goudsmit | first = Ellen M | date = 1993|volume=12 | pages = 28-32|language=en|quote= | author-link = Ellen Goudsmit|issue=|doi=|pmc=|pmid=|access-date=|via=}}</ref>

== List of diseases ==
Below, a list of diseases that predominately affect females.
{| class="wikitable sortable mw-collapsible mw-expanded"
!Conditions
!% female
!Ratio (F:M)
!US prevalence
|-
! colspan="4" scope="colgroup" | '''Neurological diseases'''
|-
|[[Alzheimer's disease]]
|66%
|2:1
|6.2 million<ref>{{Cite web|url=https://www.health.harvard.edu/blog/why-are-women-more-likely-to-develop-alzheimers-disease-202201202672|title=Why are women more likely to develop Alzheimer's disease? - Harvard Health|website=www.health.harvard.edu|access-date=2025-05-22}}</ref>
|-
|[[Empty sella syndrome]]
|
|5:1<ref name="Aruna2014">{{Cite journal | title = Partial Empty Sella Syndrome: A Case Report and Review | date = Apr 2014| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990803/|journal=Indian Journal of Clinical Biochemistry|volume=29|issue=2 | pages = 253–256 | last = Aruna | first = P. | author-link = | last2 = Sowjanya | first2 = B. | authorlink2 = | last3 = Reddy | first3 = P. Amaresh | authorlink3 = | last4 = Krishnamma | first4 = M. | authorlink4 = | last5 = Naidu | first5 = J. N. | authorlink5 = |doi=10.1007/s12291-013-0369-1|pmc=3990803|pmid=24757313|access-date=|issn=0970-1915|quote=|via=}}</ref>
|
|-
|[[Idiopathic intracranial hypertension]]
|
|
|
|-
|[[Migraine]]<ref name="Vos2015" />
|
|3:1 to 4:1<ref>{{Cite journal|title=Prevalence and burden of migraine in the United States: A systematic review|date=2024-05|url=https://pubmed.ncbi.nlm.nih.gov/38700185/|journal=Headache: The Journal of Head and Face Pain|volume=64|issue=5|pages=516–532|last=Cohen|first=Fred|last2=Brooks|first2=Caroline V.|last3=Sun|first3=Daniel|last4=Buse|first4=Dawn C.|last5=Reed|first5=Michael L.|last6=Fanning|first6=Kristina M.|last7=Lipton|first7=Richard B.|language=en|doi=10.1111/head.14709|issn=0017-8748}}</ref>
|37 million<ref>{{Cite web|url=https://americanmigrainefoundation.org/resource-library/migraine-facts/|title=The Facts About Migraine {{!}} American Migraine Foundation|website=americanmigrainefoundation.org|access-date=2025-05-22}}</ref>
|-
|[[Myalgic encephalomyelitis|Myalgic Encephalomyelitis]]/[[Chronic fatigue syndrome]]
|60-66%<ref name="Lim2020">{{Cite journal | title = Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) | date = 2020-02-24| url = https://doi.org/10.1186/s12967-020-02269-0|journal=Journal of Translational Medicine|volume=18|issue=1 | pages = 100 | last = Lim | first = Eun-Jin | last2 = Ahn | first2 = Yo-Chan | last3 = Jang | first3 = Eun-Su | last4 = Lee | first4 = Si-Woo | last5 = Lee | first5 = Su-Hwa | last6 = Son | first6 = Chang-Gue|doi=10.1186/s12967-020-02269-0|pmc=PMC7038594|pmid=32093722|issn=1479-5876}}</ref>
|1.5:1 to 2:1<ref name="Lim2020" /> up to 4:1 (CDC)<ref name="CDC-epidemiology">{{Cite web | url = https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html | title = Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | last = | first = | authorlink = | date = 2022-01-21 | website = [[Centers for Disease Control and Prevention]]|at=Immune System Changes|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|3.3 million<ref>{{Cite news|url=https://www.cdc.gov/me-cfs/about/index.html|title=ME/CFS Basics|date=2024-09-18|work=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|access-date=2025-05-22|language=en-us}}</ref>
|-
|[[Multiple sclerosis]]
|
|1.8:1 to 4:1<ref name="Jorgensen2012" /><ref name="MS-who">{{Cite web | url = https://www.nationalmssociety.org/What-is-MS/Who-Gets-MS | title = Who Gets MS? (Epidemiology) | last = | first = | date = |website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=}}</ref><ref name="Vos2015">{{Cite journal | last = Vos | first = Theo | last2 = Feigin | first2 = Valery | last3 = Degenhardt | first3 = Louisa | last4 = Ferrari | first4 = Alize J. | last5 = Whiteford | first5 = Harvey A. | date = 2015-02-06 | title = The Global Burden of Mental, Neurological and Substance Use Disorders: An Analysis from the Global Burden of Disease Study 2010| url = https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116820|journal=PLOS ONE|language=en|volume=10|issue=2| pages = e0116820|doi=10.1371/journal.pone.0116820|issn=1932-6203|pmc=4320057|pmid=25658103}}</ref>
|852,000 - 914,000<ref>{{Cite web|url=https://www.nationalmssociety.org/understanding-ms/what-is-ms/who-gets-ms/how-many-people|website=www.nationalmssociety.org|access-date=2025-05-22}}</ref>
|-
|[[Postural orthostatic tachycardia syndrome]] (POTS)
|80-85%<ref name="Dysautonomiafacts">{{Cite web | url = http://www.dysautonomiainternational.org/page.php?ID=180 | title = 10 Facts Doctors Should Know About POTS | last = | first = | date = April 19, 2018 | website = Dysautonomia International|archive-url=|archive-date=|url-status=|access-date=}}</ref>
|4:1
|1-3 million (prior to COVID-19)<ref>{{Cite journal|title=COVID-19 Increases the Prevalence of Postural Orthostatic Tachycardia Syndrome: What Nutrition and Dietetics Practitioners Need to Know|date=2022-09|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9186518/|journal=Journal of the Academy of Nutrition and Dietetics|volume=122|issue=9|pages=1600–1605|last=Harris|first=Cheryl Iny|language=en|doi=10.1016/j.jand.2022.06.002|issn=2212-2672}}</ref>
|-
! colspan="4" scope="colgroup" | '''Endocrine diseases'''
|-
|[[Graves' disease]]
|
|5:1<ref name="Jorgensen2012">{{Cite journal | title = Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort | date = May 2012| url = https://research.regionh.dk/files/36818048/J_rgensen_JAutoimmunity_2012_38_J81_Childbirths_and_risk_of_female_predominant_and_other_autoimmune_diseases_in_the_Danish_population.pdf | journal=Journal of Autoimmunity|volume=38|issue=2-3| pages=J81–87 | last = Jørgensen | first = Kristian Tore | authorlink = | last2 = Pedersen | first2 = Bo Vestergaard | authorlink2 = | last3 = Nielsen | first3 = Nete Munk | authorlink3 = | last4 = Jacobsen | first4 = Søren | authorlink4 = |doi=10.1016/j.jaut.2011.06.004|pmc=|pmid=21813263|access-date=|issn=1095-9157|quote=|via=}}</ref>
|
|-
|[[Hashimoto's thyroiditis (hypothyroidism)|Hashimoto's thyroditis]]
|
|8:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Rheumatological diseases'''
|-
|[[Fibromyalgia]]
|
|7:1 [[Fibromyalgia#1990 ACR criteria|ACR 1990 Criteria]] and 2:1 [[Fibromyalgia#2010 ACR criteria|ACR 2010 Criteria]]<ref name="fibro-medscape">{{Cite web | date = 2021-09-14 | title = Fibromyalgia: Practice Essentials, Background, Pathophysiology| url = https://emedicine.medscape.com/article/329838-overview#a5 | website = Medscape | first = Chad S | last = Boomershine|editor-first1 = Herbert S|editor-last1 = Diamond}}</ref> and CDC<ref name="FibroCDC" />

1.5:1<ref name="Hauser2018">{{Cite journal | last = Häuser | first = Winfried | last2 = Rasker | first2 = Johannes J. | last3 = Perrot | first3 = Serge | last4 = Walitt | first4 = Brian | last5 = Wolfe | first5 = Frederick | authorlink5 = Frederick Wolfe | date = 2018-09-13 | title = Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias |url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203755|journal=PLOS ONE|language=en|volume=13|issue=9| pages = e0203755|doi=10.1371/journal.pone.0203755|issn=1932-6203|pmc=|pmid=30212526}}</ref>
|4 million<ref name="FibroCDC">{{Cite web | url = https://www.cdc.gov/arthritis/basics/fibromyalgia.htm | title = Fibromyalgia {{!}} Arthritis | date = 2018-04-03 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2022-02-01}}</ref>
|-
|[[Rheumatoid arthritis]]
|
|2.4:1<ref name="Jorgensen2012" />
|1.3 million<ref>{{Cite journal|title=Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005–2018|date=2021-07-26|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8348893/|journal=Journal of Clinical Medicine|volume=10|issue=15|pages=3289|last=Xu|first=Yingke|last2=Wu|first2=Qing|language=en|doi=10.3390/jcm10153289|issn=2077-0383}}</ref>
|-
! colspan="4" scope="colgroup" |'''Gastrointestinal diseases'''
|-
|[[Primary billary cirrhosis]]
|
|4:1<ref name="Jorgensen2012" />
|
|-
|[[Celiac disease]] (IBD)
|
|1.6:1<ref name="Jorgensen2012" />
|3 million<ref>{{Cite news|url=https://celiac.org/2016/08/19/20-things-you-might-not-know-about-celiac-disease/|title=20 Things You Might Not Know About Celiac Disease {{!}} Celiac Disease Foundation|date=2016-08-19|work=Celiac Disease Foundation|access-date=2025-05-28|language=en-US}}</ref>
|-
|[[Irritable bowel syndrome]] (IBS)
|72%<ref name="Eijsbouts2021">{{Cite journal | title = Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders | date = Nov 2021| url = https://www.nature.com/articles/s41588-021-00950-8|journal=Nature Genetics|volume=53|issue=11 | pages = 1543–1552 | last = Eijsbouts | first = Chris | author-link = | last2 = Zheng | first2 = Tenghao | authorlink2 = | last3 = Kennedy | first3 = Nicholas A. | authorlink3 = | last4 = Bonfiglio | first4 = Ferdinando | authorlink4 = | last5 = Anderson | first5 = Carl A. | authorlink5 = | last6 = Moutsianas | first6 = Loukas | authorlink6 = | last7 = Holliday | first7 = Joanne | last8 = Shi | first8 = Jingchunzi | last9 = Shringarpure | first9 = Suyash | last10 = Voda | first10 = Alexandru-Ioan | last11 = Farrugia | first11 = Gianrico|language=en|doi=10.1038/s41588-021-00950-8|pmc=|pmid=|access-date=|issn=1546-1718|quote=|via=}}</ref>
|
|
|-
! colspan="4" scope="colgroup" | '''Musculoskeletal diseases and disorders'''
|-
|[[Osteoporosis]]
|
|
|
|-
! colspan="4" scope="colgroup" | '''Systemic illnesses'''
|-
|[[Sjögren's syndrome]]
|
|7.5:1<ref name="Jorgensen2012" />
|
|-
|[[Systemic lupus erythematosus]]
|
|5.2:1<ref name="Jorgensen2012" /> 4:1 to 12:1 (CDC)<ref name="CDC-sle">{{Cite web | url = https://www.cdc.gov/lupus/facts/detailed.html | title = Systemic Lupus Erythematosus (SLE) {{!}} Lupus | last = | first = | authorlink = | date = October 17, 2018 | website = [[Centers for Disease Control and Prevention]]|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|161,000 to 322,000<ref name="WH-lupus">{{Cite web | url = https://www.womenshealth.gov/lupus/lupus-and-women | title = Lupus and women | last = | first = | authorlink = | date = | website = Office on Women's Health|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|-
|[[Temporal arteritis]] (Giant cell arteritis)
|
|2.3:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Connective tissue disorders'''
|
|
|
|
|
|-
|[[Ehler's Danlos Syndrome]] Type 3 (hypermobile type)
|
|2:1<ref>{{Cite journal|title=Understanding hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorders in the context of childbearing: An international qualitative study|date=2020|url=https://www.sciencedirect.com/science/article/abs/pii/S0266613820301212|journal=Midwifery|volume=88|last=Pezaro|first=Sally|last2=Pearce|first2=Gemma|last3=Reinhold|first3=Emma}}</ref>
|American prevalence rates
are unavailable. Thought to affect up to

1 in 3,100 people worldwide.<ref>{{Cite news|url=https://www.ehlers-danlos.com/what-is-eds/|title=What is EDS? - The Ehlers Danlos Society|work=The Ehlers Danlos Society|access-date=2025-05-22|language=en-GB}}</ref>
|
|-
|[[Systemic sclerosis]]
|
|3.7:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Mental health disorders'''
|-
| [[Anxiety|Anxiety disorders]]<ref name="Vos2015" />
|
|1.2:1 to 3.2:1<ref name="WHO2009">{{Cite journal | title = Cross-National Associations Between Gender and Mental Disorders in the World Health Organization World Mental Health Surveys | date = 2009-07-01| url = https://doi.org/10.1001/archgenpsychiatry.2009.36|journal=Archives of General Psychiatry|volume=66|issue=7 | pages = 785–795 | last = Seedat | first = Soraya | last2 = Scott | first2 = Kate Margaret | last3 = Angermeyer | first3 = Matthias C. | last4 = Berglund | first4 = Patricia | last5 = Bromet | first5 = Evelyn J. | last6 = Brugha | first6 = Traolach S. | last7 = Demyttenaere | first7 = Koen | last8 = de Girolamo | first8 = Giovanni | last9 = Haro | first9 = Josep Maria | last10 = Jin | first10 = Robert | last11 = Karam | first11 = Elie G.|doi=10.1001/archgenpsychiatry.2009.36|issn=0003-990X}}</ref>
|40 million<ref>{{Cite web|url=https://adaa.org/understanding-anxiety/facts-statistics|title=Anxiety Disorders - Facts & Statistics|date=October 28, 2022|website=Anxiety & Depression Association of America}}</ref>
|-
| [[Depression|Major depressive disorder]] (depression)<ref name="Vos2015" />
|
|1.6:1 to 2.4:1<ref name="WHO2009" />
|21 million<ref>{{Cite news|url=https://mhanational.org/conditions/depression/#:~:text=Major%20depression%20is%20one%20of,are%20affected%20by%20major%20depression.|title=Depression {{!}} Mental Health America|work=Mental Health America|access-date=2025-05-28|language=en-US}}</ref>
|-
| [[Functional neurological symptom disorder|Functional Neurological Disorder (FND)]] (Conversion disorder)
|
|
|
|-
| [[Post-traumatic stress disorder]] (PTSD)
|
|1.3:1 to 6.4:1<ref name="WHO2009" />
|13 million<ref>{{Cite web|url=https://www.ptsd.va.gov/understand/common/common_adults.asp#:~:text=About%205%20out%20of%20every,some%20point%20in%20their%20life.|title=How Common is PTSD in Adults? - PTSD: National Center for PTSD|website=www.ptsd.va.gov|access-date=2025-05-28}}</ref>
|
|-
! colspan="4" scope="colgroup" | '''Other diagnoses'''
|-
|[[Asthma]]
|
|3:2 (adults), 7:9 (children, less predominant in girls)<ref name="asthmastacks">{{Cite web | url = https://stacks.cdc.gov/view/cdc/109086 | title = Asthma Surveillance — United States, 2006–2018 {{!}} MMWR Surveillance Summaries /70(5) | date = Sep 17, 2021 | website = [[Centers for Disease Control and Prevention]]|access-date=2022-02-01}}</ref>
|24.8 million (current asthma)
|-
|}

== See also ==
* [[Autoimmune disease]]
* [[Menstrual cycle]]
* [[Menstrual problems in ME/CFS]]

== Learn more ==

* [https://www.amazon.com/Doing-Harm-Medicine-Dismissed-Misdiagnosed/dp/0062470809 Doing Harm: The Truth About How Bad Medicine and Lazy Science Leave Women Dismissed, Misdiagnosed, and Sick] by [[Maya Dusenbery]]

== References ==
{{Reflist}}

[[Category:Triggers and risk factors]]
[[Category:Core topics]]
[[Category:Epidemiology]]
[[Category:Ethics]]

Female predominant diseases

2025-05-22T23:18:27Z

Galimatias:/* Epidemiology */ I added EDS stats. A note: You'll sometimes see a figure like "10 million Americans have hEDS", but this figure uses combined joint hypermobility and chronic pain rates as a proxy, and it doesn't measure hEDS diagnoses directly, so I didn't include it.

Many [[Immune system|immunological]] and [[Nervous system|neurological]] diseases disproportionately affect women.

== Epidemiology ==

==== Autoimmune Disease ====
Roughly 80% of patients with [[autoimmune disease]] are women.<ref name="Fairweather2004">{{Cite journal | title = Women and Autoimmune Diseases1 | date =Nov 2004| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328995/|journal=Emerging Infectious Diseases|volume=10|issue=11 | pages = 2005–2011 | last = Fairweather | first = DeLisa | author-link = | last2 = Rose | first2 = Noel R. | authorlink2 = |doi=10.3201/eid1011.040367|pmc=3328995|pmid=15550215|access-date=|issn=1080-6040|quote=|via=}}</ref> In other words, women have four times the risk of developing an autoimmune disease than men.<ref>{{Cite journal|title=Why women have more autoimmune diseases than men: An evolutionary perspective|date=2020-12|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC7980266/|journal=Evolutionary Applications|volume=14|issue=3|pages=629–633|last=Kronzer|first=Vanessa L.|last2=Bridges|first2=Stanley Louis|last3=Davis|first3=John M.|language=en|doi=10.1111/eva.13167|issn=1752-4571}}</ref>

(The terms "woman" and "man" refer to assigned sex at birth. Research shows gender-affirming hormone therapy does not affect an individual's risk of developing autoimmune disease. So trans women have similar risks as cisgender men, and trans men have similar risks as cisgender women.<ref>{{Cite journal|title=SAT416 The Incidence Of Autoimmune Disease In Transgender People After Initiation Of Gender-Affirming Hormone Therapy|date=2023-10|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10554423/#:~:text=Conclusion%20The%20risk%20of%20developing,risk%20of%20developing%20autoimmune%20diseases.|journal=Journal of the Endocrine Society|volume=7|issue=Supplement_1|last=Wiepjes|first=Chantal|last2=Heijer|first2=Martin Den|language=en|doi=10.1210/jendso/bvad114.2087|issn=2472-1972}}</ref>)

== Mechanisms ==

=== Immune system ===
'''Summary of sex differences in innate and adaptive immune responses'''<ref name="Klein2016">{{Cite journal | title = Sex differences in immune responses | date = Oct 2016| url = https://www.nature.com/articles/nri.2016.90|journal=Nature Reviews. Immunology|volume=16|issue=10 | pages = 626–638 | last = Klein | first = Sabra L. | author-link = | last2 = Flanagan | first2 = Katie L. | authorlink2 = |doi=10.1038/nri.2016.90|pmc=|pmid=27546235|access-date=|issn=1474-1741|quote=|via=}}</ref>
{| class="wikitable mw-collapsible mw-collapsed"
!Immune component
!Characteristic
!In Females (relative to males)
|-
|'''Innate immune system'''
|
|
|-
|[[Toll-like receptor]] (TLR) pathways
|[[TLR pathway]] gene expression
|Higher
|-
|
|[[Toll-like receptor 7|TLR7]] expression
|Higher
|-
|
|[[Interleukin 10]] (IL10) production by [[Toll-like receptor 9|TLR9]]-stimulated [[peripheral blood mononuclear cell]]
|Lower
|-
|[[antigen-presenting cell]]s (APCs)
|APC efficiency
|Higher
|-
|[[Dendritic cell]]s
|[[Toll-like receptor 7|TLR7]] activity
|Higher
|-
|[[Macrophage]]s
|[[Toll-like receptor 4|TLR4]] expression
|Lower
|-
|
|Activation
|Higher
|-
|
|[[Phagocytic capacity]]
|Higher
|-
|
|Pro-inflammatory [[cytokine]] production
|Lower
|-
|
|[[Interleukin 10|IL10]] production
|Higher
|-
|[[Neutrophil|Neutrophils]]
|[[Phagocytic capacity]]
|Higher
|-
|
|[[Toll-like receptor|TLR]] expression
|Lower
|-
|[[Natural killer cell|Natural killer cells]]
|NK cell numbers
|Lower
|-
|'''Adaptive immune system'''
|
|
|-
|[[Thymus]]
|Size of thymus
|Smaller
|-
|[[T cell]]s
|[[CD4]] T cell counts
|Higher
|-
|
|[[CD4]]/[[CD8]] T cell ratio
|Higher
|-
|
|[[CD8]] T cell counts
|Lower
|-
|
|Number of activated T cells
|Higher
|-
|
|[[T cell]] proliferation
|Higher
|-
|
|[[Cytotoxic T cell]]
|Increased activity
|-
|
|[[Th1]] versus [[Th2]] cell bias
|Th2 cell bias in females, Th1 cell bias in males
|-
|
|[[Regulatory T cell]] numbers
|Lower
|-
|[[B cell]]
|B cell numbers
|Increased
|-
| [[Immunoglobulin]]s
| Antibody production
|Higher
|}

=== Hormones ===
Women with these diseases may experiencing a worsening of symptoms at specific points in their [[menstrual cycle]], particularly just before or around their periods.<ref name="Zierau2012">{{Cite journal | title = Role of female sex hormones, estradiol and progesterone, in mast cell behavior | date = 2012-06-19| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/|journal=Frontiers in Immunology|volume=3 | pages = 169 | last = Zierau | first = Oliver | last2 = Zenclussen | first2 = Ana C. | last3 = Jensen | first3 = Federico|doi=10.3389/fimmu.2012.00169|pmc=3377947|pmid=22723800|issn=1664-3224}}</ref> [[Estradiol]] and [[progesterone]] induce [[mast cell]] maturation and degranulation,<ref name="Zierau2012" /> which may contribute to the symptoms of a wide range of allergic and mast cell-mediated diseases.

=== Genetics ===

== Diseases ==

=== Asthma ===
In humans, a much higher [[asthma]] prevalence was found in women at reproductive age as compared to men. Serum levels of [[estradiol]] and [[progesterone]] have been directly correlated with the clinical and functional features of asthma. Around 30–40% of women with asthma experience a worsening of symptoms near their period. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma.<ref name="Zierau2012" />

== Social impact ==

=== Treatment options ===

=== Research funding ===

=== Stigma ===
Men and women with these diseases are at risk of [[Stigma|stigmatization]], dismissal, minimization and [[psychologization]] of their symptoms.<ref name="Goudsmit1993">{{Cite journal | journal = Health Psychology Update | url =https://books.google.co.uk/books?hl=en&lr=&id=E1afUMVG0VEC&oi=fnd&pg=PA7 | title = All in her mind! Stereotypic views and the psychologisation of women's illness | last = Goudsmit | first = Ellen M | date = 1993|volume=12 | pages = 28-32|language=en|quote= | author-link = Ellen Goudsmit|issue=|doi=|pmc=|pmid=|access-date=|via=}}</ref>

== List of diseases ==
Below, a list of diseases that predominately affect females.
{| class="wikitable sortable mw-collapsible mw-expanded"
!Conditions
!% female
!Ratio (F:M)
!US prevalence
|-
! colspan="4" scope="colgroup" | '''Neurological diseases'''
|-
|[[Alzheimer's disease]]
|66%
|2:1
|6.2 million<ref>{{Cite web|url=https://www.health.harvard.edu/blog/why-are-women-more-likely-to-develop-alzheimers-disease-202201202672|title=Why are women more likely to develop Alzheimer's disease? - Harvard Health|website=www.health.harvard.edu|access-date=2025-05-22}}</ref>
|-
|[[Empty sella syndrome]]
|
|5:1<ref name="Aruna2014">{{Cite journal | title = Partial Empty Sella Syndrome: A Case Report and Review | date = Apr 2014| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990803/|journal=Indian Journal of Clinical Biochemistry|volume=29|issue=2 | pages = 253–256 | last = Aruna | first = P. | author-link = | last2 = Sowjanya | first2 = B. | authorlink2 = | last3 = Reddy | first3 = P. Amaresh | authorlink3 = | last4 = Krishnamma | first4 = M. | authorlink4 = | last5 = Naidu | first5 = J. N. | authorlink5 = |doi=10.1007/s12291-013-0369-1|pmc=3990803|pmid=24757313|access-date=|issn=0970-1915|quote=|via=}}</ref>
|
|-
|[[Idiopathic intracranial hypertension]]
|
|
|
|-
|[[Migraine]]<ref name="Vos2015" />
|
|3:1 to 4:1<ref>{{Cite journal|title=Prevalence and burden of migraine in the United States: A systematic review|date=2024-05|url=https://pubmed.ncbi.nlm.nih.gov/38700185/|journal=Headache: The Journal of Head and Face Pain|volume=64|issue=5|pages=516–532|last=Cohen|first=Fred|last2=Brooks|first2=Caroline V.|last3=Sun|first3=Daniel|last4=Buse|first4=Dawn C.|last5=Reed|first5=Michael L.|last6=Fanning|first6=Kristina M.|last7=Lipton|first7=Richard B.|language=en|doi=10.1111/head.14709|issn=0017-8748}}</ref>
|37 million<ref>{{Cite web|url=https://americanmigrainefoundation.org/resource-library/migraine-facts/|title=The Facts About Migraine {{!}} American Migraine Foundation|website=americanmigrainefoundation.org|access-date=2025-05-22}}</ref>
|-
|[[Myalgic encephalomyelitis|Myalgic Encephalomyelitis]]/[[Chronic fatigue syndrome]]
|60-66%<ref name="Lim2020">{{Cite journal | title = Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) | date = 2020-02-24| url = https://doi.org/10.1186/s12967-020-02269-0|journal=Journal of Translational Medicine|volume=18|issue=1 | pages = 100 | last = Lim | first = Eun-Jin | last2 = Ahn | first2 = Yo-Chan | last3 = Jang | first3 = Eun-Su | last4 = Lee | first4 = Si-Woo | last5 = Lee | first5 = Su-Hwa | last6 = Son | first6 = Chang-Gue|doi=10.1186/s12967-020-02269-0|pmc=PMC7038594|pmid=32093722|issn=1479-5876}}</ref>
|1.5:1 to 2:1<ref name="Lim2020" /> up to 4:1 (CDC)<ref name="CDC-epidemiology">{{Cite web | url = https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html | title = Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | last = | first = | authorlink = | date = 2022-01-21 | website = [[Centers for Disease Control and Prevention]]|at=Immune System Changes|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|3.3 million<ref>{{Cite news|url=https://www.cdc.gov/me-cfs/about/index.html|title=ME/CFS Basics|date=2024-09-18|work=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|access-date=2025-05-22|language=en-us}}</ref>
|-
|[[Multiple sclerosis]]
|
|1.8:1 to 4:1<ref name="Jorgensen2012" /><ref name="MS-who">{{Cite web | url = https://www.nationalmssociety.org/What-is-MS/Who-Gets-MS | title = Who Gets MS? (Epidemiology) | last = | first = | date = |website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=}}</ref><ref name="Vos2015">{{Cite journal | last = Vos | first = Theo | last2 = Feigin | first2 = Valery | last3 = Degenhardt | first3 = Louisa | last4 = Ferrari | first4 = Alize J. | last5 = Whiteford | first5 = Harvey A. | date = 2015-02-06 | title = The Global Burden of Mental, Neurological and Substance Use Disorders: An Analysis from the Global Burden of Disease Study 2010| url = https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116820|journal=PLOS ONE|language=en|volume=10|issue=2| pages = e0116820|doi=10.1371/journal.pone.0116820|issn=1932-6203|pmc=4320057|pmid=25658103}}</ref>
|852,000 - 914,000<ref>{{Cite web|url=https://www.nationalmssociety.org/understanding-ms/what-is-ms/who-gets-ms/how-many-people|website=www.nationalmssociety.org|access-date=2025-05-22}}</ref>
|-
|[[Postural orthostatic tachycardia syndrome]] (POTS)
|80-85%<ref name="Dysautonomiafacts">{{Cite web | url = http://www.dysautonomiainternational.org/page.php?ID=180 | title = 10 Facts Doctors Should Know About POTS | last = | first = | date = April 19, 2018 | website = Dysautonomia International|archive-url=|archive-date=|url-status=|access-date=}}</ref>
|4:1
|1-3 million (prior to COVID-19)<ref>{{Cite journal|title=COVID-19 Increases the Prevalence of Postural Orthostatic Tachycardia Syndrome: What Nutrition and Dietetics Practitioners Need to Know|date=2022-09|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9186518/|journal=Journal of the Academy of Nutrition and Dietetics|volume=122|issue=9|pages=1600–1605|last=Harris|first=Cheryl Iny|language=en|doi=10.1016/j.jand.2022.06.002|issn=2212-2672}}</ref>
|-
! colspan="4" scope="colgroup" | '''Endocrine diseases'''
|-
|[[Graves' disease]]
|
|5:1<ref name="Jorgensen2012">{{Cite journal | title = Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort | date = May 2012| url = https://research.regionh.dk/files/36818048/J_rgensen_JAutoimmunity_2012_38_J81_Childbirths_and_risk_of_female_predominant_and_other_autoimmune_diseases_in_the_Danish_population.pdf | journal=Journal of Autoimmunity|volume=38|issue=2-3| pages=J81–87 | last = Jørgensen | first = Kristian Tore | authorlink = | last2 = Pedersen | first2 = Bo Vestergaard | authorlink2 = | last3 = Nielsen | first3 = Nete Munk | authorlink3 = | last4 = Jacobsen | first4 = Søren | authorlink4 = |doi=10.1016/j.jaut.2011.06.004|pmc=|pmid=21813263|access-date=|issn=1095-9157|quote=|via=}}</ref>
|
|-
|[[Hashimoto's thyroiditis (hypothyroidism)|Hashimoto's thyroditis]]
|
|8:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Rheumatological diseases'''
|-
|[[Fibromyalgia]]
|
|7:1 [[Fibromyalgia#1990 ACR criteria|ACR 1990 Criteria]] and 2:1 [[Fibromyalgia#2010 ACR criteria|ACR 2010 Criteria]]<ref name="fibro-medscape">{{Cite web | date = 2021-09-14 | title = Fibromyalgia: Practice Essentials, Background, Pathophysiology| url = https://emedicine.medscape.com/article/329838-overview#a5 | website = Medscape | first = Chad S | last = Boomershine|editor-first1 = Herbert S|editor-last1 = Diamond}}</ref> and CDC<ref name="FibroCDC" />

1.5:1<ref name="Hauser2018">{{Cite journal | last = Häuser | first = Winfried | last2 = Rasker | first2 = Johannes J. | last3 = Perrot | first3 = Serge | last4 = Walitt | first4 = Brian | last5 = Wolfe | first5 = Frederick | authorlink5 = Frederick Wolfe | date = 2018-09-13 | title = Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias |url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203755|journal=PLOS ONE|language=en|volume=13|issue=9| pages = e0203755|doi=10.1371/journal.pone.0203755|issn=1932-6203|pmc=|pmid=30212526}}</ref>
|4 million<ref name="FibroCDC">{{Cite web | url = https://www.cdc.gov/arthritis/basics/fibromyalgia.htm | title = Fibromyalgia {{!}} Arthritis | date = 2018-04-03 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2022-02-01}}</ref>
|-
|[[Rheumatoid arthritis]]
|
|2.4:1<ref name="Jorgensen2012" />
|1.3 million<ref>{{Cite journal|title=Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005–2018|date=2021-07-26|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8348893/|journal=Journal of Clinical Medicine|volume=10|issue=15|pages=3289|last=Xu|first=Yingke|last2=Wu|first2=Qing|language=en|doi=10.3390/jcm10153289|issn=2077-0383}}</ref>
|-
! colspan="4" scope="colgroup" |'''Gastrointestinal diseases'''
|-
|[[Primary billary cirrhosis]]
|
|4:1<ref name="Jorgensen2012" />
|
|-
|[[Celiac disease]] (IBD)
|
|1.6:1<ref name="Jorgensen2012" />
|
|-
|[[Irritable bowel syndrome]] (IBS)
|72%<ref name="Eijsbouts2021">{{Cite journal | title = Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders | date = Nov 2021| url = https://www.nature.com/articles/s41588-021-00950-8|journal=Nature Genetics|volume=53|issue=11 | pages = 1543–1552 | last = Eijsbouts | first = Chris | author-link = | last2 = Zheng | first2 = Tenghao | authorlink2 = | last3 = Kennedy | first3 = Nicholas A. | authorlink3 = | last4 = Bonfiglio | first4 = Ferdinando | authorlink4 = | last5 = Anderson | first5 = Carl A. | authorlink5 = | last6 = Moutsianas | first6 = Loukas | authorlink6 = | last7 = Holliday | first7 = Joanne | last8 = Shi | first8 = Jingchunzi | last9 = Shringarpure | first9 = Suyash | last10 = Voda | first10 = Alexandru-Ioan | last11 = Farrugia | first11 = Gianrico|language=en|doi=10.1038/s41588-021-00950-8|pmc=|pmid=|access-date=|issn=1546-1718|quote=|via=}}</ref>
|
|
|-
! colspan="4" scope="colgroup" | '''Musculoskeletal diseases and disorders'''
|-
|[[Osteoporosis]]
|
|
|
|-
! colspan="4" scope="colgroup" | '''Systemic illnesses'''
|-
|[[Sjögren's syndrome]]
|
|7.5:1<ref name="Jorgensen2012" />
|
|-
|[[Systemic lupus erythematosus]]
|
|5.2:1<ref name="Jorgensen2012" /> 4:1 to 12:1 (CDC)<ref name="CDC-sle">{{Cite web | url = https://www.cdc.gov/lupus/facts/detailed.html | title = Systemic Lupus Erythematosus (SLE) {{!}} Lupus | last = | first = | authorlink = | date = October 17, 2018 | website = [[Centers for Disease Control and Prevention]]|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|161,000 to 322,000<ref name="WH-lupus">{{Cite web | url = https://www.womenshealth.gov/lupus/lupus-and-women | title = Lupus and women | last = | first = | authorlink = | date = | website = Office on Women's Health|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|-
|[[Temporal arteritis]] (Giant cell arteritis)
|
|2.3:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Connective tissue disorders'''
|
|
|
|
|
|-
|[[Ehler's Danlos Syndrome]] Type 3 (hypermobile type)
|
|2:1<ref>{{Cite journal|title=Understanding hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorders in the context of childbearing: An international qualitative study|date=2020|url=https://www.sciencedirect.com/science/article/abs/pii/S0266613820301212|journal=Midwifery|volume=88|last=Pezaro|first=Sally|last2=Pearce|first2=Gemma|last3=Reinhold|first3=Emma}}</ref>
|American prevalence rates
are unavailable. Thought to affect up to
1 in 3,100 people worldwide.<ref>{{Cite news|url=https://www.ehlers-danlos.com/what-is-eds/|title=What is EDS? - The Ehlers Danlos Society|work=The Ehlers Danlos Society|access-date=2025-05-22|language=en-GB}}</ref>
|
|-
|[[Systemic sclerosis]]
|
|3.7:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Mental health disorders'''
|-
| [[Anxiety|Anxiety disorders]]<ref name="Vos2015" />
|
|1.2:1 to 3.2:1<ref name="WHO2009">{{Cite journal | title = Cross-National Associations Between Gender and Mental Disorders in the World Health Organization World Mental Health Surveys | date = 2009-07-01| url = https://doi.org/10.1001/archgenpsychiatry.2009.36|journal=Archives of General Psychiatry|volume=66|issue=7 | pages = 785–795 | last = Seedat | first = Soraya | last2 = Scott | first2 = Kate Margaret | last3 = Angermeyer | first3 = Matthias C. | last4 = Berglund | first4 = Patricia | last5 = Bromet | first5 = Evelyn J. | last6 = Brugha | first6 = Traolach S. | last7 = Demyttenaere | first7 = Koen | last8 = de Girolamo | first8 = Giovanni | last9 = Haro | first9 = Josep Maria | last10 = Jin | first10 = Robert | last11 = Karam | first11 = Elie G.|doi=10.1001/archgenpsychiatry.2009.36|issn=0003-990X}}</ref>
|
|-
| [[Depression|Major depressive disorder]] (depression)<ref name="Vos2015" />
|
|1.6:1 to 2.4:1<ref name="WHO2009" />
|
|-
| [[Functional neurological symptom disorder|Functional Neurological Disorder (FND)]] (Conversion disorder)
|
|
|
|-
| [[Post-traumatic stress disorder]] (PTSD)
|
|1.3:1 to 6.4:1<ref name="WHO2009" />
|
|
|-
! colspan="4" scope="colgroup" | '''Other diagnoses'''
|-
|[[Asthma]]
|
|3:2 (adults), 7:9 (children, less predominant in girls)<ref name="asthmastacks">{{Cite web | url = https://stacks.cdc.gov/view/cdc/109086 | title = Asthma Surveillance — United States, 2006–2018 {{!}} MMWR Surveillance Summaries /70(5) | date = Sep 17, 2021 | website = [[Centers for Disease Control and Prevention]]|access-date=2022-02-01}}</ref>
|24.8 million (current asthma)
|-
|}

== See also ==
* [[Autoimmune disease]]
* [[Menstrual cycle]]
* [[Menstrual problems in ME/CFS]]

== Learn more ==

* [https://www.amazon.com/Doing-Harm-Medicine-Dismissed-Misdiagnosed/dp/0062470809 Doing Harm: The Truth About How Bad Medicine and Lazy Science Leave Women Dismissed, Misdiagnosed, and Sick] by [[Maya Dusenbery]]

== References ==
{{Reflist}}

[[Category:Triggers and risk factors]]
[[Category:Core topics]]
[[Category:Epidemiology]]
[[Category:Ethics]]

Female predominant diseases

2025-05-22T22:56:39Z

Galimatias:Updated some statistics for post-COVID era. I deleted the Chronic Lyme row because it's currently unknown whether or not there is a gender disparity

Many [[Immune system|immunological]] and [[Nervous system|neurological]] diseases disproportionately affect women.

== Epidemiology ==
Roughly 80% of patients with [[autoimmune disease]] are women.<ref name="Fairweather2004">{{Cite journal | title = Women and Autoimmune Diseases1 | date =Nov 2004| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328995/|journal=Emerging Infectious Diseases|volume=10|issue=11 | pages = 2005–2011 | last = Fairweather | first = DeLisa | author-link = | last2 = Rose | first2 = Noel R. | authorlink2 = |doi=10.3201/eid1011.040367|pmc=3328995|pmid=15550215|access-date=|issn=1080-6040|quote=|via=}}</ref> In other words, women have four times the risk of developing an autoimmune disease than men.<ref>{{Cite journal|title=Why women have more autoimmune diseases than men: An evolutionary perspective|date=2020-12|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC7980266/|journal=Evolutionary Applications|volume=14|issue=3|pages=629–633|last=Kronzer|first=Vanessa L.|last2=Bridges|first2=Stanley Louis|last3=Davis|first3=John M.|language=en|doi=10.1111/eva.13167|issn=1752-4571}}</ref>

(The terms "woman" and "man" refer to assigned sex at birth. Research shows gender-affirming hormone therapy does not affect an individual's risk of developing autoimmune disease. So trans women have similar risks as cisgender men, and trans men have similar risks as cisgender women.<ref>{{Cite journal|title=SAT416 The Incidence Of Autoimmune Disease In Transgender People After Initiation Of Gender-Affirming Hormone Therapy|date=2023-10|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10554423/#:~:text=Conclusion%20The%20risk%20of%20developing,risk%20of%20developing%20autoimmune%20diseases.|journal=Journal of the Endocrine Society|volume=7|issue=Supplement_1|last=Wiepjes|first=Chantal|last2=Heijer|first2=Martin Den|language=en|doi=10.1210/jendso/bvad114.2087|issn=2472-1972}}</ref>)

== Mechanisms ==

=== Immune system ===
'''Summary of sex differences in innate and adaptive immune responses'''<ref name="Klein2016">{{Cite journal | title = Sex differences in immune responses | date = Oct 2016| url = https://www.nature.com/articles/nri.2016.90|journal=Nature Reviews. Immunology|volume=16|issue=10 | pages = 626–638 | last = Klein | first = Sabra L. | author-link = | last2 = Flanagan | first2 = Katie L. | authorlink2 = |doi=10.1038/nri.2016.90|pmc=|pmid=27546235|access-date=|issn=1474-1741|quote=|via=}}</ref>
{| class="wikitable mw-collapsible mw-collapsed"
!Immune component
!Characteristic
!In Females (relative to males)
|-
|'''Innate immune system'''
|
|
|-
|[[Toll-like receptor]] (TLR) pathways
|[[TLR pathway]] gene expression
|Higher
|-
|
|[[Toll-like receptor 7|TLR7]] expression
|Higher
|-
|
|[[Interleukin 10]] (IL10) production by [[Toll-like receptor 9|TLR9]]-stimulated [[peripheral blood mononuclear cell]]
|Lower
|-
|[[antigen-presenting cell]]s (APCs)
|APC efficiency
|Higher
|-
|[[Dendritic cell]]s
|[[Toll-like receptor 7|TLR7]] activity
|Higher
|-
|[[Macrophage]]s
|[[Toll-like receptor 4|TLR4]] expression
|Lower
|-
|
|Activation
|Higher
|-
|
|[[Phagocytic capacity]]
|Higher
|-
|
|Pro-inflammatory [[cytokine]] production
|Lower
|-
|
|[[Interleukin 10|IL10]] production
|Higher
|-
|[[Neutrophil|Neutrophils]]
|[[Phagocytic capacity]]
|Higher
|-
|
|[[Toll-like receptor|TLR]] expression
|Lower
|-
|[[Natural killer cell|Natural killer cells]]
|NK cell numbers
|Lower
|-
|'''Adaptive immune system'''
|
|
|-
|[[Thymus]]
|Size of thymus
|Smaller
|-
|[[T cell]]s
|[[CD4]] T cell counts
|Higher
|-
|
|[[CD4]]/[[CD8]] T cell ratio
|Higher
|-
|
|[[CD8]] T cell counts
|Lower
|-
|
|Number of activated T cells
|Higher
|-
|
|[[T cell]] proliferation
|Higher
|-
|
|[[Cytotoxic T cell]]
|Increased activity
|-
|
|[[Th1]] versus [[Th2]] cell bias
|Th2 cell bias in females, Th1 cell bias in males
|-
|
|[[Regulatory T cell]] numbers
|Lower
|-
|[[B cell]]
|B cell numbers
|Increased
|-
| [[Immunoglobulin]]s
| Antibody production
|Higher
|}

=== Hormones ===
Women with these diseases may experiencing a worsening of symptoms at specific points in their [[menstrual cycle]], particularly just before or around their periods.<ref name="Zierau2012">{{Cite journal | title = Role of female sex hormones, estradiol and progesterone, in mast cell behavior | date = 2012-06-19| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/|journal=Frontiers in Immunology|volume=3 | pages = 169 | last = Zierau | first = Oliver | last2 = Zenclussen | first2 = Ana C. | last3 = Jensen | first3 = Federico|doi=10.3389/fimmu.2012.00169|pmc=3377947|pmid=22723800|issn=1664-3224}}</ref> [[Estradiol]] and [[progesterone]] induce [[mast cell]] maturation and degranulation,<ref name="Zierau2012" /> which may contribute to the symptoms of a wide range of allergic and mast cell-mediated diseases.

=== Genetics ===

== Diseases ==

=== Asthma ===
In humans, a much higher [[asthma]] prevalence was found in women at reproductive age as compared to men. Serum levels of [[estradiol]] and [[progesterone]] have been directly correlated with the clinical and functional features of asthma. Around 30–40% of women with asthma experience a worsening of symptoms near their period. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma.<ref name="Zierau2012" />

== Social impact ==

=== Treatment options ===

=== Research funding ===

=== Stigma ===
Men and women with these diseases are at risk of [[Stigma|stigmatization]], dismissal, minimization and [[psychologization]] of their symptoms.<ref name="Goudsmit1993">{{Cite journal | journal = Health Psychology Update | url =https://books.google.co.uk/books?hl=en&lr=&id=E1afUMVG0VEC&oi=fnd&pg=PA7 | title = All in her mind! Stereotypic views and the psychologisation of women's illness | last = Goudsmit | first = Ellen M | date = 1993|volume=12 | pages = 28-32|language=en|quote= | author-link = Ellen Goudsmit|issue=|doi=|pmc=|pmid=|access-date=|via=}}</ref>

== List of diseases ==
Below, a list of diseases that predominately affect females.
{| class="wikitable sortable mw-collapsible mw-expanded"
!Conditions
!% female
!Ratio (F:M)
!US prevalence
|-
! colspan="4" scope="colgroup" | '''Neurological diseases'''
|-
|[[Alzheimer's disease]]
|66%
|2:1
|6.2 million<ref>{{Cite web|url=https://www.health.harvard.edu/blog/why-are-women-more-likely-to-develop-alzheimers-disease-202201202672|title=Why are women more likely to develop Alzheimer's disease? - Harvard Health|website=www.health.harvard.edu|access-date=2025-05-22}}</ref>
|-
|[[Empty sella syndrome]]
|
|5:1<ref name="Aruna2014">{{Cite journal | title = Partial Empty Sella Syndrome: A Case Report and Review | date = Apr 2014| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990803/|journal=Indian Journal of Clinical Biochemistry|volume=29|issue=2 | pages = 253–256 | last = Aruna | first = P. | author-link = | last2 = Sowjanya | first2 = B. | authorlink2 = | last3 = Reddy | first3 = P. Amaresh | authorlink3 = | last4 = Krishnamma | first4 = M. | authorlink4 = | last5 = Naidu | first5 = J. N. | authorlink5 = |doi=10.1007/s12291-013-0369-1|pmc=3990803|pmid=24757313|access-date=|issn=0970-1915|quote=|via=}}</ref>
|
|-
|[[Idiopathic intracranial hypertension]]
|
|
|
|-
|[[Migraine]]<ref name="Vos2015" />
|
|3:1 to 4:1<ref>{{Cite journal|title=Prevalence and burden of migraine in the United States: A systematic review|date=2024-05|url=https://pubmed.ncbi.nlm.nih.gov/38700185/|journal=Headache: The Journal of Head and Face Pain|volume=64|issue=5|pages=516–532|last=Cohen|first=Fred|last2=Brooks|first2=Caroline V.|last3=Sun|first3=Daniel|last4=Buse|first4=Dawn C.|last5=Reed|first5=Michael L.|last6=Fanning|first6=Kristina M.|last7=Lipton|first7=Richard B.|language=en|doi=10.1111/head.14709|issn=0017-8748}}</ref>
|37 million<ref>{{Cite web|url=https://americanmigrainefoundation.org/resource-library/migraine-facts/|title=The Facts About Migraine {{!}} American Migraine Foundation|website=americanmigrainefoundation.org|access-date=2025-05-22}}</ref>
|-
|[[Myalgic encephalomyelitis|Myalgic Encephalomyelitis]]/[[Chronic fatigue syndrome]]
|60-66%<ref name="Lim2020">{{Cite journal | title = Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) | date = 2020-02-24| url = https://doi.org/10.1186/s12967-020-02269-0|journal=Journal of Translational Medicine|volume=18|issue=1 | pages = 100 | last = Lim | first = Eun-Jin | last2 = Ahn | first2 = Yo-Chan | last3 = Jang | first3 = Eun-Su | last4 = Lee | first4 = Si-Woo | last5 = Lee | first5 = Su-Hwa | last6 = Son | first6 = Chang-Gue|doi=10.1186/s12967-020-02269-0|pmc=PMC7038594|pmid=32093722|issn=1479-5876}}</ref>
|1.5:1 to 2:1<ref name="Lim2020" /> up to 4:1 (CDC)<ref name="CDC-epidemiology">{{Cite web | url = https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html | title = Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | last = | first = | authorlink = | date = 2022-01-21 | website = [[Centers for Disease Control and Prevention]]|at=Immune System Changes|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|3.3 million<ref>{{Cite news|url=https://www.cdc.gov/me-cfs/about/index.html|title=ME/CFS Basics|date=2024-09-18|work=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|access-date=2025-05-22|language=en-us}}</ref>
|-
|[[Multiple sclerosis]]
|
|1.8:1 to 4:1<ref name="Jorgensen2012" /><ref name="MS-who">{{Cite web | url = https://www.nationalmssociety.org/What-is-MS/Who-Gets-MS | title = Who Gets MS? (Epidemiology) | last = | first = | date = |website=National Multiple Sclerosis Society|archive-url=|archive-date=|url-status=|access-date=}}</ref><ref name="Vos2015">{{Cite journal | last = Vos | first = Theo | last2 = Feigin | first2 = Valery | last3 = Degenhardt | first3 = Louisa | last4 = Ferrari | first4 = Alize J. | last5 = Whiteford | first5 = Harvey A. | date = 2015-02-06 | title = The Global Burden of Mental, Neurological and Substance Use Disorders: An Analysis from the Global Burden of Disease Study 2010| url = https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116820|journal=PLOS ONE|language=en|volume=10|issue=2| pages = e0116820|doi=10.1371/journal.pone.0116820|issn=1932-6203|pmc=4320057|pmid=25658103}}</ref>
|852,000 - 914,000<ref>{{Cite web|url=https://www.nationalmssociety.org/understanding-ms/what-is-ms/who-gets-ms/how-many-people|website=www.nationalmssociety.org|access-date=2025-05-22}}</ref>
|-
|[[Postural orthostatic tachycardia syndrome]] (POTS)
|80-85%<ref name="Dysautonomiafacts">{{Cite web | url = http://www.dysautonomiainternational.org/page.php?ID=180 | title = 10 Facts Doctors Should Know About POTS | last = | first = | date = April 19, 2018 | website = Dysautonomia International|archive-url=|archive-date=|url-status=|access-date=}}</ref>
|4:1
|1-3 million (prior to COVID-19)<ref>{{Cite journal|title=COVID-19 Increases the Prevalence of Postural Orthostatic Tachycardia Syndrome: What Nutrition and Dietetics Practitioners Need to Know|date=2022-09|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9186518/|journal=Journal of the Academy of Nutrition and Dietetics|volume=122|issue=9|pages=1600–1605|last=Harris|first=Cheryl Iny|language=en|doi=10.1016/j.jand.2022.06.002|issn=2212-2672}}</ref>
|-
! colspan="4" scope="colgroup" | '''Endocrine diseases'''
|-
|[[Graves' disease]]
|
|5:1<ref name="Jorgensen2012">{{Cite journal | title = Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort | date = May 2012| url = https://research.regionh.dk/files/36818048/J_rgensen_JAutoimmunity_2012_38_J81_Childbirths_and_risk_of_female_predominant_and_other_autoimmune_diseases_in_the_Danish_population.pdf | journal=Journal of Autoimmunity|volume=38|issue=2-3| pages=J81–87 | last = Jørgensen | first = Kristian Tore | authorlink = | last2 = Pedersen | first2 = Bo Vestergaard | authorlink2 = | last3 = Nielsen | first3 = Nete Munk | authorlink3 = | last4 = Jacobsen | first4 = Søren | authorlink4 = |doi=10.1016/j.jaut.2011.06.004|pmc=|pmid=21813263|access-date=|issn=1095-9157|quote=|via=}}</ref>
|
|-
|[[Hashimoto's thyroiditis (hypothyroidism)|Hashimoto's thyroditis]]
|
|8:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Rheumatological diseases'''
|-
|[[Fibromyalgia]]
|
|7:1 [[Fibromyalgia#1990 ACR criteria|ACR 1990 Criteria]] and 2:1 [[Fibromyalgia#2010 ACR criteria|ACR 2010 Criteria]]<ref name="fibro-medscape">{{Cite web | date = 2021-09-14 | title = Fibromyalgia: Practice Essentials, Background, Pathophysiology| url = https://emedicine.medscape.com/article/329838-overview#a5 | website = Medscape | first = Chad S | last = Boomershine|editor-first1 = Herbert S|editor-last1 = Diamond}}</ref> and CDC<ref name="FibroCDC" />

1.5:1<ref name="Hauser2018">{{Cite journal | last = Häuser | first = Winfried | last2 = Rasker | first2 = Johannes J. | last3 = Perrot | first3 = Serge | last4 = Walitt | first4 = Brian | last5 = Wolfe | first5 = Frederick | authorlink5 = Frederick Wolfe | date = 2018-09-13 | title = Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias |url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203755|journal=PLOS ONE|language=en|volume=13|issue=9| pages = e0203755|doi=10.1371/journal.pone.0203755|issn=1932-6203|pmc=|pmid=30212526}}</ref>
|4 million<ref name="FibroCDC">{{Cite web | url = https://www.cdc.gov/arthritis/basics/fibromyalgia.htm | title = Fibromyalgia {{!}} Arthritis | date = 2018-04-03 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2022-02-01}}</ref>
|-
|[[Rheumatoid arthritis]]
|
|2.4:1<ref name="Jorgensen2012" />
|1.3 million<ref>{{Cite journal|title=Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005–2018|date=2021-07-26|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8348893/|journal=Journal of Clinical Medicine|volume=10|issue=15|pages=3289|last=Xu|first=Yingke|last2=Wu|first2=Qing|language=en|doi=10.3390/jcm10153289|issn=2077-0383}}</ref>
|-
! colspan="4" scope="colgroup" |'''Gastrointestinal diseases'''
|-
|[[Primary billary cirrhosis]]
|
|4:1<ref name="Jorgensen2012" />
|
|-
|[[Celiac disease]] (IBD)
|
|1.6:1<ref name="Jorgensen2012" />
|
|-
|[[Irritable bowel syndrome]] (IBS)
|72%<ref name="Eijsbouts2021">{{Cite journal | title = Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders | date = Nov 2021| url = https://www.nature.com/articles/s41588-021-00950-8|journal=Nature Genetics|volume=53|issue=11 | pages = 1543–1552 | last = Eijsbouts | first = Chris | author-link = | last2 = Zheng | first2 = Tenghao | authorlink2 = | last3 = Kennedy | first3 = Nicholas A. | authorlink3 = | last4 = Bonfiglio | first4 = Ferdinando | authorlink4 = | last5 = Anderson | first5 = Carl A. | authorlink5 = | last6 = Moutsianas | first6 = Loukas | authorlink6 = | last7 = Holliday | first7 = Joanne | last8 = Shi | first8 = Jingchunzi | last9 = Shringarpure | first9 = Suyash | last10 = Voda | first10 = Alexandru-Ioan | last11 = Farrugia | first11 = Gianrico|language=en|doi=10.1038/s41588-021-00950-8|pmc=|pmid=|access-date=|issn=1546-1718|quote=|via=}}</ref>
|
|
|-
! colspan="4" scope="colgroup" | '''Musculoskeletal diseases and disorders'''
|-
|[[Osteoporosis]]
|
|
|
|-
! colspan="4" scope="colgroup" | '''Systemic illnesses'''
|-
|[[Sjögren's syndrome]]
|
|7.5:1<ref name="Jorgensen2012" />
|
|-
|[[Systemic lupus erythematosus]]
|
|5.2:1<ref name="Jorgensen2012" /> 4:1 to 12:1 (CDC)<ref name="CDC-sle">{{Cite web | url = https://www.cdc.gov/lupus/facts/detailed.html | title = Systemic Lupus Erythematosus (SLE) {{!}} Lupus | last = | first = | authorlink = | date = October 17, 2018 | website = [[Centers for Disease Control and Prevention]]|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|161,000 to 322,000<ref name="WH-lupus">{{Cite web | url = https://www.womenshealth.gov/lupus/lupus-and-women | title = Lupus and women | last = | first = | authorlink = | date = | website = Office on Women's Health|archive-url=|archive-date=|url-status=|access-date=2022-02-01}}</ref>
|-
|[[Temporal arteritis]] (Giant cell arteritis)
|
|2.3:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Connective tissue disorders'''
|
|
|
|
|
|-
|[[Ehler's Danlos Syndrome]] Type 3 (hypermobile type)
|
|
|
|
|-
|[[Systemic sclerosis]]
|
|3.7:1<ref name="Jorgensen2012" />
|
|-
! colspan="4" scope="colgroup" | '''Mental health disorders'''
|-
| [[Anxiety|Anxiety disorders]]<ref name="Vos2015" />
|
|1.2:1 to 3.2:1<ref name="WHO2009">{{Cite journal | title = Cross-National Associations Between Gender and Mental Disorders in the World Health Organization World Mental Health Surveys | date = 2009-07-01| url = https://doi.org/10.1001/archgenpsychiatry.2009.36|journal=Archives of General Psychiatry|volume=66|issue=7 | pages = 785–795 | last = Seedat | first = Soraya | last2 = Scott | first2 = Kate Margaret | last3 = Angermeyer | first3 = Matthias C. | last4 = Berglund | first4 = Patricia | last5 = Bromet | first5 = Evelyn J. | last6 = Brugha | first6 = Traolach S. | last7 = Demyttenaere | first7 = Koen | last8 = de Girolamo | first8 = Giovanni | last9 = Haro | first9 = Josep Maria | last10 = Jin | first10 = Robert | last11 = Karam | first11 = Elie G.|doi=10.1001/archgenpsychiatry.2009.36|issn=0003-990X}}</ref>
|
|-
| [[Depression|Major depressive disorder]] (depression)<ref name="Vos2015" />
|
|1.6:1 to 2.4:1<ref name="WHO2009" />
|
|-
| [[Functional neurological symptom disorder|Functional Neurological Disorder (FND)]] (Conversion disorder)
|
|
|
|-
| [[Post-traumatic stress disorder]] (PTSD)
|
|1.3:1 to 6.4:1<ref name="WHO2009" />
|
|
|-
! colspan="4" scope="colgroup" | '''Other diagnoses'''
|-
|[[Asthma]]
|
|3:2 (adults), 7:9 (children, less predominant in girls)<ref name="asthmastacks">{{Cite web | url = https://stacks.cdc.gov/view/cdc/109086 | title = Asthma Surveillance — United States, 2006–2018 {{!}} MMWR Surveillance Summaries /70(5) | date = Sep 17, 2021 | website = [[Centers for Disease Control and Prevention]]|access-date=2022-02-01}}</ref>
|24.8 million (current asthma)
|-
|}

== See also ==
* [[Autoimmune disease]]
* [[Menstrual cycle]]
* [[Menstrual problems in ME/CFS]]

== Learn more ==

* [https://www.amazon.com/Doing-Harm-Medicine-Dismissed-Misdiagnosed/dp/0062470809 Doing Harm: The Truth About How Bad Medicine and Lazy Science Leave Women Dismissed, Misdiagnosed, and Sick] by [[Maya Dusenbery]]

== References ==
{{Reflist}}

[[Category:Triggers and risk factors]]
[[Category:Core topics]]
[[Category:Epidemiology]]
[[Category:Ethics]]

Serotonin

2025-05-19T23:29:46Z

Galimatias:added clarification on serotonin and mood to fix an extremely common misconception

'''Serotonin''' or '''5-Hydroxytryptamine''' or '''5HT''' is a [[monoamine]] [[neurotransmitter]] derived from [[tryptophan]]. It can be found in the [[central nervous system]], [[gastrointestinal tract]], and [[platelet]]s.

==Synthesis==
Serotonin can function as both a peripheral [[hormone]] and a neurotransmitter.

==== Peripheral hormone ====
Around 95% of the body's serotonin is produced in the gut. More specifically, cells in your intestines called enterochromaffin cells produce serotonin and release it into the bloodstream. Platelets store this serotonin and release it when needed. Typically the level of serotonin in your blood is around 1-5 ng/mL. When your inflammatory systems activate, your peripheral serotonin levels can increase 1000-fold.<ref name=":0">{{Cite journal|title=Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill|date=May 3 2021|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8124334/|journal=International Journal of Molecular Sciences|volume=22|issue=9|last=Kanova|first=Marcela|last2=Kohout|first2=P|doi=10.3390/ijms22094837}}</ref>

==== Neurotransmitter ====
Since serotonin is water soluble, it can't cross the [[blood-brain barrier]] (BBB) easily. So the central nervous system produces its own supply of serotonin separate from the rest of the body. This supply of serotonin is synthesized in the raphe nuclei of the [[brainstem]].<ref name=":0" />

L-[[Tryptophan]] → [[5-Hydroxytryptophan|L-5-Hydroxytryptophan]] (5HTP) → 5-hydroxytryptamine (serotonin, 5HT)<ref>{{Cite journal|title=Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review|date=April 8, 2019|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6463810/|journal=Frontiers in Endocrinology|volume=8|issue=10|last=Hoglund|first=Erik|last2=Overli|first2=Oyvind|last3=Winberg|first3=Svante|doi=10.3389/fendo.2019.00158}}</ref>

==Function ==

===== Homeostasis =====
Serotonin is activated by threats to homeostasis. According to Pereira et al. 2021), serotonin is linked to the regulation of:
* [[dysautonomia]]
* dyspnea
* [[fatigue]]
* glucose control
* [[hypothyroidism]]
* [[immune system]] functioning
* proprioception (the body's ability to sense it's position in space)
* [[:Category:Sensitivity signs and symptoms|sensory sensitivity]]<ref name="Pereira2021" />

===== Mood =====
There is a common misconception that serotonin is a "good mood" chemical, but that claim is a bit of an oversimplification. When it comes to emotions, research suggests serotonin acts as dopamine's counterpart.<ref>{{Cite web|url=https://neuroscience.stanford.edu/news/dopamine-and-serotonin-work-opposition-shape-learning|title=Dopamine and serotonin work in opposition to shape learning {{!}} Wu Tsai Neurosciences Institute|date=2024-11-25|website=neuroscience.stanford.edu|language=en|access-date=2025-05-19}}</ref> In general, dopamine creates rewarding sensations to push someone towards action, while serotonin predisposes someone towards patience and delayed gratification. Serotonin can also halt ruminative thinking common in depressive and anxiety disorders.<ref>{{Cite journal|title=Fifty years on: Serotonin and depression|date=2023-03|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10076339/|journal=Journal of Psychopharmacology|volume=37|issue=3|pages=237–241|last=Jauhar|first=Sameer|last2=Cowen|first2=Philip J|last3=Browning|first3=Michael|language=en|doi=10.1177/02698811231161813|issn=0269-8811}}</ref>

===== Revised Central Fatigue Hypothesis =====
Most individuals experience fatigue after prolonged physical exertion. The revised Central Fatigue Hypothesis suggests this fatigue is due to changes in serotonin and [[dopamine]] levels within certain regions of the brain.<ref>{{Cite journal|title=Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems|date=2017|url=https://www.scielo.br/j/bjmbr/a/v7RQZtcwVMyJGRJvm7mnGxC/?lang=en&stop=previous&format=html|journal=Brazilian Journal of Medical and Biological Research|volume=50|issue=12|last=Cordeiro|first=L.M.S.|last2=Rabelo|first2=P.C.R.|last3=Moraes|first3=M.M.|last4=Teixeira-Coelho|first4=F.|last5=Coimbra|first5=C.C.|last6=Wanner|first6=S.P.|last7=Soares|first7=D.D.|language=en|doi=10.1590/1414-431X20176432|issn=1414-431X}}</ref> When exercise first begins, both dopamine and serotonin levels increase. But as exercise continues, dopamine levels drop to baseline, while serotonin levels remain high. This high serotonin-to-dopamine ratio triggers feelings of temporary fatigue.

(A note: this hypothesis only focuses on how healthy individuals respond to exercise and does not directly address post-exertional malaise.)

==Serotonin acting drugs==
[[Selective serotonin reuptake inhibitor]]s (SSRIs), the most popular class of [[antidepressant]]s, and [[selective serotonin and norepinephrine reuptake inhibitor]]s (SNRIs) have proved ineffective in [[ME/CFS]].<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 = N | authorlink13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | authorlink14 = John Chia | last15 = Darragh | first15 = A | authorlink15 = Austin Darragh | last16 = Gerken | first16 = A | authorlink16 = Anne Gerken | last17 = Jo | first17 = D | authorlink17 = Daehyun Jo | last18 = Lewis | first18 = DP | authorlink18 = Donald Lewis | last19 = Light | first19 = AR | authorlink19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref><ref name="canadianconsensus-CCC">{{Citation | last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers | last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson | last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner | last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested | last8 = Flor-Henry | first8 = Pierre| authorlink8 = Pierre Flor-Henry | last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi | last10 = Powles | first10 = AC Peter | authorlink10 = A C Peter Powles | last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey | last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | pages = 7-115 | date = 2003 | pmid = | doi = 10.1300/J092v11n01_02| url = http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf}}</ref> SSRIs indiscriminately modulate serotonin.<ref name="Pereira2021" />

==In human disease==

===ME/CFS===
The [[CRFR2 upregulation hypothesis]] of ME/CFS, which is the theory behind the clinicial trials of [[CT38]], proposes that serotonin is dysregulated in ME/CFS, and that excessive serotonin desensitizes 5HT1A, which then leaves serotonin elevated and a loss of homeostasis.<ref name="Pereira2021">{{Cite journal | last = Pereira | first=Gerard | last2 = Gillies | first2 = Hunter | last3 = Chanda | first3 = Sanjay | last4 = Corbett | first4 = Michael| last5 = Vernon | first5 = Suzanne D. | last6 = Milani | first6 = Tina | last7 = Bateman | first7 = Lucinda | date = 2021 | title=Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/article/10.3389/fnsys.2021.698240|journal=Frontiers in Systems Neuroscience|volume=15 | pages = 84|doi=10.3389/fnsys.2021.698240|issn=1662-5137|pmc=PMC8441022|pmid=34539356}}</ref>

==Notable studies ==
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26147001 A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice]
*2008, [https://www.ncbi.nlm.nih.gov/pubmed/18079067 Genetic evaluation of the serotonergic system in chronic fatigue syndrome]
*2004 [http://journals.lww.com/neuroreport/Abstract/2004/12030/Reduction_of_serotonin_transporters_of_patients.2.aspx Reduction of serotonin transporters of patients with chronic fatigue syndrome]
*1997, [https://www.ncbi.nlm.nih.gov/pubmed/9226729 Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.]

==Learn more==
*2016, [http://selfhacked.com/2016/02/12/5ht2a-receptors-a-root-cause-of-anxiety-fatigue-sleep-problems-and-cirs/ 5HT2A Receptors: A Root Cause of Anxiety, Fatigue, Sleep Problems and CIRS]

==See also==
*[[5HTP]]
*[[CRFR2 upregulation hypothesis]]
*[[CT38]]

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]
[[Category:Neurotransmitters]]
[[Category:Neurology]]

Dopamine

2025-05-16T22:38:15Z

Galimatias:/* Nervous system */ dopamine imbalance hypothesis

'''Dopamine''' is a [[neurotransmitter]] with multiple roles in the body.

== Dopamine synthesis ==

Dopamine is synthesized through the following pathway:

L-[[Phenylalanine]] → L-[[Tyrosine]] → [[L-DOPA]] → Dopamine

Dopamine, in turn, is a precursor to [[norepinephrine]] and [[epinephrine]].<ref name=":1">{{Cite journal|title=The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders|date=2015-03-12|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC4357260/|journal=Frontiers in Neurology|volume=6|last=Dobryakova|first=Ekaterina|last2=Genova|first2=Helen M.|last3=DeLuca|first3=John|last4=Wylie|first4=Glenn R.|language=en|doi=10.3389/fneur.2015.00052|issn=1664-2295}}</ref>

Dopamine is incapable of crossing the blood-brain barrier, so it must be produced in [[Neuron|neurons]] for brain activity or in the [[adrenal glands]] and the gut for peripheral activity.

[[Iron]] is important in the expression of dopamine receptors in the [[brain]]<ref>{{Cite web | url = https://pubmed.ncbi.nlm.nih.gov/6138953/ | title = Brain Iron and Dopamine Receptor Function | last = Mb | first = Youdim | last2 = D | first2 = Ben-Shachar | date = 1983 | website = Advances in biochemical psychopharmacology|language=en|pmid=6138953|access-date=2020-05-28 | last3 = R | first3 = Ashkenazi | last4 = S | first4 = Yehuda}}</ref> and is also a cofactor in for [[tyrosine hydroxylase]], the enzyme that catalyzes the conversion of tyrosine to L-DOPA.

==Nervous system==

Dopamine plays a role in [[Executive function problems|executive function]], motor control, motivation, arousal.

The largest sources of dopamine in the brain are in the substantia nigra (SN) and ventral tegmental area (VTA). The SN and VTA are both components of the [[basal ganglia]]. Dopamine neurons spread to the rest of the brain via two* main pathways:<ref name=":1" />

* '''Nigrostriatal pathway:''' connects SN to the striatum
* '''Mesocorticolimbic pathway:''' connects VTA to the striatum, limbic areas, and prefrontal cortex

Some dopamine is also synthesized in the [[hypothalamus]]. It takes a third, separate pathway to the pituitary gland, where it inhibits the release of [[prolactin]] (a hormone that helps regulate the immune system).

== Immune system ==

Dopamine reduces systemic inflammation by blocking [[inflammasome]] activation.<ref>{{Cite journal | last = Yan | first = Yiqing | last2 = Jiang | first2 = Wei | last3 = Liu | first3 = Lei | last4 = Wang | first4 = Xiaqiong | last5 = Ding | first5 = Chen | last6 = Tian | first6 = Zhigang | last7 = Zhou | first7 = Rongbin | date = Jan 2015 | title = Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome | url =http://www.cell.com/cell/abstract/S0092-8674(14)01524-4|journal=Cell|language=English|volume=160|issue=1-2 | pages = 62–73|doi=10.1016/j.cell.2014.11.047|issn=0092-8674|via=}}</ref><ref>{{Cite journal | last = Bordon | first = Yvonne | authorlink = | date = Feb 2015 | title = Dopamine blocks inflammasome activation | url =https://www.nature.com/articles/nri3817|journal=Nature Reviews Immunology|language=en|volume=15|issue=2 | pages = 69–69|doi=10.1038/nri3817|issn=1474-1741|pmc=|pmid=|access-date=|quote=|via=}}</ref>

Dopamine has a role in the activity of [[lymphocytes]]. It activates native [[T cell|t cells]] but inhibits the activity of activated t cells.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856781/</ref> However, dopamine may also induce the release of [[IL-17|interleukin-17]] in [[rheumatoid arthritis]].<ref>http://www.nature.com/nrd/journal/v10/n4/full/nrd3422.html</ref>

Inflammation may also have a role in dopamine production. A study of [[Hepatitis C]] patients found looked at how [[interferon alpha]] treatment (which increases immune system activity) affected dopamine precursors. They found decreased levels of [[tetrahydrobiopterin]] ([[BH4]]), which is a cofactor in the conversion of L-Phenylalanine to L-Tyrosine and L-Tyrosine to L-DOPA. At the same time, levels of BH2 (tetrahydrobipterin's inactive form) were much higher than normal. The researchers also found reduced conversion of [[phenylalanine]] to [[tyrosine]] in the cerebrospinal fluid, which are associated with decreased dopamine in the brain.<ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/23072726/|title=Tyrosine Metabolism During Interferon-Alpha Administration: Association With Fatigue and CSF Dopamine Concentrations|last=Felger|first=JC|authorlink=|last2=Li|first2=L|authorlink2=|date=Jul 2013|website=Brain, behavior, and immunity|language=en|pmid=23072726|archive-url=|archive-date=|url-status=|access-date=2020-05-28|last3=Marvar|first3=PJ|last4=Woolwine|first4=BJ|last5=Harrison|first5=DG|last6=Raison|first6=CL|last7=Miller|first7=AH}}</ref>

== Fatigue ==

===== Dopamine Imbalance Hypothesis =====
The dopamine imbalance hypothesis suggests pathological fatigue occurs due to a dopamine imbalance in the central nervous system.<ref name=":0">{{Cite journal | last = Dobryakova | first = Ekaterina | authorlink = | last2 = Genova | first2 = Helen M. | authorlink2 = | last3 = DeLuca | first3 = John | authorlink3 = | last4 = Wylie | first4 = Glenn R. | author-link4 = | date = 2015 | title=The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders |url =https://www.frontiersin.org/articles/10.3389/fneur.2015.00052/full|journal=Frontiers in Neurology|language=English|volume=6|issue= | pages = |doi=10.3389/fneur.2015.00052|issn=1664-2295|pmc = 4357260|pmid=25814977|access-date=|quote=|via=}}</ref> More specifically, dopamine may not travel effectively through the mesocorticolimbic pathway, disrupting communication in the brain.

Support for this hypothesis is based on prior research findings regarding fatigue in conditions like [[multiple sclerosis|multiple sclerosis (MS)]], traumatic brain injury (TBI), and [[chronic fatigue syndrome]]. To summarize, research has linked fatigue to physical damage and low connectivity in regions of the brain with lots of dopamine neurons. Medications that increase dopamine levels have been shown to improve reported fatigue in chronic fatigue syndrome, TBI, and cancer.<ref name=":0" />

==Chronic fatigue syndrome==

Studies have found lower levels of the dopamine precursor [[tyrosine]]<ref>{{Cite journal | last = Georgiades | first = Evelina | authorlink = | last2 = Behan | first2 = Wilhelmina M.H. | authorlink2 = | last3 = Kilduff | first3 = Liam P. | author-link3 = | last4 = Hadjicharalambous | first4 = Marios | authorlink4 = | last5 = Mackie | first5 = Eileen E. | author-link5 = | last6 = Wilson | first6 = John | author-link6 = | last7 = Ward | first7 = Susan A. | last8 = Pitsiladis | first8 = Yannis P. | date = 2003-08-01 | title = Chronic fatigue syndrome: new evidence for a central fatigue disorder |url =https://portlandpress.com/clinsci/article/105/2/213/67612/Chronic-fatigue-syndrome-new-evidence-for-a|journal=Clinical Science|language=en|volume=105|issue=2 | pages = 213–218|doi=10.1042/CS20020354|issn=0143-5221|pmc=|pmid=|access-date=|quote=|via=}}</ref> and reduced activation in the [[basal ganglia]]<ref>http://www.fasebj.org/cgi/content/meeting_abstract/26/1_MeetingAbstracts/1035.20</ref><ref>{{Cite journal | last = Miller | first = Andrew H. | authorlink = | last2 = Jones | first2 = James F. | authorlink2 = | last3 = Drake | first3 = Daniel F. | author-link3 = | last4 = Tian | first4 = Hao | authorlink4 = | last5 = Unger | first5 = Elizabeth R. | author-link5 = Elizabeth Unger | last6 = Pagnoni | first6 = Giuseppe | author-link6 = | date = 2014-05-23 | title = Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue | url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098156|journal=PLOS ONE|language=en|volume=9|issue=5| pages = e98156|doi=10.1371/journal.pone.0098156|issn=1932-6203|pmc = 4032274|pmid=24858857|access-date=|quote=|via=}}</ref>, the region of the brain with the highest concentration of dopaminergic neurons.

== Fibromyalgia ==

Small, preliminary studies have found evidence of abnormal dopamine metabolism in the brains of [[fibromyalgia]] patients.<ref>{{Cite web | url = https://pubmed.ncbi.nlm.nih.gov/19398377/ | title = Changes in Gray Matter Density in Fibromyalgia: Correlation With Dopamine Metabolism | last = Wood | first = PB | authorlink = | last2 = Glabus | first2 = MF | authorlink2 = | date = Jun 2009 | website = The journal of pain : official journal of the American Pain Society|language=en|pmid=19398377| archive-url = | archive-date = |url-status = | access-date=2020-05-28 | last3 = R | first3 = Simpson | last4 = Jc | first4 = Patterson}}</ref><ref>{{Cite web | url = https://pubmed.ncbi.nlm.nih.gov/17023218/ | title = Reduced Presynaptic Dopamine Activity in Fibromyalgia Syndrome Demonstrated With Positron Emission Tomography: A Pilot Study | last = Wood | first = PB | authorlink = | last2 = Patterson | first2 = JC | authorlink2 = | date = Jan 2007 | website = The journal of pain : official journal of the American Pain Society|language=en|pmid=17023218| archive-url = | archive-date = |url-status = | access-date=2020-05-28 | last3 = Jj | first3 = Sunderland | last4 = Kh | first4 = Tainter | last5 = Mf | first5 = Glabus | last6 = Dl | first6 = Lilien}}</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/17610577</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/24449585</ref>

==Other conditions==

[[Parkinson's disease]] involves the loss of dopaminergic neurons in the midbrain and subsequently reduced dopamine. [[Schizophrenia]], [[ADHD]] and [[restless leg syndrome]] are also associated with altered dopamine.

Cerebralspinal iron is decreased in [[restless legs syndrome]] despite normal serum levels.<ref>{{Cite web | url = https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/restless-legs-syndrome/what-is-rls/causes.html | title = Causes of Restless Legs Syndrome (RLS) {{!}} The Johns Hopkins Center for Restless Legs Syndrome | last = Ciattei | first = Jennifer | website = hopkinsmedicine.org|language=en|access-date=2020-05-28}}</ref>

In addition to its neurological effects, reduced dopamine may also have immunological effects in these diseases.

Altered dopamine [[metabolism]] may play a role in a number of [[Autoimmune disease|autoimmune diseases]].<ref>{{Cite journal | last = Pacheco | first = Rodrigo | last2 = Contreras | first2 = Francisco | last3 = Zouali | first3 = Moncef| date = 2014 | title = The Dopaminergic System in Autoimmune Diseases |url =https://www.frontiersin.org/articles/10.3389/fimmu.2014.00117/full|journal=Frontiers in Immunology|language=English|volume=5|doi=10.3389/fimmu.2014.00117|issn=1664-3224}}</ref>

Dopaminergic neurons are thought to play a role in [[epilepsy|epileptic seizures]] arising from the [[limbic system]].<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774988/</ref>

==Altering dopamine levels==

Mice fed a [[ketogenic diet]] had increased activity of dopaminergic neurons.<ref>http://www.ncbi.nlm.nih.gov/pubmed/24769322</ref>

== See also ==
* [[Neurotransmitter]]

== Learn more ==
* [https://forums.phoenixrising.me/index.php?threads/interested-but-wary-about-mucuna-pruriens.42175/#post-682556 List of drugs and supplements with dopaminergic effects].

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]
[[Category:Neurotransmitters]]
[[Category:Adrenal glands]]

Serotonin

2025-05-15T22:22:23Z

Galimatias:/* Revised Central Fatigue Hypothesis */ added a caveat to explain scope of hypothesis

'''Serotonin''' or '''5-Hydroxytryptamine''' or '''5HT''' is a [[monoamine]] [[neurotransmitter]] derived from [[tryptophan]]. It can be found in the [[central nervous system]], [[gastrointestinal tract]], and [[platelet]]s.

==Synthesis==
Serotonin can function as both a peripheral [[hormone]] and a neurotransmitter.

==== Peripheral hormone ====
Around 95% of the body's serotonin is produced in the gut. More specifically, cells in your intestines called enterochromaffin cells produce serotonin and release it into the bloodstream. Platelets store this serotonin and release it when needed. Typically the level of serotonin in your blood is around 1-5 ng/mL. When your inflammatory systems activate, your peripheral serotonin levels can increase 1000-fold.<ref name=":0">{{Cite journal|title=Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill|date=May 3 2021|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8124334/|journal=International Journal of Molecular Sciences|volume=22|issue=9|last=Kanova|first=Marcela|last2=Kohout|first2=P|doi=10.3390/ijms22094837}}</ref>

==== Neurotransmitter ====
Since serotonin is water soluble, it can't cross the [[blood-brain barrier]] (BBB) easily. So the central nervous system produces its own supply of serotonin separate from the rest of the body. This supply of serotonin is synthesized in the raphe nuclei of the [[brainstem]].<ref name=":0" />

L-[[Tryptophan]] → [[5-Hydroxytryptophan|L-5-Hydroxytryptophan]] (5HTP) → 5-hydroxytryptamine (serotonin, 5HT)<ref>{{Cite journal|title=Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review|date=April 8, 2019|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6463810/|journal=Frontiers in Endocrinology|volume=8|issue=10|last=Hoglund|first=Erik|last2=Overli|first2=Oyvind|last3=Winberg|first3=Svante|doi=10.3389/fendo.2019.00158}}</ref>

==Function ==
Serotonin is a neurotransmitter and is activated by threats to homeostasis. According to Pereira et al. 2021), serotonin is linked to the regulation of:
* [[dysautonomia]]
* dyspnea
* [[fatigue]]
* glucose control
* [[hypothyroidism]]
* [[immune system]] functioning
* proprioception, and
* [[:Category:Sensitivity signs and symptoms|sensory sensitivity]]<ref name="Pereira2021" />

==== Revised Central Fatigue Hypothesis ====
Most individuals experience fatigue after prolonged physical exertion. The revised Central Fatigue Hypothesis suggests this fatigue is due to changes in serotonin and [[dopamine]] levels within certain regions of the brain.<ref>{{Cite journal|title=Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems|date=2017|url=https://www.scielo.br/j/bjmbr/a/v7RQZtcwVMyJGRJvm7mnGxC/?lang=en&stop=previous&format=html|journal=Brazilian Journal of Medical and Biological Research|volume=50|issue=12|last=Cordeiro|first=L.M.S.|last2=Rabelo|first2=P.C.R.|last3=Moraes|first3=M.M.|last4=Teixeira-Coelho|first4=F.|last5=Coimbra|first5=C.C.|last6=Wanner|first6=S.P.|last7=Soares|first7=D.D.|language=en|doi=10.1590/1414-431X20176432|issn=1414-431X}}</ref> When exercise first begins, both dopamine and serotonin levels increase. But as exercise continues, dopamine levels drop to baseline, while serotonin levels remain high. This high serotonin-to-dopamine ratio triggers feelings of temporary fatigue.

(A note: this hypothesis only focuses on how healthy individuals respond to exercise and does not directly address post-exertional malaise.)

==Serotonin acting drugs==
[[Selective serotonin reuptake inhibitor]]s (SSRIs), the most popular class of [[antidepressant]]s, and [[selective serotonin and norepinephrine reuptake inhibitor]]s (SNRIs) have proved ineffective in [[ME/CFS]].<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 = N | authorlink13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | authorlink14 = John Chia | last15 = Darragh | first15 = A | authorlink15 = Austin Darragh | last16 = Gerken | first16 = A | authorlink16 = Anne Gerken | last17 = Jo | first17 = D | authorlink17 = Daehyun Jo | last18 = Lewis | first18 = DP | authorlink18 = Donald Lewis | last19 = Light | first19 = AR | authorlink19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref><ref name="canadianconsensus-CCC">{{Citation | last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers | last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson | last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner | last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested | last8 = Flor-Henry | first8 = Pierre| authorlink8 = Pierre Flor-Henry | last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi | last10 = Powles | first10 = AC Peter | authorlink10 = A C Peter Powles | last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey | last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | pages = 7-115 | date = 2003 | pmid = | doi = 10.1300/J092v11n01_02| url = http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf}}</ref> SSRIs indiscriminately modulate serotonin.<ref name="Pereira2021" />

==In human disease==

===ME/CFS===
The [[CRFR2 upregulation hypothesis]] of ME/CFS, which is the theory behind the clinicial trials of [[CT38]], proposes that serotonin is dysregulated in ME/CFS, and that excessive serotonin desensitizes 5HT1A, which then leaves serotonin elevated and a loss of homeostasis.<ref name="Pereira2021">{{Cite journal | last = Pereira | first=Gerard | last2 = Gillies | first2 = Hunter | last3 = Chanda | first3 = Sanjay | last4 = Corbett | first4 = Michael| last5 = Vernon | first5 = Suzanne D. | last6 = Milani | first6 = Tina | last7 = Bateman | first7 = Lucinda | date = 2021 | title=Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/article/10.3389/fnsys.2021.698240|journal=Frontiers in Systems Neuroscience|volume=15 | pages = 84|doi=10.3389/fnsys.2021.698240|issn=1662-5137|pmc=PMC8441022|pmid=34539356}}</ref>

==Notable studies ==
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26147001 A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice]
*2008, [https://www.ncbi.nlm.nih.gov/pubmed/18079067 Genetic evaluation of the serotonergic system in chronic fatigue syndrome]
*2004 [http://journals.lww.com/neuroreport/Abstract/2004/12030/Reduction_of_serotonin_transporters_of_patients.2.aspx Reduction of serotonin transporters of patients with chronic fatigue syndrome]
*1997, [https://www.ncbi.nlm.nih.gov/pubmed/9226729 Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.]

==Learn more==
*2016, [http://selfhacked.com/2016/02/12/5ht2a-receptors-a-root-cause-of-anxiety-fatigue-sleep-problems-and-cirs/ 5HT2A Receptors: A Root Cause of Anxiety, Fatigue, Sleep Problems and CIRS]

==See also==
*[[5HTP]]
*[[CRFR2 upregulation hypothesis]]
*[[CT38]]

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]
[[Category:Neurotransmitters]]
[[Category:Neurology]]

Serotonin

2025-05-15T22:18:08Z

Galimatias:Added Central Fatigue Hypothesis

'''Serotonin''' or '''5-Hydroxytryptamine''' or '''5HT''' is a [[monoamine]] [[neurotransmitter]] derived from [[tryptophan]]. It can be found in the [[central nervous system]], [[gastrointestinal tract]], and [[platelet]]s.

==Synthesis==
Serotonin can function as both a peripheral [[hormone]] and a neurotransmitter.

==== Peripheral hormone ====
Around 95% of the body's serotonin is produced in the gut. More specifically, cells in your intestines called enterochromaffin cells produce serotonin and release it into the bloodstream. Platelets store this serotonin and release it when needed. Typically the level of serotonin in your blood is around 1-5 ng/mL. When your inflammatory systems activate, your peripheral serotonin levels can increase 1000-fold.<ref name=":0">{{Cite journal|title=Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill|date=May 3 2021|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8124334/|journal=International Journal of Molecular Sciences|volume=22|issue=9|last=Kanova|first=Marcela|last2=Kohout|first2=P|doi=10.3390/ijms22094837}}</ref>

==== Neurotransmitter ====
Since serotonin is water soluble, it can't cross the [[blood-brain barrier]] (BBB) easily. So the central nervous system produces its own supply of serotonin separate from the rest of the body. This supply of serotonin is synthesized in the raphe nuclei of the [[brainstem]].<ref name=":0" />

L-[[Tryptophan]] → [[5-Hydroxytryptophan|L-5-Hydroxytryptophan]] (5HTP) → 5-hydroxytryptamine (serotonin, 5HT)<ref>{{Cite journal|title=Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review|date=April 8, 2019|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6463810/|journal=Frontiers in Endocrinology|volume=8|issue=10|last=Hoglund|first=Erik|last2=Overli|first2=Oyvind|last3=Winberg|first3=Svante|doi=10.3389/fendo.2019.00158}}</ref>

==Function ==
Serotonin is a neurotransmitter and is activated by threats to homeostasis. According to Pereira et al. 2021), serotonin is linked to the regulation of:
* [[dysautonomia]]
* dyspnea
* [[fatigue]]
* glucose control
* [[hypothyroidism]]
* [[immune system]] functioning
* proprioception, and
* [[:Category:Sensitivity signs and symptoms|sensory sensitivity]]<ref name="Pereira2021" />

==== Revised Central Fatigue Hypothesis ====
Most individuals experience fatigue after prolonged physical exertion. The revised Central Fatigue Hypothesis suggests this fatigue is due to changes in serotonin and [[dopamine]] levels within certain regions of the brain.<ref>{{Cite journal|title=Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems|date=2017|url=https://www.scielo.br/j/bjmbr/a/v7RQZtcwVMyJGRJvm7mnGxC/?lang=en&stop=previous&format=html|journal=Brazilian Journal of Medical and Biological Research|volume=50|issue=12|last=Cordeiro|first=L.M.S.|last2=Rabelo|first2=P.C.R.|last3=Moraes|first3=M.M.|last4=Teixeira-Coelho|first4=F.|last5=Coimbra|first5=C.C.|last6=Wanner|first6=S.P.|last7=Soares|first7=D.D.|language=en|doi=10.1590/1414-431X20176432|issn=1414-431X}}</ref> When exercise first begins, both dopamine and serotonin levels increase. But as exercise continues, dopamine levels drop to baseline, while serotonin levels remain high. This high serotonin-to-dopamine ratio triggers feelings of fatigue.

==Serotonin acting drugs==
[[Selective serotonin reuptake inhibitor]]s (SSRIs), the most popular class of [[antidepressant]]s, and [[selective serotonin and norepinephrine reuptake inhibitor]]s (SNRIs) have proved ineffective in [[ME/CFS]].<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 = N | authorlink13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | authorlink14 = John Chia | last15 = Darragh | first15 = A | authorlink15 = Austin Darragh | last16 = Gerken | first16 = A | authorlink16 = Anne Gerken | last17 = Jo | first17 = D | authorlink17 = Daehyun Jo | last18 = Lewis | first18 = DP | authorlink18 = Donald Lewis | last19 = Light | first19 = AR | authorlink19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref><ref name="canadianconsensus-CCC">{{Citation | last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers | last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson | last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner | last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested | last8 = Flor-Henry | first8 = Pierre| authorlink8 = Pierre Flor-Henry | last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi | last10 = Powles | first10 = AC Peter | authorlink10 = A C Peter Powles | last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey | last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | pages = 7-115 | date = 2003 | pmid = | doi = 10.1300/J092v11n01_02| url = http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf}}</ref> SSRIs indiscriminately modulate serotonin.<ref name="Pereira2021" />

==In human disease==

===ME/CFS===
The [[CRFR2 upregulation hypothesis]] of ME/CFS, which is the theory behind the clinicial trials of [[CT38]], proposes that serotonin is dysregulated in ME/CFS, and that excessive serotonin desensitizes 5HT1A, which then leaves serotonin elevated and a loss of homeostasis.<ref name="Pereira2021">{{Cite journal | last = Pereira | first=Gerard | last2 = Gillies | first2 = Hunter | last3 = Chanda | first3 = Sanjay | last4 = Corbett | first4 = Michael| last5 = Vernon | first5 = Suzanne D. | last6 = Milani | first6 = Tina | last7 = Bateman | first7 = Lucinda | date = 2021 | title=Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/article/10.3389/fnsys.2021.698240|journal=Frontiers in Systems Neuroscience|volume=15 | pages = 84|doi=10.3389/fnsys.2021.698240|issn=1662-5137|pmc=PMC8441022|pmid=34539356}}</ref>

==Notable studies ==
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26147001 A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice]
*2008, [https://www.ncbi.nlm.nih.gov/pubmed/18079067 Genetic evaluation of the serotonergic system in chronic fatigue syndrome]
*2004 [http://journals.lww.com/neuroreport/Abstract/2004/12030/Reduction_of_serotonin_transporters_of_patients.2.aspx Reduction of serotonin transporters of patients with chronic fatigue syndrome]
*1997, [https://www.ncbi.nlm.nih.gov/pubmed/9226729 Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.]

==Learn more==
*2016, [http://selfhacked.com/2016/02/12/5ht2a-receptors-a-root-cause-of-anxiety-fatigue-sleep-problems-and-cirs/ 5HT2A Receptors: A Root Cause of Anxiety, Fatigue, Sleep Problems and CIRS]

==See also==
*[[5HTP]]
*[[CRFR2 upregulation hypothesis]]
*[[CT38]]

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]
[[Category:Neurotransmitters]]
[[Category:Neurology]]

Blood-brain barrier

2025-04-16T22:38:17Z

Galimatias:updated page and added citations. Could not find evidence of olfactory bulb being a CVO, so I deleted that.

{{Cleanup/Citations needed | date = 2021}}
The '''blood-brain barrier''' or '''BBB''' is a protects the [[central nervous system]] from potentially harmful chemicals and pathogens in the [[blood]]. In the BBB, the lining of the blood vessels (endothelium) is knitted closely together in tight junctions, becoming a powerful filter for blood that enters the brain.<ref>{{Cite journal|title=Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses|date=2022-05-25|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9174654/|journal=Frontiers in Neurology|volume=13|last=Tate|first=Warren|last2=Walker|first2=Max|last3=Sweetman|first3=Eiren|last4=Helliwell|first4=Amber|last5=Peppercorn|first5=Katie|last6=Edgar|first6=Christina|last7=Blair|first7=Anna|last8=Chatterjee|first8=Aniruddha|language=en|doi=10.3389/fneur.2022.877772|issn=1664-2295}}</ref>

== BBB Permeability ==
Blood-brain barrier permeability (BBBP) measures how much the BBB filters your blood. A more permeable BBB may potentially let in more harmful molecules, triggering local inflammation. Chronic brain inflammation can lead to cognitive symptoms like brain fog.<ref name=":0" />

Transforming growth factor beta (TGF-β) is a cytokine that can make the BBB more permeable.<ref name=":0" /> A 2015 review found people with ME/CFS frequently have higher levels of TGF-β.<ref>{{Cite journal|title=Chronic fatigue syndrome and circulating cytokines: A systematic review|date=2015 Nov|url=https://pubmed.ncbi.nlm.nih.gov/26148446/|journal=Brain, behavior, and immunity|volume=50|last=S|first=Blundell|last2=Kk|first2=Ray|last3=M|first3=Buckland|last4=Pd|first4=White|language=en|doi=10.1016/j.bbi.2015.07.004|pmid=26148446|issn=1090-2139}}</ref> A 2017 study found that higher levels of TGF-β were linked to more severe ME/CFS symptoms.<ref>{{Cite journal|title=Cytokine signature associated with disease severity in chronic fatigue syndrome patients|date=2017-08-22|url=https://pubmed.ncbi.nlm.nih.gov/28760971/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=34|last=Jg|first=Montoya|last2=Th|first2=Holmes|last3=Jn|first3=Anderson|last4=Ht|first4=Maecker|last5=Y|first5=Rosenberg-Hasson|last6=Ij|first6=Valencia|last7=L|first7=Chu|last8=Jw|first8=Younger|last9=Cm|first9=Tato|last10=Mm|first10=Davis|language=en|doi=10.1073/pnas.1710519114|pmid=28760971|issn=1091-6490}}</ref>

==Circumventricular organs ==
Circumventricular organs (CVOs) are parts of the brain which sit outside the blood brain barrier. They interact directly with the blood through dense capillaries. This direct interaction is important for [[neuroendocrine system |neuroendocrine]] organs that secrete chemicals directly into the blood, such as the pineal gland. CVOs also include sensory structures like the subfornical organ, which detects sodium levels in the blood and helps control thirst.<ref name=":1">{{Cite journal|title=Glial functions in the blood-brain communication at the circumventricular organs|date=2022-10-06|url=https://pubmed.ncbi.nlm.nih.gov/36278020/|journal=Frontiers in neuroscience|volume=16|last=S|first=Miyata|language=en|doi=10.3389/fnins.2022.991779|pmid=36278020|issn=1662-4548}}</ref>

Due to their direct connection with the bloodstream, CVOs are often the first parts of the central nervous system exposed to dangerous molecules. The [[microglia]] in charge of "guarding" the CVOs can then trigger a [[Neuroinflammation|neuroinflammatory response]].<ref name=":1" />

Sometimes, if inflammatory cytokines are present in very high levels, they can seep into the rest of the brain via the CVOs, bypassing the protective BBB.<ref>{{Cite journal|title=Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods|date=Jan 9, 2019|url=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.01033/full|journal=Frontiers in Neurology|volume=9|last=VanElzakker|first=M}}</ref>

==Diseases associated with weakened BBB==
In addition to ME/CFS, several health conditions have been associated with a weakened blood-brain barrier:<ref name=":0" /><ref name=":2">{{Cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK519556/|title=Anatomy, Head and Neck: Blood Brain Barrier|last=Dotiwala|first=Ari|date=2023|website=National Library of Medicine}}</ref>

* [[Long COVID]]
* [[Epilepsy]]
* [[HIV/AIDS]]
* [[Alzheimer's|Alzheimer's disease]]
* [[Multiple sclerosis]]

==Drugs==
Most drugs are unable to cross the BBB, which restricts treatment for certain conditions. Drugs that can cross the barrier need to be small and lipid soluble.<ref name=":2" />

==See also ==
*[[Blood]]
*[[Neurology of ME/CFS]]
*[[Neuroinflammation]]
*[[Brain]]
==Notable Research==
*[https://www.nature.com/articles/s41593-024-01576-9 Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment]<ref name=":0">{{Cite journal|title=Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment|date=2024-02-22|url=https://www.nature.com/articles/s41593-024-01576-9|journal=Nature Neuroscience|pages=1–12|last=Greene|first=Chris|last2=Connolly|first2=Ruairi|last3=Brennan|first3=Declan|last4=Laffan|first4=Aoife|last5=O’Keeffe|first5=Eoin|last6=Zaporojan|first6=Lilia|last7=O’Callaghan|first7=Jeffrey|last8=Thomson|first8=Bennett|last9=Connolly|first9=Emma|last10=Argue|first10=Ruth|last11=Martin-Loeches|first11=Ignacio|language=en|doi=10.1038/s41593-024-01576-9|issn=1546-1726}}</ref>

==Learn more ==

* [https://www.theguardian.com/society/2024/feb/22/long-covid-brain-fog-may-be-due-to-leaky-blood-brain-barrier-study?trk=public_post_comment-text Long Covid 'brain fog' may be due to leaky blood-brain barrier, study finds] The Guardian Feb 22, 2024

==References ==
{{Reflist}}

[[Category:Neurology]]
[[Category:Anatomy]]

Long COVID

2025-04-08T17:58:39Z

Galimatias:Updated post-COVID prevalence info with 2025 findings

[[File:Long-COVID.jpg|alt=Long COVID logo with Coronavirus icon |thumb]]
'''Long COVID''', '''long tail covid''', '''Post-Acute Sequelae of COVID-19''' '''(PASC)''', '''post-acute COVID-19''' and '''ongoing COVID''' are terms used to describe a group of long term health problems that are found in a significant minority of people who developed [[COVID-19]] and remain ill a number of weeks or months later.<ref name="Navabi2020">{{Cite journal | title = Long covid: How to define it and how to manage it|last = Nabavi|first = Nikki|url=https://www.bmj.com/content/370/bmj.m3489 | date = Sep 7, 2020|journal=The BMJ|volume=370|pages=bmj.m3489}}</ref><ref name="BMJ11Aug2020" /><ref name="long-haulers-redefining">{{Cite news | url=https://www.theatlantic.com/health/archive/2020/08/long-haulers-covid-19-recognition-support-groups-symptoms/615382/ | title = Long-Haulers Are Redefining COVID-19|last = Yong|first = Ed | date = Aug 19, 2020|work=The Atlantic|access-date=2020-08-21|archive-url=|archive-date=|url-status=|issn=1072-7825|quote=}}</ref><ref name="NIHR.ac.uk15Oct2020">{{Cite web|url=https://www.nihr.ac.uk/news/living-with-covid-nihr-publishes-dynamic-themed-review-into-ongoing-covid/25891 | title = Living with COVID: NIHR publishes dynamic themed review into ‘ongoing COVID’|last = National Institute for Health Research|first = | authorlink = | date = | website = [[National Institute for Health Research]] |archive-url=|archive-date=|url-status=|access-date=2020-10-15}}</ref>

The name '''Long COVID''' was coined by patient [[Elisa Perego]] in May 2020,<ref name="BMJ1Oct2020" /> and in February 2021 the [[Centers for Disease Control|CDC]] introduced the alternative name '''Post-Acute Sequelae of COVID-19''' (PASC).<ref name="PASC-blog">{{Cite web|url=https://directorsblog.nih.gov/tag/post-acute-sequelae-of-covid-19| title =
Trying to Make Sense of Long COVID Syndrome
| date = Jan 19, 2021|first = Francis|last = Collins | authorlink = Francis Collins |access-date = Mar 1, 2021}}</ref>

In February 2020, the [[World Health Organization]] stated that the expected recovery time from [[COVID-19]] was 2 weeks for mild cases, and between three and six weeks for severe cases;<ref name="WHOFeb2020">{{Cite web|url=https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---24-february-2020 | title = WHO Director-General's opening remarks at the media briefing on COVID-19|last = World Health Organization | first = | authorlink = World Health Organization | date = Feb 24, 2020 | website = [[World Health Organization]]|language=en|archive-url=|archive-date=|url-status=|access-date=2020-09-24}}</ref> follow-up studies then identified a significant number of COVID-19 patients had remained ill much longer than this: those with long COVID.<ref name="Navabi2020" /><ref name="BMJ11Aug2020" />

A similar phenomenon to long COVID occurred after the 2003 outbreak of the similar SARS coronavirus, which lead to a [[Severe acute respiratory syndrome#post-SARS|post-SARS syndrome]] being proposed that included chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep. Another study found a subgroup SARS survivors developed [[chronic fatigue syndrome]] immediately after SARS.<ref name="Moldofsky2011">{{Cite journal | last = Moldofsky|first = Harvey | last2 = Patcai | first2 = John | date = 2011-03-24 | title = Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study|url=https://doi.org/10.1186/1471-2377-11-37|journal=BMC Neurology|volume=11|issue=1 | pages = 37|doi=10.1186/1471-2377-11-37|issn=1471-2377|pmc = 3071317|pmid=21435231}}</ref>
<ref name="Lam2009">{{Cite journal|last = Lam|first = Marco Ho-Bun | last2 = Wing | first2 = Yun-Kwok | last3 = Yu | first3 = Mandy Wai-Man | last4 = Leung | first4 = Chi-Ming | last5 = Ma | first5 = Ronald C.W. | last6 = Kong | first6 = Alice P.S. | last7 = So | first7 = W.Y. | last8 = Fong | first8 = Samson Yat-Yuk | last9 = Lam | first9 = Siu-Ping | date = 2009-12-14 | title = Mental Morbidities and Chronic Fatigue in Severe Acute Respiratory Syndrome Survivors: Long-term Follow-up | url = https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/415378|journal=Archives of Internal Medicine|language=en|volume=169|issue=22|pages=2142–2147|doi=10.1001/archinternmed.2009.384|issn=0003-9926}}</ref>

==Long-haulers==
A "long-hauler" is someone with long COVID, meaning someone who became ill with confirmed or suspected [[COVID-19]], who has remained ill with long-term symptoms many weeks or months later after first becoming ill.<ref name="long-haulers-redefining" /><ref name="BMJ1Oct2020">{{Cite web|url=https://blogs.bmj.com/bmj/2020/10/01/why-we-need-to-keep-using-the-patient-made-term-long-covid/ | title = Why we need to keep using the patient made term “Long Covid” | date = 2020-10-01 | last = Perego|first =Elisa | authorlink = Elisa Perego | last2 =Callard | first2 = Felicity | authorlink2 = Felicity Callard | last3 = Stras | first3 = Laurie | authorlink3 = Laurie Stras | last4 = Melville-Jóhannesson | first4 = Barbara | authorlink4 = Barbara Melville-Jóhannesson | last5 = Pope | first5 = Rachel | authorlink5 = Rachel Pope | last6 = Alwan | first6 =
Nisreen A | authorlink6 = Nisreen Alwan|website=The BMJ|language=en-US|access-date=2020-10-11}}</ref>

==What is long COVID==
[[File:Long-COVID-1in10.jpg|alt=Long COVID poster - 1 in 10 people with COVID-19 may develop long COVID|thumb]]
Long COVID appears to be a multisystem disease, and may occur after any severity of COVID-19, including after relatively mild cases.<ref name="BMJ11Aug2020" /><ref name="BMJ1Oct2020" />

=== Signs and symptoms ===
Patient surveys have reported that the following symptoms commonly occur in long COVID.
*[[Fatigue]], which may be extreme (profound)
*[[myalgia|Muscle pain]] or body aches
*[[dyspnea|Breathlessness]]
*[[Concentration problems]]
*Inability to [[exercise]]/[[exercise intolerance]]
*[[Headache]]
*[[Insomnia]] or [[sleep dysfunction|problems sleeping]]
*Heavy chest, a feeling of pressure on the chest, or chest pain
Other reported symptoms include:
*[[Anxiety]]
*[[Paresis|Muscle weakness]]
*[[Memory problems]]
*[[Skin rash]]
*[[Sore throat]] and [[dysphagia|difficulty swallowing]]
*[[Heart palpitation]]s
*[[Fever]]
*[[Diarrhea]]
*[[Dizziness]]
*The sensation of [[pins and needles]]
*[[Cough]]
*[[Low-grade fever]]
*[[Dysgeusia|Loss of sense of taste]] and [[anosmia|loss of sense of smell]]
*[[Joint pain]]
*[[new allergies and intolerances|New onset allergies]], which may lead to [[anaphylaxis|anaphylactic shock]] in some cases<ref name="Davis2021a" />
*New onset [[diabetes]]<ref name="Rubino2020">{{Cite journal|last = Rubino|first = Francesco | last2 = Amiel | first2 = Stephanie A. | last3 = Zimmet | first3 = Paul | last4 = Alberti | first4 = George | last5 = Bornstein | first5 = Stefan | last6 = Eckel | first6 = Robert H. | last7 = Mingrone | first7 = Geltrude | last8 = Boehm | first8 = Bernhard | last9 = Cooper | first9 = Mark E. | date = 2020-08-20 | title = New-Onset Diabetes in Covid-19|url=https://doi.org/10.1056/NEJMc2018688|journal=New England Journal of Medicine|volume=383|issue=8 | pages = 789–790|doi=10.1056/NEJMc2018688|issn=0028-4793|pmc = 7304415|pmid=32530585}}</ref>
*New onset [[Hypertension|high blood pressure]]<ref name="Navabi2020" /><ref name="Lambert25Jul2020" /><ref name="NHSlongSep2020">{{Cite web|url=https://www.gov.uk/government/publications/covid-19-long-term-health-effects/covid-19-long-term-health-effects | title = COVID-19 Long Term Health Effects|last = National Health Service | first = | authorlink = National Health Service | date = Sep 7, 2020 | website = |archive-url=|archive-date=|url-status=|access-date=}}</ref><ref name="Yellin2020" />
*New [[Menstrual problems in ME/CFS|menstrual problems]]<ref name="Davis2021" />

{{Quote box|“A very common feature is the relapsing, remitting nature of the illness, where you feel as though you’ve recovered, then it hits you back|source=Dr. Nisreen Alwan, BMJ, Sep 2020}}

===World Health Organization Long COVID diagnostic criteria ===
Post COVID-19 condition ("Long COVID") definition
*history of probable or confirmed SARS-CoV-2 infection
*symptom(s) last 2 months from the start of COVID-19 (or 3 months for asymptomatic COVID-19)
*symptom(s) can't be explained by an alternative diagnosis
*no minimum number of symptoms
*symptom(s) generally affect day to day functioning
*new onset of symptoms - symptoms begin after recovery from COVID-19 or begin at the start of COVID-19 and persist
*symptoms can fluctuate or improve then relapse over time

Common symptoms:
*[[fatigue]]
*[[shortness of breath]]
*[[cognitive dysfunction]] but there are others
Other symptoms:
*[[abdominal pain]], [[menstrual and period problems]], [[parosmia|altered smell]]/[[dysgeusia|taste]], [[anxiety]] , [[blurred vision]], [[chest pain]], [[cognitive dysfunction]] (e.g. brain fog), [[cough]], [[depression]], [[dizziness]], [[fatigue]], intermittent [[fever]], gastrointestinal issues ([[diarrhoea]], [[constipation]], [[acid reflux]]), [[headache]], [[memory problems|memory issues]], [[arthralgia|joint pain]], [[myalgia|muscle pain]], [[muscle spasm]]s, [[nerve pain|neuralgias]] (nerve pain), [[new allergies and intolerances|new onset allergies]], [[paresthesia|pins and needles sensations]], [[post-exertional malaise]], [[dyspnea|shortness of breath]], [[:category:sleep disorders|sleep disorder]]s, [[heart palpitations|tachycardia/palpitations]], [[tinnitus|tinnitus and other hearing issues]]
 Notes:
*Children - separate criteria may be needed
*Clusters - clusters of 2 or more related symptoms may occur together<ref name="WHO-longcovid-criteria" />

{{See also|World Health Organization Long COVID diagnostic criteria}}

=== Four different syndromes ===
A recent review suggested that long COVID may actually be four differing syndromes:
* [[Post-COVID-19 illness#pics|Post-Intensive Care Syndrome]]
* [[Postviral fatigue syndrome|Postviral Fatigue Syndrome]] (ME/CFS)
* [[Post-Acute Sequelae of COVID-19|Long Term COVID Syndrome]]
* Permanent organ damage
Patients with long COVID may have several syndromes at once.<ref name="NIHR15Oct2020" />

== COVID-19 testing ==
While some people with long COVID did have a positive test result for COVID-19, others were denied tests due to the limited availability of tests at the time, or they tested negative but were found to have clear evidence of COVID-19 from blood count tests or chest X-rays.<ref name="NIHR15Oct2020">{{Cite web|url=https://evidence.nihr.ac.uk/themedreview/living-with-covid19 | title = Living with covid-19. A dynamic review of the evidence around ongoing covid-19 symptoms (often called long covid). | last = NIHR|first = | authorlink = | date = October 2020 | website = evidence.nihr.ac.uk|language=en-GB|archive-url=|archive-date=|url-status=|access-date=2020-10-15}}</ref><ref name="Kingstone2020" /> Some people with Long COVID have described never having a cough or fever at the start of their illness, but developed these symptoms later. Long COVID diagnosis does not depend on a previous positive test.<ref name="NIHR15Oct2020" /><ref name="Kingstone2020" />

==Clinical findings ==

There is no blood test or diagnostic biomarker to identify patients with long COVID. A study of UK patients by Dennis et al (2020) found that just over 10% of long COVID patients had abnormal findings on the standard tests and did not find an association between standard test results and degree of organ damage or long COVID severity.<ref name="Dennis2020" /> The same study used MRI scans combined with patient questionnaires to assess organ damage, finding that multi-organ impairment was common in people with long COVID, despite the fact that 80% had not been hospitalized for [[COVID-19]], the average patient age was forty-four years old, and rates of pre-existing conditions were also low.<ref name="Dennis2020" />

==Research findings ==
{{Main article|page_name=Long COVID pathophysiology}}

Surveys of data collected and published by long haulers using social media were the first evidence of what symptoms and health problems were caused by long COVID.<ref name="bodypoliticMay2020" /> Later academic studies confirmed many of the initial long hauler survey findings, although many only involved patients discharged from hospital,<ref name="Puntmann2020" /> patients who had been able to access early testing and tested positive, or patients who had sought medical care in a particular location.<ref name="Arnold2020b" /> People with mild COVID-19 symptoms, leaving people denied testing and those who may have had false negative test results and people who tested positive but were asymptomatic underrepresented in long COVID research.<ref name="bodypoliticMay2020" />

==Treatment==

===Pacing===
Pacing is a method of activity management which aims to adapt everday activities in order to avoid relapses or increased symptoms.
{{See also|Pacing}}

===Exercise therapy ===
ME/CFS patient groups have raised concerns about the use of [[graded exercise therapy]] (GET) in long COVID patients and a similar warning has been issued by [[NICE]] in the [[United Kingdom|UK]].<ref name="GETcovidForwardME" /> Graded exercise therapy, which is sometimes incorrectly referred to as "activity management" involves patients initially reducing their activity levels to a level that prevents regular crashes, and then typically increasing activity by 10% each week regardless of any increased symptoms or worsening illness. In graded exercise patients are told to ignore deterioration or increased symptoms and "push through" them.

====Theory and evidence ====
In graded exercise therapy patients are told that their symptoms are caused only by [[deconditioning|inactivity]] and other "bad habits" rather than an underlying illness. These assumptions have very weak evidence, and significant evidence exists of underlying illness in ME/CFS; there is a lack of research about exercise therapy for long COVID illness<ref name="Navabi2020" /> but some symptoms are inconsistent with this "deconditioning" assumption and some research has found physical abnormalities in some patients weeks or months after infection. Surveys of ME/CFS patients have consistently shown that large numbers of patients deteriorate as a result of graded exercise therapy, and a significant number become severely ill and never return to the level of functioning they had before the treatment.

==ME/CFS==
[[Myalgic Encephalomyelitis]] (ME) often has its onset immediately after a viral or bacterial infection.<ref name="ICC2011primer">{{citation|title=Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners|date=2012|url=http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf|last1=Carruthers|first1=BM|authorlink1=Bruce Carruthers|isbn=978-0-9739335-3-6|last2=van de Sande|first2=MI|authorlink2=Marjorie van de Sande|last3=De Meirleir|first3=KL|authorlink3=Kenny de Meirleir|last4=Klimas|first4=NG|authorlink4=Nancy Klimas|last5=Broderick|first5=G|authorlink5=Gordon Broderick|last6=Mitchell|first6=T|authorlink6=Terry Mitchell|last7=Staines|first7=D|authorlink7=Donald Staines|last8=Powles|first8=ACP|authorlink8=A C Peter Powles|last9=Speight|first9=N|authorlink9=Nigel Speight|last10=Vallings|first10=R|authorlink10=Rosamund Vallings|last11=Bateman|first11=L|authorlink11=Lucinda Bateman|last12=Bell|first12=DS|authorlink12=David Bell|last13=Carlo-Stella|first13=N|authorlink13=Nicoletta Carlo-Stella|last14=Chia|first14=J|authorlink14=John Chia|last15=Darragh|first15=A|authorlink15=Austin Darragh|last16=Gerken|first16=A|authorlink16=Anne Gerken|last17=Jo|first17=D|authorlink17=Daehyun Jo|last18=Lewis|first18=DP|authorlink18=Donald Lewis|last19=Light|first19=AR|authorlink19=Alan Light|last20=Light|first20=KC|authorlink20=Kathleen Light|last21=Marshall-Gradisnik|first21=S|authorlink21=Sonya Marshall-Gradisnik|last22=McLaren-Howard|first22=J|authorlink22=John McLaren-Howard|last23=Mena|first23=I|authorlink23=Ismael Mena|last24=Miwa|first24=K|authorlink24=Kunihisa Miwa|last25=Murovska|first25=M|authorlink25=Modra Murovska|last26=Stevens|first26=SR|authorlink26=Staci Stevens}}</ref> In fact, one of its previous names was [[postviral fatigue syndrome]]. ME has been a sequela of over [[Epidemic myalgic encephalomyelitis|one hundred outbreaks]], in addition to sporadic infections. ME/CFS is not normally diagnosed until symptoms have persisted for six months or more, and tests must be run to exclude other possible causes of the symptoms.<ref name="SEID2015">{{Citation|last = Institute of Medicine | authorlink = Institute of Medicine | title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|location=Washington, DC|publisher=The National Academies Press | date = 2015 | url=https://www.ncbi.nlm.nih.gov/books/NBK284902/}}</ref> Some contagious diseases including [[Epstein-Barr virus]], certain [[enterovirus]]es,<ref name="ICC2011primer" /> and the [[Severe acute respiratory syndrome|SARS]] coronavirus,<ref name="Moldofsky2011" /> have caused outbreaks of ME/CFS.

The 2025 Recover-Adult Study followed 11,785 adults who'd had a SARS-COV-2 infection and 1,439 uninfected adults. The study found a SARS-COV-2 infection is particularly likely to trigger ME/CFS symptoms:<ref name=":0">{{Cite journal|title=Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis: A Report from the Observational RECOVER-Adult Study|date=2025-4|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968624/|journal=Journal of General Internal Medicine|volume=40|issue=5|pages=1085–1094|last=Vernon|first=Suzanne D.|last2=Zheng|first2=Tianyu|last3=Do|first3=Hyungrok|last4=Marconi|first4=Vincent C.|last5=Jason|first5=Leonard A.|last6=Singer|first6=Nora G.|last7=Natelson|first7=Benjamin H.|last8=Sherif|first8=Zaki A.|last9=Bonilla|first9=Hector Fabio|last10=Taylor|first10=Emily|last11=Mullington|first11=Janet M.|doi=10.1007/s11606-024-09290-9|pmid=39804551|issn=0884-8734}}</ref>

* 4.5% of infected adults fully met Institute of Medicine (IOM) clinical diagnostic criteria for ME/CFS.
** 0.6% of uninfected adults fully met IOM criteria.
* 39.8% of infected adults had at least one ME/CFS symptom but didn't meet the full IOM criteria.
** 16.1% of uninfected adults partially met IOM criteria.

[[Post-exertional malaise]] was the most common ME/CFS symptom after COVID infection. Nearly 90% of people with post-infection ME/CFS also met the criteria for long COVID.<ref name=":0" />

According to [[Infectious disease|infectious diseases]] and [[Immune system|immunology]] researcher, [[Sonya Marshall-Gradisnik]], there appeared to be a correlation between the illnesses.<blockquote>"The symptom overlap between [[ME/CFS]] and long-COVID is quite astounding," Professor Marshall-Gradisnik said.Those symptoms can be [[fatigue]], they have [[pain]], [[joint pain]], [[Sleep dysfunction|sleep disturbances]], [[headaches]], they have [[Cardiac dysfunctions|cardiac]] changes. Notably, they've got [[brain fog]] and [[Cognitive dysfunction|cognitive]] issues with [[Memory problems|memory]], [and] [[Word-finding problems|word choice]] becomes a problem."<ref>{{Cite news | url=https://www.abc.net.au/news/2022-03-18/long-covid-and-chronic-fatigue-links/100916990 | title = 'Symptom overlap is quite astounding': Researchers probe links between long-COVID and chronic fatigue | date = 2022-03-17|work=ABC News|access-date=2022-06-09|language=en-AU}}</ref></blockquote>

==Patient surveys ==
'''Not peer reviewed'''
* May 2020, [https://patientresearchcovid19.com/research/report-1/ What Does COVID-19 Recovery Actually Look Like? An Analysis of the Prolonged COVID-19 Symptoms Survey by Patient-Led Research Team]<ref name="bodypoliticMay2020">{{Cite web|url=https://docs.google.com/document/u/0/d/1KmLkOArlJem-PArnBMbSp-S_E3OozD47UzvRG4qM5Yk/mobilebasic | title = What Does COVID-19 Recovery Actually Look Like? An Analysis of the Prolonged COVID-19 Symptoms Survey by Patient-Led Research Team | date = May 11, 2020|vauthors=Assaf G, Davis H, McCorkell L, Wei H, O'Neil B, Akrami A, Low R, Mercier J, A A, L T, C A, S M, N L, H N, D JD, S}}</ref> - by [[Body Politic|Body Politic and Patient Led Research Collaborative]]
::Data collected: Apr 21 - May 2 2020. Respondents: 640

* Jul 2020, [https://static1.squarespace.com/static/5e8b5f63562c031c16e36a93/t/5f459ef7798e8b6037fa6c57/1598398215120/2020+Survivor+Corps+COVID-19+%27Long+Hauler%27+Symptoms+Survey+Report+%28revised+July+25.4%29.pdf COVID-19 “Long Hauler” Symptoms Survey Report]<ref name="Lambert25Jul2020">{{Cite web|url=https://static1.squarespace.com/static/5e8b5f63562c031c16e36a93/t/5f459ef7798e8b6037fa6c57/1598398215120/2020+Survivor+Corps+COVID-19+%27Long+Hauler%27+Symptoms+Survey+Report+%28revised+July+25.4%29.pdf | title=COVID-19 “Long Hauler” Symptoms Survey Report|last = Lambert | first = Natalie J | author-link = Natalie Lambert | last2 = Survivor Corps | authorlink2 = Survivor Corps|publisher=Indiana University School of Medicine | date = Jul 2020}}</ref> - with Survivor Corps
::Data collected: Jul 25, 2020. Respondents: 1,567+
::
:* Dec 2020, [https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2 Charactering Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact] - by [https://patientresearchcovid19.com/ Body Politic and Patient Led Research Collaborative]
:** Respondents: 3,762+

==Notable studies==
*Jul 24, 2020, Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)<ref name="Puntmann2020">{{Cite journal | last = Puntmann | first = Valentina O. | last2 = Carerj | first2 = M. Ludovica | last3 = Wieters | first3 = Imke | last4 = Fahim | first4 = Masia | last5 = Arendt | first5 = Christophe | last6 = Hoffmann | first6 = Jedrzej | last7 = Shchendrygina | first7 = Anastasia | last8 = Escher | first8 = Felicitas | last9 = Vasa-Nicotera | first9 = Mariuca | date = 2020-07-27 | title = Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)|url=https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916|journal=JAMA Cardiology|language=en|doi=10.1001/jamacardio.2020.3557|issn=2380-6583}}</ref> - [https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916 (Full text)]
*Aug 11, 2020, Management of post-acute covid-19 in primary care<ref name="BMJ11Aug2020">{{cite journal | title = Management of post-acute covid-19 in primary care|last = Greenhalgh|first = Trisha | authorlink = Trisha Greenhalgh | first2 = Matthew | last2 = Knight | authorlink2 = Matthew Knight | authorlink3 = Christine A'Court | first3 = Christine | last3 = A'Court | first4 = Maria | last4 = Buxton | first5 = Laiba | last5 = Husain|journal=The BMJ | date = Aug 11, 2020|volume=370|doi=10.1136/bmj.m3026|pages=m3026 | url = https://doi.org/10.1136/bmj.m3026}}</ref> - [https://doi.org/10.1136/bmj.m3026 (Full text)]
*Aug 20, 2020, New-Onset Diabetes in Covid-19<ref name="Rubino2020" /> - [https://www.nejm.org/doi/full/10.1056/NEJMc2018688 (Full text)]
*Oct 1, 2020, Long-term consequences of COVID-19: research needs<ref name="Yellin2020">{{Cite journal|last = Yelin | first = Dana | last2 = Wirtheim | first2 = Eytan | last3 = Vetter | first3 = Pauline | last4 = Kalil | first4 = Andre C. | last5 = Bruchfeld | first5 = Judith | last6 = Runold | first6 = Michael | last7 = Guaraldi | first7 = Giovanni | last8 = Mussini | first8 = Cristina | last9 = Gudiol | first9 = Carlota | date = 2020-10-01 | title = Long-term consequences of COVID-19: research needs|url=https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30701-5/abstract|journal=The Lancet Infectious Diseases|language=English|volume=20|issue=10|pages=1115–1117|doi=10.1016/S1473-3099(20)30701-5|issn=1473-3099|pmid=32888409}}</ref> - [https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30701-5/fulltext (Full text)]
*Oct 14, 2020, Finding the 'right' GP: a qualitative study of the experiences of people with long-COVID<ref name="Kingstone2020">{{Cite journal | last = Kingstone | first = Tom | authorlink = | last2 = Taylor | first2 = Anna K. | authorlink2 = | last3 = O'Donnell | first3 = Catherine A. | authorlink3 = | last4 = Atherton | first4 = Helen | authorlink4 = | last5 = Blane | first5 = David N. | authorlink5 = | last6 = Chew-Graham | first6 = Carolyn A. | authorlink6 = Carolyn Chew-Graham | date = 2020-10-14 | title = Finding the 'right' GP: a qualitative study of the experiences of people with long-COVID|url=https://bjgpopen.org/content/early/2020/10/12/bjgpopen20X101143|journal=BJGP Open|language=en|volume=|issue=|pages=|doi=10.3399/bjgpopen20X101143|issn=2398-3795|pmc=|pmid=33051223|access-date=|quote=|via=}}</ref> - [https://bjgpopen.org/content/bjgpoa/early/2020/10/12/bjgpopen20X101143.full.pdf (Full text)]
*Oct 16, 2020, Multi-organ impairment in low-risk individuals with long COVID<ref name="Dennis2020">{{Cite journal|last = Dennis | first = Andrea | authorlink = | last2 = Wamil | first2 = Malgorzata | authorlink2 = | last3 = Kapur | first3 = Sandeep | authorlink3 = | last4 = Alberts | first4 = Johann | authorlink4 = | last5 = Badley | first5 = Andrew D. | authorlink5 = | last6 = Decker | first6 = Gustav Anton | authorlink6 = | last7 = Rizza | first7 = Stacey A. | last8 = Banerjee | first8 = Rajarshi | last9 = Banerjee | first9 = Amitava | authorlink9 = Amitava Banerjee | date = 2020-10-16 | title = Multi-organ impairment in low-risk individuals with long COVID|url=https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1|journal=medRxiv|language=en|volume=|issue=|pages=2020.10.14.20212555|doi=10.1101/2020.10.14.20212555|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1101/2020.10.14.20212555 (Full text)]
*Oct 21, 2020, Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App<ref name="Sudre2020a">{{Cite journal|last = Sudre | first = Carole H. | authorlink = | last2 = Murray | first2 = Benjamin | authorlink2 = | last3 = Varsavsky | first3 = Thomas | authorlink3 = | last4 = Graham | first4 = Mark S. | authorlink4 = | last5 = Penfold | first5 = Rose S. | authorlink5 = | last6 = Bowyer | first6 = Ruth C. | authorlink6 = | last7 = Pujol | first7 = Joan Capdevila | last8 = Klaser | first8 = Kerstin | last9 = Antonelli | first9 = Michela | date = 2020-10-19|others= | title = Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App | url = https://www.medrxiv.org/content/10.1101/2020.10.19.20214494v1|journal=medRxiv|language=en|volume=|issue=|pages=2020.10.19.20214494|doi=10.1101/2020.10.19.20214494|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.medrxiv.org/content/10.1101/2020.10.19.20214494v1.full-text (Full text)]
*Dec 2020 (pre-print) / Jul 15, 2021, Characterizing long COVID in an international cohort: 7 months of symptoms and their impact<ref name="Davis2021a">{{Cite journal|last = Davis | first = Hannah E. | authorlink = Hannah Davis | last2 = Assaf | first2 = Gina S. | last3 = McCorkell | first3 = Lisa | last4 = Wei | first4 = Hannah | last5 = Low | first5 = Ryan J. | last6 = Re'em | first6 = Yochai | last7 = Redfield | first7 = Signe | last8 = Austin | first8 = Jared P. | last9 = Akrami | first9 = Athena | date = 2021-07-15 | title = Characterizing long COVID in an international cohort: 7 months of symptoms and their impact|url=https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00299-6/abstract|journal=EClinicalMedicine|language=English|volume=38|issue=|pages=101019|doi=10.1016/j.eclinm.2021.101019|pmc=PMC8280690|pmid=34308300|issn=2589-5370}}</ref> - [https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00299-6/abstract (Abstract)]
*Dec 2020, Long COVID-19: Challenges in the diagnosis and proposed diagnostic criteria<ref name="PMC7737559">{{Cite journal|last = Raveendran | first = A.V. | date = 2021 | title=Long COVID-19: Challenges in the diagnosis and proposed diagnostic criteria|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737559/|journal=Diabetes & Metabolic Syndrome|volume=15|issue=1|pages=145–146|doi=10.1016/j.dsx.2020.12.025|issn=1871-4021|pmc=7737559|pmid=33341598}}</ref> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737559/ (Full text)]
*Dec 20, 2020, Patient outcomes after hospitalisation with COVID-19 and implications for follow-up; results from a prospective UK cohort<ref name="Arnold2020b">{{Cite journal | last = Arnold | first = David T. | authorlink = David Arnold | last2 = Hamilton | first2 = Fergus W. | last3 = Milne | first3 = Alice | last4 = Morley | first4 = Anna J. | last5 = Viner | first5 = Jason | last6 = Attwood | first6 = Marie | last7 = Noel | first7 = Alan | last8 = Gunning | first8 = Samuel | last9 = Hatrick | first9 = Jessica | date = 2021-04-01 | title = Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort|url=https://thorax.bmj.com/content/76/4/399|journal=Thorax|language=en|volume=76|issue=4 | pages = 399–401|doi=10.1136/thoraxjnl-2020-216086|issn=0040-6376|pmid=33273026}}</ref> - [https://thorax.bmj.com/content/76/4/399 (Full text)] - from the DISCOVER project
*Jan 18, 2021, Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Komaroff2021a">{{Cite journal | last = Komaroff|first = Anthony L. | authorlink = Anthony Komaroff | last2 = Bateman | first2 = Lucinda | authorlink2 = Lucinda Bateman | date = 2021 | title=Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?|url=https://www.frontiersin.org/articles/10.3389/fmed.2020.606824/full?s=03|journal=Frontiers in Medicine|language=English|volume=|issue=|pages=|doi=10.3389/fmed.2020.606824|issn=2296-858X|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fmed.2020.606824/full?s=03 (Full text)]
*Mar 27, 2021, COVID-19 Survivors’ Reports of the Timing, Duration, and Health Impacts of Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection<ref name="Lambert2021a">{{Cite journal|last = Lambert | first = Natalie | authorlink = Natalie Lambert | last2 = Corps | first2 = Survivor | authorlink2 = Survivor Corps | last3 = El-Azab | first3 = Sarah A. | authorlink3 = | last4 = Ramrakhiani | first4 = Nathan S. | authorlink4 = | last5 = Barisano | first5 = Anthony | authorlink5 = | last6 = Yu | first6 = Lu | authorlink6 = | last7 = Taylor | first7 = Kaitlyn | last8 = Esperanca | first8 = Alvaro | last9 = Downs | first9 = Charles A. | date = 2021-03-27 | title = COVID-19 Survivors’ Reports of the Timing, Duration, and Health Impacts of Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection | url = https://www.medrxiv.org/content/10.1101/2021.03.22.21254026v2|journal=medRxiv|language=en|volume=|issue=|pages=2021.03.22.21254026|doi=10.1101/2021.03.22.21254026|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1101/2021.03.22.21254026 (Full text)]
*May 11, 2021, Mayo Clinic Proceedings: Post COVID-19 Syndrome (Long Haul Syndrome): Description of a Multidisciplinary Clinic at the Mayo Clinic and Characteristics of the Initial Patient Cohort<ref name="mayo2021a">{{Cite journal | last = Vanichkachorn | first = Greg | last2 = Newcomb | first2 = Richard | last3 = Cowl | first3 = Clayton T. | last4 = Murad | first4 = M. Hassan | last5 = Breeher | first5 = Laura | last6 = Miller | first6 = Sara | last7 = Trenary | first7 = Michael | last8 = Neveau | first8 = Daniel | last9 = Higgins | first9 = Steven | date = 2021-07-01 | title = Post–COVID-19 Syndrome (Long Haul Syndrome): Description of a Multidisciplinary Clinic at Mayo Clinic and Characteristics of the Initial Patient Cohort|url=https://www.mayoclinicproceedings.org/article/S0025-6196(21)00356-6/abstract|journal=Mayo Clinic Proceedings|language=English|volume=96|issue=7|pages=1782–1791|doi=10.1016/j.mayocp.2021.04.024|issn=0025-6196|pmid=34218857}}</ref> - [https://www.mayoclinicproceedings.org/article/S0025-6196(21)00356-6/abstract (Abstract)]
*Jun 7, 2021, Insights from ME/CFS May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome<ref name="Komaroff2021b">{{Cite journal | last = Komaroff|first = Anthony L. | authorlink = Anthony Komaroff | last2 = Lipkin | first2 = W. Ian | authorlink2 = Ian Lipkin | date = 2021-06-07 | title = Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome|url=https://www.cell.com/trends/molecular-medicine/abstract/S1471-4914(21)00134-9|journal=Trends in Molecular Medicine|language=English|volume=|issue=|pages=|doi=10.1016/j.molmed.2021.06.002|issn=1471-4914|pmc=|pmid=34175230|access-date=|quote=|via=}}</ref> - [https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00134-9 (Full text)]
*Jun 23, 2021, Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms<ref name="Proal2021">{{Cite journal | last = Proal|first = Amy D. | authorlink = Amy Proal | last2 = VanElzakker | first2 = Michael B. | authorlink2 = Michael VanElzakker | date = 2021 | title=Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms|url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full|journal=Frontiers in Microbiology|language=English|volume=|issue=|pages=|doi=10.3389/fmicb.2021.698169|issn=1664-302X|pmc=8260991|pmid=34248921|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1101/2020.12.24.20248802 (Full text)]
*Oct 2021, A clinical case definition of post COVID-19 condition by a Delphi consensus<ref name="WHO-longcovid-criteria">{{citation | title = A clinical case definition of post COVID-19 condition by a Delphi consensus
| date =Oct 6, 2021 |publisher=[[World Health Organization]] | others = World Health Organization (WHO) clinical case definition working group on post COVID-19 condition | first1 = Joan B. | last1 = Soriano | first2 = Maya | last2 = Allan | first3 = Carine | last3 = Alsokhn | first4 = Nisreen A. | last4 = Alwan | authorlink4 = Nisreen Alwan | first5 = Lisa | last5 = Askie | first6 = Hannah E. | last6 = Davis | authorlink6 = Hannah Davis | first7 = Janet V. | last7 = Diaz | first8 = Tarun | last8 = Dua | first9 = Wouter | last9 = de Groote | first10 = Robert | last10 = Jakob | first11 = Marta | last11 = Lado | first12 = John | last12 = Marshall | first13 = Srin | last13 = Murthy | first14 = Jacobus | last14 = Preller | first15 = Pryanka | last15 = Relan | first16 = Nicoline | last16 = Schiess | first17 = Archana | last17 = Seahwag | ref = WHO reference number: WHO/2019-nCoV/Post_COVID-19_condition/Clinical_case_definition/2021.1 | url = https://www.who.int/publications-detail-redirect/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1}}</ref> [https://www.who.int/publications-detail-redirect/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1 (Full text)]
* Feb 2024, [https://www.nature.com/articles/s41593-024-01576-9 Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment]<ref>{{Cite journal|title=Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment|date=2024-02-22|url=https://www.nature.com/articles/s41593-024-01576-9|journal=Nature Neuroscience|pages=1–12|last=Greene|first=Chris|last2=Connolly|first2=Ruairi|last3=Brennan|first3=Declan|last4=Laffan|first4=Aoife|last5=O’Keeffe|first5=Eoin|last6=Zaporojan|first6=Lilia|last7=O’Callaghan|first7=Jeffrey|last8=Thomson|first8=Bennett|last9=Connolly|first9=Emma|last10=Argue|first10=Ruth|last11=Martin-Loeches|first11=Ignacio|language=en|doi=10.1038/s41593-024-01576-9|issn=1546-1726}}</ref>
::Report including the [[World Health Organization Long COVID diagnostic criteria]]

==Articles and editorials ==
*Jun 15, 2021, White Paper: A Detailed Study of Patients with Long-Haul COVID<ref name="Fairthealth2021">{{Cite web|url=https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/A%20Detailed%20Study%20of%20Patients%20with%20Long-Haul%20COVID--An%20Analysis%20of%20Private%20Healthcare%20Claims--A%20FAIR%20Health%20White%20Paper.pdf | publisher=FAIR Health | date = Jun 18, 2020 | title = A Detailed Study of Patients with Long-Haul COVID: An Analysis of Private Healthcare Claims. A FAIR Health White Paper}}</ref> [https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/A%20Detailed%20Study%20of%20Patients%20with%20Long-Haul%20COVID--An%20Analysis%20of%20Private%20Healthcare%20Claims--A%20FAIR%20Health%20White%20Paper.pdf (Full text)]
*Jun 24, 2021, Covid-19: Third of people infected have long term symptoms<ref name="ODowd2021">{{Cite journal|last = O'Dowd | first = Adrian | date = 2021-06-24 | title = Covid-19: Third of people infected have long term symptoms|url=https://www.bmj.com/content/373/bmj.n1626|journal=BMJ|language=en|volume=373|pages=n1626|doi=10.1136/bmj.n1626|issn=1756-1833|pmid=34168002}}</ref> [https://www.bmj.com/content/373/bmj.n1626 (Editorial)]

==Presentations, interviews and videos==
*Aug 2020, [https://solvecfs.org/wp-content/uploads/2020/08/Post-COVID%20ME-to%20Solve.pdf Will Covid-19 lead to ME/CFS in some people?] - presentation - Dr [[Anthony Komaroff]]
*Jul 2020, [https://www.youtube.com/watch?v=IIeOoS_A4c8 Message in a Bottle] video - [[LongCovidSOS]]
*Jun 2020, [https://www.biomax.com/lib/press-releases/Initial-Result-Announcment_English.pdf Health of Corona Patients at Home in Alarmingly Poor Health Even After Several Months - Dutch Lung Foundation] - Press release (English translation) - [https://www.ad.nl/binnenland/longfonds-gezondheid-thuiszittende-coronapatienten-schrikbarend-slecht~a45346fe/ Dutch]

==Letters and blogs==
*May 2020, [http://somatosphere.net/2020/mild-covid.html/ Very, very mild: Covid-19 symptoms and illness classification] - [[Felicity Callard]]
*Jul 2020, [https://meassociation.org.uk/wp-content/uploads/ForwardME-Letter-re-Covid-19-Management-and-Exercise-Caution-27.08.20.pdf Letter re Covid-19 Management and Exercise Caution]<ref name="GETcovidForwardME">{{Cite web|url=https://meassociation.org.uk/wp-content/uploads/ForwardME-Letter-re-Covid-19-Management-and-Exercise-Caution-27.08.20.pdf | date = 2020-08-27 | last = Forward-ME | authorlink = Forward-ME| title = Letter re Covid-19 Management and Exercise Caution}}</ref> - [[Forward-ME]]
*Sep 2020, [https://mecfsresearchreview.me/2020/09/17/understanding-long-covid-a-shortcut-to-solving-me-cfs/?#symptoms Understanding Long Covid, A Shortcut to Solving ME/CFS?] - [[Simon McGrath]]
*Sep 2020, [https://wellcomeopenresearch.org/articles/5-224 Why the Patient-Made Term 'Long Covid' is needed] - Open Letter
*Oct 2020, [https://blogs.bmj.com/bmj/2020/10/01/why-we-need-to-keep-using-the-patient-made-term-long-covid/ Why we need to keep using the patient made term “Long Covid”] - [[The BMJ]]
*Jan 2021, [https://directorsblog.nih.gov/tag/post-acute-sequelae-of-covid-19/ Trying to Make Sense of Long COVID Syndrome] - Dr. Francis Collins, CDC director

==National and international health bodies==
*[https://doi.org/10.1136/bmj.m2912 NICE cautions against using graded exercise therapy for patients recovering from COVID-19]<ref name="NICEcautionBMJ">{{Cite journal | last = Torjesen | first = Ingrid | date = 2020-07-21 | title = NICE cautions against using graded exercise therapy for patients recovering from covid-19|url=https://www.bmj.com/content/370/bmj.m2912|journal=The BMJ|language=en|volume=370|doi=10.1136/bmj.m2912|issn=1756-1833|pmid=32694164}}</ref>

==News articles ==
* Feb 2024, [https://www.nature.com/articles/s41593-024-01576-9 Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment]
* Oct 2020, [https://www.theguardian.com/world/2020/oct/21/women-aged-50-60-at-greatest-risk-of-long-covid-experts-suggest Women aged 50-60 at greatest risk of ‘long Covid’, experts suggest] - The Guardian

* Oct 2020, [https://www.wsj.com/articles/these-doctors-have-long-term-covid-now-theyre-pushing-for-better-care-11603144474 These Doctors Have Long-Term Covid. Now They’re Pushing for Better Care.] - Wall Street Journal
* Oct 2020, [https://time.com/5897992/long-haul-coronavirus-me-cfs/ Have We Been Thinking About Long-Haul Coronavirus All Wrong?] - Time
* Oct 2020, [https://www.nihr.ac.uk/news/living-with-covid-nihr-publishes-dynamic-themed-review-into-ongoing-covid/25891 Living with COVID: NIHR publishes dynamic-themed review into 'ongoing COVID'] - National Institute of Health Research
* Oct 2020, [https://www.theguardian.com/world/2020/oct/04/long-covid-the-evidence-of-lingering-heart-damage Long Covid: the evidence of lingering heart damage] - The Observer
* Sep 2020, [https://www.bbc.co.uk/news/uk-england-leicestershire-54106073 Coronavirus patient unable to work six months on] - BBC News
* Aug 2020, [https://www.huffingtonpost.co.uk/entry/long-term-symptoms-of-covid-19-identified-in-study-of-hospital-patients_uk_5f2bc0f6c5b64d7a55eefcfa The Most Common Long-Term Symptoms Of Covid-19] - HuffPost UK
* Aug 2022, [https://www.nature.com/articles/d41586-022-02140-w Long-COVID treatments: why the world is still waitin] - Nature
* Aug 2022, [https://www.statnews.com/2022/08/19/long-covid-plan-good-start-needs-to-go-further/ Biden’s long Covid plan is a good start. But it needs to go further] - Ryan Prior and Kimberly Knackstedt, Stat News
* Aug 2022, [https://www.latimes.com/opinion/story/2022-08-21/long-covid-treatment-research Op-Ed: We're starting to understand long COVID. Next we can fight it]
* Jul 2020, [https://www.sciencemag.org/news/2020/07/brain-fog-heart-damage-covid-19-s-lingering-problems-alarm-scientists From ‘brain fog’ to heart damage, COVID-19’s lingering problems alarm scientists] - Science Mag

==Articles for journalists covering Long COVID ==
* [https://www.cjr.org/covering_the_pandemic/how-to-cover-covid-19-patients-sensitively.php How to cover COVID-19 patients sensitively] - Fiona Lowenstein, Columbia Journalism Review
*[https://www.wearebodypolitic.com/bodytype/2021/7/6/long-covid-guide Body Politic's Comprehensive Guide to Covering Long COVID] - Fiona Lowenstein
*[https://centerforhealthjournalism.org/resources/lessons/what-reporters-need-know-when-covering-long-covid Long COVID coverage often falls short, but here's how reporters can do better] - Fiona Lowenstein, Center for Health Journalism
*2021, [https://www.theopennotebook.com/2021/01/26/how-to-report-with-accuracy-and-sensitivity-on-contested-illnesses/ How to Report with Accuracy and Sensitivity on Contested Illnesses] - Julie Rehmeyer, Open Notebook

==See also==
*[[List of famous people with long COVID]]
*[[List of open letters about long COVID]]
*[[Post-COVID-19 illness]]
*[[COVID-19]] coronavirus disease 19
*[[Myalgic encephalomyelitis|Myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Postviral fatigue syndrome]]
*[[Post-Ebola syndrome]]
*[[Encephalitis lethargica]]
*[[Paul Garner]]
*[[Nisreen Alwan]]
*[[Blood-brain barrier]]

==Learn more==
*[https://www.gov.uk/government/publications/covid-19-long-term-health-effects/covid-19-long-term-health-effects COVID-19 Long Term Health Effects]
*[https://www.bmj.com/sites/default/files/infographics/1353078336/static-infographic/background.png Infographic: "Long covid" in primary care] - BMJ journal
* List of long COVID studies (draft) - [[MEAction|#MEAction]]

==References==
{{reflist}}

[[Category:Potential comorbidities]]
[[Category:Diagnoses]]
[[Category:Long COVID]]

Positron emission tomography

2025-04-08T16:53:23Z

Galimatias:/* Sollini et al. 2021 */ added bullets to make findings more readable

'''Positron emission tomography''' ('''PET)''' is a method of biomedical imaging that uses nuclear functional imaging techniques to observe [[metabolic]] processes in the body. In clinical settings, it is predominantly used in oncology for tumor metastasis imaging, neurology, and cardiology.<ref name="pet">{{Cite journal | last = Bar-Shalom | first = Rachel | last2 = Valdivia | first2 = Ana Y. | last3 = Blaufox | first3 = M. Donald | date = 2000-07-01 | title = PET imaging in oncology|url=https://www.sciencedirect.com/science/article/pii/S0001299800800355|journal=Seminars in Nuclear Medicine|series=Entering a New Millennium|language=en|volume=30|issue=3|pages=150–185|doi=10.1053/snuc.2000.7439|issn=0001-2998}}</ref>

== Basics of PET ==

==== Radiotracers ====
PET uses radiotracers (also called radioactive tracers or radioligands), which are biological compounds that have been altered to include a radioactive atom (called a positron-emitting radioisotope). Radiotracers are biologically active, meaning they are designed to interact with your body, often by binding to a particular chemical or receptor.<ref name=":0">{{Cite journal|title=Positron emission tomography (PET) imaging with 18F-based radiotracers|date=2011-12-15|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478111/|journal=American Journal of Nuclear Medicine and Molecular Imaging|volume=2|issue=1|pages=55–76|last=Alauddin|first=Mian M|pmc=3478111|pmid=23133802|issn=2160-8407}}</ref>

The type of radiotracer used depends on what metabolic process the doctor wants to look at. For example, fludeoxyglucose (FDG) is a radiotracer that mimics [[glucose]]. Places where FDG congregate tend to have increased glucose uptake, a sign that the region has increased metabolic activity. This can be helpful for detecting tumors, which need more energy to spread through the body.<ref name="Widmann">{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmed/20473153|title=Glucose metabolism in cancer cells|last=Annibaldi|first=A.|last2=Widmann|first2=C.|date=July 2010|pages=466-470|doi=10.1097/MCO.0b013e32833a5577|journal=Current Opinion in Clinical Nutrition and Metabolic Care|volume=13|issue=4}}</ref>

==== The process ====
The radiotracer is injected into the subject's body, and the subject enters the PET machine. Over time, the radiotracer will break down, emitting gamma rays. The machine picks up these rays and translates them into a 3-dimensional image showing where the radiotracer is concentrated in the body.<ref name=":0" /> The resulting image can be thought of as a heat map, showing areas of high concentration as more brightly lit.

==== Risks ====
The risks for the amount of radiotracer injected into the body is small enough that there is usually no need to take precautions against radioactive exposure. If you are pregnant or breastfeeding, you should notify the doctor/researcher to protect against injury to the fetus or contaminating breastmilk.<ref name="jh">{{Cite web|url=https://www.hopkinsmedicine.org/healthlibrary/test_procedures/neurological/positron_emission_tomography_pet_92,p07654|title=How Does a PET Scan Work?|website=Johns Hopkins Medicine|language=en|access-date=2019-02-27}}</ref>

==== Clinical reasons for getting a PET scan: ====
PET is often used to evaluate the function of organs such as the [[heart]] and [[brain]]. Common uses include<ref name="jh" />:
* To measure perfusion of the heart muscle
* To diagnose neurological conditions such as [[Alzheimer's disease|Alzheimer’s]], [[Huntington's disease|Huntington’s]], [[Parkinson's disease|Parkinson’s]], [[epilepsy]], and stroke
* To detect the spread of cancer or evaluate cancer treatment efficacy
* To locate the specific site for surgery prior to the surgical procedure
* To evaluate the brain after [[trauma]]

== PET research in ME/CFS ==
PET research in ME has focused on measures of [[neuroinflammation]]. This has been done using a radiotracer that binds to the translocator protein (TSPO). [[Microglia]], the resident macrophages of the brain, produce TSPO when they activate.<ref name="Mejia2019">{{Cite journal|title=Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods|date=2019|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full#B8|journal=Frontiers in Neurology|volume=9|last=Lara Mejia|first=Paula S.|last2=Brumfield|first2=Sydney A.|last3=VanElzakker|first3=Michael B.|author-link3=Michael VanElzakker|language=English|doi=10.3389/fneur.2018.01033|issn=1664-2295}}</ref> Microglial activation is a commonly used measure of neuroinflammation.

==== Nakatomi et al. 2014 ====
Nakatomi et al. (2014) was the first case-control study using PET to measure neuroinflammation through TSPO expression in ME. They used [[PK11195]], a first-generation TSPO-binding radioligand. They found increased PK11195 in cingulate cortex, [[hippocampus]], [[amygdala]], thalamus, midbrain, and pons. PK11195 concentrations in certain regions had positive correlations with cognitive impairment scores (related to brain fog), [[pain]] scores, and [[depression]] scores. The study concludes that neuroinflammation is associated with neuropsychological symptoms in ME patients.<ref name="Nakatomi2014" />
[[File:PK11195.gif|thumb|312x312px|center|Statistical parametric maps showing areas of significant contrast of PK11195 in brains of ME/CFS patients versus healthy controls.<ref name="Nakatomi2014">{{Cite journal | last = Nakatomi | first = Yasuhito | authorlink = Yasuhito Nakatomi | authorlink2 = Kei Mizuno | authorlink3 = Akira Ishii | authorlink4 = Yasuhiro Wada | authorlink5 = Masaaki Tanaka | authorlink6 = Shusaku Tazawa | authorlink7 = Kayo Onoe | authorlink8 = Sanae Fukuda | authorlink9 = Joji Kawabe | date = Jun 1, 2014|others=Kazuhiro Takahashi; Yosky Kataoka; Susuma Shiomi; Kouzi Yamaguti, Masaaki Inaba; Hirohiko Kuratsune; Yasuyoshi Watanabe | title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study|url=http://jnm.snmjournals.org/content/55/6/945.full|journal=The Journal of Nuclear Medicine|volume=555|issue=6 | pages = 945-950|quote=|via=SNM Journals}}</ref>''This image was originally published in JNM. Nakatomi, Yasuhito, et al. [https://jnm.snmjournals.org/content/55/6/945 Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study]. J Nucl Med. Mar 24, 2014; 55(6):945-950. © SNMMI (non-commercial reuse only)'']]
== PET research in [[long COVID]] ==

=== Sollini et al. 2021 ===
Sollini et al. (2021) compared 13 adult long COVID patients to a group of 26 melanoma patients with a negative PET/CT. COVID patients were matched for sex/age.

* In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake.
* Long COVID patients also had brain hypometabolism in the right parahippocampal gyrus and [[thalamus]] (uncorrected p ≤ 0.001).

This study concluded that [18F}FDG PET/CT can be a tool to analyze the multi-organ nature of long COVID.<ref name="Sollini">{{Cite journal | last = Sollini | first = Martina | last2 = Morbelli | first2 = Silvia | last3 = Ciccarelli | first3 = Michele | last4 = Cecconi | first4 = Maurizio | last5 = Aghemo | first5 = Alessio | last6 = Morelli | first6 = Paola | last7 = Chiola | first7 = Silvia | last8 = Gelardi | first8 = Fabrizia | last9 = Chiti | first9 = Arturo | date = 2021-03-07 | title = Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study|url=http://link.springer.com/10.1007/s00259-021-05294-3|journal=European Journal of Nuclear Medicine and Molecular Imaging|language=en|doi=10.1007/s00259-021-05294-3|issn=1619-7070|pmc=PMC7937050|pmid=33677642}}</ref>

=== Guedj et al. 2021. ===

Guedj et al. (2021) completed PET scans for 35 long COVID patients which utilized a whole-brain voxel-based analysis. They compared these patients to a local database of 44 health subjects which were controlled by age and sex. Long COVID patients exhibited bilateral hypometabolism compared to health patients. Study supports that PET scans may be valuable for long COVID patients in order to perform a whole-brain voxel-based analysis. Additionally, prevalence of hypometabolism was statistically greater for COVID patients compared to healthy patients.<ref name="Guedj">{{Cite journal | last = Guedj | first = E. | last2 = Campion | first2 = J.Y. | last3 = Dudouet | first3 = P. | last4 = Kaphan | first4 = E. | last5 = Bregeon | first5 = F. | last6 = Tissot-Dupont | first6 = H. | last7 = Guis | first7 = S. | last8 = Barthelemy | first8 = F. | last9 = Habert | first9 = P. | date = 2021-01-26 | title = 18F-FDG brain PET hypometabolism in patients with long COVID|url=http://link.springer.com/10.1007/s00259-021-05215-4|journal=European Journal of Nuclear Medicine and Molecular Imaging|language=en|doi=10.1007/s00259-021-05215-4|issn=1619-7070|pmc=PMC7837643|pmid=33501506}}</ref>

==See also ==
*[[Brain]]
*[[Computed tomography scan|Computed Tomography Scan]]
*[[Long COVID]]
*[[Magnetic resonance imaging|Magnetic Resonance Imaging]]
*[[Neuroinflammation]]

== References ==
{{Reflist}}

[[Category:Medical tests]]
[[Category:Neurology]]

Positron emission tomography

2025-04-08T16:48:57Z

Galimatias:cleaned up text and added missing citations

'''Positron emission tomography''' ('''PET)''' is a method of biomedical imaging that uses nuclear functional imaging techniques to observe [[metabolic]] processes in the body. In clinical settings, it is predominantly used in oncology for tumor metastasis imaging, neurology, and cardiology.<ref name="pet">{{Cite journal | last = Bar-Shalom | first = Rachel | last2 = Valdivia | first2 = Ana Y. | last3 = Blaufox | first3 = M. Donald | date = 2000-07-01 | title = PET imaging in oncology|url=https://www.sciencedirect.com/science/article/pii/S0001299800800355|journal=Seminars in Nuclear Medicine|series=Entering a New Millennium|language=en|volume=30|issue=3|pages=150–185|doi=10.1053/snuc.2000.7439|issn=0001-2998}}</ref>

== Basics of PET ==

==== Radiotracers ====
PET uses radiotracers (also called radioactive tracers or radioligands), which are biological compounds that have been altered to include a radioactive atom (called a positron-emitting radioisotope). Radiotracers are biologically active, meaning they are designed to interact with your body, often by binding to a particular chemical or receptor.<ref name=":0">{{Cite journal|title=Positron emission tomography (PET) imaging with 18F-based radiotracers|date=2011-12-15|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478111/|journal=American Journal of Nuclear Medicine and Molecular Imaging|volume=2|issue=1|pages=55–76|last=Alauddin|first=Mian M|pmc=3478111|pmid=23133802|issn=2160-8407}}</ref>

The type of radiotracer used depends on what metabolic process the doctor wants to look at. For example, fludeoxyglucose (FDG) is a radiotracer that mimics [[glucose]]. Places where FDG congregate tend to have increased glucose uptake, a sign that the region has increased metabolic activity. This can be helpful for detecting tumors, which need more energy to spread through the body.<ref name="Widmann">{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmed/20473153|title=Glucose metabolism in cancer cells|last=Annibaldi|first=A.|last2=Widmann|first2=C.|date=July 2010|pages=466-470|doi=10.1097/MCO.0b013e32833a5577|journal=Current Opinion in Clinical Nutrition and Metabolic Care|volume=13|issue=4}}</ref>

==== The process ====
The radiotracer is injected into the subject's body, and the subject enters the PET machine. Over time, the radiotracer will break down, emitting gamma rays. The machine picks up these rays and translates them into a 3-dimensional image showing where the radiotracer is concentrated in the body.<ref name=":0" /> The resulting image can be thought of as a heat map, showing areas of high concentration as more brightly lit.

==== Risks ====
The risks for the amount of radiotracer injected into the body is small enough that there is usually no need to take precautions against radioactive exposure. If you are pregnant or breastfeeding, you should notify the doctor/researcher to protect against injury to the fetus or contaminating breastmilk.<ref name="jh">{{Cite web|url=https://www.hopkinsmedicine.org/healthlibrary/test_procedures/neurological/positron_emission_tomography_pet_92,p07654|title=How Does a PET Scan Work?|website=Johns Hopkins Medicine|language=en|access-date=2019-02-27}}</ref>

==== Clinical reasons for getting a PET scan: ====
PET is often used to evaluate the function of organs such as the [[heart]] and [[brain]]. Common uses include<ref name="jh" />:
* To measure perfusion of the heart muscle
* To diagnose neurological conditions such as [[Alzheimer's disease|Alzheimer’s]], [[Huntington's disease|Huntington’s]], [[Parkinson's disease|Parkinson’s]], [[epilepsy]], and stroke
* To detect the spread of cancer or evaluate cancer treatment efficacy
* To locate the specific site for surgery prior to the surgical procedure
* To evaluate the brain after [[trauma]]

== PET research in ME/CFS ==
PET research in ME has focused on measures of [[neuroinflammation]]. This has been done using a radiotracer that binds to the translocator protein (TSPO). [[Microglia]], the resident macrophages of the brain, produce TSPO when they activate.<ref name="Mejia2019">{{Cite journal|title=Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods|date=2019|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full#B8|journal=Frontiers in Neurology|volume=9|last=Lara Mejia|first=Paula S.|last2=Brumfield|first2=Sydney A.|last3=VanElzakker|first3=Michael B.|author-link3=Michael VanElzakker|language=English|doi=10.3389/fneur.2018.01033|issn=1664-2295}}</ref> Microglial activation is a commonly used measure of neuroinflammation.

==== Nakatomi et al. 2014 ====
Nakatomi et al. (2014) was the first case-control study using PET to measure neuroinflammation through TSPO expression in ME. They used [[PK11195]], a first-generation TSPO-binding radioligand. They found increased PK11195 in cingulate cortex, [[hippocampus]], [[amygdala]], thalamus, midbrain, and pons. PK11195 concentrations in certain regions had positive correlations with cognitive impairment scores (related to brain fog), [[pain]] scores, and [[depression]] scores. The study concludes that neuroinflammation is associated with neuropsychological symptoms in ME patients.<ref name="Nakatomi2014" />
[[File:PK11195.gif|thumb|312x312px|center|Statistical parametric maps showing areas of significant contrast of PK11195 in brains of ME/CFS patients versus healthy controls.<ref name="Nakatomi2014">{{Cite journal | last = Nakatomi | first = Yasuhito | authorlink = Yasuhito Nakatomi | authorlink2 = Kei Mizuno | authorlink3 = Akira Ishii | authorlink4 = Yasuhiro Wada | authorlink5 = Masaaki Tanaka | authorlink6 = Shusaku Tazawa | authorlink7 = Kayo Onoe | authorlink8 = Sanae Fukuda | authorlink9 = Joji Kawabe | date = Jun 1, 2014|others=Kazuhiro Takahashi; Yosky Kataoka; Susuma Shiomi; Kouzi Yamaguti, Masaaki Inaba; Hirohiko Kuratsune; Yasuyoshi Watanabe | title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study|url=http://jnm.snmjournals.org/content/55/6/945.full|journal=The Journal of Nuclear Medicine|volume=555|issue=6 | pages = 945-950|quote=|via=SNM Journals}}</ref>''This image was originally published in JNM. Nakatomi, Yasuhito, et al. [https://jnm.snmjournals.org/content/55/6/945 Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study]. J Nucl Med. Mar 24, 2014; 55(6):945-950. © SNMMI (non-commercial reuse only)'']]
== PET research in [[long COVID]] ==

=== Sollini et al. 2021 ===
Sollini et al. (2021) compared 13 adult long COVID patients to a group of 26 melanoma patients with a negative PET/CT. COVID patients were matched for sex/age. In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Long COVID patients also had brain hypometabolism in the right parahippocampal gyrus and [[thalamus]] (uncorrected p ≤ 0.001). This study concluded that [18F}FDG PET/CT can be a tool to analyze the multi-organ nature of long COVID.<ref name="Sollini">{{Cite journal | last = Sollini | first = Martina | last2 = Morbelli | first2 = Silvia | last3 = Ciccarelli | first3 = Michele | last4 = Cecconi | first4 = Maurizio | last5 = Aghemo | first5 = Alessio | last6 = Morelli | first6 = Paola | last7 = Chiola | first7 = Silvia | last8 = Gelardi | first8 = Fabrizia | last9 = Chiti | first9 = Arturo | date = 2021-03-07 | title = Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study|url=http://link.springer.com/10.1007/s00259-021-05294-3|journal=European Journal of Nuclear Medicine and Molecular Imaging|language=en|doi=10.1007/s00259-021-05294-3|issn=1619-7070|pmc=PMC7937050|pmid=33677642}}</ref>

=== Guedj et al. 2021. ===

Guedj et al. (2021) completed PET scans for 35 long COVID patients which utilized a whole-brain voxel-based analysis. They compared these patients to a local database of 44 health subjects which were controlled by age and sex. Long COVID patients exhibited bilateral hypometabolism compared to health patients. Study supports that PET scans may be valuable for long COVID patients in order to perform a whole-brain voxel-based analysis. Additionally, prevalence of hypometabolism was statistically greater for COVID patients compared to healthy patients.<ref name="Guedj">{{Cite journal | last = Guedj | first = E. | last2 = Campion | first2 = J.Y. | last3 = Dudouet | first3 = P. | last4 = Kaphan | first4 = E. | last5 = Bregeon | first5 = F. | last6 = Tissot-Dupont | first6 = H. | last7 = Guis | first7 = S. | last8 = Barthelemy | first8 = F. | last9 = Habert | first9 = P. | date = 2021-01-26 | title = 18F-FDG brain PET hypometabolism in patients with long COVID|url=http://link.springer.com/10.1007/s00259-021-05215-4|journal=European Journal of Nuclear Medicine and Molecular Imaging|language=en|doi=10.1007/s00259-021-05215-4|issn=1619-7070|pmc=PMC7837643|pmid=33501506}}</ref>

==See also ==
*[[Brain]]
*[[Computed tomography scan|Computed Tomography Scan]]
*[[Long COVID]]
*[[Magnetic resonance imaging|Magnetic Resonance Imaging]]
*[[Neuroinflammation]]

== References ==
{{Reflist}}

[[Category:Medical tests]]
[[Category:Neurology]]

Autism spectrum disorder

2025-03-30T20:58:31Z

Galimatias:spacing fix

'''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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==

====== Symptoms ======
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

====== Cellular Metabolism ======
Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.
{| class="wikitable"
|'''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.<ref>{{Cite journal|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|date=2019-06|url=https://pubmed.ncbi.nlm.nih.gov/31161646/|journal=Physiological Reports|volume=7|issue=11|pages=e14138|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|doi=10.14814/phy2.14138|pmc=6546966|pmid=31161646|issn=2051-817X}}</ref> A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM'''.<ref>{{Cite journal|title=Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome|date=2019-12-11|url=https://www.nature.com/articles/s41598-019-55473-4|journal=Scientific Reports|volume=9|issue=1|pages=18817|last=Ghali|first=Alaa|last2=Lacout|first2=Carole|last3=Ghali|first3=Maria|last4=Gury|first4=Aline|last5=Beucher|first5=Anne-Berengere|last6=Lozac’h|first6=Pierre|last7=Lavigne|first7=Christian|last8=Urbanski|first8=Geoffrey|language=en|doi=10.1038/s41598-019-55473-4|issn=2045-2322}}</ref>'''

|Some autistic kids have high lactate levels at rest.<ref>{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref><ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a population-based study|date=Feb 13, 2007|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2005.tb01113.x|journal=Developmental Medicine and Child Neurology|volume=47|issue=3|pages=185-189|last=Oliveira|first=G|last2=Diogo|first2=L|last3=Grazina|first3=M|last4=Garcia|first4=P}}</ref>

|-
|'''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.<ref>{{Cite journal|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|date=2019-02-27|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393470/|journal=Scientific Reports|volume=9|pages=2914|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|last10=Elson|first10=Joanna L.|doi=10.1038/s41598-019-39060-1|pmc=6393470|pmid=30814539|issn=2045-2322}}</ref>

|Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.<ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis|date=2012-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285768/|journal=Molecular Psychiatry|volume=17|issue=3|pages=290–314|last=Rossignol|first=D A|last2=Frye|first2=R E|doi=10.1038/mp.2010.136|pmc=3285768|pmid=21263444|issn=1359-4184}}</ref> 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.<ref name=":2">{{Cite journal|title=Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome|date=2024-01-30|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855807/|journal=International Journal of Molecular Sciences|volume=25|issue=3|pages=1675|last=Bizjak|first=Daniel Alexander|last2=Ohmayer|first2=Birgit|last3=Buhl|first3=Jasmine Leonike|last4=Schneider|first4=Elisabeth Marion|last5=Walther|first5=Paul|last6=Calzia|first6=Enrico|last7=Jerg|first7=Achim|last8=Matits|first8=Lynn|last9=Steinacker|first9=Jürgen Michael|doi=10.3390/ijms25031675|pmid=38338957|issn=1422-0067}}</ref> Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and [[glucose]] transport.<ref>{{Cite journal|title=Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes|date=Jan 1, 2005|url=https://diabetesjournals.org/diabetes/article/54/1/8/14686/Deficiency-of-Subsarcolemmal-Mitochondria-in|journal=Diabetes|volume=54|issue=1|pages=8-14|last=Ritov|first=Vladimir|last2=Menshikova|first2=Elizabeth|last3=He|first3=Jing|last4=Ferrell|first4=Robert}}</ref>

There aren't significant changes in complex I-IV in the ETC.<ref name=":2" /><ref>{{Cite journal|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|date=2019|url=https://pubmed.ncbi.nlm.nih.gov/30847260/|journal=PeerJ|volume=7|pages=e6500|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|doi=10.7717/peerj.6500|pmc=6398432|pmid=30847260|issn=2167-8359}}</ref>

|In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.<ref name=":3">{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref> 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.<ref name=":3" /> Smaller studies have had similar findings.<ref>{{Cite journal|title=Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms|date=May 29, 2017|url=https://onlinelibrary.wiley.com/doi/10.1155/2017/4314025|journal=Oxidative Medicine and Cellular Longevity|last=Griffiths|first=Keren|last2=Levy|first2=Richard}}</ref>
|-
|'''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 cell|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.<ref>{{Cite journal|title=An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients|date=2020-02-06|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036826/|journal=International Journal of Molecular Sciences|volume=21|issue=3|pages=1074|last=Missailidis|first=Daniel|last2=Annesley|first2=Sarah J.|last3=Allan|first3=Claire Y.|last4=Sanislav|first4=Oana|last5=Lidbury|first5=Brett A.|last6=Lewis|first6=Donald P.|last7=Fisher|first7=Paul R.|doi=10.3390/ijms21031074|pmc=7036826|pmid=32041178|issn=1422-0067}}</ref>
|Within LCLs derived from autistic people, mitochondria are more vulnerable to [[oxidative stress]]. This seems to be driven by alterations to [[glutathione]] metabolism.<ref>{{Cite journal|title=Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines|date=2014-04|url=https://www.nature.com/articles/tp201415|journal=Translational Psychiatry|volume=4|issue=4|pages=e377–e377|last=Rose|first=S.|last2=Frye|first2=R. E.|last3=Slattery|first3=J.|last4=Wynne|first4=R.|last5=Tippett|first5=M.|last6=Melnyk|first6=S.|last7=James|first7=S. J.|language=en|doi=10.1038/tp.2014.15|issn=2158-3188}}</ref> The study authors believe these changes are related to overactivity in Complex IV found in a previous study.<ref>{{Cite journal|title=Autistic disorder with complex IV overactivity: A new mitochondrial syndrome|date=2011-12|url=http://www.thieme-connect.de/DOI/DOI?10.3233/JPN-2011-0507|journal=Journal of Pediatric Neurology|volume=09|issue=4|pages=427–434|last=Frye|first=Richard E.|last2=Naviaux|first2=Robert K.|language=en|doi=10.3233/JPN-2011-0507|issn=1304-2580}}</ref>
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.<ref>{{Cite journal|title=Mitochondrial Dysfunction in Autism|date=2010-12-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915058/|journal=JAMA : the journal of the American Medical Association|volume=304|issue=21|pages=2389–2396|last=Giulivi|first=Cecilia|last2=Zhang|first2=Yi-Fan|last3=Omanska-Klusek|first3=Alicja|last4=Ross-Inta|first4=Catherine|last5=Wong|first5=Sarah|last6=Hertz-Picciotto|first6=Irva|last7=Tassone|first7=Flora|last8=Pessah|first8=Isaac N.|doi=10.1001/jama.2010.1706|pmc=3915058|pmid=21119085|issn=0098-7484}}</ref>

|}

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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. <ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Autism spectrum disorder

2025-03-30T20:57:40Z

Galimatias:Mitochondrial dysfunction in lymphocytes

'''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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==

====== Symptoms ======
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

====== Cellular Metabolism ======
Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.
{| class="wikitable"
|'''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.<ref>{{Cite journal|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|date=2019-06|url=https://pubmed.ncbi.nlm.nih.gov/31161646/|journal=Physiological Reports|volume=7|issue=11|pages=e14138|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|doi=10.14814/phy2.14138|pmc=6546966|pmid=31161646|issn=2051-817X}}</ref> A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM'''.<ref>{{Cite journal|title=Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome|date=2019-12-11|url=https://www.nature.com/articles/s41598-019-55473-4|journal=Scientific Reports|volume=9|issue=1|pages=18817|last=Ghali|first=Alaa|last2=Lacout|first2=Carole|last3=Ghali|first3=Maria|last4=Gury|first4=Aline|last5=Beucher|first5=Anne-Berengere|last6=Lozac’h|first6=Pierre|last7=Lavigne|first7=Christian|last8=Urbanski|first8=Geoffrey|language=en|doi=10.1038/s41598-019-55473-4|issn=2045-2322}}</ref>'''

|Some autistic kids have high lactate levels at rest.<ref>{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref><ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a population-based study|date=Feb 13, 2007|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2005.tb01113.x|journal=Developmental Medicine and Child Neurology|volume=47|issue=3|pages=185-189|last=Oliveira|first=G|last2=Diogo|first2=L|last3=Grazina|first3=M|last4=Garcia|first4=P}}</ref>

|-
|'''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.<ref>{{Cite journal|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|date=2019-02-27|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393470/|journal=Scientific Reports|volume=9|pages=2914|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|last10=Elson|first10=Joanna L.|doi=10.1038/s41598-019-39060-1|pmc=6393470|pmid=30814539|issn=2045-2322}}</ref>

|Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.<ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis|date=2012-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285768/|journal=Molecular Psychiatry|volume=17|issue=3|pages=290–314|last=Rossignol|first=D A|last2=Frye|first2=R E|doi=10.1038/mp.2010.136|pmc=3285768|pmid=21263444|issn=1359-4184}}</ref> 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.<ref name=":2">{{Cite journal|title=Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome|date=2024-01-30|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855807/|journal=International Journal of Molecular Sciences|volume=25|issue=3|pages=1675|last=Bizjak|first=Daniel Alexander|last2=Ohmayer|first2=Birgit|last3=Buhl|first3=Jasmine Leonike|last4=Schneider|first4=Elisabeth Marion|last5=Walther|first5=Paul|last6=Calzia|first6=Enrico|last7=Jerg|first7=Achim|last8=Matits|first8=Lynn|last9=Steinacker|first9=Jürgen Michael|doi=10.3390/ijms25031675|pmid=38338957|issn=1422-0067}}</ref> Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and [[glucose]] transport.<ref>{{Cite journal|title=Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes|date=Jan 1, 2005|url=https://diabetesjournals.org/diabetes/article/54/1/8/14686/Deficiency-of-Subsarcolemmal-Mitochondria-in|journal=Diabetes|volume=54|issue=1|pages=8-14|last=Ritov|first=Vladimir|last2=Menshikova|first2=Elizabeth|last3=He|first3=Jing|last4=Ferrell|first4=Robert}}</ref>

There aren't significant changes in complex I-IV in the ETC.<ref name=":2" /><ref>{{Cite journal|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|date=2019|url=https://pubmed.ncbi.nlm.nih.gov/30847260/|journal=PeerJ|volume=7|pages=e6500|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|doi=10.7717/peerj.6500|pmc=6398432|pmid=30847260|issn=2167-8359}}</ref>

|In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.<ref name=":3">{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref> 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.<ref name=":3" /> Smaller studies have had similar findings.<ref>{{Cite journal|title=Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms|date=May 29, 2017|url=https://onlinelibrary.wiley.com/doi/10.1155/2017/4314025|journal=Oxidative Medicine and Cellular Longevity|last=Griffiths|first=Keren|last2=Levy|first2=Richard}}</ref>
|-
|'''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 cell|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.<ref>{{Cite journal|title=An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients|date=2020-02-06|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036826/|journal=International Journal of Molecular Sciences|volume=21|issue=3|pages=1074|last=Missailidis|first=Daniel|last2=Annesley|first2=Sarah J.|last3=Allan|first3=Claire Y.|last4=Sanislav|first4=Oana|last5=Lidbury|first5=Brett A.|last6=Lewis|first6=Donald P.|last7=Fisher|first7=Paul R.|doi=10.3390/ijms21031074|pmc=7036826|pmid=32041178|issn=1422-0067}}</ref>
|Within LCLs derived from autistic people, mitochondria are more vulnerable to [[oxidative stress]]. This seems to be driven by alterations to [[glutathione]] metabolism.<ref>{{Cite journal|title=Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines|date=2014-04|url=https://www.nature.com/articles/tp201415|journal=Translational Psychiatry|volume=4|issue=4|pages=e377–e377|last=Rose|first=S.|last2=Frye|first2=R. E.|last3=Slattery|first3=J.|last4=Wynne|first4=R.|last5=Tippett|first5=M.|last6=Melnyk|first6=S.|last7=James|first7=S. J.|language=en|doi=10.1038/tp.2014.15|issn=2158-3188}}</ref>
The study authors believe these changes are related to overactivity in Complex IV found in a previous study.<ref>{{Cite journal|title=Autistic disorder with complex IV overactivity: A new mitochondrial syndrome|date=2011-12|url=http://www.thieme-connect.de/DOI/DOI?10.3233/JPN-2011-0507|journal=Journal of Pediatric Neurology|volume=09|issue=4|pages=427–434|last=Frye|first=Richard E.|last2=Naviaux|first2=Robert K.|language=en|doi=10.3233/JPN-2011-0507|issn=1304-2580}}</ref>
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.<ref>{{Cite journal|title=Mitochondrial Dysfunction in Autism|date=2010-12-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915058/|journal=JAMA : the journal of the American Medical Association|volume=304|issue=21|pages=2389–2396|last=Giulivi|first=Cecilia|last2=Zhang|first2=Yi-Fan|last3=Omanska-Klusek|first3=Alicja|last4=Ross-Inta|first4=Catherine|last5=Wong|first5=Sarah|last6=Hertz-Picciotto|first6=Irva|last7=Tassone|first7=Flora|last8=Pessah|first8=Isaac N.|doi=10.1001/jama.2010.1706|pmc=3915058|pmid=21119085|issn=0098-7484}}</ref>

|}

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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. <ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Autism spectrum disorder

2025-03-30T00:04:23Z

Galimatias:fixed hyperlink again

'''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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==

====== Symptoms ======
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

====== Cellular Metabolism ======
Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.
{| class="wikitable"
|Summary
|ME/CFS
|ASD
|-
|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.<ref>{{Cite journal|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|date=2019-06|url=https://pubmed.ncbi.nlm.nih.gov/31161646/|journal=Physiological Reports|volume=7|issue=11|pages=e14138|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|doi=10.14814/phy2.14138|pmc=6546966|pmid=31161646|issn=2051-817X}}</ref> A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM'''.<ref>{{Cite journal|title=Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome|date=2019-12-11|url=https://www.nature.com/articles/s41598-019-55473-4|journal=Scientific Reports|volume=9|issue=1|pages=18817|last=Ghali|first=Alaa|last2=Lacout|first2=Carole|last3=Ghali|first3=Maria|last4=Gury|first4=Aline|last5=Beucher|first5=Anne-Berengere|last6=Lozac’h|first6=Pierre|last7=Lavigne|first7=Christian|last8=Urbanski|first8=Geoffrey|language=en|doi=10.1038/s41598-019-55473-4|issn=2045-2322}}</ref>'''

|Some autistic kids have high lactate levels at rest.<ref>{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref><ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a population-based study|date=Feb 13, 2007|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2005.tb01113.x|journal=Developmental Medicine and Child Neurology|volume=47|issue=3|pages=185-189|last=Oliveira|first=G|last2=Diogo|first2=L|last3=Grazina|first3=M|last4=Garcia|first4=P}}</ref>

|-
|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.<ref>{{Cite journal|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|date=2019-02-27|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393470/|journal=Scientific Reports|volume=9|pages=2914|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|last10=Elson|first10=Joanna L.|doi=10.1038/s41598-019-39060-1|pmc=6393470|pmid=30814539|issn=2045-2322}}</ref>

|Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.<ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis|date=2012-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285768/|journal=Molecular Psychiatry|volume=17|issue=3|pages=290–314|last=Rossignol|first=D A|last2=Frye|first2=R E|doi=10.1038/mp.2010.136|pmc=3285768|pmid=21263444|issn=1359-4184}}</ref> 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)

|-
|Both conditions have mitochondrial dysfunction in skeletal muscle. However, the dysfunction in ME/CFS seems to be more structural, while the dysfunction in autism is more related to a part of [[cellular respiration]] called the electron transport chain (ETC). ETC is also called [[oxidative phosphorylation]].
|Within ME/CFS patients, the subsarcolemmal mitochondria have fewer cristae (folds), which may affect the production of certain chemicals.<ref name=":2">{{Cite journal|title=Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome|date=2024-01-30|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855807/|journal=International Journal of Molecular Sciences|volume=25|issue=3|pages=1675|last=Bizjak|first=Daniel Alexander|last2=Ohmayer|first2=Birgit|last3=Buhl|first3=Jasmine Leonike|last4=Schneider|first4=Elisabeth Marion|last5=Walther|first5=Paul|last6=Calzia|first6=Enrico|last7=Jerg|first7=Achim|last8=Matits|first8=Lynn|last9=Steinacker|first9=Jürgen Michael|doi=10.3390/ijms25031675|pmid=38338957|issn=1422-0067}}</ref> Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and [[glucose]] transport.<ref>{{Cite journal|title=Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes|date=Jan 1, 2005|url=https://diabetesjournals.org/diabetes/article/54/1/8/14686/Deficiency-of-Subsarcolemmal-Mitochondria-in|journal=Diabetes|volume=54|issue=1|pages=8-14|last=Ritov|first=Vladimir|last2=Menshikova|first2=Elizabeth|last3=He|first3=Jing|last4=Ferrell|first4=Robert}}</ref>

There aren't significant changes in complex I-IV in the ETC.<ref name=":2" /><ref>{{Cite journal|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|date=2019|url=https://pubmed.ncbi.nlm.nih.gov/30847260/|journal=PeerJ|volume=7|pages=e6500|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|doi=10.7717/peerj.6500|pmc=6398432|pmid=30847260|issn=2167-8359}}</ref>

|In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.<ref name=":3">{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref> 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.<ref name=":3" /> Smaller studies have had similar findings.<ref>{{Cite journal|title=Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms|date=May 29, 2017|url=https://onlinelibrary.wiley.com/doi/10.1155/2017/4314025|journal=Oxidative Medicine and Cellular Longevity|last=Griffiths|first=Keren|last2=Levy|first2=Richard}}</ref>

|}

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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. <ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Autism spectrum disorder

2025-03-30T00:01:49Z

Galimatias:changed hyperlink

'''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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==

====== Symptoms ======
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

====== Cellular Metabolism ======
Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.
{| class="wikitable"
|Summary
|ME/CFS
|ASD
|-
|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.<ref>{{Cite journal|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|date=2019-06|url=https://pubmed.ncbi.nlm.nih.gov/31161646/|journal=Physiological Reports|volume=7|issue=11|pages=e14138|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|doi=10.14814/phy2.14138|pmc=6546966|pmid=31161646|issn=2051-817X}}</ref> A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM'''.<ref>{{Cite journal|title=Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome|date=2019-12-11|url=https://www.nature.com/articles/s41598-019-55473-4|journal=Scientific Reports|volume=9|issue=1|pages=18817|last=Ghali|first=Alaa|last2=Lacout|first2=Carole|last3=Ghali|first3=Maria|last4=Gury|first4=Aline|last5=Beucher|first5=Anne-Berengere|last6=Lozac’h|first6=Pierre|last7=Lavigne|first7=Christian|last8=Urbanski|first8=Geoffrey|language=en|doi=10.1038/s41598-019-55473-4|issn=2045-2322}}</ref>'''

|Some autistic kids have high lactate levels at rest.<ref>{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref><ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a population-based study|date=Feb 13, 2007|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2005.tb01113.x|journal=Developmental Medicine and Child Neurology|volume=47|issue=3|pages=185-189|last=Oliveira|first=G|last2=Diogo|first2=L|last3=Grazina|first3=M|last4=Garcia|first4=P}}</ref>

|-
|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.<ref>{{Cite journal|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|date=2019-02-27|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393470/|journal=Scientific Reports|volume=9|pages=2914|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|last10=Elson|first10=Joanna L.|doi=10.1038/s41598-019-39060-1|pmc=6393470|pmid=30814539|issn=2045-2322}}</ref>

|Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.<ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis|date=2012-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285768/|journal=Molecular Psychiatry|volume=17|issue=3|pages=290–314|last=Rossignol|first=D A|last2=Frye|first2=R E|doi=10.1038/mp.2010.136|pmc=3285768|pmid=21263444|issn=1359-4184}}</ref> 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)

|-
|Both conditions have mitochondrial dysfunction in skeletal muscle. However, the dysfunction in ME/CFS seems to be more structural, while the dysfunction in autism is more related to a part of [[cellular respiration]] called the electron transport chain (ETC).
|Within ME/CFS patients, the subsarcolemmal mitochondria have fewer cristae (folds), which may affect the production of certain chemicals.<ref name=":2">{{Cite journal|title=Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome|date=2024-01-30|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855807/|journal=International Journal of Molecular Sciences|volume=25|issue=3|pages=1675|last=Bizjak|first=Daniel Alexander|last2=Ohmayer|first2=Birgit|last3=Buhl|first3=Jasmine Leonike|last4=Schneider|first4=Elisabeth Marion|last5=Walther|first5=Paul|last6=Calzia|first6=Enrico|last7=Jerg|first7=Achim|last8=Matits|first8=Lynn|last9=Steinacker|first9=Jürgen Michael|doi=10.3390/ijms25031675|pmid=38338957|issn=1422-0067}}</ref> Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and [[glucose]] transport.<ref>{{Cite journal|title=Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes|date=Jan 1, 2005|url=https://diabetesjournals.org/diabetes/article/54/1/8/14686/Deficiency-of-Subsarcolemmal-Mitochondria-in|journal=Diabetes|volume=54|issue=1|pages=8-14|last=Ritov|first=Vladimir|last2=Menshikova|first2=Elizabeth|last3=He|first3=Jing|last4=Ferrell|first4=Robert}}</ref>

There aren't significant changes in complex I-IV in the ETC.<ref name=":2" /><ref>{{Cite journal|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|date=2019|url=https://pubmed.ncbi.nlm.nih.gov/30847260/|journal=PeerJ|volume=7|pages=e6500|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|doi=10.7717/peerj.6500|pmc=6398432|pmid=30847260|issn=2167-8359}}</ref>

|In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.<ref name=":3">{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref> 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.<ref name=":3" /> Smaller studies have had similar findings.<ref>{{Cite journal|title=Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms|date=May 29, 2017|url=https://onlinelibrary.wiley.com/doi/10.1155/2017/4314025|journal=Oxidative Medicine and Cellular Longevity|last=Griffiths|first=Keren|last2=Levy|first2=Richard}}</ref>

|}

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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. <ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Autism spectrum disorder

2025-03-29T23:58:43Z

Galimatias:I added the metabolic comparison table (will add final and most important row when I have time). I also deleted the autistic burnout triggers that I added last time, leaving only the part about rest being necessary for recovery.

'''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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==

====== Symptoms ======
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

====== Cellular Metabolism ======
Autism and ME/CFS have similar alterations to their cellular metabolism. However, there are distinct differences between the conditions.
{| class="wikitable"
|Summary
|ME/CFS
|ASD
|-
|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.<ref>{{Cite journal|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|date=2019-06|url=https://pubmed.ncbi.nlm.nih.gov/31161646/|journal=Physiological Reports|volume=7|issue=11|pages=e14138|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|doi=10.14814/phy2.14138|pmc=6546966|pmid=31161646|issn=2051-817X}}</ref> A subgroup of people who have heightened blood lactate levels while resting are more likely to have PEM'''.<ref>{{Cite journal|title=Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome|date=2019-12-11|url=https://www.nature.com/articles/s41598-019-55473-4|journal=Scientific Reports|volume=9|issue=1|pages=18817|last=Ghali|first=Alaa|last2=Lacout|first2=Carole|last3=Ghali|first3=Maria|last4=Gury|first4=Aline|last5=Beucher|first5=Anne-Berengere|last6=Lozac’h|first6=Pierre|last7=Lavigne|first7=Christian|last8=Urbanski|first8=Geoffrey|language=en|doi=10.1038/s41598-019-55473-4|issn=2045-2322}}</ref>'''

|Some autistic kids have high lactate levels at rest.<ref>{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref><ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a population-based study|date=Feb 13, 2007|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2005.tb01113.x|journal=Developmental Medicine and Child Neurology|volume=47|issue=3|pages=185-189|last=Oliveira|first=G|last2=Diogo|first2=L|last3=Grazina|first3=M|last4=Garcia|first4=P}}</ref>

|-
|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.<ref>{{Cite journal|title=MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants|date=2019-02-27|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393470/|journal=Scientific Reports|volume=9|pages=2914|last=Venter|first=Marianne|last2=Tomas|first2=Cara|last3=Pienaar|first3=Ilse S.|last4=Strassheim|first4=Victoria|last5=Erasmus|first5=Elardus|last6=Ng|first6=Wan-Fai|last7=Howell|first7=Neil|last8=Newton|first8=Julia L.|last9=Van der Westhuizen|first9=Francois H.|last10=Elson|first10=Joanna L.|doi=10.1038/s41598-019-39060-1|pmc=6393470|pmid=30814539|issn=2045-2322}}</ref>

|Up to 5% of autistic children may have mitochondrial disease caused by mtDNA mutations, a rate MUCH higher than that of the general public.<ref>{{Cite journal|title=Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis|date=2012-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285768/|journal=Molecular Psychiatry|volume=17|issue=3|pages=290–314|last=Rossignol|first=D A|last2=Frye|first2=R E|doi=10.1038/mp.2010.136|pmc=3285768|pmid=21263444|issn=1359-4184}}</ref> 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)

|-
|Both conditions have mitochondrial dysfunction in skeletal muscle. However, the dysfunction in ME/CFS seems to be more structural, while the dysfunction in autism is more related to the [[electron transport chain]] (ETC).
|Within ME/CFS patients, the subsarcolemmal mitochondria have fewer cristae (folds), which may affect the production of certain chemicals.<ref name=":2">{{Cite journal|title=Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome|date=2024-01-30|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855807/|journal=International Journal of Molecular Sciences|volume=25|issue=3|pages=1675|last=Bizjak|first=Daniel Alexander|last2=Ohmayer|first2=Birgit|last3=Buhl|first3=Jasmine Leonike|last4=Schneider|first4=Elisabeth Marion|last5=Walther|first5=Paul|last6=Calzia|first6=Enrico|last7=Jerg|first7=Achim|last8=Matits|first8=Lynn|last9=Steinacker|first9=Jürgen Michael|doi=10.3390/ijms25031675|pmid=38338957|issn=1422-0067}}</ref> Subsarcolemmal mitochondria are thought to be involved in fatty acid oxidation, insulin signaling, and [[glucose]] transport.<ref>{{Cite journal|title=Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes|date=Jan 1, 2005|url=https://diabetesjournals.org/diabetes/article/54/1/8/14686/Deficiency-of-Subsarcolemmal-Mitochondria-in|journal=Diabetes|volume=54|issue=1|pages=8-14|last=Ritov|first=Vladimir|last2=Menshikova|first2=Elizabeth|last3=He|first3=Jing|last4=Ferrell|first4=Robert}}</ref>

There aren't significant changes in complex I-IV in the ETC.<ref name=":2" /><ref>{{Cite journal|title=Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types|date=2019|url=https://pubmed.ncbi.nlm.nih.gov/30847260/|journal=PeerJ|volume=7|pages=e6500|last=Tomas|first=Cara|last2=Brown|first2=Audrey E.|last3=Newton|first3=Julia L.|last4=Elson|first4=Joanna L.|doi=10.7717/peerj.6500|pmc=6398432|pmid=30847260|issn=2167-8359}}</ref>

|In a 2008 study, 4 out of 23 children who had quadriceps muscle biopsies showed structural abnormalities in their mitochondria.<ref name=":3">{{Cite journal|title=Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis|date=2008-11-26|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003815|journal=PLOS ONE|volume=3|issue=11|pages=e3815|last=Weissman|first=Jacqueline R.|last2=Kelley|first2=Richard I.|last3=Bauman|first3=Margaret L.|last4=Cohen|first4=Bruce H.|last5=Murray|first5=Katherine F.|last6=Mitchell|first6=Rebecca L.|last7=Kern|first7=Rebecca L.|last8=Natowicz|first8=Marvin R.|language=en|doi=10.1371/journal.pone.0003815|issn=1932-6203}}</ref> 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.<ref name=":3" /> Smaller studies have had similar findings.<ref>{{Cite journal|title=Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms|date=May 29, 2017|url=https://onlinelibrary.wiley.com/doi/10.1155/2017/4314025|journal=Oxidative Medicine and Cellular Longevity|last=Griffiths|first=Keren|last2=Levy|first2=Richard}}</ref>

|}

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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. <ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Spinal cord

2025-02-17T22:27:10Z

Galimatias:organized info and added citations.

[[File:Spinal Cord Sectional Anatomy.png|400px|thumb|right|Spinal Cord Sectional Anatomy]]

The '''spinal cord''' contains around 200 million neurons that run through your spine.<ref name=":0">{{Cite journal|title=The Cellular Composition and Glia-Neuron Ratio in the Spinal Cord of a Human and a Non-Human Primate: Comparison with other Species and Brain Regions|date=2018-4|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845477/|journal=Anatomical record (Hoboken, N.J. : 2007)|volume=301|issue=4|pages=697–710|last=BAHNEY|first=JAMI|last2=VON BARTHELD|first2=CHRISTOPHER S.|doi=10.1002/ar.23728|pmc=5845477|pmid=29150977|issn=1932-8486}}</ref> They carry information between your body and [[brain]].

The "myelitis" in Myalgic Encephalo'''myelitis''' refers to spinal cord inflammation. "''Myel''" means 'relating to the spinal cord'. "''Itis''" means 'inflammation'. <ref name="INMER2005">{{Cite web|url=http://www.investinme.org/Article%20010-Encephalopathy%20Hooper.shtml | title = Invest in ME Research - The Terminology of ME & CFS | last = Hooper | first = Malcolm | date = Feb 2005 | website = Invest in ME Research|archive-url=|archive-date=|access-date=2018-08-13}}</ref><ref>{{Cite news | url=https://medical-dictionary.thefreedictionary.com/encephalomyelitis | title = encephalomyelitis|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref><ref>{{Cite news | url=https://www.thefreedictionary.com/myel- | title = myel-|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref><ref>{{Cite news | url=https://www.thefreedictionary.com/-itis | title = Itis|work=TheFreeDictionary.com|access-date=2018-08-12 | last = | first = | date = |archive-url=|archive-date=}}</ref>

== Meninges and Spinal Cord ==
Your spinal cord has three layers of protective membranes called meninges.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK559056/|title=Neuroanatomy, Spinal Cord|last=Khan|first=Yusuf|last2=Lui|first2=Forshing|date=July 24, 2023|website=National Library of Medicine}}</ref>

* '''Dura mater''': the tough outer layer.
** '''Subdural space:''' the space between the dura and arachnoid layers.
* '''Arachnoid mater:''' the middle layer. It's called 'arachnoid' due to its web-like appearance.<ref>{{Cite journal|title=The arachnoid and the myth of Arachne|date=1999-07|url=https://pubmed.ncbi.nlm.nih.gov/10414578/#:~:text=It%20was%20not%20until%20the,ancient%20Greek%20myth%20of%20Arachne.|journal=Neurosurgery|volume=45|issue=1|pages=152–155; discussion 155–157|last=Sanan|first=A.|last2=van Loveren|first2=H. R.|doi=10.1097/00006123-199907000-00034|pmid=10414578|issn=0148-396X}}</ref>
** '''Subarachnoid space:''' the space between the arachnoid and pia layers. It contains [[cerebrospinal fluid]] (CSF) to provide extra cushion for the nerves.
* '''Pia mater''': the delicate, innermost layer that attaches to the spinal cord. a very delicate layer that attaches to the spinal cord and follows the contours of the cord or brain.

==== Spinal Cord Immune System ====
Your spinal cord also contains [[Glial cell|glial cells]], which support your neurons' functioning. In humans, there are about 5-7 glial cells per nerve cell.<ref name=":0" />

The [[brain]] and spinal cord have their own [[immune system]].<ref>{{Cite web|url=https://www.sciencedaily.com/releases/2019/02/190219132853.htm | title = Scientists create new map of brain's immune system | last = | first = | authorlink = | date = Feb 19, 2019 | website = ScienceDaily|language=en|archive-url=|archive-date=|access-date=2019-03-31}}</ref> [[Microglia]] cells are a part of that immune system.<ref>{{Cite web | title = Brain immune system is key to recovery from motor neuron degeneration: Results in study point to new approaches for ALS therapy|url=https://www.sciencedaily.com/releases/2018/02/180220143439.htm|website=ScienceDaily|access-date=2019-03-31|language=en | date = Feb 20, 2018 | last = | first = | authorlink = |archive-url=|archive-date=}}</ref>

Injury to the brain or spinal cord, such as those caused by [[stroke]] or [[trauma]], result in a considerable weakening of the immune system.<ref>{{Cite web | title = An interconnection between the nervous and immune system: Neuroendocrine reflex triggers infections|url=https://www.sciencedaily.com/releases/2017/09/170919102530.htm|website=ScienceDaily|access-date=2019-03-31|language=en | date = Sep 29, 2017 | last = | first = | authorlink = |archive-url=|archive-date=}}</ref>
=== ME patient autopsies have shown changes to the spinal cord ===
*[[Sophia Mirza]]'s autopsy showed her [[Sophia Mirza#Death|spine contained massive infection.]] (Note: Sophia's Death Notice has her death due to [[Chronic fatigue syndrome|CFS]])
*[[Lynn Gilderdale]] had [[Lynn Gilderdale#Death|ganglionitis which is an inflammation of dorsal root ganglia of her spine]], typical for a neurological illness.
*[[Merryn Crofts]]'s autopsy showed [[Merryn Crofts#Ganglionitis|she had ganglionitis]].

== Learn more ==
*[https://www.youtube.com/watch?v=fbt3H3JxRMA 2-Minute Neuroscience: Spinal Cord Cross-section]
*[https://www.youtube.com/watch?v=MM7YNKJj_Lg 2-Minute Neuroscience: Exterior of the Spinal Cord]
*[https://en.wikipedia.org/wiki/Spinal_nerve Spinal nerve]

== See also ==
*[[Central nervous system]]
*[[Vertebral column]]

== References ==
{{Reflist}}

[[Category:Body systems]]
[[Category:Neurology]]
[[Category:Central nervous system]]
[[Category:Anatomy]]

Autism spectrum disorder

2025-02-02T19:30:07Z

Galimatias:autistic burnout section

'''Autism spectrum disorder''' 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.<ref>{{Cite web|url=https://www.cdc.gov/autism/data-research/index.html|title=Data and Statistics on Autism Spectrum Disorder|last=CDC|date=2024-07-19|website=Autism Spectrum Disorder (ASD)|language=en-us|access-date=2025-01-25}}</ref>

== Causes ==
A 2017 Swedish study suggests autism is 83% heritable.<ref>{{Cite journal|title=The Heritability of Autism Spectrum Disorder|date=2017-09-26|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818813/|journal=JAMA|volume=318|issue=12|pages=1182–1184|last=Sandin|first=Sven|last2=Lichtenstein|first2=Paul|last3=Kuja-Halkola|first3=Ralf|last4=Hultman|first4=Christina|last5=Larsson|first5=Henrik|last6=Reichenberg|first6=Abraham|doi=10.1001/jama.2017.12141|pmc=5818813|pmid=28973605|issn=0098-7484}}</ref> 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.<ref>{{Cite journal|title=The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology|date=2015|url=https://www.annualreviews.org/content/journals/10.1146/annurev-pathol-012414-040405#right-ref-B9|journal=Annual Reviews|volume=10|pages=111-144|last=Chen|first=Jason|last2=Penagarikano|first2=Olga|last3=Belgard|first3=T. Grant|last4=Swarup|first4=Vivek|last5=Geschwind|first5=Daniel}}</ref>

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.<ref>{{Cite journal|title=Association between Viral Infections and Risk of Autistic Disorder: An Overview|date=2021-03-10|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999368/|journal=International Journal of Environmental Research and Public Health|volume=18|issue=6|pages=2817|last=Shuid|first=Ahmad Naqib|last2=Jayusman|first2=Putri Ayu|last3=Shuid|first3=Nazrun|last4=Ismail|first4=Juriza|last5=Kamal Nor|first5=Norazlin|last6=Mohamed|first6=Isa Naina|doi=10.3390/ijerph18062817|pmc=7999368|pmid=33802042|issn=1661-7827}}</ref>
* Prenatal exposure to the the insecticide dichlorodiphenyltrichloroethane (DDT).<ref>{{Cite journal|title=Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort|date=2018-11-01|url=https://pubmed.ncbi.nlm.nih.gov/30111184/|journal=The American Journal of Psychiatry|volume=175|issue=11|pages=1094–1101|last=Brown|first=Alan S.|last2=Cheslack-Postava|first2=Keely|last3=Rantakokko|first3=Panu|last4=Kiviranta|first4=Hannu|last5=Hinkka-Yli-Salomäki|first5=Susanna|last6=McKeague|first6=Ian W.|last7=Surcel|first7=Heljä-Marja|last8=Sourander|first8=Andre|doi=10.1176/appi.ajp.2018.17101129|pmc=6377859|pmid=30111184|issn=1535-7228}}</ref>
* 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.<ref>{{Cite journal|title=Residential proximity to freeways and autism in the CHARGE study|date=2011-06|url=https://pubmed.ncbi.nlm.nih.gov/21156395/|journal=Environmental Health Perspectives|volume=119|issue=6|pages=873–877|last=Volk|first=Heather E.|last2=Hertz-Picciotto|first2=Irva|last3=Delwiche|first3=Lora|last4=Lurmann|first4=Fred|last5=McConnell|first5=Rob|doi=10.1289/ehp.1002835|pmc=3114825|pmid=21156395|issn=1552-9924}}</ref>

It's important to note that environmental triggers generally do not cause autism by themselves.<ref>{{Cite web|url=https://www.niehs.nih.gov/health/topics/conditions/autism|title=Autism|website=National Institute of Environmental Health Sciences|language=en|access-date=2025-01-25}}</ref> 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.<ref name=":0">{{Cite web|url=https://medschool.ucla.edu/news-article/is-autism-genetic|title=Is Autism Genetic?|date=2024-04-10|website=UCLA Medical School|language=en|access-date=2025-01-26}}</ref> Research repeatedly demonstrates no connection between autism and childhood vaccination.<ref>{{Cite journal|title=The myth of vaccination and autism spectrum|date=January 2022|url=https://www.sciencedirect.com/science/article/pii/S1090379821002312|journal=European Journal of Paediatric Neurology|volume=36|pages=151-158|last=Gabis|first=Lydia|last2=Attia|first2=Odelia|last3=Goldman|first3=Mia|last4=Barak|first4=Noy|last5=Tefera|first5=Paula|last6=Shefer|first6=Shahar}}</ref>

== Similarities to ME/CFS ==
People with autism can develop many of the same symptoms as ME/CFS, including:<ref name="Bileviciute Ljungar, 2018" />

* [[Brain fog]]
* Fatigue, especially after stressful situations
* [[Irritable bowel syndrome]] (IBS)<ref>{{Cite journal|title=Gastrointestinal issues and Autism Spectrum Disorder|date=2020-7|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608248/|journal=Child and adolescent psychiatric clinics of North America|volume=29|issue=3|pages=501–513|last=Madra|first=Moneek|last2=Ringel|first2=Roey|last3=Margolis|first3=Kara G.|doi=10.1016/j.chc.2020.02.005|pmc=8608248|pmid=32471598|issn=1056-4993}}</ref>
* Sensory sensitivity
* Sleep disturbances

== Autistic Burnout ==

====== Autistic Burnout Symptoms ======
Autistic burnout is a phenomenon characterized by:<ref>{{Cite journal|title=“Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew”: Defining Autistic Burnout|date=2020-06-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313636/|journal=Autism in Adulthood|volume=2|issue=2|pages=132–143|last=Raymaker|first=Dora M.|last2=Teo|first2=Alan R.|last3=Steckler|first3=Nicole A.|last4=Lentz|first4=Brandy|last5=Scharer|first5=Mirah|last6=Delos Santos|first6=Austin|last7=Kapp|first7=Steven K.|last8=Hunter|first8=Morrigan|last9=Joyce|first9=Andee|last10=Nicolaidis|first10=Christina|doi=10.1089/aut.2019.0079|pmc=7313636|pmid=32851204|issn=2573-9581}}</ref>

* '''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 ======
The term "autistic burnout" was coined around 2005 and reached mainstream awareness around 2018.<ref>{{Cite journal|title=What Is Autistic Burnout? A Thematic Analysis of Posts on Two Online Platforms|date=2022-03-01|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992925/|journal=Autism in Adulthood: Challenges and Management|volume=4|issue=1|pages=52–65|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda L.|last3=Adikari|first3=Achini|last4=Lowe|first4=Jennifer|last5=Dissanayake|first5=Cheryl|doi=10.1089/aut.2021.0021|pmc=8992925|pmid=36605565|issn=2573-9581}}</ref> Some research may also call it "autistic regression."<ref>{{Cite journal|title=Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update|date=2021-03|url=https://pubmed.ncbi.nlm.nih.gov/33491292/|journal=Autism Research: Official Journal of the International Society for Autism Research|volume=14|issue=3|pages=582–598|last=Tan|first=Christine|last2=Frewer|first2=Veronica|last3=Cox|first3=Georgina|last4=Williams|first4=Katrina|last5=Ure|first5=Alexandra|doi=10.1002/aur.2463|pmid=33491292|issn=1939-3806}}</ref> 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.<ref>{{Cite journal|title=Measuring and validating autistic burnout|date=Apr, 25, 2024|url=https://onlinelibrary.wiley.com/doi/10.1002/aur.3129|journal=Autism Research|volume=17|issue=7|pages=1417-1449|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Li|first3=Xia|last4=Dissanayake|first4=Cheryl}}</ref> (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.<ref name=":1">{{Cite journal|title=Defining autistic burnout through experts by lived experience: Grounded Delphi method investigating #AutisticBurnout|date=Jun 4, 2021|url=https://journals.sagepub.com/doi/10.1177/13623613211019858|journal=Autism|volume=25|issue=8|last=Higgins|first=Julianne|last2=Arnold|first2=Samuel|last3=Weise|first3=Janelle|last4=Pellicano|first4=Elizabeth|last5=Trollor|first5=Jullian}}</ref>

This distinction is important because it affects treatment. Currently rest is the primary method of recovery from autistic burnout. However, some depression therapies, such as Behavioral Activation Therapy (BAT), urge people to push through tiredness to combat feelings of apathy. BAT is not recommended for people experiencing autistic burnout.<ref name=":1" />

====== Autistic Burnout Triggers ======
Autistic burnout typically occurs when the stressors of a person's life overwhelm their coping mechanisms. Research suggest a large contributing factor is masking - when a person suppresses their autistic traits to avoid discrimination. This may look like memorizing scripts for conversations, consciously maintaining eye contact, or leaving their ear defenders at home to avoid looking 'different'. The chronic stress of masking may contribute to [[Mitochondrion|mitochondrial dysfunction]] and ultimately end in a burnout episode.<ref>{{Cite journal|title=A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology|date=2022-11-25|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732262/|journal=Frontiers in Psychiatry|volume=13|pages=985713|last=Mahony|first=Caitlyn|last2=O'Ryan|first2=Colleen|doi=10.3389/fpsyt.2022.985713|pmc=9732262|pmid=36506457|issn=1664-0640}}</ref><ref name=":2">{{Cite journal|title=A conceptual model of risk and protective factors for autistic burnout|date=Apr 13, 2022|url=https://pubmed.ncbi.nlm.nih.gov/35416430/|journal=Autism Research|volume=15|issue=6|pages=976-987|last=Mantzalas|first=Jane|last2=Richdale|first2=Amanda|last3=Dissanayake|first3=Cheryl}}</ref>

Transitional periods like puberty or graduation can also be a risk factor. These periods often involve an increase in demands on a person's energy and time, while also removing access to the routines and support networks that helped a person cope in the past.<ref name=":2" />

==Notable studies==
*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.<ref>{{Cite journal|title=Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, multisite pain, and fatigue|date=2024-11-23|url=https://www.nature.com/articles/s41398-024-03184-4|journal=Translational Psychiatry|volume=14|issue=1|pages=1–9|last=Li|first=Yiran|last2=Xie|first2=Tian|last3=Vos|first3=Melissa|last4=Snieder|first4=Harold|last5=Hartman|first5=Catharina A.|language=en|doi=10.1038/s41398-024-03184-4|pmc=11585586|pmid=39580447|issn=2158-3188}}</ref>
*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 [[Interleukin 6|IL-6]].
*2022 - In a study of 973 autistic adults, 21% had a formal diagnosis of one or more [[Central sensitization|central sensitivity syndromes]] (CSS). These included [[fibromyalgia]], ME/CFS, IBS, [[Restless legs syndrome|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.<ref name="Bileviciute Ljungar, 2018" /> [http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 (Abstract)]

==Learn more==
*

==References==
<references>
<ref name="Bileviciute Ljungar, 2018">
{{Citation | last1 = Bileviciute Ljungar | first1 = Indre | author-link1 = Indre Bileviciute Ljungar | last2 = Maroti | first2 = Daniel | author-link2 = | last3 = Bejerot | first3 = Susanne | author-link3 = | title = Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder | journal = Scandinavian Journal of Psychology | volume = | issue = | page = | date = 2018 | pmid = | doi = | url = http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A1190903&dswid=7740 }}</ref>
</references>

[[Category:Diagnoses]]

Autism spectrum disorder

2025-02-02T17:04:54Z

Galimatias:added studies

Autism spectrum disorder

2025-01-26T00:23:08Z

Galimatias:added causes, similarities to ME/CFS, and one notable study. I hope to add more detail and possibly an autistic burnout page later on.

Talk:Microbiome

2025-01-25T00:11:58Z

Galimatias:Created page with "== -- ~~~~ == Nose Flora and Skin Flora need expansion. I'd recommend adding Vaginal flora too."

== -- [[User:Galimatias|Galimatias]] ([[User talk:Galimatias|talk]]) 00:11, January 25, 2025 (UTC) ==

Nose Flora and Skin Flora need expansion. I'd recommend adding Vaginal flora too.

Microbiome

2025-01-25T00:11:05Z

Galimatias:I expanded information on Damiano study. I also wrote a section for the oral flora. I removed 'ulcerative colitis" from the list of similar dysbiosis issues since the study referenced there was not using the same metric as the other studies, so direct comparison is difficult.

{{Cleanup/Citations needed | date = Mar 2021}}
The '''microbiome''' is the community of microorganisms (such as [[bacteria]], [[fungus|fungi]], and [[virus]]es) that inhabit a particular environment, especially the human body.
<ref>{{Cite web|website=Merrian-Webster Medical Dictionary|access-date=2021-02-20 | title = Definition of MICROBIOME|url=https://www.merriam-webster.com/dictionary/microbiome}}</ref>

==Anatomical areas==
The microorganisms live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].<ref>{{Cite journal|title=Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome|date=2017-04-26|url=https://pubmed.ncbi.nlm.nih.gov/28441964/|journal=Microbiome|volume=5|issue=1|pages=44|last=Nagy-Szakal|first=Dorottya|last2=Williams|first2=Brent L.|last3=Mishra|first3=Nischay|last4=Che|first4=Xiaoyu|last5=Lee|first5=Bohyun|last6=Bateman|first6=Lucinda|last7=Klimas|first7=Nancy G.|last8=Komaroff|first8=Anthony L.|last9=Levine|first9=Susan|last10=Montoya|first10=Jose G.|last11=Peterson|first11=Daniel L.|doi=10.1186/s40168-017-0261-y|pmc=5405467|pmid=28441964|issn=2049-2618}}</ref>

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. Around 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].<ref>{{Cite journal|title=Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens|date=October 2003|url=https://www.sciencedirect.com/science/article/abs/pii/S1369527403001176|journal=Current Opinion in Microbiology|volume=6|issue=5|pages=457-461|last=Vendantam|first=Gayatari|last2=Hecht|first2=David}}</ref>

A 2021 study by Damiano found significant differences in the composition of gut bacteria between CFS/ME patients and healthy controls. People with ME/CFS had:<ref name="Damiano2021" />

* Higher relative abundance of bacteria in the genus ''Bacteroides'' (phylum Bacteriodetes) and the genus ''Phascolarctobacterium'' (phylum Firmicutes)
* Lower relative abundance of bacteria in the genus ''Anaerostipes'' and genus ''Ruminococcus'' (both from phylum Firmicutes)

However, the study authors were unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME, or if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name="Damiano2021" />

Damiano et al. suggest the intestinal microbial profile recorded in their study is consistent with the profiles reported for other autoimmune conditions. For example, a 2021 review on pediatric [[inflammatory bowel disease]] found a reduced abundance of bacteria in genus ''Anaerostipes.''<ref>{{Cite journal|title=Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review|date=2021-02-02|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884334/|journal=Frontiers in Pediatrics|volume=9|pages=626232|last=Zhuang|first=Xiaojun|last2=Liu|first2=Caiguang|last3=Zhan|first3=Shukai|last4=Tian|first4=Zhenyi|last5=Li|first5=Na|last6=Mao|first6=Ren|last7=Zeng|first7=Zhirong|last8=Chen|first8=Minhu|doi=10.3389/fped.2021.626232|pmc=7884334|pmid=33604319|issn=2296-2360}}</ref> A 2014 study found a higher abundance of the genus ''Bacteroides'' in people with [[systemic lupus erythematous]].<ref>{{Cite journal|title=Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus|date=September 30, 2014|url=https://journals.asm.org/doi/10.1128/mbio.01548-14|journal=mBio|volume=5|issue=5|last=Hevia|first=Arancha|last2=Milani|first2=Christian|last3=Lopez|first3=Patricia|last4=Cuervo|first4=Adriana|last5=Arboleya|first5=Silvia|last6=Duranti|first6=Sabrina|last7=Turroni|first7=Francesca|last8=Suarez|first8=Ana|last9=Gueimonde|first9=Miguel|doi=10.1128/mbio.01548-14}}</ref>

===Oral flora===

The microbiome in the oral cavity (mouth and throat) is the second largest after the gut microbiome. The state of your oral microbiome can affect the rest of your body in two major ways<ref>{{Cite journal|title=Oral microbiota in human systematic diseases|date=2022-03-02|url=https://www.nature.com/articles/s41368-022-00163-7|journal=International Journal of Oral Science|volume=14|issue=1|pages=1–11|last=Peng|first=Xian|last2=Cheng|first2=Lei|last3=You|first3=Yong|last4=Tang|first4=Chengwei|last5=Ren|first5=Biao|last6=Li|first6=Yuqing|last7=Xu|first7=Xin|last8=Zhou|first8=Xuedong|language=en|doi=10.1038/s41368-022-00163-7|pmc=8891310|pmid=35236828|issn=2049-3169}}</ref>:

# Microorganisms in the mouth can travel "downstream" to the gut microbiome.
# An oral infection can cause bacteria and their metabolites (digestive byproducts) to enter the bloodstream. This can activate the immune system and cause widespread inflammation.

The 2021 Damiano study above also found differences in the composition of oral bacteria between CFS/ME patients and healthy controls. People with CFS/ME had higher relative abundance of bacteria in the genus ''Rothia'' (phylum Actinobacteria).<ref name="Damiano2021" />

==ME/CFS==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan | first1 = Shaheen E| last2 = Kirchgessner | first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13 | date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[myalgic encephalomyelitis]]\[[chronic fatigue syndrome]].

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[interleukin 1|IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref>{{Cite journal | last = Sheedy | first = John R. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = Kenny De Meirleir | date = Jul 2009 | title = Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4 | pages = 621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> decreased levels of [[bifidobacteria]],<ref>{{Cite journal | last = Logan | first = Alan C | authorlink = | last2 = Venket Rao | first2 = A | authorlink2 = | last3 = Irani | first3 = Dinaz | authorlink3 = | date = Jun 2003 | title = Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6 | pages = 915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following [[exercise]]). In the blood, the study found increased [[Clostridium]] fifteen minutes after exercise and increased [[bacilli]] 48 hours later.<ref name="Shukla2015" /><ref>{{citation | last = Johnson | first = Cort | date = December 21, 2015 | title = Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>{{citation needed | date = 2021 | reason=Add original research}}

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viruses can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation | last = Racaniello | first = Vincent | date = 10 December 2014 | title = How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref>{{Cite journal | last = Sheedy | first = John R. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = Kenny De Meirleir | date = Jul 2009 | title = Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4 | pages = 621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal | last = Giloteaux | first = Ludovic | authorlink = Ludovic Giloteaux | last2 = Goodrich | first2 = Julia K. | authorlink2 = | last3 = Walters | first3 = William A. | authorlink3 = | last4 = Levine | first4 = Susan M. | authorlink4 = Susan Levine | last5 = Ley | first5 = Ruth E. | authorlink5 = | last6 = Hanson | first6 = Maureen R. | authorlink6 = Maureen Hanson | date = Dec 2016 | title = Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal | last = Wang | first = Taiwu | last2 = Yu | first2 = Lei | last3 = Xu | first3 = Cong | last4 = Pan | first4 = Keli | last5 = Mo | first5 = Minglu | last6 = Duan | first6 = Mingxiang | last7 = Zhang | first7 = Yao | last8 = Xiong | first8 = Hongyan | date = 2018-09-11 | title = Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function | url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9| pages = e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal | last = Proal | first = Amy | authorlink = Amy Proal | last2 = Marshall | first2 = Trevor | authorlink2 = Trevor Marshall | date = Nov 2018 | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name="Damiano2021">{{Cite journal | last = Lupo | first = Giuseppe Francesco Damiano | author-link = | last2 = Rocchetti | first2 = Gabriele | authorlink2 = | last3 = Lucini | first3 = Luigi | authorlink3 = | last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso | last5 = Manara | first5 = Elena | authorlink5 = | last6 = Bertelli | first6 = Matteo | authorlink6 = | last7 = Puglisi | first7 = Edoardo | last8 = Capelli | first8 = Enrica | authorlink8 = Enrica Capelli | date = March 2021 | title = Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1 | pages = 7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation | last = Bakalar | first = Nicholas | date = 7 July 2016 | title = Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation | last = Cha | first = Ariana Eunjung | date = Jun 30, 2016 | title = New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation | last = Ramanujan | first = Krishna | date = 24 June 2016 | title = Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation | last = Johnson | first = Cort | date = 21 February 2016 | title = Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women | url = http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Probiotics]]
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Indoor microbiome]]
*[[Dr Markov's chronic bacterial intoxication syndrome (CBIS) theory of ME/CFS]] (Dr Markov has evidence that ME/CFS is caused by a dysbiosis in the kidneys)

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<ref name="Maslowski2011">{{Citation| doi = 10.1038/ni0111-5| issn = 1529-2916| volume = 12 | issue = 1| pages = 5–9| last1 = Maslowski | first1 = Kendle M. | last2 = Mackay | first2 = Charles R.| title = Diet, gut microbiota and immune responses| journal = Nature Immunology | date = January 2011 | pmid = 21169997}}</ref>
<ref name="koren2012">{{Citation| doi = 10.1016/j.cell.2012.07.008| issn = 1097-4172| volume = 150 | issue = 3| pages = 470–480| last1 = Koren | first1 = Omry | last2 = Goodrich | first2 = Julia K. | last3 = Cullender | first3 = Tyler C. | last4 = Spor | first4 = Aymé| last5 = Laitinen | first5 = Kirsi | last6 = Bäckhed | first6 = Helene Kling | last7 = Gonzalez | first7 = Antonio | last8 = Werner | first8 = Jeffrey J. | last9 = Angenent | first9 = Largus T. | last10 = Knight | first10 = Rob| last11 = Bäckhed | first11 = Fredrik | last12 = Isolauri | first12 = Erika | last13 = Salminen | first13 = Seppo | last14 = Ley | first14 = Ruth E.| title = Host remodeling of the gut microbiome and metabolic changes during pregnancy| journal = Cell| date = 2012-08-03 | pmid = 22863002}}</ref>
<ref name="Dinan2012">{{Citation| doi = 10.1016/j.psyneuen.2012.03.007| issn = 0306-4530| volume = 37 | issue = 9| pages = 1369–1378| last1 = Dinan | first1 = Timothy G. | last2 = Cryan | first2 = John F.| title = Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology| journal = Psychoneuroendocrinology| access-date = 2016-12-13 | date = September 2012| url = http://www.sciencedirect.com/science/article/pii/S0306453012000935}}</ref>
<ref name="Fremont2013">{{Citation| doi = 10.1016/j.anaerobe.2013.06.002| issn = 1095-8274| volume = 22 | issue = | pages = 50–56| last1 = Frémont | first1 = Marc| last2 = Coomans | first2 = Danny | last3 = Massart | first3 = Sebastien | last4 = De Meirleir | first4 = Kenny| title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients| journal = Anaerobe | date = August 2013 | pmid = 23791918}}</ref>
<ref name="Borody2012">{{Citation| issn = 1328-8040| volume = 31 | issue = 3| pages = 3| last1 = Borody | first1 = Thomas J. | last2 = Nowak | first2 = Anna | last3 = Finlayson | first3 = Sarah| title = The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy| journal = Journal of the Australasian College of Nutritional and Environmental Medicine| access-date = 2016-12-13 | date = December 2012| url = http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/}}</ref>
<ref name="Morris, 2016">{{Citation | last1 = Morris | first1 = Gerwyn | authorlink1 = Gerwyn Morris | last2 = Berk | first2 = Michael | authorlink2 = Michael Berk | last3 = Carvalho | first3 = A.F. | authorlink3 = | last4 = Caso | first4 = J.R. | authorlink4 = | last5 = Sanz | first5 = Y. | authorlink5 = | last6 = Maes | first6 = Michael | authorlink6 = Michael Maes | title = The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome. | journal = Current Pharmaceutical Design | volume = | issue = | pages = | date = 2016 | pmid = 27634186 }}</ref>
<ref name="Nagy-Szakal, 2017">{{Citation | last1 = Nagy-Szakal | first1 = Dorottya | authorlink1 = Dorottya Nagy-Szakal | last2 = Williams | first2 = Brent L. | authorlink2 = | last3 = Mishra | first3 = Nischay | authorlink3 = | last4 = Che | first4 = Xiaoyu | authorlink4 = | last5 = Lee | first5 = Bohyun | authorlink5 = | last6 = Bateman | first6 = Lucinda | authorlink6 = Lucinda Bateman | last7 = Klimas | first7 = Nancy G. | authorlink7 = Nancy Klimas | last8 = Komaroff | first8 = Anthony L. | authorlink8 = Anthony Komaroff | last9 = Levine | first9 = Susan | authorlink9 = Susan Levine | last10 = Montoya | first10 = Jose G. | authorlink10 = Jose Montoya | last11 = Peterson | first11 = Daniel L. | authorlink11 = Daniel Peterson | last12 = Ramanan | first12 = Devi | authorlink12 = | last13 = Jain | first13 = Komal | authorlink13 = | last14 = Eddy | first14 = Meredith L. | authorlink14 = | last15 = Hornig | first15 = Mady | authorlink15 = Mady Hornig | last16 = Lipkin | first16 = W. Ian | authorlink16 = Ian Lipkin | title = Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome | journal = Microbiome | volume = 5 | issue = 44 | pages = | date = 2017 | pmid = | doi = 10.1186/s40168-017-0261-y }}</ref>
<ref name="Newberry, 2018">{{Citation | last1 = Newberry | first1 = F. | authorlink1 = | last2 = Hsieh | first2 = S.-Y. | authorlink2 = | last3 = Wileman | first3 = T. | authorlink3 = | last4 = Carding | first4 = S.R. | authorlink4 = Simon Carding | title = Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome? | journal = Clinical Science | volume = 132 | issue = 5 | pages = 523–542 | date = 2018 | pmid = | doi = 10.1042/CS20171330 }}</ref>
</references>

[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2025-01-23T23:59:40Z

Galimatias:added requested citation

{{Cleanup/Citations needed | date = Mar 2021}}
The '''microbiome''' is the community of microorganisms (such as [[bacteria]], [[fungus|fungi]], and [[virus]]es) that inhabit a particular environment, especially the human body.
<ref>{{Cite web|website=Merrian-Webster Medical Dictionary|access-date=2021-02-20 | title = Definition of MICROBIOME|url=https://www.merriam-webster.com/dictionary/microbiome}}</ref>

==Anatomical areas==
The microorganisms live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].<ref>{{Cite journal|title=Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome|date=2017-04-26|url=https://pubmed.ncbi.nlm.nih.gov/28441964/|journal=Microbiome|volume=5|issue=1|pages=44|last=Nagy-Szakal|first=Dorottya|last2=Williams|first2=Brent L.|last3=Mishra|first3=Nischay|last4=Che|first4=Xiaoyu|last5=Lee|first5=Bohyun|last6=Bateman|first6=Lucinda|last7=Klimas|first7=Nancy G.|last8=Komaroff|first8=Anthony L.|last9=Levine|first9=Susan|last10=Montoya|first10=Jose G.|last11=Peterson|first11=Daniel L.|doi=10.1186/s40168-017-0261-y|pmc=5405467|pmid=28441964|issn=2049-2618}}</ref>

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==ME/CFS==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan | first1 = Shaheen E| last2 = Kirchgessner | first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13 | date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[myalgic encephalomyelitis]]\[[chronic fatigue syndrome]].

A 2021 study by Damiano and colleagues observed significant differences in several types of bacteria in the saliva and gut in CFS/ME patients compared to controls, but was unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME and if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name="Damiano2021" /> The study showed that the intestinal microbial profile recorded in a group of ME/CFS patients was consistent with the reported for other autoimmune conditions, such as Crohn’s disease, [[ulcerative colitis]] and [[systemic lupus erythematous]].{{citation needed | date = 2021}}

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[interleukin 1|IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref>{{Cite journal | last = Sheedy | first = John R. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = Kenny De Meirleir | date = Jul 2009 | title = Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4 | pages = 621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> decreased levels of [[bifidobacteria]],<ref>{{Cite journal | last = Logan | first = Alan C | authorlink = | last2 = Venket Rao | first2 = A | authorlink2 = | last3 = Irani | first3 = Dinaz | authorlink3 = | date = Jun 2003 | title = Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6 | pages = 915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following [[exercise]]). In the blood, the study found increased [[Clostridium]] fifteen minutes after exercise and increased [[bacilli]] 48 hours later.<ref name="Shukla2015" /><ref>{{citation | last = Johnson | first = Cort | date = December 21, 2015 | title = Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>{{citation needed | date = 2021 | reason=Add original research}}

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viruses can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation | last = Racaniello | first = Vincent | date = 10 December 2014 | title = How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref>{{Cite journal | last = Sheedy | first = John R. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = Kenny De Meirleir | date = Jul 2009 | title = Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4 | pages = 621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal | last = Giloteaux | first = Ludovic | authorlink = Ludovic Giloteaux | last2 = Goodrich | first2 = Julia K. | authorlink2 = | last3 = Walters | first3 = William A. | authorlink3 = | last4 = Levine | first4 = Susan M. | authorlink4 = Susan Levine | last5 = Ley | first5 = Ruth E. | authorlink5 = | last6 = Hanson | first6 = Maureen R. | authorlink6 = Maureen Hanson | date = Dec 2016 | title = Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal | last = Wang | first = Taiwu | last2 = Yu | first2 = Lei | last3 = Xu | first3 = Cong | last4 = Pan | first4 = Keli | last5 = Mo | first5 = Minglu | last6 = Duan | first6 = Mingxiang | last7 = Zhang | first7 = Yao | last8 = Xiong | first8 = Hongyan | date = 2018-09-11 | title = Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function | url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9| pages = e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal | last = Proal | first = Amy | authorlink = Amy Proal | last2 = Marshall | first2 = Trevor | authorlink2 = Trevor Marshall | date = Nov 2018 | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name="Damiano2021">{{Cite journal | last = Lupo | first = Giuseppe Francesco Damiano | author-link = | last2 = Rocchetti | first2 = Gabriele | authorlink2 = | last3 = Lucini | first3 = Luigi | authorlink3 = | last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso | last5 = Manara | first5 = Elena | authorlink5 = | last6 = Bertelli | first6 = Matteo | authorlink6 = | last7 = Puglisi | first7 = Edoardo | last8 = Capelli | first8 = Enrica | authorlink8 = Enrica Capelli | date = March 2021 | title = Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1 | pages = 7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation | last = Bakalar | first = Nicholas | date = 7 July 2016 | title = Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation | last = Cha | first = Ariana Eunjung | date = Jun 30, 2016 | title = New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation | last = Ramanujan | first = Krishna | date = 24 June 2016 | title = Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation | last = Johnson | first = Cort | date = 21 February 2016 | title = Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women | url = http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Probiotics]]
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Indoor microbiome]]
*[[Dr Markov's chronic bacterial intoxication syndrome (CBIS) theory of ME/CFS]] (Dr Markov has evidence that ME/CFS is caused by a dysbiosis in the kidneys)

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<ref name="koren2012">{{Citation| doi = 10.1016/j.cell.2012.07.008| issn = 1097-4172| volume = 150 | issue = 3| pages = 470–480| last1 = Koren | first1 = Omry | last2 = Goodrich | first2 = Julia K. | last3 = Cullender | first3 = Tyler C. | last4 = Spor | first4 = Aymé| last5 = Laitinen | first5 = Kirsi | last6 = Bäckhed | first6 = Helene Kling | last7 = Gonzalez | first7 = Antonio | last8 = Werner | first8 = Jeffrey J. | last9 = Angenent | first9 = Largus T. | last10 = Knight | first10 = Rob| last11 = Bäckhed | first11 = Fredrik | last12 = Isolauri | first12 = Erika | last13 = Salminen | first13 = Seppo | last14 = Ley | first14 = Ruth E.| title = Host remodeling of the gut microbiome and metabolic changes during pregnancy| journal = Cell| date = 2012-08-03 | pmid = 22863002}}</ref>
<ref name="Dinan2012">{{Citation| doi = 10.1016/j.psyneuen.2012.03.007| issn = 0306-4530| volume = 37 | issue = 9| pages = 1369–1378| last1 = Dinan | first1 = Timothy G. | last2 = Cryan | first2 = John F.| title = Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology| journal = Psychoneuroendocrinology| access-date = 2016-12-13 | date = September 2012| url = http://www.sciencedirect.com/science/article/pii/S0306453012000935}}</ref>
<ref name="Fremont2013">{{Citation| doi = 10.1016/j.anaerobe.2013.06.002| issn = 1095-8274| volume = 22 | issue = | pages = 50–56| last1 = Frémont | first1 = Marc| last2 = Coomans | first2 = Danny | last3 = Massart | first3 = Sebastien | last4 = De Meirleir | first4 = Kenny| title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients| journal = Anaerobe | date = August 2013 | pmid = 23791918}}</ref>
<ref name="Borody2012">{{Citation| issn = 1328-8040| volume = 31 | issue = 3| pages = 3| last1 = Borody | first1 = Thomas J. | last2 = Nowak | first2 = Anna | last3 = Finlayson | first3 = Sarah| title = The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy| journal = Journal of the Australasian College of Nutritional and Environmental Medicine| access-date = 2016-12-13 | date = December 2012| url = http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/}}</ref>
<ref name="Morris, 2016">{{Citation | last1 = Morris | first1 = Gerwyn | authorlink1 = Gerwyn Morris | last2 = Berk | first2 = Michael | authorlink2 = Michael Berk | last3 = Carvalho | first3 = A.F. | authorlink3 = | last4 = Caso | first4 = J.R. | authorlink4 = | last5 = Sanz | first5 = Y. | authorlink5 = | last6 = Maes | first6 = Michael | authorlink6 = Michael Maes | title = The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome. | journal = Current Pharmaceutical Design | volume = | issue = | pages = | date = 2016 | pmid = 27634186 }}</ref>
<ref name="Nagy-Szakal, 2017">{{Citation | last1 = Nagy-Szakal | first1 = Dorottya | authorlink1 = Dorottya Nagy-Szakal | last2 = Williams | first2 = Brent L. | authorlink2 = | last3 = Mishra | first3 = Nischay | authorlink3 = | last4 = Che | first4 = Xiaoyu | authorlink4 = | last5 = Lee | first5 = Bohyun | authorlink5 = | last6 = Bateman | first6 = Lucinda | authorlink6 = Lucinda Bateman | last7 = Klimas | first7 = Nancy G. | authorlink7 = Nancy Klimas | last8 = Komaroff | first8 = Anthony L. | authorlink8 = Anthony Komaroff | last9 = Levine | first9 = Susan | authorlink9 = Susan Levine | last10 = Montoya | first10 = Jose G. | authorlink10 = Jose Montoya | last11 = Peterson | first11 = Daniel L. | authorlink11 = Daniel Peterson | last12 = Ramanan | first12 = Devi | authorlink12 = | last13 = Jain | first13 = Komal | authorlink13 = | last14 = Eddy | first14 = Meredith L. | authorlink14 = | last15 = Hornig | first15 = Mady | authorlink15 = Mady Hornig | last16 = Lipkin | first16 = W. Ian | authorlink16 = Ian Lipkin | title = Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome | journal = Microbiome | volume = 5 | issue = 44 | pages = | date = 2017 | pmid = | doi = 10.1186/s40168-017-0261-y }}</ref>
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[[Category:Body systems]]
[[Category:Microbiome]]

Neuron

2025-01-21T23:38:52Z

Galimatias:Added basic structure and communication sections

{{stub}}
[[File:Neuroncelldiagram.svg|320px|right|Neurons]]'''Neurons''' are [[nervous system]] cells that process and transmit information. They communicate with each other through chemicals called [[Neurotransmitter|neurotransmitters]].<ref>{{Cite web|url=https://www.ninds.nih.gov/health-information/public-education/brain-basics/brain-basics-life-and-death-neuron|title=Brain Basics: The Life and Death of a Neuron|date=November 29, 2024|website=National Institute of Neurological Disorders and Stroke}}</ref>

== Basic Structure ==
While there are many different types of neurons, most have the same basic structure.<ref name=":0">{{Cite web|url=https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/how-do-neurons-work|title=How do neurons work?|website=Queensland Brain Institute|access-date=January 21, 2025}}</ref>

* '''Cell Body (soma):''' The core of the cell that holds the nucleus and other organelles.
* '''Dendrites:''' Tree-like branches that receive information from other neurons.
** '''Spines:''' These are tiny bumps on the dendrites where neurotransmitters connect to the cell.
* '''Axon:''' A long 'tail' coming off the cell body. This is where the neuron sends information to other cells.
** '''Synaptic Terminals:''' Endpoints of the axon where the neuron releases neurotransmitters.

Neurons that cross between different brain regions often have '''myelin sheaths'''.<ref>{{Cite web|url=https://qbi.uq.edu.au/brain/brain-anatomy/axons-cable-transmission-neurons|title=Axons: The cable transmission of neurons|website=Queensland Brain Institute|access-date=January 21, 2025}}</ref> [[Myelin]] is a fatty substance that coats an axon. It provides insulation so the neuron's electrical signal can travel longer distances without degrading.

== Communication ==
Neural communication works through a process of electrical and chemical signaling.<ref name=":0" /> As an example, let's imagine a signal traveling through three neurons labeled ''A'', ''B'', and ''C''.

# Neuron A releases neurotransmitters out of its axon terminal. The chemicals float into the gap between Neurons A and B, called the '''synapse'''.
# The neurotransmitters latch onto the receptors on Neuron B's dendrites, much like a key into a lock.
# The ions from these neurotransmitters raise or lower the electric charge within Neuron B. Raising the electrical charge is called '''excitation.''' Lowering the cell's electric charge is called '''inhibition'''.
# When Neuron B's electrical charge raises to a certain level, the cell will '''spike'''. This event is also called an '''action potential'''.
# An electrical signal travels down Neuron B's axon to the terminal. The cell releases its neurotransmitter load into the synapse, where they will connect with Neuron C.

It's important to remember that a single neuron is often getting dozens or even hundreds of inputs at one time.<ref name=":0" /> These signals can combine or cancel each other out. Ultimately, it's the total result of all these inputs that determines whether a neuron will spike or not.

==See also ==

==Learn more ==

==References ==

[[Category:Neurology]]

P-value

2025-01-21T22:06:30Z

Galimatias:added requested citation

{{stub}}
A '''p value''' is a value calculated from a research study, which is intended to show whether an outcome is likely to have occurred by chance, when taking into consideration a number of other factors.<ref>{{Cite web|url=https://medical-dictionary.thefreedictionary.com/p+value| title = Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health|website=TheFreeDictionary.com|access-date=2019-04-21 | date = | last = | first = | authorlink = |archive-date=|url-status=| year = 2003 | editor-last = |edition=7th|archive-url=}}</ref><ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/P+value| title = Definition of P VALUE | last = Merrian-Webster Dictionary | first = | authorlink = | date = |website=Merrian-Webster Dictionary|language=en|archive-url=|archive-date=|url-status=|access-date=2019-04-21}}</ref> ''P'' values are not actually defined as a probability.<ref name=":0">{{Cite journal | last = Kuffner | first = Todd A. | authorlink = | last2 = Walker | first2 = Stephen G. | date = Jan 2, 2019| title = Why are p-Values Controversial?|url=https://doi.org/10.1080/00031305.2016.1277161|journal=The American Statistician|volume=73|issue=1|pages=1–3|doi=10.1080/00031305.2016.1277161|issn=0003-1305|quote=|via=}}</ref> '''P-hacking''' is the manipulation of research data to produce a clinically significant result for the calculated p value; meaning manipulating research results in order to achieve '''''p < 0.05''''' rather than publishing a [[null result]].<ref>{{Cite journal|title=The Extent and Consequences of P-Hacking in Science|date=2015-03-13|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359000/|journal=PLoS Biology|volume=13|issue=3|pages=e1002106|last=Head|first=Megan L.|last2=Holman|first2=Luke|last3=Lanfear|first3=Rob|last4=Kahn|first4=Andrew T.|last5=Jennions|first5=Michael D.|doi=10.1371/journal.pbio.1002106|pmc=4359000|pmid=25768323|issn=1544-9173}}</ref>

==Theory==

==Evidence==

==Null hypothesis significance testing==

==Articles and blogs ==
*2010, [https://www.sciencenews.org/article/odds-are-its-wrong Odds are it's wrong] - Article

* 2016, [https://www.tandfonline.com/doi/full/10.1080/00031305.2016.1154108?src=recsys The ASA's Statement on p-Values: Context, Process, and Purpose] - Editorial

==Notable studies ==

*2012, A peculiar prevalence of p values just below .05<ref>{{Cite journal | last = Masicampo | first = E.J. | authorlink = | last2 = Lalande | first2 = Daniel R. | date = Nov 2012| title = A peculiar prevalence of p values just below .05|url=https://doi.org/10.1080/17470218.2012.711335|journal=Quarterly Journal of Experimental Psychology|language=en|volume=65|issue=11|pages=2271–2279|doi=10.1080/17470218.2012.711335|issn=1747-0218|quote=|via=}}</ref> [https://doi.org/10.1080/17470218.2012.711335 (Abstract)]

*2013, The life of p: “Just significant” results are on the rise<ref>{{Cite journal | last = Leggett | first = Nathan C. | authorlink = | last2 = Thomas | first2 = Nicole A. | authorlink2 = | last3 = Loetscher | first3 = Tobias | authorlink3 = | last4 = Nicholls | first4 = Michael E.R. | authorlink4 = | authorlink5 = | date = Dec 1, 2013| title = The life of p: “Just significant” results are on the rise|url=https://doi.org/10.1080/17470218.2013.863371|journal=The Quarterly Journal of Experimental Psychology|volume=66|issue=12|pages=2303–2309|doi=10.1080/17470218.2013.863371|issn=1747-0218|pmid=24205936|quote=|via=}}</ref> [https://www.tandfonline.com/doi/full/10.1080/17470218.2013.863371?src=recsys (Abstract)]

*2015, [https://journals.sagepub.com/doi/full/10.1080/17470218.2014.982664 What ''p''-Hacking really looks like: A comment on Masicampo & Lalande (2012)]<ref>{{Cite journal | last = Lakens | first = Daniël | authorlink = | date = Apr 1, 2015 | title = Comment: What p-hacking really looks like: A comment on Masicampo and LaLande (2012)|url=https://doi.org/10.1080/17470218.2014.982664|journal=Quarterly Journal of Experimental Psychology|language=en|volume=68|issue=4 | pages = 829–832|doi=10.1080/17470218.2014.982664|issn=1747-0218|quote=|via=}}</ref> [https://www.researchgate.net/profile/Daniel_Lakens2/publication/269284058_What_p_-hacking_really_looks_like_A_comment_on_Masicampo_and_LaLande_2012/links/550e87c20cf212874168dbb0/What-p-hacking-really-looks-like-A-comment-on-Masicampo-and-LaLande-2012.pdf (Full text)]

*2015, Blinded by the Light: How a Focus on Statistical “Significance” May Cause p-Value Misreporting and an Excess of ''p''-Values Just Below .05 in Communication Science<ref>{{Cite journal | last = Vermeulen | first = Ivar | authorlink = | last2 = Beukeboom | first2 = Camiel J. | authorlink2 = | last3 = Batenburg | first3 = Anika | authorlink3 = | last4 = Avramiea | first4 = Arthur | authorlink4 = | last5 = Stoyanov | first5 = Dimo | authorlink5 = | last6 = van de Velde | first6 = Bob | last7 = Oegema | first7 = Dirk| date = Oct 2, 2015 | title = Blinded by the Light: How a Focus on Statistical “Significance” May Cause p-Value Misreporting and an Excess of p-Values Just Below .05 in Communication Science|url=https://doi.org/10.1080/19312458.2015.1096333|journal=Communication Methods and Measures|volume=9|issue=4|pages=253–279|doi=10.1080/19312458.2015.1096333|issn=1931-2458|quote=|via=}}</ref> [https://www.researchgate.net/profile/Camiel_Beukeboom/publication/285358940_Blinded_by_the_Light_How_a_Focus_on_Statistical_Significance_May_Cause_p_-Value_Misreporting_and_an_Excess_of_p_-Values_Just_Below_05_in_Communication_Science/links/56603d2f08ae1ef929857cde/Blinded-by-the-Light-How-a-Focus-on-Statistical-Significance-May-Cause-p-Value-Misreporting-and-an-Excess-of-p-Values-Just-Below-05-in-Communication-Science.pdf (Full text)]

*2016, Degrees of Freedom in Planning, Running, Analyzing, and Reporting Psychological Studies: A Checklist to Avoid ''p''-Hacking<ref>{{Cite journal | last = van Assen | first = Marcel A. L.M. | authorlink = | last2 = van Aert | first2 = Robbie C.M. | authorlink2 = | last3 = Bakker | first3 = Marjan | authorlink3 = | last4 = Augusteijn | first4 = Hilde E.M. | author-link4 = | last5 = Veldkamp | first5 = Coosje L.S. | authorlink5= | last6 = Wicherts | first6 = Jelte M. | date = 2016 | title=Degrees of Freedom in Planning, Running, Analyzing, and Reporting Psychological Studies: A Checklist to Avoid p-Hacking | url =https://www.frontiersin.org/articles/10.3389/fpsyg.2016.01832/full|journal=Frontiers in Psychology|language=English|volume=7|issue=|pages=|doi=10.3389/fpsyg.2016.01832|issn=1664-1078|quote=|via=}}</ref> [https://www.frontiersin.org/articles/10.3389/fpsyg.2016.01832/full (Full text)]

*2016, Why are ''p''-Values Controversial?<ref name=":0" /> [https://www.tandfonline.com/doi/full/10.1080/00031305.2016.1277161?src=recsys (Full text)]

==See also==
* [[:Category:Clinical trial terminology|Clinical trial terminology]]
* [[Randomized controlled trial]]
* [[Research bias in ME/CFS]]

==Learn more==

==References==
{{reflist}}

[[Category:Research terminology]]

Serotonin

2025-01-21T21:59:33Z

Galimatias:fixed typo

'''Serotonin''' or '''5-Hydroxytryptamine''' or '''5HT''' is a [[monoamine]] [[neurotransmitter]] derived from [[tryptophan]]. It can be found in the [[central nervous system]], [[gastrointestinal tract]], and [[platelet]]s.

==Synthesis==
Serotonin can function as both a peripheral [[hormone]] and a neurotransmitter.

==== Peripheral hormone ====
Around 95% of the body's serotonin is produced in the gut. More specifically, cells in your intestines called enterochromaffin cells produce serotonin and release it into the bloodstream. Platelets store this serotonin and release it when needed. Typically the level of serotonin in your blood is around 1-5 ng/mL. When your inflammatory systems activate, your peripheral serotonin levels can increase 1000-fold.<ref name=":0">{{Cite journal|title=Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill|date=May 3 2021|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8124334/|journal=International Journal of Molecular Sciences|volume=22|issue=9|last=Kanova|first=Marcela|last2=Kohout|first2=P|doi=10.3390/ijms22094837}}</ref>

==== Neurotransmitter ====
Since serotonin is water soluble, it can't cross the [[blood-brain barrier]] (BBB) easily. So the central nervous system produces its own supply of serotonin separate from the rest of the body. This supply of serotonin is synthesized in the raphe nuclei of the [[brainstem]].<ref name=":0" />

L-[[Tryptophan]] → [[5-Hydroxytryptophan|L-5-Hydroxytryptophan]] (5HTP) → 5-hydroxytryptamine (serotonin, 5HT)<ref>{{Cite journal|title=Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review|date=April 8, 2019|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6463810/|journal=Frontiers in Endocrinology|volume=8|issue=10|last=Hoglund|first=Erik|last2=Overli|first2=Oyvind|last3=Winberg|first3=Svante|doi=10.3389/fendo.2019.00158}}</ref>

==Function ==
Serotonin is a neurotransmitter and is activated by threats to homeostasis. According to Pereira et al. 2021), serotonin is linked to the regulation of:
* [[dysautonomia]]
* dyspnea
* [[fatigue]]
* glucose control
* [[hypothyroidism]]
* [[immune system]] functioning
* proprioception, and
* [[:Category:Sensitivity signs and symptoms|sensory sensitivity]]<ref name="Pereira2021" />

==Serotonin acting drugs==
[[Selective serotonin reuptake inhibitor]]s (SSRIs), the most popular class of [[antidepressant]]s, and [[selective serotonin and norepinephrine reuptake inhibitor]]s (SNRIs) have proved ineffective in [[ME/CFS]].<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 = N | authorlink13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | authorlink14 = John Chia | last15 = Darragh | first15 = A | authorlink15 = Austin Darragh | last16 = Gerken | first16 = A | authorlink16 = Anne Gerken | last17 = Jo | first17 = D | authorlink17 = Daehyun Jo | last18 = Lewis | first18 = DP | authorlink18 = Donald Lewis | last19 = Light | first19 = AR | authorlink19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref><ref name="canadianconsensus-CCC">{{Citation | last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers | last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson | last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner | last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested | last8 = Flor-Henry | first8 = Pierre| authorlink8 = Pierre Flor-Henry | last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi | last10 = Powles | first10 = AC Peter | authorlink10 = A C Peter Powles | last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey | last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | pages = 7-115 | date = 2003 | pmid = | doi = 10.1300/J092v11n01_02| url = http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf}}</ref> SSRIs indiscriminately modulate serotonin.<ref name="Pereira2021" />

==In human disease==

===ME/CFS===
The [[CRFR2 upregulation hypothesis]] of ME/CFS, which is the theory behind the clinicial trials of [[CT38]], proposes that serotonin is dysregulated in ME/CFS, and that excessive serotonin desensitizes 5HT1A, which then leaves serotonin elevated and a loss of homeostasis.<ref name="Pereira2021">{{Cite journal | last = Pereira | first=Gerard | last2 = Gillies | first2 = Hunter | last3 = Chanda | first3 = Sanjay | last4 = Corbett | first4 = Michael| last5 = Vernon | first5 = Suzanne D. | last6 = Milani | first6 = Tina | last7 = Bateman | first7 = Lucinda | date = 2021 | title=Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/article/10.3389/fnsys.2021.698240|journal=Frontiers in Systems Neuroscience|volume=15 | pages = 84|doi=10.3389/fnsys.2021.698240|issn=1662-5137|pmc=PMC8441022|pmid=34539356}}</ref>

==Notable studies ==
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26147001 A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice]
*2008, [https://www.ncbi.nlm.nih.gov/pubmed/18079067 Genetic evaluation of the serotonergic system in chronic fatigue syndrome]
*2004 [http://journals.lww.com/neuroreport/Abstract/2004/12030/Reduction_of_serotonin_transporters_of_patients.2.aspx Reduction of serotonin transporters of patients with chronic fatigue syndrome]
*1997, [https://www.ncbi.nlm.nih.gov/pubmed/9226729 Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.]

==Learn more==
*2016, [http://selfhacked.com/2016/02/12/5ht2a-receptors-a-root-cause-of-anxiety-fatigue-sleep-problems-and-cirs/ 5HT2A Receptors: A Root Cause of Anxiety, Fatigue, Sleep Problems and CIRS]

==See also==
*[[5HTP]]
*[[CRFR2 upregulation hypothesis]]
*[[CT38]]

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]
[[Category:Neurotransmitters]]
[[Category:Neurology]]

Serotonin

2025-01-21T21:58:16Z

Galimatias:Added explanation of serotonin synthesis

'''Serotonin''' or '''5-Hydroxytryptamine''' or '''5HT''' is a [[monoamine]] [[neurotransmitter]] derived from [[tryptophan]]. It can be found in the [[central nervous system]], [[gastrointestinal tract]], and [[platelet]]s.

==Synthesis==
Serotonin can function as both a peripheral [[hormone]] and a neurotransmitter.

==== Peripheral hormone ====
Around 95% of the body's serotonin is produced in the gut. More specifically, cells in your intestines called enterochromaffin cells produce serotonin and release it into the bloodstream. Platelets store this serotonin and release it when needed. Typically the level of serotonin in your blood is around 1-5 ng/mL. When your inflammatory systems activate, your peripheral serotonin levels can increase 1000-fold.<ref name=":0">{{Cite journal|title=Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill|date=May 3 2021|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8124334/|journal=International Journal of Molecular Sciences|volume=22|issue=9|last=Kanova|first=Marcela|last2=Kohout|first2=P|doi=10.3390/ijms22094837}}</ref>

==== Neurotransmitter ====
Since serotonin is water soluble, it can't cross the [[blood-brain barrier]] (BBB) easily. So on the central nervous system produces its own supply of serotonin separate from the rest of the body. This supply of serotonin is synthesized in the raphe nuclei of the [[brainstem]].<ref name=":0" />

L-[[Tryptophan]] → [[5-Hydroxytryptophan|L-5-Hydroxytryptophan]] (5HTP) → 5-hydroxytryptamine (serotonin, 5HT)<ref>{{Cite journal|title=Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review|date=April 8, 2019|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6463810/|journal=Frontiers in Endocrinology|volume=8|issue=10|last=Hoglund|first=Erik|last2=Overli|first2=Oyvind|last3=Winberg|first3=Svante|doi=10.3389/fendo.2019.00158}}</ref>

==Function ==
Serotonin is a neurotransmitter and is activated by threats to homeostasis. According to Pereira et al. 2021), serotonin is linked to the regulation of:
* [[dysautonomia]]
* dyspnea
* [[fatigue]]
* glucose control
* [[hypothyroidism]]
* [[immune system]] functioning
* proprioception, and
* [[:Category:Sensitivity signs and symptoms|sensory sensitivity]]<ref name="Pereira2021" />

==Serotonin acting drugs==
[[Selective serotonin reuptake inhibitor]]s (SSRIs), the most popular class of [[antidepressant]]s, and [[selective serotonin and norepinephrine reuptake inhibitor]]s (SNRIs) have proved ineffective in [[ME/CFS]].<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 = N | authorlink13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | authorlink14 = John Chia | last15 = Darragh | first15 = A | authorlink15 = Austin Darragh | last16 = Gerken | first16 = A | authorlink16 = Anne Gerken | last17 = Jo | first17 = D | authorlink17 = Daehyun Jo | last18 = Lewis | first18 = DP | authorlink18 = Donald Lewis | last19 = Light | first19 = AR | authorlink19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref><ref name="canadianconsensus-CCC">{{Citation | last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers | last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson | last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner | last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested | last8 = Flor-Henry | first8 = Pierre| authorlink8 = Pierre Flor-Henry | last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi | last10 = Powles | first10 = AC Peter | authorlink10 = A C Peter Powles | last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey | last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | pages = 7-115 | date = 2003 | pmid = | doi = 10.1300/J092v11n01_02| url = http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf}}</ref> SSRIs indiscriminately modulate serotonin.<ref name="Pereira2021" />

==In human disease==

===ME/CFS===
The [[CRFR2 upregulation hypothesis]] of ME/CFS, which is the theory behind the clinicial trials of [[CT38]], proposes that serotonin is dysregulated in ME/CFS, and that excessive serotonin desensitizes 5HT1A, which then leaves serotonin elevated and a loss of homeostasis.<ref name="Pereira2021">{{Cite journal | last = Pereira | first=Gerard | last2 = Gillies | first2 = Hunter | last3 = Chanda | first3 = Sanjay | last4 = Corbett | first4 = Michael| last5 = Vernon | first5 = Suzanne D. | last6 = Milani | first6 = Tina | last7 = Bateman | first7 = Lucinda | date = 2021 | title=Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/article/10.3389/fnsys.2021.698240|journal=Frontiers in Systems Neuroscience|volume=15 | pages = 84|doi=10.3389/fnsys.2021.698240|issn=1662-5137|pmc=PMC8441022|pmid=34539356}}</ref>

==Notable studies ==
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26147001 A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice]
*2008, [https://www.ncbi.nlm.nih.gov/pubmed/18079067 Genetic evaluation of the serotonergic system in chronic fatigue syndrome]
*2004 [http://journals.lww.com/neuroreport/Abstract/2004/12030/Reduction_of_serotonin_transporters_of_patients.2.aspx Reduction of serotonin transporters of patients with chronic fatigue syndrome]
*1997, [https://www.ncbi.nlm.nih.gov/pubmed/9226729 Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.]

==Learn more==
*2016, [http://selfhacked.com/2016/02/12/5ht2a-receptors-a-root-cause-of-anxiety-fatigue-sleep-problems-and-cirs/ 5HT2A Receptors: A Root Cause of Anxiety, Fatigue, Sleep Problems and CIRS]

==See also==
*[[5HTP]]
*[[CRFR2 upregulation hypothesis]]
*[[CT38]]

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]
[[Category:Neurotransmitters]]
[[Category:Neurology]]