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Serotonin
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'''Serotonin''' or '''5-Hydroxytryptamine''' or '''5HT''' is a [[monoamine]] [[neurotransmitter]] derived from [[tryptophan]]. It is found in the [[gastrointestinal tract]], [[platelet]]s, and the [[central nervous system]]. ==5-Hydroxytryptophan== [[5-Hydroxytryptophan]] (5HTP) is the precursor to serotonin (5HT). ==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 5HT<sub>1A</sub>, 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]]
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