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2000
Volume 24, Issue 7
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

Autism Spectrum Disorder (ASD) constitutes a group of neurodevelopmental disorders characterized by impairments in verbal and nonverbal communication skills, social interactions, and stereotypes of behavior, with an estimated frequency of 1.2% of children throughout the world. The lack of specific treatments or molecular biomarkers underscores the complexities of ASD as a non-unified clinical entity. Comorbid medical conditions are particularly associated with gastrointestinal issues that may suggest potential interactions between the brain and gut. This review suggests that serotonin plays a significant role in the enteric and central nervous systems in relation to ASD. The modulatory role of serotonin in the enteric nervous system is examined in relation to the pathophysiology of ASD in order to shed light on prospective biomarkers and therapeutic targets that could increase the precision of diagnosis and treatment.

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2025-02-18
2025-10-27

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References

  1. ZafeiriouD. VerveriA. VargiamiE. The serotonergic system: Its role in pathogenesis and early developmental treatment of autism.Curr. Neuropharmacol.20097215015710.2174/157015909788848848 19949574
     [Google Scholar]
  2. DhankharS. MujwarS. GargN. Artificial Intelligence in the management of neurodegenerative disorders.CNS Neurol. Disord. Drug Targets202423893194010.2174/0118715273266095231009092603 37861051
     [Google Scholar]
  3. KciukM. GargN. DhankharS. Exploring the comprehensive neuroprotective and anticancer potential of afzelin.Pharmaceuticals202417670110.3390/ph17060701 38931368
     [Google Scholar]
  4. HarrisJ. Leo Kanner and autism: A 75-year perspective.Int. Rev. Psychiatry201830131710.1080/09540261.2018.1455646 29667863
     [Google Scholar]
  5. MustA. EliasziwM. PhillipsS.M. The effect of age on the prevalence of obesity among US youth with autism spectrum disorder.Child. Obes.2017131253510.1089/chi.2016.0079 27704874
     [Google Scholar]
  6. GarfieldJ.L. PetersonC.C. PerryT. Social cognition, language acquisition and the development of the theory of mind.Mind Lang.200116549454110.1111/1468‑0017.00180
     [Google Scholar]
  7. TeleanuR.I. NiculescuA.G. RozaE. VladâcencoO. GrumezescuA.M. TeleanuD.M. Neurotransmitters-Key factors in neurological and neurodegenerative disorders of the central nervous system.Int. J. Mol. Sci.20222311595410.3390/ijms23115954 35682631
     [Google Scholar]
  8. SoniD KhanH ChauhanS Exploring therapeutic potential: Targeting TRPM7 in neurodegenerative diseases. Int Immunopharmacol2024142Pt B11314210.1016/j.intimp.2024.113142 39298812
  9. TiwariC. KhanH. GrewalA.K. Opiorphin: An endogenous human peptide with intriguing application in diverse range of pathologies.Inflammopharmacology20243253037305610.1007/s10787‑024‑01526‑8 39164607
     [Google Scholar]
  10. RoerigB. FellerM.B. Neurotransmitters and gap junctions in developing neural circuits.Brain Res. Brain Res. Rev.20003218611410.1016/S0165‑0173(99)00069‑7 10751659
     [Google Scholar]
  11. KennedyM.B. Synaptic signaling in learning and memory.Cold Spring Harb. Perspect. Biol.201682a01682410.1101/cshperspect.a016824 24379319
     [Google Scholar]
  12. DiCicco-BloomE. LordC. ZwaigenbaumL. The developmental neurobiology of autism spectrum disorder.J. Neurosci.200626266897690610.1523/JNEUROSCI.1712‑06.2006 16807320
     [Google Scholar]
  13. IsraelyanN. MargolisK.G. Reprint of: Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders.Pharmacol. Res.201914011512010.1016/j.phrs.2018.12.023 30658882
     [Google Scholar]
  14. EspositoD. CrucianiG. ZaccaroL. A systematic review on autism and hyperserotonemia: State-of-the-art, limitations, and future directions.Brain Sci.202414548110.3390/brainsci14050481 38790459
     [Google Scholar]
  15. JacksonL. WeedonM.N. GreenH.D. Influence of family history on penetrance of hereditary cancers in a population setting.EClinicalMedicine20236410215910.1016/j.eclinm.2023.102159 37936660
     [Google Scholar]
  16. BertrandP.P. BertrandR.L. Serotonin release and uptake in the gastrointestinal tract.Auton. Neurosci.20101531-2475710.1016/j.autneu.2009.08.002 19729349
     [Google Scholar]
  17. RazaS. Effects of prenatal exposure to valproic acid on the development of juvenile-typical social play in rats.Behav. Pharmacol.201526870771910.1097/FBP.0000000000000169
     [Google Scholar]
  18. BlanchardR.J. McKittrickC.R. BlanchardD.C. Animal models of social stress: Effects on behavior and brain neurochemical systems.Physiol. Behav.200173326127110.1016/S0031‑9384(01)00449‑8 11438351
     [Google Scholar]
  19. Yubero-LahozS. RobledoP. FarréM. TorreR. Platelet SERT as a peripheral biomarker of serotonergic neurotransmission in the central nervous system.Curr. Med. Chem.201320111382139610.2174/0929867311320110003 23409709
     [Google Scholar]
  20. KvietysP. The gastrointestinal circulation.San Rafael, CAMorgan & Claypool Publishers2009
     [Google Scholar]
  21. OliverK.H. Novel implications of lost serotonin transporter function on platelet biology Dissertation.2016
     [Google Scholar]
  22. TianJ. GaoX. YangL. Repetitive restricted behaviors in autism spectrum disorder: From mechanism to development of therapeutics.Front. Neurosci.20221678040710.3389/fnins.2022.780407
     [Google Scholar]
  23. HsiaoE.Y. Gastrointestinal issues in autism spectrum disorder.Harv. Rev. Psychiatry201422210411110.1097/HRP.0000000000000029 24614765
     [Google Scholar]
  24. WangJ. MaB. WangJ. ZhangZ. ChenO. Global prevalence of autism spectrum disorder and its gastrointestinal symptoms: A systematic review and meta-analysis.Front. Psychiatry20221396310210.3389/fpsyt.2022.963102 36081466
     [Google Scholar]
  25. BarlattaniT. Autism spectrum disorders and psychiatric comorbidities: A narrative review.J. Psychopathol.202312
     [Google Scholar]
  26. PuricelliC. RollaR. GigliottiL. The gut-brain-immune axis in autism spectrum disorders: A state-of-art report.Front. Psychiatry20221275517110.3389/fpsyt.2021.755171 35185631
     [Google Scholar]
  27. WoodC.P. Gut-Brain Endocannabinoid Control of Obesity and Anxiety.RiversideUniversity of California2023
     [Google Scholar]
  28. WilliamsKJ Janus-faced mothering and a cruel story of blame: The representations and lived effects of mothering an autistic child.2019
     [Google Scholar]
  29. MilesJ.H. Autism spectrum disorders-A genetics review.Genet. Med.201113427829410.1097/GIM.0b013e3181ff67ba 21358411
     [Google Scholar]
  30. WerlingD.M. GeschwindD.H. Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins.Mol. Autism2015612710.1186/s13229‑015‑0004‑5 25973164
     [Google Scholar]
  31. KrishnanA. ZhangR. YaoV. Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder.Nat. Neurosci.201619111454146210.1038/nn.4353 27479844
     [Google Scholar]
  32. KingdomR. WrightC.F. Incomplete penetrance and variable expressivity: From clinical studies to population cohorts.Front. Genet.20221392039010.3389/fgene.2022.920390 35983412
     [Google Scholar]
  33. ChandanaS.R. BehenM.E. JuhászC. Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism.Int. J. Dev. Neurosci.2005232-317118210.1016/j.ijdevneu.2004.08.002 15749243
     [Google Scholar]
  34. RodnyyA.Y. KondaurovaE.M. TsybkoA.S. PopovaN.K. KudlayD.A. NaumenkoV.S. The brain serotonin system in autism.Rev. Neurosci.202435112010.1515/revneuro‑2023‑0055 37415576
     [Google Scholar]
  35. KowalewskaB. DrozdzW. KowalewskiL. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in autism research: Literature review.Ir. J. Psychol. Med.202239327228610.1017/ipm.2021.15 33818321
     [Google Scholar]
  36. HulleyM. The serotonin transporter gene (SLC6A4) shows differential regulation between children with ASD and typically developing children in a South African population. Thesis presented for the degree of Master of Science in the Department of Molecular and Cell Biology Faculty of Science University of Cape Town2016
     [Google Scholar]
  37. McCauleyJ.L. OlsonL.M. DowdM. Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid‐compulsive subset of autism.Am. J. Med. Genet. B. Neuropsychiatr. Genet.2004127B110411210.1002/ajmg.b.20151 15108191
     [Google Scholar]
  38. PrasadH.C. SteinerJ.A. SutcliffeJ.S. BlakelyR.D. Enhanced activity of human serotonin transporter variants associated with autism.Philos. Trans. R. Soc. Lond. B Biol. Sci.2009364151416317310.1098/rstb.2008.0143 18957375
     [Google Scholar]
  39. TapnikarS. Neurogenic plasticity in a serotonin transporter knockout model: Effects of maternal and offspring genotype.Open Access Te Herenga Waka-Victoria University of Wellington2021
     [Google Scholar]
  40. StilleyS.E. BlakelyR.D. Rare opportunities for insights into serotonergic contributions to brain and bowel disorders: Studies of the SERT Ala56 mouse.Front. Cell. Neurosci.20211567756310.3389/fncel.2021.677563 34149362
     [Google Scholar]
  41. NieslerB. KuertenS. DemirI.E. SchäferK.H. Disorders of the enteric nervous system - A holistic view.Nat. Rev. Gastroenterol. Hepatol.202118639341010.1038/s41575‑020‑00385‑2 33514916
     [Google Scholar]
  42. MurrayM.L. HsiaY. GlaserK. Pharmacological treatments prescribed to people with autism spectrum disorder (ASD) in primary health care.Psychopharmacology201423161011102110.1007/s00213‑013‑3140‑7 23681164
     [Google Scholar]
  43. LeipzigR.M. CummingR.G. TinettiM.E. Drugs and falls in older people: A systematic review and meta-analysis: I. Psychotropic drugs.J. Am. Geriatr. Soc.1999471303910.1111/j.1532‑5415.1999.tb01898.x 9920227
     [Google Scholar]
  44. LuoY. KataokaY. OstinelliE.G. CiprianiA. FurukawaT.A. National prescription patterns of antidepressants in the treatment of adults with major depression in the US between 1996 and 2015: A population representative survey based analysis.Front. Psychiatry2020113510.3389/fpsyt.2020.00035 32116850
     [Google Scholar]
  45. FiggittD.P. McClellanK.J. Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders.Drugs200060492595410.2165/00003495‑200060040‑00006 11085201
     [Google Scholar]
  46. GualtieriC.T. JohnsonL.G. Antidepressant side effects in children and adolescents.J. Child Adolesc. Psychopharmacol.2006161-214715710.1089/cap.2006.16.147 16553535
     [Google Scholar]
  47. HooksK.B. KonsmanJ.P. O’MalleyM.A. Microbiota-gut-brain research: A critical analysis.Behav. Brain Sci.201942e6010.1017/S0140525X18002133 30207256
     [Google Scholar]
  48. DhankharS. GargN. ChauhanS. SainiM. SinghT.G. SinghR. Unravelling the microbiome’s role in healing diabetic wounds.Curr. Pharm. Biotechnol.202425113 38920078
     [Google Scholar]
  49. DowlingL.R. StrazzariM.R. KeelyS. KaikoG.E. Enteric nervous system and intestinal epithelial regulation of the gut-brain axis.J. Allergy Clin. Immunol.2022150351352210.1016/j.jaci.2022.07.015 36075637
     [Google Scholar]
  50. ZhangH. WangZ. WangG. Understanding the connection between gut homeostasis and psychological stress.J. Nutr.2023153492493910.1016/j.tjnut.2023.01.026 36806451
     [Google Scholar]
  51. FattorussoA. Di GenovaL. Dell’IsolaG. MencaroniE. EspositoS. Autism spectrum disorders and the gut microbiota.Nutrients201911352110.3390/nu11030521 30823414
     [Google Scholar]
  52. Di GesùC.M. MatzL.M. BuffingtonS.A. Diet-induced dysbiosis of the maternal gut microbiome in early life programming of neurodevelopmental disorders.Neurosci. Res.202116831910.1016/j.neures.2021.05.003 33992660
     [Google Scholar]
  53. MajhiS. KumarS. SinghL. A Review on autism spectrum disorder: Pathogenesis, biomarkers, pharmacological and non-pharmacological interventions.CNS Neurol. Disord. Drug Targets202322565967710.2174/1871527321666220428134802
     [Google Scholar]
  54. DingJ.H. JinZ. YangX.X. Role of gut microbiota via the gut-liver-brain axis in digestive diseases.World J. Gastroenterol.202026406141616210.3748/wjg.v26.i40.6141 33177790
     [Google Scholar]
  55. YılmazC. GökmenV. Neuroactive compounds in foods: Occurrence, mechanism and potential health effects.Food Res. Int.202012810874410.1016/j.foodres.2019.108744 31955786
     [Google Scholar]
  56. van ThielI.A.M. BotschuijverS. de JongeW.J. SeppenJ. Painful interactions: Microbial compounds and visceral pain.Biochim. Biophys. Acta Mol. Basis Dis.20201866116553410.1016/j.bbadis.2019.165534 31634534
     [Google Scholar]
  57. AuteriM. ZizzoM.G. SerioR. GABA and GABA receptors in the gastrointestinal tract: From motility to inflammation.Pharmacol. Res.201593112110.1016/j.phrs.2014.12.001 25526825
     [Google Scholar]
  58. ÁlvarezJ. Fernández RealJ.M. GuarnerF. Gut microbes and health.Gastroenterol. Hepatol.2021447519535 33652061
     [Google Scholar]
  59. FrankiensztajnL.M. ElliottE. KorenO. The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders.Curr. Opin. Neurobiol.202062768210.1016/j.conb.2019.12.003 31972462
     [Google Scholar]
  60. PurchiaroniF. TortoraA. GabrielliM. The role of intestinal microbiota and the immune system.Eur. Rev. Med. Pharmacol. Sci.2013173323333 23426535
     [Google Scholar]
  61. DantzerR. Neuroimmune interactions: From the brain to the immune system and vice versa.Physiol. Rev.201898147750410.1152/physrev.00039.2016 29351513
     [Google Scholar]
  62. WangH.X. WangY.P. Gut microbiota-brain axis.Chin. Med. J.2016129192373238010.4103/0366‑6999.190667 27647198
     [Google Scholar]
  63. HolingueC. NewillC. LeeL.C. PasrichaP.J. Daniele FallinM. Gastrointestinal symptoms in autism spectrum disorder: A review of the literature on ascertainment and prevalence.Autism Res.2018111243610.1002/aur.1854 28856868
     [Google Scholar]
  64. BuieT. CampbellD.B. FuchsG.J.III Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: A consensus report.Pediatrics2010125Suppl. 1S1S1810.1542/peds.2009‑1878C 20048083
     [Google Scholar]
  65. SamsamM. AhangariR. NaserS.A. Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance.World J. Gastroenterol.201420299942995110.3748/wjg.v20.i29.9942 25110424
     [Google Scholar]
  66. WerlingD.M. Investigation of sex-differential genetic risk factors for autism spectrum disorders.Los AngelesUniversity of California2014
     [Google Scholar]
  67. PosserudM.B. Skretting SolbergB. EngelandA. HaavikJ. KlungsøyrK. Male to female ratios in autism spectrum disorders by age, intellectual disability and attention‐deficit/hyperactivity disorder.Acta Psychiatr. Scand.2021144663564610.1111/acps.13368 34494265
     [Google Scholar]
  68. MingroniM.A. Resolving the IQ paradox: Heterosis as a cause of the Flynn effect and other trends.Psychol. Rev.2007114380682910.1037/0033‑295X.114.3.806 17638507
     [Google Scholar]
  69. RiceC. Prevalence of autism spectrum disorders - Autism and developmental disabilities monitoring network, United States, 2006 2009. Available from: https://www.cdc.gov/mmwr/pdf/ss/ss5810.pdf
  70. RutterM. CaspiA. FergussonD. Sex differences in developmental reading disability: New findings from 4 epidemiological studies.JAMA2004291162007201210.1001/jama.291.16.2007 15113820
     [Google Scholar]
  71. WerlingD.M. GeschwindD.H. Sex differences in autism spectrum disorders.Curr. Opin. Neurol.201326214615310.1097/WCO.0b013e32835ee548 23406909
     [Google Scholar]
  72. ArnoldM.L. From nervous system changes to systemic change in Science: Investigating sex differences in the impact of maternal immune activation on offspring brain development and behavior, and building social justice in science through pedagogy and community initiatives to increase belonging.BerkeleyUniversity of California2022
     [Google Scholar]
  73. HusY. SegalO. Challenges surrounding the diagnosis of autism in children.Neuropsychiatr. Dis. Treat.2021173509352910.2147/NDT.S282569 34898983
     [Google Scholar]
  74. ZhengJ. ChenS. Exploring China’s success at the Olympic Games: A competitive advantage approach.Eur. Sport Manag. Q.201616214817110.1080/16184742.2016.1140797
     [Google Scholar]
  75. AronsonJK FernerRE Biomarkers-A general review Curr Protoc Pharmacol2017769”1-92310.1002/cpph.19 28306150
     [Google Scholar]
  76. FrederiksenK.S. WaldemarG. Aggression, agitation, hyperactivity, and irritability.In: Neuropsychiatric symptoms of cognitive impairment and dementia neuropsychiatric symptoms of neurological disease.ChamSpringer201710.1007/978‑3‑319‑39138‑0_9
     [Google Scholar]
  77. JagadapillaiR. QiuX. OjhaK. Potential cross talk between autism risk genes and neurovascular molecules: A pilot study on impact of blood brain barrier integrity.Cells20221114221110.3390/cells11142211 35883654
     [Google Scholar]
  78. RobsonM.J. QuinlanM.A. MargolisK.G. p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.Proc. Natl. Acad. Sci. USA201811543E10245E1025410.1073/pnas.1809137115 30297392
     [Google Scholar]
  79. TackJ. CamilleriM. ChangL. Systematic review: Cardiovascular safety profile of 5‐HT4 agonists developed for gastrointestinal disorders.Aliment. Pharmacol. Ther.201235774576710.1111/j.1365‑2036.2012.05011.x 22356640
     [Google Scholar]
  80. WangS. IshimaT. ZhangJ. Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve.J. Neuroinflammation202017124110.1186/s12974‑020‑01916‑z 32799901
     [Google Scholar]
  81. JiJ. JinW. LiuS.J. JiaoZ. LiX. Probiotics, prebiotics, and postbiotics in health and disease.MedComm202346e42010.1002/mco2.420 37929014
     [Google Scholar]
  82. CryanJ.F. O’RiordanK.J. CowanC.S.M. The microbiota-gut-brain axis.Physiol. Rev.20199941877201310.1152/physrev.00018.2018 31460832
     [Google Scholar]
  83. LiN. ChenH. ChengY. Fecal microbiota transplantation relieves gastrointestinal and autism symptoms by improving the gut microbiota in an open-label study.Front. Cell. Infect. Microbiol.20211175943510.3389/fcimb.2021.759435 34737978
     [Google Scholar]
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Serotonergic Dynamics in Autism Spectrum Disorder: Unraveling the Intricate Connection
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 24, 511 (2025); https://doi.org/10.2174/0118715273378214250213114328
/content/journals/cnsnddt/10.2174/0118715273378214250213114328
/content/journals/cnsnddt/10.2174/0118715273378214250213114328
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  • Article Type:     Review Article
Keyword(s): autism; disorder; genetic; neurological; Serotonin; spectrum

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