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Psychiatric Disorders pp 493–510Cite as

The Contribution of Inflammation to Autism Spectrum Disorders: Recent Clinical Evidence

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2011))

Abstract

Autism comprises a complex and heterogeneous spectrum of neurodevelopmental disorders, usually termed autism spectrum disorders (ASD). It is more prevalent in males than females, and genetic and environmental factors are believed to account in similar percentages to the development of ASD. In recent years, the contribution of inflammation and inflammatory mediators to disease aetiology and perpetuation has been the object of intense research. In this chapter, inflammatory aspects that contribute to ASD are discussed, including abnormal microglia activation and polarization phenotypes, increased systemic levels of pro-inflammatory mediators, and altered patterns of immune cell response to activation stimuli. Also, inflammation in the context of gut microbiome and the impact of inflammation on gender prevalence of ASD are considered. Finally, treatment impact on inflammatory parameters and the potential for use of anti-inflammatory drugs, alone or in combination with antipsychotics, to manage ASD are examined.

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References

  1. Christensen D, Baio J, Braun K, Bilder D, Charles J, Constantino J, Daniels J, Durkin M, Fitzgerald R, Kurzius-Spencer M, Lee L-C, Pettygrove S, Robinson C, Schulz E, Wells C, Wingate M, Zahorodny W, Yeargin-Allsopp M (2016) Prevalence and characteristics of autism spectrum disorder among children aged 8 years — autism and developmental disabilities monitoring network, 11 sites, United States, 2012. MMWR Surveill Summ 65:1–23

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rosenfeld CS (2015) Microbiome disturbances and autism spectrum disorders. In: Drug metabolism and disposition: the biological fate of chemicals, vol 43, pp 1557–1571

    Google Scholar 

  3. Wing L, Gould J, Gillberg C (2011) Autism spectrum disorders in the DSM-V: better or worse than the DSM-IV? Res Dev Disabil 32:768–773

    Article  PubMed  Google Scholar 

  4. Bogdashina O (2003) Sensory perceptual issues in autism and Asperger syndrome: different sensory experiences - different perceptual worlds. Jessica Kingsley Publishers, London

    Google Scholar 

  5. Vivanti G, Prior M, Williams K, Dissanayake C (2014) Predictors of outcomes in autism early intervention: why don’t we know more? Front Pediatr 2:58

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jobski K, Höfer J, Hoffmann F, Bachmann C (2017) Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review. Acta Psychiatr Scand 135:8–28

    Article  CAS  PubMed  Google Scholar 

  7. Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, Mahajan M, Manaa D, Pawitan Y, Reichert J, Ripke S, Sandin S (2014) Most genetic risk for autism resides with common variation. Nat Genet 46:881–885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bent S, Hendren RL (2010) Improving the prediction of response to therapy in autism. Neurotherapeutics 7:232–240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Xu N, Li X, Zhong Y (2015) Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediators Inflamm 2015:531518

    PubMed  PubMed Central  Google Scholar 

  10. Vuong HE, Hsiao EY (2017) Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry 81:411–423

    Article  PubMed  Google Scholar 

  11. Fond G, Boukouaci W, Chevalier G, Regnault A, Eberl G, Hamdani N, Dickerson F, Macgregor A, Boyer L, Dargel A, Oliveira J, Tamouza R, Leboyer M (2015) The “psychomicrobiotic”: targeting microbiota in major psychiatric disorders: a systematic review. Pathol Biol 63:35–42

    Article  CAS  PubMed  Google Scholar 

  12. Rodriguez JI, Kern JK (2011) Evidence of microglial activation in autism and its possible role in brain underconnectivity. Neuron Glia Biol 7:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  13. Takano T (2015) Role of microglia in autism: recent advances. Dev Neurosci 37:195–202

    Article  CAS  PubMed  Google Scholar 

  14. Perry VH, Nicoll JA, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6:193–201

    Article  PubMed  Google Scholar 

  15. Ginhoux F, Lim S, Hoeffel G, Low D, Huber T (2013) Origin and differentiation of microglia. Front Cell Neurosci 7:45

    Article  PubMed  PubMed Central  Google Scholar 

  16. Prata J, Santos SG, Almeida MI, Coelho R, Barbosa MA (2017) Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations. J Neuroinflammation 14:179

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Perry VH, Teeling J (2013) Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Semin Immunopathol 35:601–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fernandes A, Miller-Fleming L, Pais TF (2014) Microglia and inflammation: conspiracy, controversy or control? Cell Mol Life Sci 71:3969–3985

    Article  CAS  PubMed  Google Scholar 

  19. Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen RL, Pessah IN, Hertz-Picciotto I, Van de Water JA, Sharp FR, Ashwood P (2009) Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun 23:124–133

    Article  CAS  PubMed  Google Scholar 

  20. Warren RP, Foster A, Margaretten NC (1987) Reduced natural killer cell activity in autism. J Am Acad Child Adolesc Psychiatry 26:333–335

    Article  CAS  PubMed  Google Scholar 

  21. Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, Ji L, Brown T, Malik M (2009) Elevated immune response in the brain of autistic patients. J Neuroimmunol 207:111–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Futatsubashi M, Takebayashi K, Yoshihara Y, Omata K, Matsumoto K, Tsuchiya KJ, Iwata Y, Tsujii M, Sugiyama T, Mori N (2013) Microglial activation in young adults with autism spectrum disorder. JAMA Psychiat 70:49–58

    Article  Google Scholar 

  23. Kalkman HO, Feuerbach D (2017) Microglia M2A polarization as potential link between food allergy and autism spectrum disorders. Pharmaceuticals (Basel) 10:pii: E95

    Article  CAS  Google Scholar 

  24. Geschwind DH, Levitt P (2007) Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 17:103–111

    Article  CAS  PubMed  Google Scholar 

  25. Young AM, Chakrabarti B, Roberts D, Lai MC, Suckling J, Baron-Cohen S (2016) From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition. Mol Autism 7:9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Ishizuka K, Fujita Y, Kawabata T, Kimura H, Iwayama Y, Inada T, Okahisa Y, Egawa J, Usami M, Kushima I, Uno Y, Okada T, Ikeda M, Aleksic B, Mori D, Someya T, Yoshikawa T, Iwata N, Nakamura H, Yamashita T, Ozaki N (2017) Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders. Transl Psychiatry 7:e1184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Knuesel I, Chicha L, Britschgi M, Schobel SA, Bodmer M, Hellings JA, Toovey S, Prinssen EP (2014) Maternal immune activation and abnormal brain development across CNS disorders. Nat Rev Neurol 10:643–660

    Article  CAS  PubMed  Google Scholar 

  28. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67–81

    Article  CAS  PubMed  Google Scholar 

  29. Careaga M, Rogers S, Hansen RL, Amaral DG, Van de Water J, Ashwood P (2017) Immune endophenotypes in children with autism spectrum disorder. Biol Psychiatry 81:434–441

    Article  CAS  PubMed  Google Scholar 

  30. Pardo CA, Farmer CA, Thurm A, Shebl FM, Ilieva J, Kalra S, Swedo S (2017) Serum and cerebrospinal fluid immune mediators in children with autistic disorder: a longitudinal study. Mol Autism 8:1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Delves PJ, MArtin SJ, Burton DR, Roitt IM (2011) Roitt’s essential immunology, 12th edn. Wiley-Blackwell, London

    Google Scholar 

  32. Erickson MA, Dohi K, Banks WA (2012) Neuroinflammation: a common pathway in CNS diseases as mediated at the blood-brain barrier. Neuroimmunomodulation 19:121–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Goines PE, Croen LA, Braunschweig D, Yoshida CK, Grether J, Hansen R, Kharrazi M, Ashwood P, Van de Water J (2011) Increased midgestational IFN-gamma, IL-4 and IL-5 in women bearing a child with autism: a case-control study. Mol Autism 2:13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Schwarz E, Guest PC, Rahmoune H, Wang L, Levin Y, Ingudomnukul E, Ruta L, Kent L, Spain M, Baron-Cohen S, Bahn S (2011) Sex-specific serum biomarker patterns in adults with Asperger’s syndrome. Mol Psychiatry 16:1213–1220

    Article  CAS  PubMed  Google Scholar 

  35. Abdallah MW, Larsen N, Grove J, Bonefeld-Jorgensen EC, Norgaard-Pedersen B, Hougaard DM, Mortensen EL (2013) Neonatal chemokine levels and risk of autism spectrum disorders: findings from a Danish historic birth cohort follow-up study. Cytokine 61:370–376

    Article  CAS  PubMed  Google Scholar 

  36. Krakowiak P, Goines PE, Tancredi DJ, Ashwood P, Hansen RL, Hertz-Picciotto I, Van de Water J (2017) Neonatal cytokine profiles associated with autism spectrum disorder. Biol Psychiatry 81:442–451

    Article  CAS  PubMed  Google Scholar 

  37. Masi A, Glozier N, Dale R, Guastella AJ (2017) The immune system, cytokines, and biomarkers in autism spectrum disorder. Neurosci Bull 33:194–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Xie J, Huang L, Li X, Li H, Zhou Y, Zhu H, Pan T, Kendrick KM, Xu W (2017) Immunological cytokine profiling identifies TNF-alpha as a key molecule dysregulated in autistic children. Oncotarget 8:82390–82398

    Article  PubMed  PubMed Central  Google Scholar 

  39. Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Mori N (2011) Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One 6:e20470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ (2015) Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20:440–446

    Article  CAS  PubMed  Google Scholar 

  41. Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189

    Article  CAS  PubMed  Google Scholar 

  42. Maes M, Bosmans E, Meltzer HY, Scharpe S, Suy E (1993) Interleukin-1 beta: a putative mediator of HPA axis hyperactivity in major depression? Am J Psychiatry 150:1189–1193

    Article  CAS  PubMed  Google Scholar 

  43. Nishimoto N, Kishimoto T (2006) Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2:619–626

    Article  CAS  PubMed  Google Scholar 

  44. Wei H, Chadman KK, McCloskey DP, Sheikh AM, Malik M, Brown WT, Li X (2012) Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta 1822:831–842

    Article  CAS  PubMed  Google Scholar 

  45. Rohleder N, Aringer M, Boentert M (2012) Role of interleukin-6 in stress, sleep, and fatigue. Ann N Y Acad Sci 1261:88–96

    Article  CAS  PubMed  Google Scholar 

  46. Gomes FC, Sousa Vde O, Romao L (2005) Emerging roles for TGF-beta1 in nervous system development. Int J Dev Neurosci 23:413–424

    Article  CAS  PubMed  Google Scholar 

  47. Ricci S, Businaro R, Ippoliti F, Lo Vasco VR, Massoni F, Onofri E, Troili GM, Pontecorvi V, Morelli M, Rapp Ricciardi M, Archer T (2013) Altered cytokine and BDNF levels in autism spectrum disorder. Neurotox Res 24:491–501

    Article  CAS  PubMed  Google Scholar 

  48. Han YM, Cheung WK, Wong CK, Sze SL, Cheng TW, Yeung MK, Chan AS (2017) Distinct cytokine and chemokine profiles in autism spectrum disorders. Front Immunol 8:11

    PubMed  PubMed Central  Google Scholar 

  49. Abdallah MW, Pearce BD, Larsen N, Greaves-Lord K, Norgaard-Pedersen B, Hougaard DM, Mortensen EL, Grove J (2012) Amniotic fluid MMP-9 and neurotrophins in autism spectrum disorders: an exploratory study. Autism Res 5:428–433

    Article  PubMed  Google Scholar 

  50. Van Lint P, Libert C (2007) Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol 82:1375–1381

    Article  PubMed  CAS  Google Scholar 

  51. Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P (2011) The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract 2011:161358

    Article  PubMed  PubMed Central  Google Scholar 

  52. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J (2011) Altered T cell responses in children with autism. Brain Behav Immun 25:840–849

    Article  CAS  PubMed  Google Scholar 

  53. Akintunde ME, Rose M, Krakowiak P, Heuer L, Ashwood P, Hansen R, Hertz-Picciotto I, Van de Water J (2015) Increased production of IL-17 in children with autism spectrum disorders and co-morbid asthma. J Neuroimmunol 286:33–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Guerini FR, Bolognesi E, Chiappedi M, Ghezzo A, Manca S, Zanette M, Sotgiu S, Mensi MM, Zanzottera M, Agliardi C, Costa AS, Balottin U, Clerici M (2018) HLA-G ∗14bp insertion and the KIR2DS1-HLAC2 complex impact on behavioral impairment in children with autism spectrum disorders. Neuroscience 370:163–169

    Article  CAS  PubMed  Google Scholar 

  55. Guerini FR, Bolognesi E, Chiappedi M, Ripamonti E, Ghezzo A, Zanette M, Sotgiu S, Mensi MM, Carta A, Canevini MP, Zanzottera M, Agliardi C, Costa AS, Balottin U, Clerici M (2018) HLA-G coding region polymorphism is skewed in autistic spectrum disorders. Brain Behav Immun 67:308–313

    Article  CAS  PubMed  Google Scholar 

  56. Meltzer A, Van de Water J (2017) The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 42:284–298

    Article  CAS  PubMed  Google Scholar 

  57. Voineagu I, Eapen V (2013) Converging pathways in autism spectrum disorders: interplay between synaptic dysfunction and immune responses. Front Hum Neurosci 7:738

    Article  PubMed  PubMed Central  Google Scholar 

  58. Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, Geschwind DH (2011) Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474:380–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Young AM, Campbell E, Lynch S, Suckling J, Powis SJ (2011) Aberrant NF-kappaB expression in autism spectrum condition: a mechanism for neuroinflammation. Front Psych 2:27

    CAS  Google Scholar 

  60. Krakowiak P, Walker CK, Tancredi D, Hertz-Picciotto I, Van de Water J (2017) Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism Res 10:89–98

    Article  PubMed  Google Scholar 

  61. Depino AM (2013) Peripheral and central inflammation in autism spectrum disorders. Mol Cell Neurosci 53:69–76

    Article  CAS  PubMed  Google Scholar 

  62. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J (2011) Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25:40–45

    Article  CAS  PubMed  Google Scholar 

  63. Yang CJ, Liu CL, Sang B, Zhu XM, Du YJ (2015) The combined role of serotonin and interleukin-6 as biomarker for autism. Neuroscience 284:290–296

    Article  CAS  PubMed  Google Scholar 

  64. Yang C-J, Tan H-P, Yang F-Y, Liu C-L, Sang B, Zhu X-M, Du Y-J (2015) The roles of cortisol and pro-inflammatory cytokines in assisting the diagnosis of autism spectrum disorder. Res Autism Spectr Disord 9:174–181

    Article  Google Scholar 

  65. Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA, Ozonoff S, Pessah IN, Van de Water J (2008) Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol 204:149–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mohamed El Gohary T, Abd El Aziz N, Darweesh M, Shukery Sadaa E (2015) Plasma level of transforming growth factor β 1 in children with autism spectrum disorder. Egy J Ear Nose Throat Allied Sci 16:69

    Article  Google Scholar 

  67. Heuer L, Ashwood P, Schauer J, Goines P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J (2008) Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Res 1:275–283

    Article  PubMed  PubMed Central  Google Scholar 

  68. Mostafa GA, Al-Ayadhi LY (2011) Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflammation 8:39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mostafa GA, Al-Ayadhi LY (2012) The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children. Eur J Paediatr Neurol 16:464–468

    Article  PubMed  Google Scholar 

  70. Careaga M, Hansen RL, Hertz-Piccotto I, Van de Water J, Ashwood P (2013) Increased anti-phospholipid antibodies in autism spectrum disorders. Mediators Inflamm 2013:935608

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Buie T, Campbell DB, Fuchs GJ III, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H (2010) Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 125(Suppl 1):S1–S18

    Article  PubMed  Google Scholar 

  72. Coury DL, Ashwood P, Fasano A, Fuchs G, Geraghty M, Kaul A, Mawe G, Patterson P, Jones NE (2012) Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics 130(Suppl 2):S160–S168

    Article  PubMed  Google Scholar 

  73. Mazurek MO, Vasa RA, Kalb LG, Kanne SM, Rosenberg D, Keefer A, Murray DS, Freedman B, Lowery LA (2013) Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. J Abnorm Child Psychol 41:165–176

    Article  PubMed  Google Scholar 

  74. Valicenti-McDermott M, McVicar K, Rapin I, Wershil BK, Cohen H, Shinnar S (2006) Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. J Dev Behav Pediatr 27:S128–S136

    Article  PubMed  Google Scholar 

  75. Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA (2011) Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol 11:22

    Article  PubMed  PubMed Central  Google Scholar 

  76. Schneider CK, Melmed RD, Barstow LE, Enriquez FJ, Ranger-Moore J, Ostrem JA (2006) Oral human immunoglobulin for children with autism and gastrointestinal dysfunction: a prospective, open-label study. J Autism Dev Disord 36:1053–1064

    Article  PubMed  Google Scholar 

  77. Wang LW, Tancredi DJ, Thomas DW (2011) The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr 32:351–360

    Article  PubMed  Google Scholar 

  78. Sommer F, Backhed F (2013) The gut microbiota--masters of host development and physiology. Nat Rev Microbiol 11:227–238

    Article  CAS  PubMed  Google Scholar 

  79. Navarro F, Liu Y, Rhoads JM (2016) Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol 22:10093–10102

    Article  PubMed  PubMed Central  Google Scholar 

  80. Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, Youn E, Summanen PH, Granpeesheh D, Dixon D, Liu M, Molitoris DR, Green JA 3rd. (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16:444–453

    Article  CAS  PubMed  Google Scholar 

  81. Finegold SM, Downes J, Summanen PH (2012) Microbiology of regressive autism. Anaerobe 18:260–262

    Article  CAS  PubMed  Google Scholar 

  82. Kang DW, Park JG, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, Krajmalnik-Brown R (2013) Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One 8:e68322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Parracho HM, Bingham MO, Gibson GR, McCartney AL (2005) Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 54:987–991

    Article  PubMed  Google Scholar 

  84. De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R (2013) Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 8:e76993

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Kang DW, Ilhan ZE, Isern NG, Hoyt DW, Howsmon DP, Shaffer M, Lozupone CA, Hahn J, Adams JB, Krajmalnik-Brown R (2018) Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. Anaerobe 49:121–131

    Article  CAS  PubMed  Google Scholar 

  86. Babinska K, Tomova A, Celusakova H, Babkova J, Repiska G, Kubranska A, Filcikova D, Siklenkova L, Ostatnikova D (2017) Fecal calprotectin levels correlate with main domains of the autism diagnostic interview-revised (ADI-R) in a sample of individuals with autism spectrum disorders from Slovakia. Physiol Res 66:S517–S522

    Article  CAS  PubMed  Google Scholar 

  87. Berding K, Donovan SM (2016) Microbiome and nutrition in autism spectrum disorder: current knowledge and research needs. Nutr Rev 74:723–736

    Article  PubMed  Google Scholar 

  88. Schwarz JM, Bilbo SD (2012) Sex, glia, and development: interactions in health and disease. Horm Behav 62:243–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Schneider T, Roman A, Basta-Kaim A, Kubera M, Budziszewska B, Schneider K, Przewlocki R (2008) Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. Psychoneuroendocrinology 33:728–740

    Article  CAS  PubMed  Google Scholar 

  90. Bale TL (2016) The placenta and neurodevelopment: sex differences in prenatal vulnerability. Dialogues Clin Neurosci 18:459–464

    Article  PubMed  PubMed Central  Google Scholar 

  91. Bronson SL, Bale TL (2014) Prenatal stress-induced increases in placental inflammation and offspring hyperactivity are male-specific and ameliorated by maternal antiinflammatory treatment. Endocrinology 155:2635–2646

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Mueller BR, Bale TL (2008) Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci 28:9055–9065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Steeb H, Ramsey JM, Guest PC, Stocki P, Cooper JD, Rahmoune H, Ingudomnukul E, Auyeung B, Ruta L, Baron-Cohen S, Bahn S (2014) Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome. Mol Autism 5:4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Masi A, Breen EJ, Alvares GA, Glozier N, Hickie IB, Hunt A, Hui J, Beilby J, Ravine D, Wray J, Whitehouse AJO, Guastella AJ (2017) Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder. Mol Autism 8:63

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Yan Y, Jiang W, Liu L, Wang X, Ding C, Tian Z, Zhou R (2015) Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell 160:62–73

    Article  CAS  PubMed  Google Scholar 

  96. Sarkar C, Basu B, Chakroborty D, Dasgupta PS, Basu S (2010) The immunoregulatory role of dopamine: an update. Brain Behav Immun 24:525–528

    Article  CAS  PubMed  Google Scholar 

  97. Torres-Rosas R, Yehia G, Pena G, Mishra P, del Rocio Thompson-Bonilla M, Moreno-Eutimio MA, Arriaga-Pizano LA, Isibasi A, Ulloa L (2014) Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med 20:291–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Baganz NL, Blakely RD (2013) A dialogue between the immune system and brain, spoken in the language of serotonin. ACS Chem Nerosci 4:48–63

    Article  CAS  Google Scholar 

  99. Ahern GP (2011) 5-HT and the immune system. Curr Opin Pharmacol 11:29–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Tobiasova Z, van der Lingen KH, Scahill L, Leckman JF, Zhang Y, Chae W, McCracken JT, McDougle CJ, Vitiello B, Tierney E, Aman MG, Arnold LE, Katsovich L, Hoekstra PJ, Volkmar F, Bothwell AL, Kawikova I (2011) Risperidone-related improvement of irritability in children with autism is not associated with changes in serum of epidermal growth factor and interleukin-13. J Child Adolesc Psychopharmacol 21:555–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Choi JE, Widjaja F, Careaga M, Bent S, Ashwood P, Hendren RL (2014) Change in plasma cytokine levels during risperidone treatment in children with autism. J Child Adolesc Psychopharmacol 24:586–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Akhondzadeh S, Fallah J, Mohammadi MR, Imani R, Mohammadi M, Salehi B, Ghanizadeh A, Raznahan M, Mohebbi-Rasa S, Rezazadeh SA, Forghani S (2010) Double-blind placebo-controlled trial of pentoxifylline added to risperidone: effects on aberrant behavior in children with autism. Prog Neuropsychopharmacol Biol Psychiatry 34:32–36

    Article  CAS  PubMed  Google Scholar 

  103. Ghaleiha A, Rasa SM, Nikoo M, Farokhnia M, Mohammadi MR, Akhondzadeh S (2015) A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: effects on aberrant behavior in children with autism. Psychiatry Res 229:181–187

    Article  CAS  PubMed  Google Scholar 

  104. Asadabadi M, Mohammadi MR, Ghanizadeh A, Modabbernia A, Ashrafi M, Hassanzadeh E, Forghani S, Akhondzadeh S (2013) Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl) 225:51–59

    Article  CAS  Google Scholar 

  105. Tsilioni I, Taliou A, Francis K, Theoharides TC (2015) Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Transl Psychiatry 5:e647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Melamed IR, Heffron M, Testori A, Lipe K (2018) A pilot study of high-dose intravenous immunoglobulin 5% for autism: impact on autism spectrum and markers of neuroinflammation. Autism Res 11:421–433

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the project (NORTE-01-0145-FEDER-000012), funded by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). MIA is funded by a postdoctoral fellowship (SFRH/BPD/91011/2012), from Fundação para a Ciência e a Tecnologia (FCT).

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Authors and Affiliations

  1. i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal

    J. Prata, A. S. Machado, O. von Doellinger, M. I. Almeida, M. A. Barbosa, R. Coelho & S. G. Santos

  2. FMUP-Faculty of Medicine, University of Porto, Porto, Portugal

    J. Prata, A. S. Machado, O. von Doellinger & R. Coelho

  3. Department of Psychiatry and Mental Health, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal

    J. Prata

  4. Department of Clinical Neurosciences and Mental Health, Centro Hospitalar UniversitÃrio São João, Porto, Portugal

    A. S. Machado & R. Coelho

  5. Department of Psychiatry and Mental Health, Centro Hospitalar do Tâmega e Sousa, Penafiel, Portugal

    O. von Doellinger

  6. INEB-Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal

    M. I. Almeida, M. A. Barbosa & S. G. Santos

  7. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal

    M. A. Barbosa & S. G. Santos

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  1. J. Prata
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  2. A. S. Machado
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  3. O. von Doellinger
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  4. M. I. Almeida
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  5. M. A. Barbosa
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  6. R. Coelho
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  7. S. G. Santos
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Correspondence to S. G. Santos .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    Firas H. Kobeissy

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Prata, J. et al. (2019). The Contribution of Inflammation to Autism Spectrum Disorders: Recent Clinical Evidence. In: Kobeissy, F. (eds) Psychiatric Disorders. Methods in Molecular Biology, vol 2011. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9554-7_29

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  • DOI: https://doi.org/10.1007/978-1-4939-9554-7_29

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  • Publisher Name: Humana, New York, NY

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  • Online ISBN: 978-1-4939-9554-7

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