Neurodevelpoment and vaccines: from epigenetics to clinics

Journal title PNEI REVIEW
Author/s Cristina Panisi, Ernesto Burgio
Publishing Year 2018 Issue 2018/1 Language Italian
Pages 16 P. 76-91 File size 1136 KB
DOI 10.3280/PNEI2018-001007
DOI is like a bar code for intellectual property: to have more infomation click here

Below, you can see the article first page

If you want to buy this article in PDF format, you can do it, following the instructions to buy download credits

Article preview

FrancoAngeli is member of Publishers International Linking Association, Inc (PILA), a not-for-profit association which run the CrossRef service enabling links to and from online scholarly content.

Reduced perception of usefulness of vaccines and fear of undesirable effects have motivated the growing hesitation towards vaccinoprofilaxis in recent years. In particular, fear that vaccines can cause autism is the main reason for hesitation. The attempt to put fear of autism in the background by focusing on fear of infectious diseases seems an ineffective strategy as it drives choices based on emotions instead of awareness. With the aim of attenuating fear of autism through a better knowledge of this condition, the pathogenetic model that best accounts for the onset and the clinical characteristics of autism spectrum disorders will be described. The dissertation will lead to the conclusion that a simplistic traditional cause-effect model is unable to justify the epidemiological and clinical characteristics of autism. Therefore, not the making of a single risk factor guilty, but the awareness of the complexity of the pathogenetic model can lead to an effective intervention of primary prevention for neurodevelopmental disorders.

Keywords: Vaccinations, Vaccine hesitancy, Neurodevelopmental disorders, Epigenetics, Neuroinflammation, Primary prevention.

  1. Knuesel I., Chicha L., Britschgi M., Schobel S.A., Bodmer M., Hellings J.A., Toovey S. and Prinssen E.P. (2014). Maternal immune activation and abnormal brain development across CNS disorders. Nat. Rev. Neurol., 10: 643-660.
  2. Kundakovic M., Gudsnuk K., Herbstman J.B., Tang D., Perera F.P. and Champagne F.A. (2015). DNA methylation of BDNF as a biomarker of early-life adversity. PNAS, 112(22): 6807-6813.
  3. Landrigan P.J., Sonawane B., Butler R.N., Trasande L., Callan R. and Droller D. (2005). Early environmental origins of neurodegenerative disease in later life. Environ. Health. Perspect. 113(9): 1230-1233.
  4. Levy S.E., Mandell D.S. and Schultz R.T. (2009). Autism. Lancet, 374(9701): 1627-1638. DOI: 10.1016/S0140-6736(09)61376-
  5. Lord C., Shulman C. and DiLavore P. (2004). Regression and word loss in autistic spectrum disorders. J. Child Psychol. Psychiatry, 45(5): 936-955.
  6. Moya-Pérez A., Luczynski P., Renes I.B., Wang S., Borre Y., Anthony Ryan C., Knol J., Stanton C., Dinan T.G. and Cryan J.F. (2017). Intervention strategies for cesarean section–induced alterations in the microbiota-gut-brain axis. Nutr. Rev., 75(4): 225-240.
  7. McElhanon B.O., McCracken C., Karpen S. and Sharp W.G. (2014). Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics, 133(5): 872-883.
  8. Panisi C. (2016). Aspetti immunitari dell’autismo. In: Keller R., a cura di, I disturbi dello spettro autistico in adolescenza e in età adulta. Trento: Edizioni Centro Studi Erickson.
  9. Patterson P.H. (2009). Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav. Brain. Res., 204(2): 313-321.
  10. Pellegrino P., Clementi E. and Radice S. (2015). On vaccines adjuvants and autoimmunity: Current evidence and future perspectives. Autoimmun. Rev., 14(10): 880-888.
  11. Poland C. and Brunson E.K. (2015). The need for a multi-disciplinary perspective on vaccine hesitancy and acceptance. Vaccine, 33(2): 277-279.
  12. Reisinger S., Khan D., Kong E., Berger A., Pollak A. and Pollak D.D. (2015). The poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery. Pharmacol. Ther., 149: 213-226.
  13. Schwarz J.M. and Bilbo S.D. (2012). Sex, glia, and development: interactions in health and disease. Horm. Behav., 62(3): 243-253.
  14. Shoenfeld Y. and Agmon-Levin N. (2011). ‘ASIA’–autoimmune/infl ammatory syndrome induced by adjuvants. J. Autoimmun., 36(1): 4-8.
  15. Kipnis J. (2016). Multifaceted interactions between adaptive immunity and the central nervous system. Science, 353(6301): 766-771.
  16. Aldinger K.A., Lane C.J., Veenstra-VanderWeele J. and Levitt P. (2015). Patterns of Risk for Multiple Co-Occurring Medical Conditions Replicate Across Distinct Cohorts of Children with Autism Spectrum Disorder. Autism Res., 8(6): 771-781.
  17. Anholt G.E., Cath D.C., van Oppen P., Eikelenboom M., Smit J.H., van Megen H. and van Balkom A.J. (2010). Autism and ADHD symptoms in patients with OCD: are they associated with specifi c OC symptom dimensions or OC symptom severity?. J. Autism. Dev. Disord., 40(5): 580-589.
  18. Ashwood P., Corbett B.A., Kantor A., Schulman H., Van de Water J. and Amaral D.G. (2011). In search of cellular immunophenotypes in the blood of children with autism. PLoS One. 6(5): e19299.
  19. Bach J.F. (2002). The effect of infections on susceptibility to autoimmune and allergic diseases. NEJM, 347(12): 911-920.
  20. Bilbo S.D. and Schwarz J.M. (2012). The immune system and developmental programming of brain and behavior. Front. Neuroendocrinol., 33(3): 267-286.
  21. Backhed F., Roswall J., Peng Y., Feng Q., Jia H., Kovatcheva-Datchary P., Li Y., Xia Y., Xie H., Zhong H., Khan M.T., Zhang J., Li J., Xiao L., Al-Aama J., Zhang D., Lee Y.S., Kotowska D., Colding C., Tremaroli V., Yin Y., Bergman S., Xu X., Madsen L., Kristiansen K., Dahlgren J. and Wang J. (2015). Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe 17: 690-703.
  22. Blomström Å., Karlsson H., Gardner R., Jörgensen L., Magnusson C. and Dalman C. (2016). Associations Between Maternal Infection During Pregnancy, Childhood Infections, and the Risk of Subsequent Psychotic Disorder--A Swedish Cohort Study of Nearly 2 Million Individuals. Schizophr. Bull., 42: 125-133.
  23. Stilling R.M., Dinan T.G. and Cryan J.F. (2014). Microbial genes, brain & behavior – epigenetic regulation of the gut–brain axis. Genes Brain Behav.,13(1): 69-86.
  24. Sweeten T.L., Bowyer S.L., Posey D.J., Halberstadt G.M. and McDougle C.J. (2003). Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics, 112(5): e420.
  25. Swiatczak B. and Rescigno M. (2012). How the interplay between antigen presenting cells and microbiota tunes host immune responses in the gut. Semin. Immunol., 24(1): 43-49.
  26. Tang B., Jia H., Kast R.J. and Thomas E.A. (2013). Epigenetic changes at gene promoters in response to immune activation in utero. Brain Behav. Immun,, 30: 168-175.
  27. Vargas D.L., Nascimbene C., Krishnan C., Zimmerman A.W. and Pardo C.A. (2005). Neuroglial activation and neuroinfl ammation in the brain of patients with autism. Ann. Neurol., 57(1): 67-81.
  28. Virtanen H.E., Rajpert-De Meyts E., Main K.M., Skakkebaek N.E. and Toppari J. (2005). Testicular dysgenesis syndrome and the development and occurrence of male reproductive disorders. Toxicol. Appl. Pharmacol., 207(2 Suppl): 501-505.
  29. Wiertsema S.P., Chidlow G.R., Kirkham L.A., Corscadden K.J., Mowe E.N., Vijayasekaran S., Coates H.L., Harnett G.B. and Richmond P.C. (2011). High Detection Rates of Nucleic Acids of a Wide Range of Respiratory Viruses in the Nasopharynx and the Middle Ear of Children With a History of Recurrent Acute Otitis Media. J. Med. Virol., 83: 2008-2017.
  30. World Health Organization (2013). VACCINE SAFETY BASICS learning manual Module 2- Type of vaccines and adverse reactions. Testo disponibile al sito:, consultato il 01/03/2018.
  31. Brookmeyer R., Johnson E., Ziegler-Graham K. and Arrighi H.M. (2007). Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement., 3(3): 186-191.
  32. Burgio E. (2011). Il problema dell’incremento dei tumori infantili. Cancerogenesi transplacentare e transgenerazionale. In: Ridolfi R., a cura di, Progetto Ambiente e Tumori. Milano: AIOM.
  33. Burgio E. (2013). Notes on the epigenetic origins of childhood cancer. Epidemiol. Prev., 37(1 Suppl 1): 261-265.
  34. Burgio E. (2015). Environment and Fetal Programming: the origins of some current “pandemics”. J. Pediatr. Neonat. Individual Med., 4(2): e040237. DOI: 10.7363/04023
  35. Burgio E., Lopomo A. and Migliore L. (2015). Obesity and diabetes: from genetics to epigenetics. Mol. Biol. Rep., 42(4): 799-818.
  36. Burgio E. e Panisi C. (2017). La pandemia silenziosa dei disturbi del neurosviluppo. PNEI Review 1: 17-32.
  37. Centers for Disease Control and Prevention. (2007). Prevalence of autism spectrum disorders – Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2002. MMWR Surveill. Summ., 56(SS1): 12-28.
  38. Centers for Disease Control and Prevention. (2012). Prevalence of autism spectrum disorder – Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill. Summ., 61(SS03): 1-19.
  39. Choi G.B., Yim Y.S., Wong H., Kim S., Kim H., Kim S.V., Hoeffer C.A., Littman D.R. and Huh J.R. (2016). The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science, 351(6276): 933-939.
  40. Crépeaux G., Eidi H., David M.O., Baba-Amer Y., Tzavara E., Giros B., Authier F.J., Exley C., Shaw C.A., Cadusseau J. and Gherardi R.K. (2017). Non-linear doseresponse of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity. Toxicology, 375: 48-57.
  41. De Theije C.G., Wu J., da Silva S.L., Kamphuis P.J., Garssen J., Korte S.M. and Kraneveld A.D. (2011). Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management. Eur. J. Pharmacol., 668 Suppl 1: S70-80.
  42. Dittman S., Wharton M., Vitek C., Ciotti M., Galazka A., Guichard S., Hardy I., Kartoglu U., Koyama S., Kreysler J., Martin B., Mercer D., Rønne T., Roure C., Steinglass R., Strebel P., Sutter R. and Trostle M. (2000). Successful Control of Epidemic Diphtheria in the States of the Former Union of Soviet Socialist Republics: Lessons Learned. J. Infec. Dis., 181 Suppl 1: S10-S22. DOI: 10.1086/31553
  43. El Aidy S., Dinan T.G. and Cryan J.F. (2015). Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication. Clin. Ther., 37(5): 954-967.
  44. Esposito S., Prada E., Mastrolia M.V., Tarantino G., Codecà C. and Rigante D. (2014). Autoimmune/infl ammatory syndrome induced by adjuvants (ASIA): clues and pitfalls in the pediatric background. Immunol. Res., 60(2-3): 366-375.
  45. Estes M.L. and McAllister A.K. (2015). Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat. Rev. Neurosci., 16(8): 469-486.
  46. Estes M.L. and McAllister A.K. (2016a). Maternal immune activation: implications for neuropsychiatric disorders. Science, 353(6301): 772-777.
  47. Estes M.L. and McAllister A.K. (2016b). IMMUNOLOGY. Maternal TH17 cells take a toll on baby’s brain. Science, 351(6276): 919-920.
  48. Fombonne E. (2009). Epidemiology of pervasive developmental disorders. Pediatr. Res., 65(6): 591-598.
  49. Gatti A.M. and Montanari S. (2017). New Quality-Control Investigations on Vaccines: Micro- and Nanocontamination. Int. J. Vaccines Vaccin., 4(1): 00072.
  50. Gillman M.W., Barker D., Bier D., Cagampang F., Challis J., Fall C., Godfrey K., Gluckman P., Hanson M., Kuh D., Nathanielsz P., Nestel P. and Thornburg K.L. (2007). Meeting report on the 3rd International Congress on Developmental Origins of Health and Disease (DOHaD). Pediatr. Res., 61(5 Pt 1): 625-629.
  51. Gluckman P.D. and Hanson M.A. (2004). Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res., 56(3): 311-317. DOI: 10.1203/01.PDR.0000135998.08025.F
  52. Hahné S., Macey J., Tipples G., Varughese P., King A., van Binnendijk R., Ruijs H., van Steenbergen J., Timen A., van Loon A. M. and de Melker H. (2005) Rubella outbreak in an unvaccinated religious community in the Netherlands spreads to Canada. Euro Surveill., 10(20): E050519.1.
  53. Hahné S., Macey J., van Binnendijk R., Kohl R., Dolman S., van der Veen Y., Tipples G., Ruijs H., Mazzulli T., Timen A., van Loon A. and de Melker H. (2009),. Rubella Outbreak in the Netherlands, 2004-2005: High Burden of Congenital Infection and Spread to Canada. Ped. Infect. Dis. J., 28(9): 795-800.
  54. Holt P.G. and Jones C.A. (2000). The development of the immune system during pregnancy and early life. Allergy, 55(8): 688-697.
  55. Hsiao E.Y., McBride S.W., Hsien S., Sharon G., Hyde E.R., McCue T., Codelli J.A., Chow J., Reisman S.E., Petrosino J.F., Patterson P.H. and Mazmanian S.K. (2013). Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 155: 1451-1463.

Cristina Panisi, Ernesto Burgio, Neurosviluppo e vaccini: dall’epigenetica alla clinica in "PNEI REVIEW" 1/2018, pp 76-91, DOI: 10.3280/PNEI2018-001007