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Autism and Environmental Links

Autism and Environmental Links. Presented by Laura Lott RNC-NIC, MPH Student at Walden University PUBH 6165-6 Instructor: Dr Robert Marino Spring Quarter, 2010. www.rcgates.com/images/autism_symbol1.gif. I. Welcome. II. What is Autism? definitions of autism prevalence of Autism

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Autism and Environmental Links

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  1. Autism and Environmental Links Presented by Laura Lott RNC-NIC, MPH Student at Walden University PUBH 6165-6 Instructor: Dr Robert Marino Spring Quarter, 2010 www.rcgates.com/images/autism_symbol1.gif

  2. I. Welcome. II. What is Autism? definitions of autism prevalence of Autism III. Causes of Autism? . Genetics . Environmental Factors . Genetic-Environmental Factors IV. Genetic Susceptibility, Autoimmune Diseases, Autism and Environmental Triggers infectious agents as environmental triggers for autoimmune diseases/autism . Microbes associated with specific autoimmune disease . Vaccines associated with autoimmune disorders . Autoimmune Diseases, Environmental triggers, and Autism. Are they Linked? AGENDA

  3. V. Shared Characteristics of Autoimmune Diseases and Autism VI. Autoimmune Diseases, Infectious Triggers and the Hygiene Hypothesis VII. Autism, Autoimmune Diseases, Dyslexia, ADHD, Hyperlexia are they all connected? are they all part of a major subgroup on the autism spectrum? VIII. Summary . where do we go from here? Solutions XI. Questions? AGENDA

  4. Learning Objectives By the end of this conference participants will be able to: • Define, describe and understand autism as part of a spectrum of disorders • Describe autism spectrum disorders as polygenic and multi-causal • Identify associated environmental triggers • Understand and describe the links between ASD, autoimmune diseases and environmental triggers • Explain the mechanism of environmental triggers in relation to genetic susceptibility, autoimmune diseases and autism spectrum disorders. http://www.cdc.gov/ncbddd/autism/index.html Hertz-Piciotto, J. et al (2006). The Charge Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism, Environmental Health Perspectives, 114 (7) Comi, A. et al. (1999). Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism, Journal of Child Neurology, 14:388 Atladottir, HO., et al (2009). Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders, Pediatrics, 124(2), 687-694 Molina, V. & Schoenfeld, Y. (2005). Infection, Vaccines and Other Environmental Triggers of Autoimmunity, Autoimmunity, 38(3), 235-245

  5. Definition under the year 2000 statistical manual of mental disorders (DSM): Autism is one of five disorders under the category of Pervasive Developmental Disorders (PDD). Pervasive Developmental Disorders are also known as Autism Spectrum Disorders or ASD. The CDC (2009) defines ASD as a group of developmental disabilities that can cause significant social, communication, and behavioral challenges. What is Autism? http://www.cdc.gov/ncbddd/autism/index.html

  6. Prevalence of Autism Spectrum Disorders According to the CDC (2009): . the current prevalence of ASD in the US averages 1 in 110 children. . Between 2002-2006 there was an average increase in prevalence of 57% across 10 surveillance sites through the Autism and Developmental Disabilities Monitoring (ADDM) Network. http://www.cdc.gov/ncbddd/autism/addm.html http://www.cdc.gov/mmwr/preview/mmwrhtml/ss58101l.htm

  7. Causes of Autism Spectrum Disorders? • A. Genetic Cause • B. Environmental Cause • C. Genetic-Environmental Cause teachersnetwork.org/…uploads/genetics.jpg www.pollutionissues.com/images/paz_02_im0179.jpg Images2.sina.com/english/china/p/2008/1109/U1

  8. A. Genetics http://media-2.web.britannica.com/eb-media/46/59346-004-9EC58E43.jpg • Strong Familial Tendency – if one sibling has an ASD there is a 10-20 fold increased risk of other siblings also having the disorder (Hertz-Picciotto, I., et al. 2006). • Autism is associated with several distinct genetic syndromes such as: Angelman Syndrome; tuberous sclerosis; phenylketonuria; Joubert Syndrome; Mobius Syndrome and chromosomal abnormalities such as Fragile X (Hertz-Picciotto, I., et al. 2006) Hertz-Piciotto, I., et al (2006) The Charge Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism, Environmental Health Perspectives, 114(7)

  9. Genetics alone cannot explain the increased prevalence in autism spectrum disorders • Although autism is associated with several known genetic disorders, the majority of autism cases (90%) are not linked to them. • No single gene has been identified with autism • Most likely polygenic involvement • A minimum of 40% of autism cases likely associated with environmental causes Hertz-Picciotto,I. et al (2006) The charge Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism, Environmental Health Perspectives, 114(7)

  10. B. Environmental Causes • Chemical Exposures Chemicals known to be associated with development of autism include: Thalidomide; Valproic Acid; and Lead Poisoning. Other environmental chemicals are known to produce autism-like behaviors in animal studies including Trimethyl tin (TMT) and organomercurials such as methylmercury, both of which can cause limbic damage in susceptible animal models (Lathe, R. 2008) Lathe,R. (2008) Environmental Factors and Limbic vulnerability in Childhood Autism, American Journal of Biochemistry and Biotechnology

  11. GABR Blockers • Chlorinated hydrocarbon insecticides (including: heptachlor, chlordane, dieldrin and toxaphene). Use in the US was discontinued between 1987-1990 however, these chemicals are persistent in the environment and human tissues. • Several uses of Lindane continue for example in the control of head lice and scabies. • New class of GABR antagonists are in use for domestic and agricultural applications. • 30-35% of children with autism have seizures. An altered GABAA receptor (GABR) system is found fairly frequently in people with autism and this has been proposed as a major underlying cause of seizure susceptibility. Do children with GABR deficiencies have a heightened susceptibility to adverse responses when exposed to environmental GABR blockers? Pessah,I. (2006) Can Exposure to Environmental Toxicants Influence Autism Susceptibility?, Autism Society of America

  12. Bioaccumulation of Environmental Chemicals • Example: Methyl-mercury http://health.state.tn.us/images/mercury3.jpg

  13. 1. Infectious agents: Rubella, CMV, Herpes, Measles and Mumps (Hertz-Picciotto, I. 2006) 2. Maternal Risk Factors Advanced Maternal age and cumulative effect of environmental toxins . 3. Air Pollutants 4. Obstetric Complications Breech, traumatic delivery, low 5 min apgar score, low birth weight, RDS, rhesus incompatibility, c-section, resuscitation, severe fetal/ neonatal infection, pre-eclampsia, pre-term delivery 5. Assistive Reproductive Technology 6. Chronic Diseases in Mother Hypertension, IDDM, Auto immune disorders Maternal Environmental Exposures www.thesahara.info/mrsa/mrsa_cytomegalovirus.jpg www.scientificamerican.com/media/inline www.myportfolio.usc.edu/enowak/air-pollution.jpg

  14. Genetic Susceptibility Environmental Triggers Heavy metal exposure/bioaccumulation Air pollution Infections vaccines C. Genetic-Environmental Causes www.roche.com/.../061106/original/p004.jpg http://www.niehs.nih.gov/.../labs/Img/cs/index.cfm wwwwww www.icare4autism.files.wordpress.com/2009/01/

  15. Genetic Susceptibility, Autoimmune Diseases, Autism and Environmental Triggers • Environmental Triggers: • 1. Infections • 2. Vaccines www.health.msn.com/PopUp.aspx?cp- www.lucinafoundation.org/assets/autoimmune-di www.alignmap.com/wp-content/Graphics/vaccine.gif www.cherished79.files.wordpress.com/...autism.jpg

  16. Infections as Environmental Triggers for Autoimmune Disorders/Autism • Infectious Triggers include bacteria, viruses, and parasites • How? Mainly by molecular mimicry • Genetic susceptibility triggered by microbial antigens can lead to development of autoimmune diseases. Molina,V., & Shoenfeld, Y. (2005) Infection, vaccines and other environmental triggers of autoimmunity, Autoimmunity, 38(3), 235-245

  17. Molecular Mimicry http://www.bcm.edu/.../images/ms-infect1(345x530).jpg

  18. Examples of microbes associated with specific autoimmune disorders • Epstein Barr Virus – Multiple Sclerosis • Human Parvovirus B19 – Rheumatoid Arthritis and Lupus (SLE) • Measles and Mumps infection after age 15yrs associated with MS • Campylobacter jejuni associated with Gullian Barre Syndrome (GBS) • Streptococcal Infections associated with PANDAS (pediatric autoimmune neuropsychiatric disorders) Molina,v. & Shoenfeld, Y (2005) Infection, vaccines and other environmental triggers of autoimmunity, Autoimmunity, 38(3) 235-245

  19. Vaccines as Environmental Triggers of Autoimmune Disorders • Examples of vaccines associated with autoimmune diseases • Diphtheria and Tetanus toxoid, polio and measles vaccines – GBS • MMR vaccines – Thrombocytopenia (ITP) and IBD • Rubella vaccine – acute and chronic arthritis in adult women • Hepatitis B Vaccine – has been connected with MS • Flu vaccine – associated with GBS • Measles Vaccine – most commonly associated with Autism Three major neurological autoimmune disorders have been addressed in association with vaccination:GBS, MS and Autism Molina, V., & Shoenfeld, Y. (2005) Infection, vaccines and other environmental triggers of autoimmunity, Autoimmunity, 38(3), 235-245

  20. How Do Vaccines Trigger Autoimmune Diseases? • Two Types of Vaccines: Active (live microbe) and Passive (inactivated). • It has been proposed that the same mechanism that triggers autoimmune diseases by microbes also occurs in genetically susceptible people through vaccinations • Much debate has focused on thimerosal in childhood vaccines prior to 1999 causing a cumulative exposure to ethylmercury and being a possible trigger for autism. • However, the prevalence of autism continues to grow despite the removal of thimerosal from childhood vaccines suggesting that this is not a trigger. Molina,V., & Shoenfeld,Y. (2005) Infection, vaccines and other environmental triggers of autoimmunity, Autoimmunity, 38(3), 235-345 Schecter,R. & Grether, J. (2008) Continuing Increases in Autism Reported to California’s Developmental Services System, Arch Gen Psychiatry, 65(1), 19-24

  21. Autoimmune Diseases, Environmental Triggers and Autism: Are they linked? • A study by Comi,A., et al (1999) reports an increased incidence of autoimmune diseases in mothers and first-degree relatives of children with autism. • The most common autoimmune disorders associated with autism were Type I diabetes, Rheumatoid Arthritis, Hypothyroidism, and Systemic Lupus Erythematosus (SLE). Comi,A., et al (1999) Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism, Journal of Child Neurology, 14; 388

  22. Familial Predisposition Associated Immune Abnormalities A relationship with viruses (or other environmental triggers) A sex preponderance Autism ratio of boys to girls is about 4:1 Autoimmune Disorders ratio is about 3:1 with women affected more than men. incidence and prevalence of autism and auto immune disorders is increasing. Shared Characteristics of Autoimmune Disorders and Autism The world wide prevalence of rheumatoid arthritis is estimated to be about 1-2% with auto-immune disorders affecting about 8% of the US population Fairweather, D. & Rose, NR (2004). Approximately 1% of children in the US are affected by autism spectrum disorders (CDC, 2006). Fairweather, D. & Rose, NR (2004) Women and autoimmune diseases, Emerging Infectious Disease, available from http://www.cdc.gov/ncidod/EID/vol10no11/04-0367.htm CDC (2006) ADDM, MMWR Surveillance Summary, 58 (SS-10) Fai

  23. Changes in Prevalence of ASDs Among Children 8 yrs old, 2002-2006 New Cases ASD per 10,000 child-years Increased Incidence and Prevalence of ASD CDC (2006) New Autism Data available from http://www.cdc.gov/mmwr/preview/mmwrhtml/225810a1.htm http://www.environmentalhealthnews.org/ehs/images/2009/january/2009-0109autism.png

  24. Autoimmune Diseases, Infectious Triggers and the Hygiene Hypothesis • Autoimmune diseases can be triggered by infectious agents and vaccines as already discussed. • In addition to vaccines can autoimmune diseases also be triggered by other environmental agents such as antibiotics and antiseptic cleaning agents? • The Hygiene Hypothesis proposes autoimmune disorders can also be triggered by the above agents and are also contributing to increases in asthma and allergies. Moore, E. (2007) Infection and Autoimmune Disease, General Medicine available from http://autoimmunedisease.suite101.com/article.cfm/infection_and_autoimmune_disease

  25. Antibiotic Use, Autism and Autoimmune Diseases • Under the Hygiene Hypothesis is the use of antibiotics contributing to the increase in autism spectrum disorders, autoimmune disorders, and other chronic diseases such as asthma and allergies? • In addition to the above connection, is it possible that antibiotics have led to an increase in these disorders because they contributed to the survival of infants and children with immune system dysfunctions who would not have survived infancy or childhood prior to their use?

  26. Association Between Autoimmune Diseases and Autism Confirmed • A recent study by Atladottir, HO, et al (2009) confirms an association between autism and autoimmune disorders. • Associations between Type I Diabetes and Infantile Autism • Associations between Rheumatoid Arthritis and ASD • Association between maternal Celiac Disease and ASD Atladottir, HO., et al (2009) Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders, Pediatrics, 124(2), 687-694

  27. How Big is the Public Health Crisis if Autoimmune diseases and Autism Spectrum Disorders are linked? • How to identify and develop prevention measures for autoimmune diseases and ASD. • Identification of genetic biomarkers in women?

  28. Autism, Dyslexia, ADHD, Hyperlexia, Autoimmune Diseases. • Currently we know the causes of less than 25% of all neuro-developmental disabilities, including dyslexia, ADHD, and Autism. (Weiss, B., & Landrigan, P. 2000). • Are they all linked? • Are they just different expressions of a common genetic predisposition, and triggered by environmental factors? • Can an autoimmune disease or a genetic susceptibility to an autoimmune disease in a mother be manifested as autism in a son? Is the gene located on the X chromosome? Is this a distinct subgroup within the autism spectrum? Growing evidence would suggest the answer is yes. Are Dyslexia and ADHD a lesser expression of the same disorder within this subgroup? Comi,A. et al (1999) Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism, Journal of Child Psychology, 14, 388-394 Weiss,B. & Landrigan, P. (2000) The Developing Brain and the Environment: An Introduction, Environmental Health Perspectives, 108(3)

  29. Summary of Causes of Autism • 1. Approximately 10% of all cases of autism are associated with known genetic syndromes. • 2. Some cases of autism have been linked to adverse birth outcomes such as pre-term delivery • 3. A minimum of 40% of all cases of autism are thought to be linked to environmental exposures • 4. Autism has been linked with autoimmune disorders and mounting evidence suggests a genetic predisposition with environmental triggers. Hertz-Picciotto,I et al (2006) The CHARGE Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism, Environmental Health Perspectives, 114(7)

  30. Where to Go From Here? • Autism is likely polygenic and multi-causal. There is a need to separate and distinguish between the different causes. • Are there other distinct genetic syndromes within the Autism Spectrum that have not yet been classified? • Autoimmune Diseases, environmental triggers, and autism. Finding the common link. • Environmental Causes? Viruses, Bacteria and What Else? Hertz-Picciotto, I. et al (2006) The CHARGE Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism, Environmental Health Perspectives, 114(7)

  31. Solutions? Separate out distinct sub-groups of populations on the autism spectrum a. specific genetic syndromes b. maternal risk factors/preterm birth c. environmental exposures d. autoimmune diseases and environmental triggers – identify specific genetic biomarkers Atladottir, HO., et al. (2009). Association of Familial History of Autoimmune Diseases and Autism Spectrum Disorders, Pediatrics, 124(2), 687-694 Comi, AM., et al. (1999). Familial clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism, Journal of Child Neurology, 14(388) Fairweather, D. & Rose, NR.(2004). Women and Autoimmune Diseases, Emerging Infectious Diseases, 10(11) Hertz-Picciotto, I., et al. (2006). The Charge Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism, Environmental Health Perspectives, 114(7) Lathe, R. (2008). Environmental Factors and Limbic Vulnerability in Childhood Autism, American Journal of Biochemistry and Biotechnology, 4(2), 183-197 March of Dimes. (2010). Preterm Birth, available from http://www.marchofdimes.org Molina, V. & Schoenfeld, Y. (2005). Infection, Vaccines, and Other Environmental Triggers of Autoimmunity, Autoimmunity, 38(3), 235-245

  32. QUESTIONS?

  33. References • Atladottir, HO., Et al. (2009). Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders, Pediatrics, 124(2), 687-694 • Buchmayer, S., et al (2009). Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity? Pediatrics, 124(5), e817-e825 • CDC (2009.) Prevalence of the Autism Spectrum Disorders (ASDs) in Multiple Areas of the United States, 2004 and 2006, MMWR Surveillance Summary, 58(SS-10_ • Comi, AM., et al. (1999). Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism, Journal Child Neurology, 14(388) • Fairweather, D. & Rose, NR. (2004). Women and Autoimmune Diseases, Emerging Infectious Diseases, 10(11) • Hertz-Picciotto, I., et al. (2006). The CHARGE Study: An Epidemiolgic Investigation of Genetic and Environmental Factors Contributing to Autism, Environmental Health Perspectives, 114(7) • Hughes, D. (2007) Increased Autism Risk May Be Linked to Assisted Reproductive Technology, Neuropsychiatry, 8(12) • Juul-Dam, N., Townsend, J., & Courchesne, E. (2001). Prenatal, Perinatal, and Neonatal Factors in Autism, Pervasive Developmental Disorder-Not Otherwise Specified, and the General Population, Pediatrics, 107(4), e63 • Lathe, R. (2008). Environmental Factors and Limbic Vulnerability in Childhood Autism, American Journal of Biochemistry and Biotechnology, 4(2), 183-197 • March of Dimes (2010) Preterm Birth, available from http://www.marchofdimes.org • Molina, V. & Shoenfeld, Y. (2005). Infection, vaccines and other environmental triggers of autoimmunity, Autoimmunity, 38(3), 235-245 • Moore, E. (2007). Infection and Autoimmune Disease, General Medicine • Paoloni-Giacobino, A. & Chaillet, JR. (2004) Genomic Imprinting and assisted reproduction, Reproductive Health, 1(6) • Schechter, R. & Grether, J. (2008). Continuing Increases in Autism Reported to California’s Developmental Services System, Arch Gen Psychiatry, 65(1) • Pessah, IN. (2006). Can Exposure to Environmental Toxicants Influence Autism Susceptibility? Autism Society of America • Weiss, B. & Landrigan, P. (2000). The Developing Brain and the Environment: An Introduction, Environmental Health Perspectives, 108(3) • Windham, G. et al. (2006). Autism Spectrum Disorders in Relation to Distribution of Hazardous Air Pollutants in the San Francisco Bay Area, Environmental Health Perspectives, 114(9) • Wu, J. et al. (2009) Association between Local Traffic-Generated Air Pollution and Preeclampsia and Preterm Delivery in the South Coast Air Basin of California, Environmental Health Perspectives, 117(11), 1773-1779

  34. Resources/Further Reading • Autism Society of America. www.autism-society.org • Blaxill, M. (2004). What’s Going On? The Question of Time Trends in Autism, Public Health Reports, 119 • CDC (2010). Facts About ADS, available from http://www.cdc.gov/ncbddd/autism/facts.html • Folstein, S. & Mankoski, R. (2000). Chromosome 7q: where Autism Meets Language Disorder? American Journal of Human Genetics, 67, 278-281 • Garvey, M., Giedd, J. & Swedo, S. (1998). PANDAS: The Search for Environmental Triggers of Pediatric Neuropsychiatric Disorders. Lessons From Rheumatic Fever, Journal Child Neurology, 13, 413-423 • Healy, J. & Aram, D. (1986). Hyperlexia and Dyslexia: A family study, Annals of Dyslexia, 36(1), 237-252 • Herbert, MR. et al. (2006). Autism and Environmental Genomics, Neurotoxicology, 27, 671-684 • Kinney, DK, et al. (2010). Environmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder? Medical Hypotheses, 74, 102-106 • Maimburg, RD. & Vaeth, M. (2006). Perinatal Risk Factors and infantile autism, Acta Psychiatr Scand 114, 257-264 • Morse, SM, et al. (2009). Early School Age Outcomes of Late Preterm Infants, Pediatrics, 123(4), e622-e629 • O’Connor, S. et al. (2004). Infectious Etiologies of Chronic Diseases: Focus on Women, Emerging Infectious Diseases, 10(11) • Petrini, J. et al. (2009). Increased Risk of Adverse Neurological Development for Late Preterm Infants, The Journal of Pediatrics, 154(2), 169-176.e3 • Schettler, T. (2004). Autism: Do Environmental Factors Play a Role in Causation? Science and Environmental Health Network • Stone, J. et al. (2004). Evidence for Sex-Specific Risk Allelles in Autism Spectrum Disorder, American Society of Human Genetics, 75(6), 1117-1123 • Szpir, M. (2006). Tracing the Origins of Autism, Environmental Health Perspectives, 114(7)

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