Q: What causes autism?

A: There is no one cause of autism. Multiple factors in our food and broader environment combine with inherited factors to contribute to autism. All of these factors can play different roles, and can take on various levels of significance in different individuals—all of us are unique in our susceptibility to diseases and disorders, like autism.

In the real world, we are exposed to a complex equation of factors that can ultimately influence our health. As Harvard pediatric neurologist Martha Herbert, M.D. puts it, there is an important difference between “cause” and “risk.” It isn’t even appropriate to talk about a “cause” of autism. Instead, it is more fitting to talk about multiple, interactive risks in our broader environment that may accumulate and contribute to autism. In any child, these environmental factors have the potential to modify the genetic susceptibility she or he is born with.

Q: Is there scientific evidence that environmental toxins contribute to autism?

A: Increased risk for autism and autistic behaviors from prenatal and early-life exposures to toxic chemicals has been documented by the following studies.

• Pollution. Living near a pollution site or near an EPA Superfund site.1, 2 Hazardous air pollutants, including metals and chlorinated solvents.3 Maternal residence near a freeway.4
• Pesticides. Residence near agricultural organochlorine pesticide (OP) applications.5 Prenatal exposure to the OP pesticide chlorpyrifos.6 Exposure to OPs is associated with vitamin D deficiency, providing a clue to a possible contributing dietary factor.7 There are several plausible physiological mechanisms for the effects of pesticides on abnormal brain development, including autism. Many pesticides can cause excitation and dysregulation of neural signaling in the brain due to inhibition of acetylcholinesterase and disruption of neural receptors, called GABAs.8
• Heavy metals. Exposure to environmental neurotoxins including mercury, aluminum, lead and cadmium.9, 10, 11, 12, 13, 14, 15 There is evidence of the biological plausibility of mercury in autism. Mercury disrupts sulfur metabolism, which leads to oxidative stress, commonly elevated in people with autism. This analysis is complicated by and informed by the fact that individuals have varying sensitivity to mercury. Thus, the interaction of genetic (ability to detoxify) and environmental factors (mercury exposure) may be of significance in autism.16

Q: Is there evidence that diet plays a role in autism?

A: There is a growing and complex body of science linking autism risk to dietary factors. Diet is an important factor in immune health, helping the body fight off the effects of toxic exposures. For example, children exposed to lead who are well-nourished absorb less lead into their bodies than poorly nourished children. Exposure is routine via the food supply to toxins that persist in the environment, and bio-accumulate in the food chain. Meats, fish and dairy products commonly contain PCBs, dioxins, mercury, pesticides, brominated flame retardants and perfluorinated chemicals (PFCs). Novel ingredients introduced to the food supply via food processing, such as mercury in high fructose corn syrup or synthetic food dyes, may provide additional routes of exposure to toxins.17 Chemicals in food packaging and cookware, like bisphenol A (BPA), phthalates and PFCs, also provide routine exposures to toxins.

Both animal and human studies support the critical role of maternal diet and metabolic status in programming brain circuitry that regulates behavior. A diet high in fat and obesity during pregnancy may make offspring more susceptible to behavior disorders such as ADHD and autism.18 Metabolic abnormalities linked to mitochondrial dysfunction may play a role in the etiology of autism and vulnerability to oxidative stress, induced by many environmental toxins.19 Certain bacteria in the gut may play a role in the regressive form of autism.20

Gastrointestinal (GI) disorders and metabolic conditions are common in children with autism.21 Immune abnormalities, including inflammation of the intestinal track and increased intestinal permeability, or “gut leak,” have been reported in children with autism. Alterations in serotonin, which send signals to the gut, may be implicated in some GI dysfunctions.22 One small study found that participants with autism were more likely to be overweight, have high intake of foods containing gluten and casein and were more likely than controls to have intestinal dysfunctions.23

Q: Can dietary interventions help people with autism?

A: Parents and clinicians of many children with autism report improvement in behavior and symptoms through specific dietary regimens, including dairy-free and gluten-free diets. Dr. Martha Herbert documents successful dietary, environmental and behavioral interventions based on individualized needs that improve or eliminate autistic behaviors in some individuals.24, 25 Other published studies examining the effects of dietary interventions on autism report mixed results.26, 27, 28, 29, 30 The lack of a consensus on the effects of various dietary interventions may be due to the fact that such studies can’t possibly account for differences in individual dietary needs.

Q: How do diet, environment and genes interact in autism?

A: Dr. Herbert and other researchers, including Dr. Russell Blaylock, are now hypothesizing new theories of causation, based on the intricate interplay of environmental toxins, nutrition and gene expression.31 Epigenetics is key to this new understanding. Genes carry the information that tells the body what to do and when to do it; the reading of this information is called “gene expression.” Epigenetics describes how the proteins forming the environment around genes—the epigenome—changes how they are expressed. We now know environmental toxins, like mercury and pesticides, along with nutritional deficiencies, can change the epigenome and alter the regulation of how genes are expressed, with adverse impacts on the development of the brain and nervous system. Most surprising to people is the realization that these environmental changes—epigenetic changes—can be inherited without any change in the underlying DNA. Epigenetic dysregulation32 is associated with the development of autism; examples include:

• “Turned on” or activated genes produce proteins or enzymes that help the body protect itself against oxidative stress, a core process by which our environment can harm us. Exposing the body to inorganic mercury, for example, can alter normal sulfur metabolism, impairing methylation, which is necessary for the body to excrete some toxins. Some individuals with autism have genetic polymorphisms that impair sulfur metabolism, methylation and this process of detoxification.33
• Foodborne and chemical “excitotoxins” elevate glutamate levels and can cause degeneration of nerve cells.34
• Environmental toxins impact the function of particular nervous system cells, called microglia, altering gene expression in individuals with Rett Syndrome, a disorder on the autism spectrum.35

As we learn more about autism, it appears that the etiology of autism has much in common with that of cancer in that there is never one cause, but rather is the result of multiple assaults on the immune system.

Endnotes

1. May, Heather. Utah researcher says autism-pollution link needs serious study. The Salt Lake Tribune. 2011. Retrieved from: www.sltrib.com/sltrib/entertainment/51847423-183/autism-chemicals-utah-metals.html.csp.

2. DeSoto MC. Ockham’s razor and autism: the case for developmental neurotoxins contributing to a disease of neurodevelopment. Neurotoxicology 2009; 30(3): 331-337.

3. Windham GC, Zhang L, Gunier R, Croen LA, Grether JK. Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco bay area. Environ Health Perspect. 2006;114(9): 1438-44.

4. Volk, HE, Hertz-Picciotto, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspectives 2011; 119(6):873-877.

5. Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect. 2007 Oct;115(10):1482-9.

6. Eskenazi B,Marks, AR, Bradman A, Harley K et al. Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children. Environ Health Perspect. 2007 May; 115(5): 792–798.

7. Yang JH, Lee YM, Bae SG, Jacobs DR Jr, Lee DH. Associations between organochlorine pesticides and vitamin D deficiency in the U.S. population. PLoS One. 2012;7(1):e30093. Epub 2012 Jan 25.

8. Shelton JF, Hertz-Picciotto I, Pessah IN. Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environ Health Perspectives 2012;120(7):944-951.

9. Blaylock, RL. A possible central mechanism in autism spectrum disorders, part 3: the role of excitotoxin food additives and the synergistic effects of other environmental toxins. Altern Ther Health Med. Mar-April 15:2 2009. 56-60.

10. DeSoto, Catherine M. Blood Levels of Mercury Are Related to Diagnosis of Autism: A Reanalysis of an Important Data Set. Journal of Child Neurology. 22:11 2007. 1308-1311. http://jcn.sagepub.com/content/22/11/1308.short.

11. Deth, Richard, Muratore, Christina, Benzecry, Jorge, Power-Charnitsky, Verna-Ann, Waly, Mostafa. How environmental and genetic factors combine to cause autism hypothesis. Neurotoxicity. 29:1 2008. 190-201. www.sciencedirect.com/science/article/pii/S0161813X0700215X.

12. Palmer, Raymond F., Blanchard, Steven, Stein, Zachary, Mandell, David, Miller, Claudia. Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas. Health & Place. 12:2 2006. 203-209. http://www.sciencedirect.com/science/article/pii/S1353829204001170.

13. Shandley, Kerrie , Austin, David W. Ancestry of Pink Disease (Infantile Acrodynia) Identified as a Risk Factor for Autism Spectrum Disorders. Journal of Toxicology and Environmental Health, Part A. 74:18 2010. 1185-1194. http://www.tandfonline.com/doi/abs/10.1080/15287394.2011.590097.

14. Zahir, Farhana, Rizwi, Shamim J., Haq, Soghra, K., Khan, Rizwan, H. Low dose mercury toxicity and human health. 20:2 2005. 351-360. http://www.sciencedirect.com/science/article/pii/S1382668905000700.

15. DeSota MC, Hitlan RT. Sorting out the spinning of autism: heavy metals and the question of incidence. Acta Neurobiol Exp (Wars) 2010; 70(2): 165-76.

16. Garrecht M, Austin DW. The plausibility of a role for mercury in the etiology of autism: a cellular perspective. Toxicological & Environmental Chemistry 93(5-6):1251-1273.

17. Dufault R, Lukiw WJ, Crider R, Schnoll R, Wallinga D, Deth R. A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States. Clin Epigenetics. 2012 Apr 10;4(1):6.

18. Sullivan EL, Nousen L, Chamlou K. Maternal high fat diet consumption during the prenatal period programs offspring behavior. Physiol Behav. 2012; Oct.17 e publication. www.ncbi.nlm.nih.gov/pubmed/23085399.

19. Zecavati N, Spence SJ. Neurometabolic disorders and dysfunction in autism spectrum disorders. Curr Neurol Neurosci Rep. 2009;9(2):129-136.

20. Finegold SM. Desilfovibrio species are potenti8ally important in regressive autism. Med Hypotheses 2011;77(2):270-74.

21. Coury DL, Ashwood P, Fasano A, Fuchs G et al. Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics 2012;130:S160-168.

22. Coury et al, 2012.

23. Souza NC, Mendonca JN, Portari GV, Jordao JAA et al. intestinal permeability and nutritional status in developmental disorders. Altern Ther Health Med 2012;18(2):19-24.

24. Herbert, Martha, with Weintraub, Karen. 2012. The Autism Revolution, Harvard Health Publications.

25. Herbert MR. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol. 2010; 23(2): 103-110.

26. Brown, AC, Mehl-Madrona L. Autoimmune and gastrointestinal dysfunctions: does a subset of children with autism reveal a broader connection? Expert Rev Gastroenterol Hepatol. Aug 5 4 2011; 465- 77.

27. Jyonouchi H, Geng L, Cushing-Ruby A, Quraishi H. Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study. J Neuroinflammation. Nov 21 2008. 5-52.

28. Knivsberg, A.M., Reichelt, K.L., Hoien, T., Nodland, M. A Randomized, Controlled study of dietary intervention in autistic syndromes. Nutritional Neuroscience. 5:4 2002. 251-261. www.ingentaconnect.com/content/maney/nns/2002/00000005/00000004/art00005.

29. Knivsberg, Ann-Mari, Reichelt, Karl-L, Hoien, Torleiv, Nodland, Magne. Effect of a dietary intervention on autistic behavior. Focus on Autism and other Developmental Disabilities 2003;18(4): 248-257. http://foa.sagepub.com/content/18/4/248.short.

30 Whiteley, Paul, Rodgers, Jacqui, Savery, Dawn, Shattock, Paul. A Gluten-Free Diet as an Intervention for Autism and Associated Spectrum Disorders: Preliminary Findings. Autism 3:1 1999. 45-65. http://aut.sagepub.com/content/3/1/45.short.

31. Blaylock RL, Strunecka A.Immune-glutamatergic dysfunction as a central mechanism of the autism spectrum disorders. Curr Med Chem. 2009;16(2):157-70.

32. Grafodatskaya D, Chung B, Szatmari P, Weksberg R. Autism spectrum disorders and epigenetics. J Am Acad Child Adolesc Psychiatry. 2010;49(8):794-809.

33. Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology. 2008 Jan;29(1):190-201. Epub 2007 Oct 13.

34. Blaylock RL.A possible central mechanism in autism spectrum disorders, part 3: the role of excitotoxin food additives and the synergistic effects of other environmental toxins. Altern Ther Health Med. 2009 Mar-Apr;15(2):56-60.

35. Maezawa I, calafiore M, Wulff H, Jin LW. Does microglial dysfunction play a role in autism and Rett syndrome? Neuron Glia Biol. 2011;7(1):85-97.