The prevalence of Autism is increasing. The CDC estimates that 1 in 88 children has Autism, and the prevalence has been increasing. Some people fear that immunizations might be to blame, although research has not supported this idea. New York Times had an opinion article last month that implicates a different aspect of the immune system in the development of a subset of cases of Autism: inflammation.
The article discusses results from a large Denmark cohort study of 700,000 women followed over 2 decades that showed an association between maternal autoimmune diseases, which are characterized by chronic inflammation, and Autism (not cited, but presumably work by Atladottir et al.). Maternal rheumatoid arthritis increased Autism risk by 80%, while celiac disease increased it by 350%! Women who had bacterial or viral infections during early pregnancy also had increased risk for Autistic offspring – perhaps due to the natural inflammatory response to fight off the infection. Other laboratory-based studies have also supported a link between maternal inflammation and autism.
The author of the article, Moises Velasquez-Manoff, recently wrote a book entitled An Epidemic of Absence. The book supports what is commonly called the hygiene hypothesis (although the author would prefer a more descriptive name, such as the “the microbial deprivation hypothesis”), which is the idea that the increase in developed countries of autoimmune disease is associated with a lack of exposure in childhood to infectious agents, parasites, and symbiotic microorganisms (eg probiotics). The hypothesis was put forth in the late 1980s, and the connection between the hygiene hypothesis and autism has been gaining traction in the scientific community in recent years.
As I mentioned, this was a newspaper opinion article. And it did get generate some mixed reactions. An obvious question is – does is accurately reflect the research? One of the scientists mentioned in the article as a key player in the research about prenatal inflammation and autism is Paul Patterson. You can check out his blog here: http://infectiousbehavior.wordpress.com/ He has a post where he comments on the New York Times article and offers more specific references. Here are some of his thoughts on the article:
But how accurate are his claims [in the article]? Moises says in his third sentence (!) that “At least a subset of autism – perhaps one-third, and very likely more – looks like a type of inflammatory disease. and it begins in the womb.” The work of Tony Persico, which I highlighted in a July 18 post here, estimates that an immune-related cluster of symptoms is present in about 18% of his autism patient population. Carlos Pardo found evidence of an immune activated state (activated microglia and astrocytes, and strikingly elevated cytokines) in the brains of most of his postmortem autism cases. Several of the Pardo findings have been reproduced by others at UCSD, UCDavis and here at Caltech. In addition, many studies have demonstrated immune abnormalities in the blood in autism…. there are several reliable studies showing that a high proportion of ASD kids have gastrointestinal problems, many of which could be related to inflammation, such as “leaky gut”, wherein the intestinal barrier allows large molecules to leak out into the circulation. So, I fully agree with Moises that there is a very significant proportion of ASD patients with immune-related problems. Whether it is a third or more than that, is open for debate and further research.Interesting stuff.
References:
Atladottir, H. O. et al. Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders. PEDIATRICS 124, 687–694 (2009).
Atladottir, H. O. et al. Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders. PEDIATRICS 124, 687–694 (2009).
CDC. “New Data on Autism Spectrum Disorders.” (2012). Retrieved from: http://www.cdc.gov/Features/CountingAutism/
Patterson, Paul. “Huge interest in NYT article: An immune disorder at the root of autism.” (2012). Retrieved from: http://infectiousbehavior.wordpress.com/2012/08/28/huge-interest-in-nyt-article-an-immune-disorder-at-the-root-of-autism/
Velasquez-Manoff, Moises. “An Immune Disorder at the Root of Autism.” New York Times. (2012). Retrieved from: http://www.nytimes.com/2012/08/26/opinion/sunday/immune-disorders-and-autism.html?pagewanted=all&_r=0
I think that Autism being an inflammatory linked disease is very interesting and also very possible, however, I think many people are making a huge jump from correlation to causation. When we look at different maternal health conditions on the relative risk of autism in the fetus, I think that we should also be looking at other non-immune based disease in the mothers. What happens to the autism risk in children of mothers who have cancer during pregnancy, what about mothers with heart disease? Perhaps the correlation being observed between mothers with autoimmune disease and increased risk of autism in the child are simple caused by a less stable growing environment for the fetus. Most diseases are hard on the entire body, not just the affected tissues. I would really like to see some statistics on autism risk in children of mothers who had conditions during pregnancy that were similarly stressful on the body to the addressed conditions without the autoimmune aspect. Again, although I do think that this hypothesis is a strong one and although I do think that this correlation will prove to be at least partially causal, a lot more work needs to be done to confirm these ideas. I think that it is just as likely that an environmental factor, which caused the mother to develop the autoimmune condition could also result in the autoimmunity of the child with autism; they are most likely sharing at least some environmental conditions.
ReplyDeleteThat is a good point about the difference between causation and correlation. It is always important to keep that distinction clear when reading articles, especially non-academic articles. I think that the author was clear that these are correlations, but given that this was in the New York Times, there are probably lots of readers who do make that leap.
DeleteSome of the inflammatory issues highlighted in the article were not autoimmune – like viral and bacterial infections during pregnancy. I am not sure which diseases would not be “immune based.” Isn’t the immune system always involved in disease? Cancer and heart disease both involve an immune response, as well as inflammation. I feel like the last decade of research has implicated inflammation in almost every chronic disease – which probably makes sense given that inflammation is a part of just about any immune response. Even psychological stress can increase inflammation! However, I think that perhaps a study that involves an explicit measure or biomarker of inflammation might be one way to address your concerns with respect to having a good comparison group. There are probably some people with disease or under stress who exhibit high levels of inflammation others who don’t. Likewise for seemingly healthy people. A study could take into account people’s level of inflammation as well as their disease status. If maternal inflammation is truly an important mechanism in Autism, I would think that there would be higher risk among mothers with high levels of inflammation, independent of disease status.
References
American Heart Association. “Inflammation and Heart Disease.” (2012). Retrieved from http://www.heart.org/HEARTORG/Conditions/More/MyHeartandStrokeNews/Inflammation-and-Heart-Disease_UCM_432150_Article.jsp
Cohen, S. et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. PNAS 109(16): 5995-5999 (2012). Retrieved from http://www.pnas.org/content/109/16/5995.full.pdf+html
Rakoff-Nahoum, S. Why Cancer and Inflammation? Yale J Biol Med 79(3-4): 123–130 (2006). Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994795/