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Commentary on the LA Times Series on Autism

January 3, 2012 18 comments

Posted by Autism Speaks scientific advisory board member Irva Hertz-Picciotto, PhD, MPH. As an epidemiologist at the University of California-Davis MIND Institute, Hertz-Picciotto studies exposures to environmental chemicals, their interactions with nutrition and pregnancy and their effects on prenatal and early child development.

Alan Zarembo’s series on autism in the LA Times  covers a great deal of territory and has brought to light a wide range of personal stories that exemplify the complexity of issues surrounding autism diagnosis, treatment choices and effectiveness, impact on families and population incidence. Zarembo should be commended for the substantial work he has done researching inequities in the delivery of services. Of notable concern, he has put a spotlight on what appear to be serious racial and ethnic disparities in the California Department of Developmental Services (DDS) system and the provision of therapies. If his figures are correct, this result should stimulate an analysis of how to right this situation and ensure that appropriate opportunities are made available to all families with affected children.

Zarembo has also highlighted adults living with an autism spectrum disorder (ASD) but diagnosed late in life. We have too long overlooked the struggles faced by adults with autism as they try to find ways to be productive, live independently and connect with others.

My remaining comments pertain to Zarembo’s conclusions about the rise in autism diagnoses and the role of environmental factors. First, he is right that there is substantial variability in rates of diagnoses in different regions, and that we should not confuse diagnoses with the actual incidence of disease. Not all persons who meet criteria have been correctly diagnosed, and the degree to which this is true has likely changed over time.

Nevertheless, impressions are not the same as a scientific analysis. Zarembo has not demonstrated that the rise is purely social and cultural.  My colleague Lora Delwiche and I published the first quantitative analysis of how much of the increase in diagnosed cases in California could be explained by artifacts (changes in diagnostic criteria, earlier age at diagnosis and inclusion of milder cases).1 We used California state data that provided statistics over many years and found that the numbers simply do not add up. In other words, the actual increase has been far larger than these artifacts could have produced. Combining our results with those of another research team, it appears that about half of the increase in diagnoses in California is due to changes in diagnostic criteria or practices.2 These results left about a three-fold increase unexplained as of 2007. And autism diagnoses in California have continued to rise both in areas with low rates and in areas with high rates. Zarembo is interested in explaining the geographic variation, but the explanations for variation spatially are not necessarily the explanations for variation over time.

These statements were particularly misleading:

“No study points to an environmental reason for the worldwide explosion in cases over the last two decades.

Given the slow pace of genetic change in large populations, genes can’t account for the surge either.

That suggests the explanation for the boom lies mainly in social and cultural forces, notably a broader concept of autism and greater vigilance in looking for it.”

The logic that leads from the first two sentences to the third involves huge assumptions.

How many studies have been done of environmental causes? Very few!  And of these, most were extremely poor studies involving very small samples or lacking individual-level data. Is it surprising we’ve uncovered few leads?  The funding for environmental factors has been paltry – somewhere around $40 to $60 million over the last 10 years, while more than $1 billion has been spent on studying autism genetics.  To imply that environmental factors can be dismissed and that only social/cultural factors should be pursued is nonsensical.

It should be noted, however, that if anyone is looking for “one” environmental factor to explain the increase, they will certainly be disappointed. It doesn’t exist. Autism is far too complex. Moreover, to the extent the increase is due to diagnostic differences over time, we need to find explanations both for the increasing numbers of diagnoses and for the autism that has been around “all along.” In fact, data are emerging about quite a number of environmental factors. In 2011, major papers were published supporting contributions from maternal nutrition around the time of conception (here and here), traffic-related air pollution, and season of conception.3-6 Earlier papers indicated associations with pesticides  (here and here) and air pollution.7-9

One concern raised about the increase in diagnoses is a type of ‘inflation’ from inclusion of a growing number of high-functioning persons whose diagnosis is more likely to be Asperger syndrome than classic autism. This may apply to some studies of changes over time, but in our analysis of CHARGE study data, most of the cases were low functioning.10 This would likely be true for the majority of persons with ASD served by the California Department of Developmental Services (DDS), because in order to qualify for state services, they must have “significant functional limitations” in three areas of major life activities. This requirement would exclude most of those who are higher functioning.

With regard to genetics, Zarembo’s article leaves out the most current information: the largest and most statistically robust study of twin pairs found that 38 percent of concordance is due to shared genetics with 58 percent due to shared environmental factors (most likely prenatal and perinatal).11 This result completely overturns the widespread assumption, based on a number of previous small studies, that the causes of autism are overwhelmingly heritable, or genetic. Unfortunately, most analyses of twins make the incorrect assumption that genes and environment do not interact to influence risk for disordered brain development. This interaction is real, and one study has already shown a whole class of genes that primarily affect development in children whose mothers had not taken prenatal vitamin supplements during the months preceding and immediately following conception. 3

In summary, Zarembo’s investigative journalism provides unusual depth into difficult aspects of autism occurrence and the social policies that bear on the lives of affected families. He has raised several critical challenges facing the autism community. What was lacking from his series is a more balanced view of the role environment likely plays and the need to advance the agenda of discovering modifiable causative factors.

Autism Speaks is one of a few organizations that have begun to turn in this direction. I look forward to a continued strong commitment by Autism Speaks and others willing to support and significantly expand the scientific research aimed at identifying and understanding environmental contributions to autism, factors driving increased prevalence and ways to intervene so as to eliminate or lower human exposure levels. This will be the fastest road to reducing the occurrence of ASD in the next generation.

References
1             Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009;20: 84-90.
2             King M, Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol. 2009; 38:1224-34.
3             Schmidt, R J, et al. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 2011;22:476-85.
4             Cheslack-Postava K, Liu K, Bearman PS. Closely spaced pregnancies are associated with increased odds of autism in California sibling births. Pediatrics 2011;127:246-53.
5             Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect 2011;119: 873-7.
6             Zerbo O, Iosif AM, Delwiche L, Walker C, Hertz-Picciotto I. Month of conception and risk of autism. Epidemiology 2011;22:469-75.
7             Roberts EM, et al. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect. 2007;115:1482-9.
8             Eskenazi B, et al. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ Health Perspect 2007;115:792-8.
9             Windham G, Zhang L, Gunier R, Croen L, Grether J. 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.
10           Hertz-Picciotto, I. et al. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect. 2006;114: 1119-25.
11           Hallmayer, J. et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011(68):1095-102.

Media Highlights From IMFAR

May 12, 2011 10 comments

The 10th Annual The International Meeting for Autism Research (IMFAR) will host nearly 2000 researchers, delegates, autism specialists, and students in the world’s largest gathering of researchers and clinicians devoted to a better understanding of autism.

At the official press conference, scientists discussed key studies to be presented during IMFAR. David Amaral, Ph.D., the President of the International Society for Autism Research, led with opening remarks. Speakers included Eric Courchesne, Ph.D., Antonio Hardan, M.D., David Mandell, Sc.D. and Irva Hertz-Picciotto, Ph.D. Dana Marnane, Vice President of Awareness and Events at Autism Speaks, moderated the conference.

This video was shot by Alex Plank and the Wrong Planet crew.

• Geraldine Dawson, Ph.D. became Autism Speaks’ first chief science officer in January of 2008. In this role, Dr. Dawson serves as the scientific leader of Autism Speaks, working with the scientific community, stakeholders, and science staff, to shape, expand, and communicate the foundation’s scientific vision and strategy. Dr. Dawson presented the Autism Speaks strategic plan on the second day of IMFAR. She also took the time to be interviewed by Wrong Planet’s Alex Plank.

• Autism Speaks Science Board member John Elder Robison, author of Look Me in the Eye: My Life with Asperger’s and Be Different: Adventured of a Free-Range Aspergian, is reporting from IMFAR. You read can his blogs herehere, and here.

• 2011 saw a new approach for Autism Speaks’ Innovative Technology for Autism (ITA) initiative with the running of a student design competition called Autism Connects. The design brief was pretty straight forward: to create technology design ideas for individuals with autism to better connect with the world around them, and to allow individuals who do not have autism to better understand and connect with those who do. You can find out more about this program here.

•  David Mandell, Sc.D. conducted a study, ‘The Effect of Childhood Autism on Parental Employment,’ which was covered by ABC Los Angeles, in the clip below.

•  New research is coming out of the International Meeting for Autism Research, includes ‘Adults with autism face health problems with age.’ For the full article, visit here. The clip below is from ABC Los Angeles.

FOX 5 San Diego also covered IMFAR, where Shannon Des Roches, who blogs at Squidalicious, is featured.

• The Fly: into Autism crew was in attendance and performed some of their hit songs.  FLY reflects and honors the diversity of its inspiring voices with an eclectic blend of rap, punk rock, ballads, soul, even Broadway. It boldly opens ears, eyes and hearts to the miracles of autism.


Video Credit: John Robison 

• Alex Plank caught up with Clara Lajonchere, Ph.D, the Vice President of Clinical Programs for Autism Speaks.

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