The Search for Autism Triggers

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 ‘Pesticides and Neurosteroids Questioned at the University of California’

Two different academic departments—both at the University of California—have recently published studies that raise important questions about the role of in utero exposure to chemicals as contributors to risk of autism.

The first study involves pesticides, the second neurosteroids (a brain steroid similar to cortisone, progesterone and gonadal hormones).

Study #1:

One of the authors of the study about pesticides is Dr. Irva Hertz-Picciotto, a professor and environmental epidemiologist best known for her studies of autism. She is Chief of the Department of Public Health Service’s Environmental and Occupational Health Division at UC Davis, as well a faculty member of the MIND (Medical Investigation of Neurodevelopmental Disorders) Institute in Sacramento. The publisher of over 170 scientific articles, many of her studies have detected “autism clusters” related to various risk factors. She believes “It’s time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California.”1 (California is the top agriculture-producing state in the United States and about 200 million pounds of active pesticide ingredients are applied yearly throughout the state).2, 3

Last autumn the results of a study she co-authored were published. This study asked if pregnant women living close to agricultural pesticides in central California’s farming communities had higher rates of babies born with developmental delays (DD) and autism (ASD).4 The study was robust—there were close to 1000 participants and it covered 11 years (1997-2008). Distance from home addresses (about 1/3 of the women lived less than 1 mile from agricultural pesticide areas) and pounds of pesticides were measured and compared.

Children in the study were recruited from regional centers of the California Department of Developmental Services, other clinics, and general outreach. All children were administered the Autism Diagnostic Observation Schedule (ADOS)—considered the gold standard and used with all ages, and their parents were given the Autism Diagnostic Interview —revised, to either confirm their diagnosis or reclassify them. Children without a diagnosis were also given the Social Communication Questionnaire (SCQ) to rule out ASD.

The researchers found:

• Proximity to pesticides during gestation was associated with a 60% increased risk for ASD.
• Four specific pesticide chemicals were studied. Chemicals seemed to have different effects depending on the specific trimester of pregnancy.
• The most commonly applied chemical (chlorpyrifos—see below) was found to produce greatest risk in the 2nd trimester. When women lived near fields treated with chlorpyrifos their children were 3.3 times more likely to have autism.
•   The second most common chemical—pyrethroid—was found to most increase risk either immediately prior to conception or in the 3rd trimester of pregnancy. Application of pyrethroid just prior to conception meant an increased risk of 82% and during the 3rd trimester, the risk was 87% higher.

A few words about pesticides: simply put, they are used because they block certain nerve functions in insects, thus yielding greater volume of viable (not infested or damaged) crops and increased profit for farmers, processors, and distributors.

The most commonly applied chemicals in the study—chlorpyrifos—used since 1965, and applied to at least 60 different crops, have been known for years to sicken farm workers. Traces have been found in our waterways. It was banned for home use in 2001 after being linked to neurological effects in children. In 2012 the U.S. Environmental Protection Agency also restricted its use around schools. In 2014 The EPA announced only trained and licensed professionals with county permits could use the chemicals. These restrictions are anticipated to be in effect by the 3rd quarter of 2015.5

The second most common chemicals studied—pyrethroids —are often thought of as safer, as they are frequently confused with pyrethrum, a naturally occurring mixture of chemicals found in some chrysanthemum flowers. Pyrethroids, however, are manufactured chemicals designed to be more effectively toxic and to last longer in the environment. Also, in their final, formulated product form, they are usually mixed with solvents, which can increase toxicity. They have been identified in California water bodies adjacent to urban/residential areas.6

Study #2:

This study, conducted by several researchers in veterinary and human medicine, led to the question of whether levels of neurosteroids during gestation or in the blood of newborns can increase the risk of autism.

There is a horse disorder, known as neonatal maladjustment syndrome, which has long puzzled horse owners and veterinarians. Foals affected by this disorder appear detached, have no interest in nursing, fail to recognize their mothers, and generally isolate themselves away from other animals. These foals are born with high levels of neurosteroids in their blood, whereas foals that readily interacted with their mothers have normal neurosteroid levels.

The behavioral similarities to children with autism are striking.

For years the syndrome was attributed to lack of oxygen during the birthing process. But University of California at Davis Veterinary Medicine staff—including Monica Aleman, Associate Professor of Medicine and Epidemiology, Isaac Pessah, Professor of Molecular Biosciences, and John Madigan, Professor of Medicine and Epidemiology—began searching for other causes, noting that most foals with the syndrome survive with no lingering health problems that would be expected from insufficient oxygen.7

One of their primary suspects was a group of naturally occurring neurosteroids, molecules key to sustaining pregnancy by keeping foals calm in utero. In humans, these chemicals are thought to affect moods, stress levels, socialization, sleep, information processing and memory and risk of convulsions.8

The researchers found it significant that foals born via cesarean section or who had unusually rapid births were especially prone to experience the syndrome. Their theory is that the intense physical pressure of exiting the birth canal (during the second stage of labor) is an important signal that tells the foal to stop producing the neurosteroids. Without this “stop” signal, higher levels of neurosteroids remain in the body after birth.

The behavioral similarities of the foals with the syndrome to human children with autism may have scientific basis. Neurosteroids are also emerging as potential risk factors in human autism. A 2013 study in Poland found autistic children tested at ages 3 and 9 had significantly higher salivary concentrations of steroid hormones.9

They suggested that salivary levels may serve as biomarkers of autism and may be useful for monitoring progress of therapy.

Temple Grandin has written about her childhood craving for deep pressure in order to calm herself. She eventually designed a box for this purpose. It was patterned after cattle squeeze chutes she saw at her aunt’s ranch.10

Professor Madigan at UC Davis has now similarly developed a squeeze technique for newborn foals exhibiting neonatal maladjustment syndrome. He intervenes just moments after birth in the approximately 5% of foals who are born emotionally detached from their mothers and who often attempt to move to a corner and then just stand there.

Madigan ties a soft rope harness around the foal’s body and gently squeezes it to apply pressure. The foal tends to drop over asleep. After several minutes of pressure, the harness is released, and the foal awakens. It is generally no longer detached, instead seeking its mother to interact and feed!

The UC Davis Department of Veterinary researchers have also infused healthy neonatal foals from healthy mares with neurosteroids to see if the syndrome could be induced. They found that infusion resulted in neurobehavioral alterations like those of neonatal maladjustment syndrome, though they were short lasting. Infusion was also associated with measurable concentrations of progestagens (a hormone that binds progesterone).

Conclusions:

Both of these studies raise reasonable questions about the role of environmental factors as risk factors for autism.

Clearly pesticides produce neurological impact. Whether they can directly or partially trigger autism is a valid question that deserves the continuing attention of legitimate researchers.

Chemicals in our bloodstream also obviously produce neurological impact and it’s likely their impact changes across situations and individuals. Currently many research projects are being conducted on the relationship between autism and the levels of numerous endogenous chemicals in pregnant women, newborns, and young children.

Other studies look at the risk of recurrence of autism in a given family and seem to confirm earlier studies, including twin studies that find up to 90% of autism is genetic rather than environmental.12, 13

It’s a complex subject. Autism is not a unitary condition—thus the term autism spectrum disorder. Causation is likely similarly multifaceted. There may be hundreds or thousands of factors, both genetic and environmental, and they may overlap in ways we don’t suspect.

There may also be missing heritability factors, as well as underlying conditions that cause cells to be particularly sensitive to all sorts of things—viruses (during pregnancy and in a newborn), toxins including pesticides, and endogenous hormones and neurosteroids. One current promising investigative project is analyzing data related to family medical conditions, environmental exposure history including drugs, viruses and chemicals, genetic profiling and chromosomal abnormalities, and immune function.14

The two studies reviewed here are worth our attention and both are currently being followed up by related investigations. Let’s hope autism researchers continue to stay open minded, innovative, and rigorous. As parents and professionals, we’re well served to hold ourselves to the same standards.

Psychologist Debra Moore, Ph.D. recently retired from 35 years of practice in Sacramento, CA, where one of her specialties was Asperger’s and HFA. She is the organizer of three LinkedIn groups: LinkedtoAspergers, Helping Hand Mentors, and Aspie Teens, and has facilitated groups for ASD teens and adults for many years. She and Temple Grandin are co-authoring a new book to be released by Future Horizons in early 2016. With a shared passion of helping people maximize their abilities and participation in the world, the authors will outline for parents and professionals effective ways to help ASD teens and adults become “unstuck” and move from isolation and apathy into meaningful, independent, and satisfying lives.

References

1. Cone, M. Autism epidemic not caused by shifts in diagnoses; environmental factors likely. Environmental Health News, 2009 January 9.
2. California Department of Food and Agriculture, 2010.
3. California Department of Pesticide Regulation, 2014.
4. Shelton, J., et al. Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study. Environmental Health Perspectives, Vol 122, 10, October 2014.
5. www.cdpr.ca.gov/docs/registration/reevaluation/chemicals/chlorpyrifos.htm
6. Environmental Protection Agency website: www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html
7. UC Davis: News and Information, 2.3.2015. http://news.ucdavis.edu/search/news_detail.lasso?id=10791
8. Paul SM, Purdy RH (1992). “Neuroactive steroids”. FASEB J. 6 (6): 2311–22.
9. Majewsha, et al. Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children.
10. Grandin, Temple. (1996). Thinking in Pictures. New York: Vintage Press (Random House).
11. Sandin, S. et al. JAMA 311, 1770-1777 (2014).
12. Bolton P. et al. J. Child Psychol. Psychiatry 35, 877-900 (1994).
13. Ozonoff S. et al. Pediatrics 128, e488-495 (2011)
14. Autism Phenome Project (APP) and Autism Genetic Resource Exchange (AGRE): UC Davis MIND Institute. www.ucdmc.ucdavis.edu/mindinstitute/research/app

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