American parents awarded £600,000 in compensation after their son developed autism as a result of MMR vaccine

EEV: Requested Repost of the December Court Order :

Clean PDF File Herecampbell-smith-mojabi-proffer-12-13-2012

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: December 13, 2012

* * * * * * * * * * * * * * * * *
SAEID B. MOJABI and PARIVASH *

UNPUBLISHED

VAHABI, as parents and legal *
representatives of their minor son, *

RYAN B. MOJABI, *

*

No. 06-227V

Petitioners, *

Chief Special Master

*

Campbell-Smith

v. *
*

Proffer on Award of

SECRETARY OF HEALTH *

Compensation; Measles-

AND HUMAN SERVICES, *

Mumps-Rubella (MMR);

*

Respondent. *

Table Injury; Encephalitis.

*

* * * * * * * * * * * * * * * * *

 

 

David L. Terzian, Rawls, McNelis and Mitchell, P.C., Richmond, VA, for petitioners.

 

Traci R. Patton, U.S. Dep’t of Justice, Washington, DC, for respondent.

 

                                           DECISION AWARDING DAMAGES[1]

 

On March 23, 2006, Saeid Mojabi and Parivash Vahabi (petitioners), as the parents and legal representatives of their minor son, Ryan, filed a petition pursuant to the

1

 

National Vaccine Injury Compensation Program (“Vaccine Program”).[2]  Petitioners alleged that as a result of “all the vaccinations administered to [Ryan] from March 25, 2003, through February 22, 2005, and more specifically, measles-mumps-rubella (MMR) vaccinations administered to him on December 19, 2003 and May 10, 2004,” Ryan suffered “a severe and debilitating injury to his brain, described as Autism Spectrum Disorder (‘ASD’).”  Petition at 1.  Petitioners specifically asserted that Ryan “suffered a Vaccine Table Injury, namely, an encephalopathy” as a result of his receipt of the MMR vaccination on December 19, 2003.  Id.  In the alternative, petitioners asserted that “as a cumulative result of his receipt of each and every vaccination between March 25, 2003 and February 22, 2005, Ryan has suffered . . . neuroimmunologically mediated dysfunctions in the form of asthma and ASD.”  Id. at 1-2.     Continue reading “American parents awarded £600,000 in compensation after their son developed autism as a result of MMR vaccine”

Chemical derived from broccoli sprouts shows promise in treating autism

At special request I am posting our video from our other operating site, Here.

– Most of those who responded to sulforaphane showed significant improvements by the first measurement at four weeks and continued to improve during the rest of the treatment. After 18 weeks of treatment, the average ABC and SRS scores of those who received sulforaphane had decreased 34 and 17 percent, respectively, with improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation and mannerisms.
– Zimmerman adds that before they learned which subjects got the sulforaphane or placebo, the impressions of the clinical team — including parents — were that 13 of the participants noticeably improved. For example, some treated subjects looked them in the eye and shook their hands, which they had not done before. They found out later that all 13 had been taking sulforaphane, which is half of the treatment group.
* Sulforaphane treatment of autism spectrum disorder PNAS 10 2014 Continue reading “Chemical derived from broccoli sprouts shows promise in treating autism”

Probiotic therapy alleviates autism-like behaviors in mice

Contact: Deborah Williams-Hedges mr@caltech.edu 626-395-3227 California Institute of Technology

Autism spectrum disorder (ASD) is diagnosed when individuals exhibit characteristic behaviors that include repetitive actions, decreased social interactions, and impaired communication. Curiously, many individuals with ASD also suffer from gastrointestinal (GI) issues, such as abdominal cramps and constipation.

Using the co-occurrence of brain and gut problems in ASD as their guide, researchers at the California Institute Technology (Caltech) are investigating a potentially transformative new therapy for autism and other neurodevelopmental disorders.

Continue reading “Probiotic therapy alleviates autism-like behaviors in mice”

5-fold increase in ADHD medication use in children and adolescents

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

 

New Rochelle, NY, September 10, 2013—Use of stimulant medications to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents has increased significantly over the past several years. This trend toward increased use of prescription stimulants extends beyond ADHD to other types of neuropsychiatric disorders in children and teens as well, including Autism Spectrum Disorder (ASD), according to a study published in Journal of Child and Adolescent Psychopharmacology (JCAP), a peer-reviewed journal from Mary Ann Liebert, Inc., publishersThe article is available on the JCAP website.

Søren Dalsgaard, MD, PhD, Helena Skyt Nielsen, PhD, and Marianne Simonsen, PhD, Aarhus University (Denmark), Lundbeck Foundation Initiative for Integrative Psychiatric Research (Denmark), and Hospital of Telemark (Norway), conducted a study of more than 850,000 children born in Denmark between 1990 and 2001. They found that 61% of children with ADHD, 16% of children with ASD, and 3% of those with other psychiatric disorders were treated with one or more medications typically prescribed for ADHD—methylphenidate, dexamphetamine, and atomoxetine. The data indicated significant increases in the prescription rates of these medications during the years 2003 to 2010.

“This study utilizes a population-based national cohort of children and adolescents, and assesses stimulant treatment in children and adolescents with ASD,” says Harold S. Koplewicz, MD, Editor-in-Chief of JCAP, and President, Child Mind Institute, New York, NY. “This is the largest and first prospective study to quantify the change in the use of treatment with ADHD medications over time.”

###

About the Journal

Journal of Child and Adolescent Psychopharmacology (JCAP) is an authoritative peer-reviewed journal published 10 times a year online with Open Access options and in print. The Journal is dedicated to child and adolescent psychiatry and behavioral pediatrics, covering clinical and biological aspects of child and adolescent psychopharmacology and developmental neurobiology. Complete tables of content and a sample issue may be viewed on the JCAP website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Cyberpsychology, Behavior, and Social Networking and Games for Health Journal. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s over 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

U.S. Court Confrims M.M.R. Vaccine Caused Autism or Cumulative (Verified through Multiple Sources) From DEC 2012 Judgment

EEV: Court Document Clip: Followed by links to Last article from Jan 2013 and links to court documents

* This was requested article research

National Vaccine Injury Compensation Program (“Vaccine Program”).2 Petitioners
alleged that as a result of “all the vaccinations administered to [Ryan] from March 25,
2003, through February 22, 2005, and more specifically, measles-mumps-rubella (MMR)
vaccinations administered to him on December 19, 2003 and May 10, 2004,” Ryan
suffered “a severe and debilitating injury to his brain, described as Autism Spectrum
Disorder (‘ASD’).” Petition at 1. Petitioners specifically asserted that Ryan “suffered a
Vaccine Table Injury, namely, an encephalopathy” as a result of his receipt of the MMR
vaccination on December 19, 2003. Id. In the alternative, petitioners asserted that “as a
cumulative result of his receipt of each and every vaccination between March 25, 2003
and February 22, 2005, Ryan has suffered . . . neuroimmunologically mediated
dysfunctions in the form of asthma and ASD.” Id. at 1-2.

CAMPBELL-SMITH.MOJABI-PROFFER.12.13.2012

RyanvHHSMMR[1]Measles Judgement

American parents awarded £600,000 in compensation after their son developed  autism as a result of MMR vaccine

  • Saeid and  Parivash Mojabi claimed their son suffered a ‘severe brain injury’
  • The  Californian couple said that son Ryan was diagnosed with Autism Spectrum  Disorder

By  David Gardner

PUBLISHED: 20:32 EST, 14  January 2013 |  UPDATED: 20:33 EST, 14 January 2013

Vaccine: An American couple have been awarded more than £600,000 by a U.S court after claiming their son developed autism as a result of the MMR jab (file picture)
Vaccine: An American couple have been awarded more than  £600,000 by a U.S court after claiming their son developed autism as a result of  the MMR jab (file picture)

Parents who claim their 10-year-old boy  developed autism as a result of being injected with an MMR vaccine when he was a  baby have been awarded more than £600,000 in a landmark court decision in  America.

Saeid and Parivash Mojabi claimed that son  Ryan suffered a ‘severe and debilitating injury to his brain’ after being  administered with two measles-mumps-rubella vaccinations in December, 2003 and  in May the following year.

They said in court papers that Ryan was  diagnosed with Autism Spectrum Disorder.

The ruling comes months after a judge in  Italy awarded £140,000 to an Italian couple who said their son had autism after  his routine childhood MMR inoculation.

The American decision – although it doesn’t  lay fault for the child’s disability with the drug – fuels anti-MMR campaigners  challenging the view of the majority of the medical profession that holds the  vaccinations are safe.

The claim was against the US government which  set up a Vaccine Programme. Although a judgement rules whether or not each case  is eligible for compensation and the amount – in this case against the US Health  Department – it does not apportion blame.

The San Jose, California, based family took  their case to the US Court of Federal Claims in 2006.

Under the National Vaccine Injury  Compensation Programme, parents can petition the US government for compensation  for injuries or deaths allegedly caused by compulsory childhood  vaccines.

A judgement in Ryan’s case, which was first  filed in 2006, was made on December 13 last year by the Office of Special  Masters set up by US Congress to decide on compensation claims. The defendant in  the case was the US Secretary of Health and Human Services.

The damages payment takes into account the  boy’s future loss of earnings because it’s unlikely he will be able to  work.

In statements to the court, Ryan’s  grandmother Paravaneh Shah-Mohammadi and his aunt Pooran Vahabi told how the boy  appeared ‘lethargic’, ‘hardly responsive to noises and people around him,’and  ‘unable to hold himself upright’ after having the first MMR  vaccination.

Under the National Vaccine Injury Compensation Programme, parents can petition the US government for compensation for injuries or deaths allegedly caused by compulsory childhood vaccinesUnder the National Vaccine Injury Compensation  Programme, parents can petition the US government for compensation for injuries  or deaths allegedly caused by compulsory childhood vaccines (file  picture)

The number of autism cases in the UK has  soared over the past four decades. At the last count researchers found one in 64  British children have some kind of autistic condition.

In the Eighties, only four in every 10,000  children showed any signs of autism.

The Department of Health and NHS doctors  insist that better diagnosis of autism and environmental factors are responsible  for the dramatic rise in the number of cases and dismissed MMR vaccinations as a  cause.

No link between the jabs and autism has been  found in the British courts.

In America, nearly 5,000 families blame the  MMR injection for causing their children’s autism.

Boost: The case is likely to fuel the arguments of anti-MMR campaigners (file picture)Boost: The case is likely to fuel the arguments of  anti-MMR campaigners (file picture)

In 2008, a girl called Hannah Poling was  awarded £1 million damages by the US government when a court ruled that  receiving nine vaccines in one day, including the MMR, had caused her autistic  condition.

But the court said that Hannah had an  underlying cell disorder, mitochondria, which had been aggravated by the  vaccinations and manifested itself as autism.

In Ryan’s case, Chief Special Master Patricia  Campbell-Smith decided his family was eligible for damages under the US  government’s Vaccine Programme.

Read more: http://www.dailymail.co.uk/news/article-2262534/American-parents-awarded-600-000-compensation-son-developed-autism-result-MMR-vaccine.html#ixzz2bPIwE6WR Follow us: @MailOnline on Twitter | DailyMail on Facebook

Clues about autism may come from the gut

Contact: Joseph Caspermeyer Joseph.Caspermeyer@asu.edu Arizona State University

Bacterial flora inhabiting the human gut have become one of the hottest topics in biological research. Implicated in a range of important activities including digestion, fine-tuning body weight, regulating immune response, and producing neurotransmitters affect that brain and behavior, these tiny workers form diverse communities. Hundreds of species inhabit the gut, and although most are beneficial, some can be very dangerous.

In new research appearing in the journal PLOS ONE, a team led by Rosa Krajmalnik-Brown, a researcher at Arizona State University’s Biodesign Institute, present the first comprehensive bacterial analysis focusing on commensal or beneficial bacteria in children with autism spectrum disorder (ASD).

After publishing earlier research exploring crucial links between intestinal microflora and gastric bypass, Krajmlanik-Brown convinced James Adams— director of the ASU Autism/Asperger’s Research Program—that similar high throughput techniques could be used to mine the microbiome of patients with autism. (Previously, Adams had been studying the relationship between the gut microbiome and autism using traditional culturing techniques.)

“One of the reasons we started addressing this topic is the fact that autistic children  have a lot of GI problems that can last into adulthood,” Krajmalnik-Brown  says. “Studies have shown that when we manage these problems, their behavior improves dramatically.”

Following up on these tantalizing hints, the group hypothesized the existence of distinctive features in the intestinal microflora found in autistic subjects compared to typical children. The current study confirmed these suspicions, and found that children with autism had significantly fewer types of gut bacteria, probably making them more vulnerable to pathogenic bacteria.  Autistic subjects also had significantly lower amounts of three critical bacteria, Prevotella, Coprococcus, and Veillonellaceae.

Krajmalnik-Brown, along with the paper’s lead authors Dae-Wook Kang and Jin Gyoon Park, suggest that knowledge gleaned through such research may ultimately be used both as a quantitative e diagnostic tool to pinpoint autism and as a guide to developing effective treatments for ASD-associated GI problems.  The work also offers hope for new prevention and treatment methods for ASD itself, which has been on a mysterious and rapid ascent around the world.

A disquieting puzzle

Autism is defined as a spectrum disorder, due to the broad range of symptoms involved and the influence of both genetic and environmental factors, features often confounding efforts at accurate diagnosis. The diseases’ prevalence in children exceeds juvenile diabetes, childhood cancer and pediatric AIDS combined.

Controversy surrounds the apparent explosive rise in autism cases. Heightened awareness of autism spectrum disorders and more diligent efforts at diagnosis must account for some of the increase, yet many researchers believe a genuine epidemic is occurring. In addition to hereditary components, Western-style diets and overuse of antibiotics at an early age may be contributing to the problem by lowering the diversity of the gut microflora.

In terms of severe developmental ailments affecting children and young adults, autism is one of the most common, striking about 1 in 50 children. The disorder—often pitiless and perplexing—is characterized by an array of physical and behavioral symptoms including anxiety, depression, extreme rigidity, poor social functioning and an overall lack of independence.

To date, studies of the gut microbiome in autistic subjects have focused primarily on pathogenic bacteria, some of which have been implicated in alterations to brain function.  One example involves gram-negative bacteria containing lipopolysaccharides in their cell walls, which can induce inflammation of the brain and lead to the accumulation of high levels of mercury in the cerebrum.

A new approach

Krajmalnik-Brown and lead author Dae-Wook Kang are researchers in the Biodesign Institute’s Swette Center for Environmental Biotechnology, which is devoted to the use of microbial communities for the benefit of human and environmental health. Their new study is the first to approach autism from a different angle, by examining the possible role of so-called commensal or beneficial bacteria.

Up to a quadrillion (1014) bacteria inhabit the human intestine, contributing to digestion, producing vitamins and promoting GI health. Genes associated with human intestinal flora are 100 times as plentiful as the body’s human genes, forming what some have referred to as a second genome. Various environmental factors can destabilize the natural microbiome of the gut, including antibiotics and specific diets.

In the current study, a cohort of 20 healthy and 20 autistic subjects between 3 and 16 years of age were selected and their gut microflora from fecal samples analyzed by means of a technique known as pyrosequencing. Pyrosequencing is a high-throughput method, allowing many DNA samples to be combined as well as many sequences per sample to be analyzed.

Lower diversity of gut microbes was positively correlated with the presence of autistic symptoms in the study. The authors stress that bacterial richness and diversity are essential for maintaining a robust and adaptable bacterial community capable of fighting off environmental challenges. “We believe that a diverse gut is a healthy gut,” Krajmalnik-Brown says.

The new study detected decreased microbial diversity in the 20 autistic subjects whose fecal samples were analyzed. Specifically, three bacterial genera—Prevotella, Coprococcus and Veillonellaceae—were diminished in subjects with autism, when compared with samples from normal children. (Surprisingly, these microbial changes did not seem directly correlated with the severity of GI symptoms.)

The three genera represent important groups of carbohydrate-degrading and/or fermenting microbes.  Such bacteria could be critical for healthy microbial-gut interactions or play a supportive role for  a wide network of different microorganisms in the gut. The latter would explain the decreased diversity observed in autistic samples.

Bacteria: in sickness and in health

Among the fully classified genera in the study, Prevotella was the most conspicuously reduced in autistic subjects. Prevotella is believed to play a key role in the composition of the human gut microbiome. For this reason, the group undertook a sub-genus investigation of autistic subjects. They found that a species known as Prevotella copri occurred only in very low levels in the autistic samples. The species is a common component in normal children exhibiting more diverse and robust microbial communities.

“We think of Prevotella as a healthy, good thing to have,” Krajmalnik-Brown notes. (Michael Polan’s recent New York Times Magazine story on the microbiome points to the fact that he is proud that his gut microbiome is rich in Prevotella regarding it as a possible sign of a healthy non-Western diet.)

Jin Gyoon Park (the other lead author),  who works in the Virginia G. Piper Center for Personalized Diagnostics, under Joshua LaBaer’s direction, conducted a rigorous bioinformatic and statistical analysis of the intestinal microflora. He believes that the microbiome can be mined in future work to find diagnostic biomarkers for autism and many other diseases. Quantitative diagnoses of this sort have so far been lacking for autism, a disease for which subjective behavior indices are typically used to identify the disorder.

In describing the next steps for the research group, Kang and Park point to more detailed, gene-level analyses aimed at probing bacterial function and further illuminating relationships between human health and the complexities of the microbiome.  Additionally, the group will use the current results as a guide for new treatment studies for autism aimed at modifying bacterial composition in the gut.

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A new, interdisciplinary consortium (Autism Microbiome Consortium) has been formed to investigate the underpinings of autism and the gut microbiome, bringing together the combined skills of neurologists, psychiatrists, neuroimmunologists, epidemiologists, pediatricians, geneticists, biochemists, microbiologists and others. In addition to Rosa Krajmalnik-Brown and James Adams, the group consists of:

Jack Gilbert (University of Chicago), Catherine Lozupone (University of Colorado), Rob Knight (University of Colorado and HHMI). Mady Hornig (Columbia University), Sarkis Mazmanian (California Institute of Technology), Tanya Murphy (University of South Florida), , Paul Patterson (California Institute of Technology), John Alverdy (University of Chicago), Janet Jansson (Lawrence Berkeley Lab), KImberly Johnson (University of Colorado).

Written by: Richard Harth Science Writer: Biodesign Institute richard.harth@asu.edu

UCSB researchers successfully treat autism in infants

Contact: Andrea Estrada andrea.estrada@ia.ucsb.edu 805-893-4620 University of California – Santa Barbara

(Santa Barbara, Calif.) –– Most infants respond to a game of peek-a-boo with smiles at the very least, and, for those who find the activity particularly entertaining, gales of laughter. For infants with autism spectrum disorders (ASD), however, the game can be distressing rather than pleasant, and they’ll do their best to tune out all aspects of it –– and that includes the people playing with them.

That disengagement is a hallmark of ASD, and one of the characteristics that amplifies the disorder as infants develop into children and then adults.

A study conducted by researchers at the Koegel Autism Center at UC Santa Barbara has found that replacing such games in favor of those the infant prefers can actually lessen the severity of the infants’ ASD symptoms, and, perhaps, alleviate the condition altogether. Their work is highlighted the current issue of the Journal of Positive Behavioral Interventions.

Lynn Koegel, clinical director of the center and the study’s lead author, described the game-playing protocol as a modified Pivotal Response Treatment (PVT). Developed at UCSB, PRT is based on principles of positive motivation. The researchers identified the activities that seemed to be more enjoyable to the infants and taught the respective parents to focus on those rather than on the typical games they might otherwise choose. “We had them play with their infants for short periods, and then give them some kind of social reward,” Koegel said. “Over time, we conditioned the infants to enjoy all the activities that were presented by pairing the less desired activities with the highly desired ones.” The social reward is preferable to, say, a toy, Koegel noted, because it maintains the ever-crucial personal interaction.

“The idea is to get them more interested in people,” she continued, “to focus on their socialization. If they’re avoiding people and avoiding interacting, that creates a whole host of other issues. They don’t form friendships, and then they don’t get the social feedback that comes from interacting with friends.”

According to Koegel, by the end of the relatively short one- to three-month intervention period, which included teaching the parents how to implement the procedures, all the infants in the study had normal reactions to stimuli. “Two of the three have no disabilities at all, and the third is very social,” she said. “The third does have a language delay, but that’s more manageable than some of the other issues.”

On a large scale, Koegel hopes to establish some benchmark for identifying social deficits in infants so parents and health care providers can intervene sooner rather than later. “We have a grant from the Autism Science Foundation to look at lots of babies and try to really figure out which signs are red flags, and which aren’t,” she said. “A number of the infants who show signs of autism will turn out to be perfectly fine; but we’re saying, let’s not take the risk if we can put an intervention in play that really works. Then we don’t have to worry about whether or not these kids would develop the full-blown symptoms of autism.”

Historically, ASD is diagnosed in children 18 months or older, and treatment generally begins around 4 years. “You can pretty reliably diagnose kids at 18 months, especially the more severe cases,” said Koegel. “The mild cases might be a little harder, especially if the child has some verbal communication. There are a few measures –– like the ones we used in our study –– that can diagnose kids pre-language, even as young as six months. But ours was the first that worked with children under 12 months and found an effective intervention.”

Given the increasing number of children being diagnosed with ASD, Koegel’s findings could be life altering –– literally. “When you consider that the recommended intervention for preschoolers with autism is 30 to 40 hours per week of one-on-one therapy, this is a fairly easy fix,” she said. “We did a single one-hour session per week for four to 12 weeks until the symptoms improved, and some of these infants were only a few months old. We saw a lot of positive change.”

Meds taken during pregnancy increase risk of Autism

 

Wednesday, 24 April 2013

Women who take valproate (Depacon) during pregnancy may increase the risk of childhood autism and its spectrum disorders in their children, a population-based study showed.

In utero exposure to the drug was associated with a five-fold elevated risk of autism and three-fold elevated risk for autism spectrum disorder, Jakob Christensen, PhD, of Denmark’s Aarhus University Hospital, and colleagues found.

The absolute risks were 2.5% and 4.4%, respectively, and remained significantly elevated after adjustment for parents’ epilepsy and psychiatric disease, the group reported in the April 24 issue of the Journal of the American Medical Association.

“For women of childbearing potential who use anti-epileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control,” they concluded.

But “because autism spectrum disorders are serious conditions with lifelong implications for affected children and their families, even a moderate increase in risk may have major health importance,” they added.

The American Academy of Neurology recommends avoiding valproate in pregnancy whenever possible due to cognitive and physical birth defect problems for children exposed in utero.

 

http://macedoniaonline.eu/content/view/23192/54/

U.S. autism estimates climb to 1 in 50 school-age children: 72% increase since 2007

Thu, 21 Mar 2013 00:05 GMT

Reuters

* Boys four times more likely than girls to have diagnosis

* Milder cases made up much of the increase  (Adds CDC and expert interview, byline, background)

By Julie Steenhuysen

March 20 (Reuters) – As many as one in 50 U.S. school age children have a diagnosis of autism, up 72 percent since 2007, but much of the increase involves milder cases, suggesting the rise is linked to better recognition of autism symptoms and not more cases, government researchers said on Wednesday.

Overall, the telephone survey of more than 100,000 parents found about 2 percent of children ages 6 to 17 have autism, up from 1.16 percent in 2007, the last time the study was conducted.

“That translates to 1 million school age children ages 6 to 17 who were reported by their parents to have autism spectrum disorder,” said Stephen Blumberg, a senior scientist at the National Center for Health Statistics, a part of the U.S. Centers for Disease Control and Prevention, who led the study.

As with prior estimates, boys were much more likely to be diagnosed with autism than girls, with 1 in 31 school-age boys, or 3.2 percent, having an autism diagnosis, compared with 1 in 143, or 0.7 percent of girls, having a diagnosis.

“Boys were more than 4 times as likely as girls to have autism spectrum disorder,” Blumberg said.

He said the increase among boys accounted for nearly all of the overall increase in autism diagnoses.

DIFFERENT METHODOLOGY

The new findings differ sharply from autism data released just a year ago by the CDC, which said 1 in 88 children in the United States had autism, a spectrum of disabilities that can range from highly functioning individuals to those with severe speech and intellectual disabilities.

In general, individuals with autism struggle with difficulties in communication, behavior and social interaction.

In the current study, the researchers surveyed parents of children age 6 to 17 as part of the 2011-2012 National Survey of Children’s Health or NSCH. They compared their findings to the same study done in 2007, which found 1 in 86 children had an autism diagnosis.

The estimate from last year involved a review of medical and educational records of 8 year olds in 14 sites around the country. Data in the records were last collected in 2008, so the finding of 1 in 88 is not far off from the 1 in 86 figure in 2007, the starting point of the current study.

Blumberg said much of the increase in the estimates from the current parent survey was the result of diagnoses of children with previously unrecognized autism.

Increased awareness of autism differences in children and better detection of autism symptoms by doctors, especially in children with milder cases, likely accounts for the increased diagnoses.

“We think the improved recognition is really a recognition of autism spectrum disorders in children with previously unrecognized autism as opposed to new cases,” Blumberg said

Symptoms of autism can be seen in children as young as 18 months of age, and doctors are urged to conduct a screening for developmental delays on all children by age 2. But doctors often fail to detect mild cases of autism until children enter school, when parents become aware of their child’s troubles making friends and teachers notice differences in the child’s ability to interact socially, the team said.

“This is not saying anything about an increased risk for autism but rather that the NSCH is capturing more of the cases that had been missed previously,” said Michael Rosanoff of the advocacy group Autism Speaks.

For families, the findings mean detection of autism, particularly milder forms, is improving but could still happen earlier.

“Even mildly affected children who are in general education settings can struggle without and benefit from appropriate autism spectrum disorder services,” he said in an e-mail.

While scientists believe genetics account for 80 to 90 percent of the risk for developing autism, a growing number of studies are beginning to suggest that a father’s age at the time of conception may play a role by increasing risks for genetic mistakes in the sperm that could be passed along to offspring.

And new research by a British team found that older fathers are more likely to have grandchildren with autism, suggesting that risk factors for autism may build up over generations.

(Reporting by Julie Steenhuysen; Editing by Doina Chiacu and Cynthia Osterman)

http://www.trust.org/alertnet/news/us-autism-estimates-climb-to-1-in-50-school-age-children/

 

Drug treatment corrects autism symptoms in mouse model : suramin

Contact: Debra Kain ddkain@ucsd.edu 619-543-6163 University of California – San Diego

An old drug gives hope for new treatment in autism

Autism results from abnormal cell communication. Testing a new theory, researchers at the University of California, San Diego School of Medicine have used a newly discovered function of an old drug to restore cell communications in a mouse model of autism, reversing symptoms of the devastating disorder.

The findings are published in the March 13, 2013 issue of the journal PLOS ONE.

“Our (cell danger) theory suggests that autism happens because cells get stuck in a defensive metabolic mode and fail to talk to each other normally, which can interfere with brain development and function,” said Robert Naviaux, MD, PhD, professor of medicine and co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego. “We used a class of drugs that has been around for almost a century to treat other diseases to block the ‘danger’ signal in a mouse model, allowing cells to return to normal metabolism and restore cell communication.”

“Of course, correcting abnormalities in a mouse is a long way from a cure for humans,” said Naviaux, “but we are encouraged enough to test this approach in a small clinical trial of children with autism spectrum disorder in the coming year. This trial is still in the early stages of development. We think this approach – called antipurinergic therapy or APT – offers a fresh and exciting new path that could lead to development of a new class of drugs to treat autism.”

Autism spectrum disorders (ASDs) are complex disorders defined by abnormalities in the development of language, social and repetitive behaviors. Hundreds of different genetic and environment factors are known to confer risk.  In this study, nearly a dozen UC San Diego scientists from different disciplines collaborated to find a unifying mechanism that explains autism.  Their work is the result of one of just three international “Trailblazer” awards given by the group Autism Speaks in 2011.

Describing a completely new theory for the origin and treatment of autism using APT, Naviaux and colleagues introduce the concept that a large majority of both genetic and environmental causes for autism act by producing a sustained cell danger response – the metabolic state underlying innate immunity and inflammation.

“When cells are exposed to classical forms of dangers, such as a virus, infection or toxic environmental substance, a defense mechanism is activated,” Naviaux explained.  “This results in changes to metabolism and gene expression, and reduces the communication between neighboring cells. Simply put, when cells stop talking to each other, children stop talking.”

Since mitochondria – the so-called “power plants” of the cell – play a central role in both infectious and non-infectious cellular stress, innate immunity and inflammation, Naviaux and colleagues searched for a signaling system in the body that was both linked to mitochondria and critical for innate immunity.  They found it in extracellular nucleotides like adenosine triphosphate (ATP) and other mitokines – signaling molecules made by distressed mitochondria. These mitokines have separate metabolic functions outside of the cell where they bind to and regulate receptors present on every cell of the body.  Fifteen types of purinergic receptors are known to be stimulated by these extracellular nucleotides, and the receptors are known to control a broad range of biological characteristics with relevance to autism.

The researchers tested suramin – a well-known inhibitor of purinergic signaling used medically for the treatment of African sleeping sickness since shortly after it was synthesized in 1916 – in mice.  They found that this APT mediator corrected autism-like symptoms in the animal model, even if the treatment was started well after the onset of symptoms.  The drug restored 17 types of multi-symptom abnormalities including normalizing brain synapse structure, cell-to-cell signaling, social behavior, motor coordination and normalizing mitochondrial metabolism.

“The striking effectiveness shown in this study using APT to ‘reprogram’ the cell danger response and reduce inflammation showcases an opportunity to develop a completely new class of anti-inflammatory drugs to treat autism and several other disorders,” Naviaux said.

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Additional contributors to the study include Zarazuela Zolkipli, Lin Wang, Tomohiro Nakayama, Jane C. Naviaux, Thuy P. Le, Michael Schuchbauer, Mihael Rogac, Qingbo Tang, Laura L. Dugan, and Susan B. Powell.

Funding for the project was provided by Autism Speaks, the UCSD Christini Fund, the Jane Botsford-Johnson Foundation, the Wright Family Foundation, the Lennox Foundation, the Larry L. Hillblom Foundation, the Gerber Foundation, and Hailey’s Wish Foundation.

Study finds higher levels of several toxic metals in children with autism

James Adams uatism research

James Adams, a professor of materials science and engineering, has done extensive research into autism. He directs the ASU Autism/Asperger’s Research Program. Photo: Jessica Slater/ASU

Posted February 25, 2013

In a recently published study in the journal Biological Trace Element Research, Arizona State University researchers report that children with autism had higher levels of several toxic metals in their blood and urine compared to typical children. The study involved 55 children with autism ages 5–16 years compared to 44 controls of similar age and gender.

The autism group had significantly higher levels of lead in their red blood cells (+41 percent) and significantly higher urinary levels of lead (+74 percent), thallium (+77 percent), tin (+115 percent), and tungsten (+44 percent).  Lead, thallium, tin, and tungsten are toxic metals that  can impair brain development and function, and also interfere with the normal functioning of other body organs and systems.

A statistical analysis was conducted to determine if the levels of toxic metals were associated with autism severity, using three different scales of autism severity. It was found that 38-47 percent of the variation of autism severity was associated with the level of several toxic metals, with cadmium and mercury being the most strongly associated.

In the paper about the study, the authors state “We hypothesize that reducing early exposure to toxic metals may help ameliorate symptoms of autism, and treatment to remove toxic metals may reduce symptoms of autism; these hypotheses need further exploration, as there is a growing body of research to support it.”

The study was led by James Adams, a President’s Professor in the School for Engineering of Matter, Transport and Energy, one of ASU’s Ira A. Fulton Schools of Engineering.  He directs the ASU Autism/Asperger’s Research Program.

Adams previously published a study on the use of DMSA, an FDA-approved medication for removing toxic metals.  The open-label study found that DMSA was generally safe and effective at removing some toxic metals. It also found that DMSA therapy improved some symptoms of autism. The biggest improvement was for children with the highest levels of toxic metals in their urine.

Overall, children with autism have higher average levels of several toxic metals, and levels of several toxic metals are strongly associated with variations in the severity of autism for all three of the autism severity scales investigated.

The study was funded by the Autism Research Institute and the Legacy Foundation.

Media Contact: Joe Kullman, joe.kullman@asu.edu (480) 965-8122 Ira A. Fulton Schools of Engineering

Folic acid supplements early in pregnancy may reduce child’s risk of autism by 40 percent

Contact: Timothy S. Paul tp2111@columbia.edu 212-305-2676 Columbia University’s Mailman School of Public Health

Large study in Norway finds early timing of supplements is critical

Prenatal folic acid supplements appear to reduce the risk for autistic spectrum disorders, according to a study published today (February 13) in the Journal of the American Medical Association (JAMA).

The Centers for Disease Control and Prevention estimate that about 1 in 88 children in the U.S. have been identified with an Autism Spectrum Disorder (ASD). ASDs are amongst the most heritable of mental disorders, but little is known about how the disorder develops. Consequently, methods for diagnosis, prevention, and treatment are limited.

Folic acid (Vitamin B9) is required for DNA synthesis and repair in the human body, and its naturally occurring form—folate—is found in leafy vegetables, peas, lentils, beans, eggs, yeast, and liver. Taking folic acid supplements during early pregnancy is known to protect against spina bifida and other neural tube defects in children. In the United States, Canada, and Chile, folic acid is added to flour, so as to automatically provide these supplements to consumers. Norway does not enrich its flour, and since 1998, the Norwegian Directorate of Health has recommended that all women planning to become pregnant take a daily supplement of folic acid from one month before the start of pregnancy through the first trimester.

Despite this policy, studies from North America and Europe have shown that many pregnant women have a lower dietary intake of folate than what is necessary to prevent neural tube defects.

The report in JAMA emerged from the Norwegian Mother and Child Cohort Study (MoBa) and its sub-study of autism, the Autism Birth Cohort (ABC) Study. This international collaboration (see list of members below) comprises the largest prospective birth cohort devoted to the investigation of gene-environment interactions and biomarker discovery for neuropsychiatric disorders.

A total of 85,176 MoBa babies—born from 2002-2008—and their parents participated in the study. Prenatal dietary habits were recorded, and families were regularly surveyed for 3-10 years to measure the development of autism spectrum disorders. A total of 270 cases of autism spectrum disorders were identified in the study population (114 autistic disorder; 56 Asperger syndrome; 100 atypical or unspecified autism; i.e., pervasive developmental disorder not otherwise specified, PDD-NOS).

Mothers who took folic acid supplements in early pregnancy had a 40% reduced risk of having children with autistic disorder compared with mothers who did not take folic acid. The reduction in risk was observed in those who took folic acid during the time interval from 4 weeks before to 8 weeks after the start of pregnancy. Autistic disorder is the most severe form of autism spectrum disorders in children. No reduction in risk was observed for PDD-NOS. For Asperger syndrome, the number of children was too low to obtain sufficient statistical power in the analyses.

The use of folic acid in early pregnancy increased substantially from 2002 to 2008 among women who participated in MoBa. In 2002, 43% of mothers took folic acid supplements; by 2008, 85% of mothers did. However, many women began taking folic acid later than recommended, and only half started before the beginning of pregnancy.

The timing of a mother’s intake of folate appears to be a critical factor. Her child’s risk of autism was reduced only when the supplements were taken between 4 weeks before to 8 weeks after the start of pregnancy.

“We examined the rate of autism spectrum disorders in children born to mothers who did or did not take folic acid during pregnancy. There was a dramatic reduction in the risk of autistic disorder in children born to mothers who took folic acid supplements,” says Pål Surén, first author and epidemiologist at the Norwegian Institute of Public Health (NIPH).

The researchers also analyzed whether the risk of autistic disorder was influenced by the use of other dietary supplements. They did not find any association between the mother’s use of fish oil supplements (cod liver oil and omega-3 fatty acids) in early pregnancy and the risk of autistic disorder, and no association for the mother’s use of other vitamins and minerals.

In recent years, researchers have started to investigate whether folic acid has other beneficial effects on the development of the fetus’ brain and spinal cord. A study of language development from MoBa, published in 2011, showed that children whose mothers took folic acid supplements in early pregnancy had only half the risk of severe language delay at age three years compared with other children. A separate 2011 study from the University of California, Davis, demonstrated a lower risk of autism spectrum disorders in children of mothers who had used prenatal vitamin supplements during pregnancy. Prenatal vitamin supplements contain folic acid in combination with other vitamins and minerals.

Joint senior author Ezra Susser, professor of Epidemiology at Columbia University’s Mailman School of Public Health and professor of Psychiatry at the College of Physicians and Surgeons, stated, “Our findings extend earlier work on the significance of folate in brain development and raise the possibility of an important and inexpensive public health intervention for reducing the burden of autism spectrum disorders.”

“This elegant work illustrates the power of the ABC cohort for not only chipping away at the riddle of what causes autism, but for developing new methods for early recognition, prevention and treatment,” says W. Ian Lipkin, John Snow Professor of Epidemiology at the Mailman School of Public Health and principal investigator of the ABC cohort.

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About the study

The ABC Study is a collaboration between the Norwegian Institute of Public Health and Columbia University in New York funded by the National Institute of Neurological Disorders and Stroke of the U.S. National Institutes of Health.

The article was published in JAMA on February 13th, 2013. The authors are: Pål Surén, Christine Roth, Michaeline Bresnahan, Margaretha Haugen, Mady Hornig, Deborah Hirtz, Kari Kveim Lie, W. Ian Lipkin, Per Magnus, Ted Reichborn-Kjennerud, Synnve Schjølberg, George Davey Smith, Anne-Siri Øyen, Ezra Susser, and Camilla Stoltenberg.

Some Children lose the symptoms and the diagnosis of autism as they grow older

Some Children Lose Autism Diagnosis: Small Group With Confirmed Autism Now On Par With Mainstream Peers

Jan. 15, 2013 — Some children who are accurately diagnosed in early childhood with autism lose the symptoms and the diagnosis as they grow older, a study supported by the National Institutes of Health has confirmed. The research team made the finding by carefully documenting a prior diagnosis of autism in a small group of school-age children and young adults with no current symptoms of the disorder.

The report is the first of a series that will probe more deeply into the nature of the change in these children’s status. Having been diagnosed at one time with an autism spectrum disorder (ASD), these young people now appear to be on par with typically developing peers. The study team is continuing to analyze data on changes in brain function in these children and whether they have subtle residual social deficits. The team is also reviewing records on the types of interventions the children received, and to what extent they may have played a role in the transition.

“Although the diagnosis of autism is not usually lost over time, the findings suggest that there is a very wide range of possible outcomes,” said NIMH Director Thomas R. Insel, M.D. “For an individual child, the outcome may be knowable only with time and after some years of intervention. Subsequent reports from this study should tell us more about the nature of autism and the role of therapy and other factors in the long term outcome for these children.”

The study, led by Deborah Fein, Ph.D., at the University of Connecticut, Storrs, recruited 34 optimal outcome children, who had received a diagnosis of autism in early life and were now reportedly functioning no differently than their mainstream peers. For comparison, the 34 children were matched by age, sex, and nonverbal IQ with 44 children with high-functioning autism, and 34 typically developing peers. Participants ranged in age from 8 to 21 years old.

Prior studies had examined the possibility of a loss of diagnosis, but questions remained regarding the accuracy of the initial diagnosis, and whether children who ultimately appeared similar to their mainstream peers initially had a relatively mild form of autism. In this study, early diagnostic reports by clinicians with expertise in autism diagnosis were reviewed by the investigators. As a second step to ensure accuracy, a diagnostic expert, without knowledge of the child’s current status, reviewed reports in which the earlier diagnosis had been deleted. The results suggested that children in the optimal outcome group had milder social deficits than the high functioning autism group in early childhood, but had other symptoms, related to communication and repetitive behavior, that were as severe as in the latter group.

The investigators evaluated the current status of the children using standard cognitive and observational tests and parent questionnaires. The optimal outcome children had to be in regular education classrooms with no special education services aimed at autism. They now showed no signs of problems with language, face recognition, communication, and social interaction.

This study cannot provide information on what percentage of children diagnosed with ASD might eventually lose the symptoms. Study investigators have collected a variety of information on the children, including structural and functional brain imaging data, psychiatric outcomes, and information on the therapies that the children received. Analysis of those data, which will be reported in subsequent papers, may shed light on questions such as whether the changes in diagnosis resulted from a normalizing of brain function, or if these children’s brains were able to compensate for autism-related difficulties. The verbal IQs of the optimal outcome children were slightly higher than those with high functioning autism. Additional study may reveal whether IQ may have been a factor in the transition they made.

“All children with ASD are capable of making progress with intensive therapy, but with our current state of knowledge most do not achieve the kind of optimal outcome that we are studying,” said Dr. Fein. “Our hope is that further research will help us better understand the mechanisms of change so that each child can have the best possible life.”

High Fructose Corn Syrup Direct Correlation with Autism in the U.S. – Clin Epigenetics. 2012

EEV: Highlights Although there are many potential causes. We chose to highlight HFCS, due to its toxin amplification.

1) Ca, Mg and Zn, or losses or displacement of any of these minerals from the consumption of HFCS

2) mercury (Hg) and fructose may both modulate PON1 activity

3) mercury (Hg) that may occur from the low Hg concentrations sometimes found in HFCS as a result of the manufacturing process

4) HFCS, may further enhance the toxic effects of lead (Pb) on cognitive and behavioral development in children

2nd Source http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378453/

Initial Study date: 10 APR 2012

A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States

Renee Dufault1,2*Walter J Lukiw3Raquel Crider4Roseanne Schnoll5David Wallinga6 and Richard Deth7

Author Affiliations

1 Food Ingredient and Health Research Institute, Ocean View, HI, USA

2 United Tribes Technical College, Bismarck, ND, USA

3 Department of Neuroscience and Ophthalmology, Louisiana State University Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA

4 Shepherd University, Shepherdstown, WV, USA

5 Department of Health and Nutrition Sciences, Brooklyn College of City, University of New York, Brooklyn, NY, USA

6 Institute for Agriculture and Trade Policy, Minneapolis, MN, USA

7 Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA

For all author emails, please log on.

Clinical Epigenetics 2012, 4:6 doi:10.1186/1868-7083-4-6

The electronic version of this article is the complete one and can be found online at: http://www.clinicalepigeneticsjournal.com/content/4/1/6

Received: 9 December 2011
Accepted: 10 April 2012
Published: 10 April 2012

© 2012 Dufault et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The number of children ages 6 to 21 in the United States receiving special education services under the autism disability category increased 91% between 2005 to 2010 while the number of children receiving special education services overall declined by 5%. The demand for special education services continues to rise in disability categories associated with pervasive developmental disorders. Neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors, such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as mercury or organophosphate pesticides. Gene expression patterns differ geographically between populations and within populations. Gene variants of paraoxonase-1 are associated with autism in North America, but not in Italy, indicating regional specificity in gene-environment interactions. In the current review, we utilize a novel macroepigenetic approach to compare variations in diet and toxic substance exposure between these two geographical populations to determine the likely factors responsible for the autism epidemic in the United States.

Keywords:

Autism; DNA methylation; Environmental epigenetics; Heavy metals; HFCS; PON1; SAM; Zn

Introduction to macroepigenetics with autism as a case study

Autism is a developmental disorder defined by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The condition is considered a pervasive developmental disorder (PDD) that appears in the first three years of life and affects brain development impacting social and communication skills. Autism is defined by a common set of behaviors, including, but not limited to, observed deficits in nonverbal and verbal communication, lack of social reciprocity, and failure to develop and maintain appropriate peer relationships [1]. Recent estimates suggest that 31% of children with Autism Spectrum Disorder (ASD) also meet diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD) and another 24% of children with ASD exhibit sub-threshold clinical symptoms for ADHD [2]. The number of children affected by this debilitating disorder remains unknown. As part of this review, we analyze the current United States (U. S.) Department of Education Special Education data to estimate the increase in autism prevalence from 2005 to 2010.

The cause(s) of autism also remain(s) unknown. D’Amelio et al. found paraoxonase-1 (PON1) gene variants associated with autism in subgroups of the U. S. population but not in Italy [3]. They attributed the gene variation to greater household use of organophosphate (OP) pesticides in the U.S. compared to Italy. We think a more plausible explanation may lie in the U. S. food supply. As part of this investigation, we also reviewed and analyzed the U.S. Department of Agriculture (USDA) Food Availability Spreadsheets to identify which foods are most frequently consumed by Americans and of those which most frequently contain OP pesticide residue as reported by the U.S. Pesticide Data Program.

During this investigation, we conducted a literature review of all studies published on autism since we published our first Mercury Toxicity Model [4], which explains how mercury exposure, nutritional deficiencies and metabolic disruptions contribute to the development of autism. We evaluated all of the relevant studies and expanded our Mercury Toxicity Model. We then used the expanded model to compare the U.S. and Italian populations to determine what, if any, factors could explain the difference in PON1 gene variation and autism prevalence between the two countries. We propose the term “macroepigenetics” to describe the process of examining food supplies and their impact on body metabolism and gene function along with what is known about environmental exposures across populations.

In studying the larger factors outside the gene and human body that impact gene expression, we can better explain some of the gene-environment interactions that create disease conditions such as autism. There is agreement among many in the psychiatry profession that gene-environment interaction research is essential to understanding the etiology of autism and the other pervasive developmental disorders found in the ASD category [5]. How the scientific community arrives at this understanding is key to solving the problem of rising autism prevalence. By demonstrating the macroepigenetic approach to determine the factors likely responsible for the autism prevalence in the U.S., we hope more scientists will follow our interdisciplinary lead and use macroepigenetics as a research strategy.

Current U. S. autism prevalence and special education trends

Before the 1980s the prevalence of autism in the U. S. was about 0.05% [6]. In 2006, the Center for Disease Control and Prevention (CDC) reported that the estimated prevalence of autism had increased to between 0.6 and 0.7% of all children [7]. Many scientists and parents believe the autism prevalence rate in the U.S. is much higher than these CDC statistics indicate. U.S. government scientists and collaborators published an article in 2007 indicating that 1.1% of U.S. children aged 3 to 17 years were currently diagnosed with ASD [8].

Special education data have been used in the past to estimate autism prevalence trends in the U.S. [9]. In birth cohorts from 1975 to 1995, increases in autism were greatest for annual cohorts born from 1987 to 1992 [9]. From 1992 to 1995, the autism prevalence increased with each successive year but the increases did not appear as great [9]. Our review of the current special education data indicates the number of children ages 6 to 21 receiving special education services under the Autism category has increased 91% from 2005 to 2010. The number of children in the Developmental Delay category has increased 38% and the number of children receiving special education and related services under the Other Health Impaired (OHI) category has increased 26% from 2005 to 2010. Children with a diagnosis of ADHD are included in the OHI category. These increases are startling given that the overall number of children receiving special education services decreased by 5% from 2005 to 2010. Table 1 provides a graphical representation of the data obtained from the Data Accountability Center and analyzed during this review [10].

Table 1. Number of U.S. students ages 6 to 21 receiving special education services by disability category and year

Data from the 1997 to 2008 National Health Interview Surveys conducted by the CDC confirm these findings of increasing prevalence in autism and developmental disabilities associated with or sharing the diagnostic criteria for autism [11]. Regardless of the source of data it seems clear that autism prevalence is rising in the U.S. compared to other countries, such as Italy, where the autism prevalence in the general population is estimated at only 0.1% [12]. Because autism prevalence rates vary by country, population and geographic location, it is becoming more evident that gene-environment interactions are at play with dietary factors. The influence of environment factors on gene expression is primarily mediated by epigenetic mechanisms, including deoxyribonucleic acid (DNA) methylation along with methylation, acetylation, ubiquitination and phosphorylation of histones. Epigenetic regulation is particularly important during neurodevelopment [13].

A macroepigenetic model to explain gene-environment interactions in autism

In public health, epidemiology arguably has led the way in researching gene-environment interactions by studying how genotypes, environmental exposures and disorder outcomes occur in the human population [5]. However, this epidemiological approach has often resulted in contradictory scientific conclusions when its practitioners do not consider the dietary factors that interact and modulate the molecular and genetic mechanisms underlying human metabolism and brain function [14]. This has been the case despite the existence of literature from the field of “nutrigenomics”, which has specifically studied the effects of food and food ingredients on gene expression. In identifying the public health and the social and/or environmental determinants of disease, it seems invalid to study epidemiology without nutrigenomics, or vice versa. In other words, a more macro-level approach to unraveling the full range of environmental and genetic factors contributing to these kinds of neurological disorders ought to include nutrition factors as a component of the environment. By combining information derived from both nutrigenomic and epidemiology studies, a macroepigenetic model has already been developed to explain some of the gene-environment interactions with dietary factors that lead to the development of autism and ADHD [4].

Figure 1 shows the Mercury Toxicity model that provides a macroepigenetic explanation of how human neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as the heavy metals mercury and copper [4]. Elimination of heavy metals requires the expression of the metallothionein (MT) gene, which synthesizes the Zn-dependent metal binding protein metallothionein [15]. With dietary zinc (Zn) loss and copper (Cu) gain from the consumption of high fructose corn syrup (HFCS) [16], metabolic processes required to eliminate heavy metals are impaired in children with autism [4]. Mercury has been found in samples of high fructose corn syrup and is allowable in trace amounts in certain food colors so long as the concentration does not exceed one part per million [17,18]. Mercury (Hg) and specific other heavy metals, including lead (Pb), copper (Cu), cadmium (Cd), silver (Ag) and bismuth (Bi), are capable of displacing the Zn atom in the MT protein molecule [15]. This ‘pathogenic’ displacement of Zn impairs the MT molecule and its ability to pick up the heavy metal and carry it out of the body. If the diet is deficient in Zn or the absorption of Zn is impaired, then the body may not produce enough MT protein to carry and excrete the heavy metal load [19,20]. Children with autism may be Zn deficient and often have MT dysfunction [2123]. Because of their diminished capacity to excrete toxic heavy metals, the severity of their condition is associated with their toxic metal burden [24]. This macroepigenetic model proposes that autism prevalence is related to the consumption of HFCS and the overall exposure to Hg in the U.S. [4]. However, other dietary factors associated with the consumption of HFCS may further contribute to the development of autism in the U.S.

                        Figure 1. The original Mercury Toxicity Model. The original Mercury Toxicity Model was published in 2009 by Dufault et al. in the Behavioral and Brain Functions journal. The model is a flow chart of what can happen in the body when there is exposure to mercury (Hg) from ingestion of foods (via HFCS, food colors and fish) or inhalation of air. Human neurodevelopment can be adversely impacted when MT gene expression is altered or suppressed by dietary transcription factors such as zinc (Zn) insufficiency or deficiency. Without proper MT expression and function, mercury excretion may not be possible and oxidative stress in the brain from mercury insult leads to reduced neuronal plasticity and impaired learning. Hg in fish is a problem when there is not enough selenium (Se) in the fish to counteract the Hg and the glutathione (GSH) system is disrupted leading to further oxidative stress.

Additional dietary factors associated with consumption of HFCS

U.S. per capita consumption of HFCS in 2009 was 35.7 pounds per year [25]. The peak years for annual consumption of HFCS coincided with the peak growth rates of ASD in California, the only state that reports number of cases of ASD dating back to the mid-1980s [4]. The Mercury Toxicity Model shows the HFCS characteristics most likely contributing to autism include the zinc-depleting effect that comes from consuming HFCS and certain food colors found in processed foods, and the additional Hg exposure that may occur from the low Hg concentrations sometimes found in HFCS as a result of the manufacturing process [4,17]. This model can be expanded to include additional adverse effects associated with the consumption of HFCS that likely contribute to the development of autism through PON1 gene modulation and lead intoxication.

U.S. Department of Agriculture (USDA) scientists warn that when dietary intake of magnesium (Mg) is low, consumption of HFCS leads to lower calcium (Ca) and phosphorus (P) balances adversely affecting macromineral homeostasis in humans [26]. This is an unfortunate finding because there is evidence to suggest that dietary intake of Mg is low among Americans, most of whom consume a high fructose diet. In 2003, CDC scientists reported that substantial numbers of U.S. adults fail to consume adequate Mg in their diets [27]. Children with autism were found to have significantly lower plasma Mg concentrations than normal subjects [28]. Adams et al. found significant reductions in red blood cell (RBC) Ca, serum and white blood cell (WBC) Mg and an increase in RBC copper in autistic children as compared to controls [29]. Recently, USDA scientists reported that the National Health and Nutrition Examination Survey (NHANES) data for 2005 to 2006 indicate that overall, nearly one half of all individuals one year and over had inadequate intakes of dietary Mg [30]. With a substantial number of Americans consuming inadequate amounts of dietary Mg along with HFCS diets, one may predict that substantial numbers of Americans are likely experiencing a calcium (Ca) deficit as well.

Insufficient intake of dietary Ca, Mg and Zn, or losses or displacement of any of these minerals from the consumption of HFCS, may further enhance the toxic effects of lead (Pb) on cognitive and behavioral development in children [31]. A significant and independent inverse relationship between dietary Ca intake and blood Pb concentrations was found in 3,000 American children examined as part of NHANES II [32]. Elevated blood Pb levels are indicative of Pb intoxication, which is found in some children diagnosed with autism and associated with the development of ADHD [33,34]. It may be that inadequate intake of Ca or Mg combined with a HFCS zinc-depleting diet increases the risk of developing autism and ADHD from Pb intoxication.

Inadequate intake of Ca or Mg may further contribute to these developmental disorders by impacting human serum paraoxonase-1 (PON1) gene expression. PON1 is a calcium dependent enzyme responsible for OP pesticide detoxification as well as hydrolysis of the thiolactone form of homocysteine [35,36]. PON1 is synthesized in the liver and secreted in blood where it is incorporated into high density lipoproteins (HDL). The availability and catalytic activity of PON1 are impaired in many children with ASD making them more susceptible to the toxic effects of OP pesticide residues which are most frequently found in grain [37,38]. Figure 2 shows the expanded Mercury Toxicity Model that includes changes both in Pb toxicity and PON1 activity when dietary intake of Mg is low and consumption of HFCS leads to greater loss of calcium (Ca) and phosphorus (P), thereby adversely affecting macromineral homeostasis.

Figure 2. The expanded Mercury Toxicity Model. Figure 2 shows the expanding Mercury Toxicity Model that includes changes both in lead (Pb) toxicity and human serum paraoxonase (PON1) activity when dietary intake of Mg is low and consumption of high fructose corn syrup (HFCS) leads to lower calcium (Ca) and phosphorus (P) balances, adversely affecting macromineral homeostasis. With insufficient dietary intake of Ca and/or Mg, children become more susceptible to Pb intoxication and OP exposures with decreasing PON1 activity. Pb intoxication and OP exposures can both lead to oxidative stress in the brain reducing neuronal plasticity.

PON1 activity and organophosphate exposure in U.S

One can assert that with the consumption of a HFCS intensive diet and inadequate Mg intakes, PON1 activity may decrease, along with resulting Ca losses in genetically predisposed individuals. Although there are no human data yet to support this assertion, PON1 activity in rats decreased when fed a HFCS diet to mimic the human metabolic syndrome [39]. PON1 activity has been extensively studied in humans and there are a number of factors known to modulate or alter PON1 expression including, but not limited to, Hg exposure, sex and age [40,41]. Age plays the most relevant role, as PON1 activity is very low before birth and gradually increases during the first few years of life in humans [41]. In one study, scientists at UC Berkeley found the PON1 levels in many children may remain lower than those of their mothers for several years, especially those with genotypes associated with decreased PON1 activities [42]. The scientists concluded that these children may be more susceptible to OP pesticides throughout their childhood and more vulnerable to conditions associated with oxidative stress such as autism [42]. In a different study, scientists at UC Berkeley found that two-year-old children were less likely to display symptoms of PDD when their mothers had higher paraoxonase levels during their pregnancy [43]. Proper function and adequate expression of the PON1 gene is essential both for prenatal development and child health because exposure to OP pesticides is a common occurrence in the U.S.

The CDC tracks exposure to OP pesticides or their metabolites through the National Biomonitoring Program (NBP). Exposure data are reported for the population as a whole and for subgroups. While most American groups are exposed to OP pesticides, children ages 6 to 11 have significantly higher exposures than adults and are at greatest risk from OP neurotoxicity [44]. Harvard University researchers recently reported finding OP pesticide residues in a number of foods frequently consumed by children [45]. The researchers expressed concern that the children were at times being exposed to multiple pesticide residues in single food commodities. OP pesticide exposures occur primarily from the consumption of foods containing pesticide residues.

It is well known that pesticide exposure can impair neurodevelopment in children, but recent studies have found that pesticide exposure during pregnancy can also cause delayed mental development in children [46]. A review of epidemiological studies in 2008 found that prenatal and childhood exposure to OPs impairs neurobehavioral development [47]. Higher concentrations of urinary dialkyl phosphate (DAP) measured during pregnancy was significantly associated with lower cognitive scores in children at seven years of age. Those children in the highest quintile of maternal DAP concentrations had an IQ score seven points lower than those children in the lowest quintile [48]. In a group of newborns with the highest levels of the organophosphate chlorpyrifos measurable in their umbilical cord blood, birth weight averaged 150 grams less than the group with the lowest exposure [49]. Prenatal pesticide exposure showed deficits consistent with developmental delays of 1.5 to 2 years [49].

Diet is the main source of OP exposure in children. Under the 1996 Food Quality Protection Act, the U.S. Secretary of Agriculture is directed to collect pesticide residue data on commodities frequently consumed by infants and children. USDA Pesticide Data Program (PDP) provides the residue data to comply with this law [50]. We reviewed the PDP data from 2004 to 2008 and identified the foods most frequently found to contain organophosphate insecticide residues. In addition, we obtained the per capita availability data from the USDA to determine the amount of each food commodity the average American consumes [25]. The results of our review indicate that wheat and corn are the commodities most likely contributing to OP exposure in U. S. children. Estimated per capita wheat consumption was approximately 95 pounds per year while estimated per capita corn consumption was approximately 23 pounds per year. The primary use of corn is for the production of corn sweeteners, such as HFCS; however, pesticide residue data were not gathered for this commodity by the PDP. Table 2 provides a complete breakdown of the results of this data review.

Table 2. PDP residue detections by year sampled wi th U.S. per capita consumption data

From Table 2 it is clear consumers are at risk of exposure to multiple OP pesticide residues from consuming the very same commodity. Cumulative exposures will continue to occur in the U.S. where OP pesticide use is widespread by the agricultural industry. Although OP pesticide use is equally widespread in other countries, there is genetic variation across populations that determine degree of susceptibility to OP exposure. The PON1 gene variants associated with autism in subgroups of the U.S. population but not in Italy could be attributed to the fact that HFCS consumption rarely occurs in Italy, thereby lessening the conditions for PON1 modulation.

HFCS consumption and PON1 modulation in autism in the U.S

In the 27-member European Union (EU), of which Italy is an original participant, HFCS is known as “isoglucose” and currently it is rarely consumed by Italians. Americans on the other hand consume on average 35.7 pounds per year, which may increase their overall Hg exposure [17,25]. Figure 3 shows U.S. per capita food consumption in pounds per year for HFCS beginning in the early 1970s and increasing throughout the 1980s to reach a peak between 1999 and 2002. In our previous publication, we reported the peak years for annual consumption of HFCS in the U.S. occurred within the same period as when the annual growth rates of autism peaked in California [4].

Figure 3. U.S. per capita consumption of high fructose corn syrup 1966-2004. Figure 3 shows the United States (US) per capita consumption of high fructose corn syrup (HFCS) in pounds per year as calculated by the United States Department of Agriculture (USDA)/Economic Research Service.

American per capita consumption of HFCS has exceeded 20 pounds per year since 1980 while Italians consume negligible amounts of the same ingredient. As was previously mentioned, mercury (Hg) and fructose may both modulate PON1 activity [3941]. While excessive fructose exposure in the U.S. may primarily occur through the consumption of foods containing HFCS, mercury exposure may occur in a number of ways. A comparison of common sources of mercury exposure in the U.S. and Italy may offer a further explanation of the PON1 gene variation associated with autism in the U.S. but not in Italy.

In addition to HFCS, primary sources of inorganic and elemental Hg exposure may occur from consumption of food colors and preservatives made with mercury-cell chlorine or chlor-alkali products, seafood consumption, Hg in dental amalgam, thimerosal in vaccines, and depending on geographic location, inhalation of Hg contaminated air [4,5154]. Children living near coal-fired power plants are often exposed to higher levels of Hg in their breathing air and have a higher prevalence of autism [55]. Because Hg emissions from coal-fired power plants are not yet regulated in either the U.S. or Italy, this particular source of Hg exposure is unlikely to explain the overall difference in autism prevalence between these two countries. With respect to the consumption of seafood, use of Hg dental amalgam, thimerosal in vaccines or Hg-containing food colors and preservatives, there is also no appreciable difference between Italy and the U.S. [5658]. The only remaining variable in our model is the excessive consumption of HFCS by Americans, which results in greater chronic exposures to both inorganic Hg and, by definition, fructose [4].

Inorganic Hg may interact with cysteine residues on PON1 preventing its activation in the liver and impairing the body’s ability to protect itself against OP pesticides and oxidative stressors involved in autism [41]. As noted above, PON1 is responsible for hydrolysis of homocysteine thiolactone, and plasma PON1 activity is negatively correlated with homocysteine levels [36,59]. Homocysteine is a metabolic biomarker for oxidative stress and impaired methylation capacity. A recent study of the Inuit population found a significant inverse correlation between PON1 activity and Hg levels, as well as a direct correlation with selenium levels [60]. With increasing Hg and fructose exposure and reductions in dietary Ca, one can expect to see reduced PON1 activity and increasing homocysteine levels in children with ASD.

Indeed, Pasca et al. recently reported finding that both PON1 arylesterase and PON1 paraoxonase activities were decreased in children with autism [61,62]. James et al. found that children with autism had higher plasma homocysteine levels than controls but demonstrated significant improvements in transmethylation metabolites and glutathione (GSH) after receiving folate and vitamin B12 [63]. Patel and Curtis found that in addition to glutathione and B12 injections one to three times per week, children with autism and ADHD showed significant improvement in many areas of social interaction, concentration, writing, language and behavior when fed an organic diet low in fructose and free of food additives and food colors [64].

Mothers of autistic children in the U.S. were also found to have significant increases in mean plasma homocysteine levels compared to controls [65]. Schmidt et al. found that women who took vitamin supplements during the periconceptional period reduced the risk of autism in their children [66]. Those women who did not take vitamins during this period were more likely to have a child with autism and were at even greater risk when they had specific genetic variants within one-carbon metabolism pathways. This suggests that folate and other dietary methyl donors may alter epigenetic regulation of gene expression in their children, thereby reducing the risk of autism [66].

Methionine synthase links oxidation to epigenetics

Epigenetic regulation of gene expression is highly dependent upon methylation of both DNA and histones, and methylation capacity is in turn dependent upon activity of the folate and vitamin B12-dependent enzyme methionine synthase, which converts homocysteine to methionine. Lower methionine synthase activity decreases the level of the methyl donor S-adenosylmethionine (SAM) while simultaneously increasing the level of the methylation inhibitor S-adenosylhomocysteine (SAH) [67]. The combined effect of changes in the SAM to SAH ratio, therefore, exerts a powerful influence over more than 200 methylation reactions, including DNA and histone methylation [68].

Methionine synthase activity is inhibited by oxidative stress, and its inhibition results in the diversion of homocysteine to produce the antioxidant glutathione (GSH), providing an important adaptive response [69]. However, oxidative inhibition of methionine synthase leads to epigenetic effects via the resultant decrease in the SAM to SAH ratio and decreased DNA and histone methylation. Epigenetic changes in gene expression can recruit further adaptive responses to oxidative stress. Figure 4 illustrates how these changes may occur when the body is under oxidative stress from exposure to OP pesticides, heavy metals, and calcium depleting substances, such as HFCS. Decreased methionine synthase activity during oxidative stress also increases homocysteine thiolactone formation [70], raising the importance of PON1. As was previously mentioned, PON1 is essential for reducing homocysteine levels, which are thought to be harmful. Elevated plasma homocysteine (tHcy) levels are associated with genome-wide DNA hypomethylation that may carry over from one generation to the next, increasing the risk of autism [71]. Epigenetic changes affecting germline cells can give rise to these transgenerational effects [72]. James et al. found that parents share similar metabolic deficits in methylation capacity and glutathione-dependent antioxidant/detoxification capacity with their children with autism [71].

Figure 4. Methionine synthase links oxidative stress to epigenetic regulation. Figure 4 shows how exposure to toxic substances, such as OP pesticides, HFCS, or heavy metals, inhibits methionine synthase through effects of oxidative stress. As a result, decrease of SAM to SAH ratio will lead to a decrease in DNA methylation and consequently to altered PON1 gene expression.

Synergistic effect of multiple neurotoxins

Based upon the discussion above, it is clear that methionine synthase activity is crucial for translating changes in oxidative status into epigenetic effects, and this role is confirmed by the improved metabolic profile in autistic subjects given folate and vitamin B12 [63]. This relationship has given rise to the “Redox/Methylation Hypothesis of Autism”, which proposed that oxidative insults arising from environmental exposures, such as Hg and pesticides, can cause neurodevelopmental disorders by disrupting epigenetic regulation [73]. The macroepigenetic Mercury Toxicity Model expanded in this paper provides additional support for the “Redox/Methylation Hypothesis of Autism” while contributing important insight into the oxidative stress feedback mechanisms that may occur as a result of malnutrition resulting from dietary exposures to toxins. The delivery of children exhibiting autistic behaviors might be associated with the prenatal diet of their mothers. The severity of these behaviors can be further exacerbated by toxic dietary exposures of the children, which can improve with dietary changes aimed at eliminating these exposures. Children with autism could well be exhibiting an epigenetic response to several neurotoxic substances at once, including, but not limited to, inorganic Hg, Pb, OP pesticides and/or HFCS. The combined effect of these substances acting together is likely greater than the sum of the effects of the substances acting by themselves. This effect likely reduces neuronal plasticity and impairs learning capacity in autistic children.

Conclusion

The number of children ages 6 to 21 in the U.S. receiving special education services under the autism disability category increased 91% between 2005 to 2010 despite fewer children receiving special education services overall during the same time period. A comparison of autism prevalence between the U.S. and Italy using the Mercury Toxicity Model suggests the increase in autism in the U.S. is not related to mercury exposure from fish, coal-fired power plants, thimerosal, or dental amalgam but instead to the consumption of HFCS. Consumption of HFCS may lead to mineral imbalances, including Zn, Ca and P loss and Cu gain and is a potential source of inorganic mercury exposure. These mineral imbalances create multiple pathways for oxidative stress in the brain from exposure to OP pesticides and heavy metals, such as Pb or Hg. Inorganic mercury and fructose exposure from HFCS consumption may both modulate PON1 gene expression. With a reduction in PON1 activity, there is a potential for increasing homocysteine levels which are associated with genome-wide DNA hypomethylation that may carry over from one generation to the next, affecting both neurodevelopment and autism prevalence.

Abbreviations

ADHD: Attention-Deficit-Hyperactivity-Disorder; Ag: Silver; APA: American Psychiatric Association; ASD: Autism Spectrum Disorder; Bi: Bismuth; Ca: Calcium; Cd: Cadmium; CDC: Center for Disease Control and Prevention; Cu: Copper; DAP: Dialkyl phosphate; DSM: Diagnostic and Statistical Manual of Mental Disorders; EU: European Union; GSH: Glutathione; HDL: High density lipoprotein; HFCS: High fructose corn syrup; Hg: Mercury; Mg: Magnesium; MT: Metallothionein; NBP: National Biomonitoring Program; NHANES: National Health and Nutrition Examination Survey; OHI: Other Health Impaired; OP: organophosphate pesticide; P: phosphorus; Pb: lead; PDD: Pervasive Developmental Delay; PDP: Pesticide Data Program; PON1: paraoxonase-1; RBC: red blood cell; SAH: S-adenosylhomocysteine; SAM: S-adenosylmethionine; tHcy: total plasma homocysteine; USDA: United States Department of Agriculture; WBC: White blood cell; Zn: Zinc.

Competing interests

RDeth has in the past received compensation as an expert witness on the topic of autism. All of the other authors declare that they have no competing interests.

Authors’ contributions

RDufault spearheaded the review and recruited interdisciplinary collaborators to contribute to the development of the manuscript. RDufault was the lead investigator and literature reviewer for the expansion of the mercury toxicity model. RDufault acquired, analyzed and interpreted the new data sets. WJL, RS and RDeth helped revise the manuscript critically for important intellectual content. RDeth provided Figure 4 and was the primary author of the methionine synthase section. All authors read and approved the final manuscript. RS validated all of the references. RC validated the data in Table 1 to ensure it was correctly gathered from existing data bases. RC also double checked the calculations in Table 1 to ensure they were error free. DW helped draft and edit the manuscript.

Lead author’s information

After retiring with honors from her position as an environmental health officer with the U.S. Public Health Service, R. Dufault obtained her teaching license and taught elementary special education for 3.5 years at which time she gained an understanding of how children with autism and ADHD in the U.S. receive special education services. As a volunteer, she currently teaches an epigenetics course on-line through the Food Ingredient and Health Research Institute.

Acknowledgements

The authors would like to thank Drs. Robert Lustig, Blaise LeBlanc and Steven Gilbert for the feedback each provided on this manuscript and/or the concepts therein. Funding for this research project was provided primarily by donations to the Food Ingredient and Health Research Institute. Research in the Lukiw laboratory is supported through Grant Number P20RR016456 from the National Center for Research Resources, a Translational Research Initiative Grant from LSU Health Sciences Center New Orleans, an Alzheimer Association Investigator-Initiated Research Grant IIRG-09-131729, and NIH NIA Grants AG18031 and AG038834.

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Link Found Between Child Prodigies and Autism

COLUMBUS, Ohio – A new study of eight child prodigies suggests a possible link between these children’s special skills and autism.

Of the eight prodigies studied, three had a diagnosis of autism spectrum disorders. As a group, the prodigies also tended to have slightly elevated scores on a test of autistic traits, when compared to a control group.

In addition, half of the prodigies had a family member or a first- or second-degree relative with an autism diagnosis.

The fact that half of the families and three of the prodigies themselves were affected by autism is surprising because autism occurs in only one of 120 individuals, said Joanne Ruthsatz, lead author of the study and assistant professor of psychology at Ohio State University’s Mansfield campus.

ruthsatz
Joanne Ruthsatz

“The link between child prodigies and autism is strong in our study,” Ruthsatz said. “Our findings suggest child prodigies have traits in common with autistic children, but something is preventing them from displaying the deficits we associate with the disorder.”

The study also found that while child prodigies had elevated general intelligence scores, where they really excelled was in working memory – all of them scored above the 99th percentile on this trait.

Ruthsatz conducted the study with Jourdan Urbach of Yale University. Their results were published in a recent issue of the journal Intelligence.

For the study, the researchers identified eight child prodigies through the internet and television specials and by referral. The group included one art prodigy, one math prodigy, four musical prodigies and two who switched domains (one from music to gourmet cooking, and one from music to art). The study included six males and two females.

The researchers met with each prodigy individually over the course of two or three days. During that time, the prodigies completed the Stanford-Binet intelligence test, which included sub-tests on fluid reasoning, knowledge, quantitative reasoning, visual spatial abilities and working memory.

In addition, the researchers administered the Autism-Spectrum Quotient assessment, which scores the level of autistic traits. The prodigies’ scores on the test were compared to a control group of 174 adults who were contacted randomly by mail.

Ruthsatz said the most striking data was that which identified autistic traits among the prodigies.

The prodigies showed a general elevation in autistic traits compared to the control group, but this elevation was on average even smaller than that seen in high-functioning autistic people diagnosed with Asperger’s syndrome.

Autism is a developmental disability characterized by problems with communicating and socializing and a strong resistance to change. People with Asperger’s are more likely than those with autism to have normal intelligence, but tend to have difficulties with social interaction.

The prodigies did score higher than the control group and the Asperger’s group on one subsection of the autism assessment: attention to detail.

“These prodigies had an absolutely amazing memory for detail,” she said. “They don’t miss anything, which certainly helps them achieve the successes they have.”

Ruthsatz said it was not the three prodigies who were diagnosed with autism who were driving this particular finding. In fact, the three autistic prodigies scored an average of 8 on attention to detail, compared to 8.5 for the entire group of prodigies.

On the intelligence test, the prodigies scored in the gifted range, but were not uniformly exceptional. While five of the eight prodigies scored in the 90th percentile or above on the IQ test, one scored at the 70th percentile and another at the 79th percentile.


“Our findings suggest child prodigies have traits in common with autistic children, but something is preventing them from displaying the deficits we associate with the disorder.”


But just as they did in the autism assessment, the prodigies stood out in one of the sub-tests of the intelligence test. In this case, the prodigies showed an exceptional working memory, with all of them scoring above the 99th percentile.

Working memory is the system in the brain that allows people to hold multiple pieces of information in mind for a short time in order to complete a task.

The findings paint a picture of what it takes to create a prodigy, Ruthsatz said.

“Overall, what we found is that prodigies have an elevated general intelligence and exceptional working memory, along with an elevated autism score, with exceptional attention to detail,” Ruthsatz said.

These results suggest that prodigies share some striking similarities with autistic savants – people who have the developmental disabilities associated with autism combined with an extraordinary talent or knowledge that is well beyond average.

“But while autistic savants display many of the deficits commonly associated with autism, the child prodigies do not,” Ruthsatz said. “The question is why.”

The answer may be some genetic mutation that allows prodigies to have the extreme talent found in savants, but without the deficits seen in autism. But the answer will require more study, Ruthsatz said.

“Our findings suggest that prodigies may have some moderated form of autism that actually enables their extraordinary talent.”

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Contact: Joanne Ruthsatz, Ruthsatz.4@osu.edu (It is best to reach Dr. Ruthsatz first by email.)

Written by Jeff Grabmeier, (614) 292-8457; Grabmeier.1@osu.edu

Einstein scientists propose new theory of autism: Symptoms of the disorder may be reversible: Fever may hold clues

Contact: Deirdre Branley dbranley@aecom.yu.edu 718-430-2923 Albert Einstein College of Medicine

2009 study posted for filing

Symptoms of the disorder may be reversible: Fever may hold clues

April 1, 2009 — (BRONX, NY) — Scientists at Albert Einstein College of Medicine of Yeshiva University have proposed a sweeping new theory of autism that suggests that the brains of people with autism are structurally normal but dysregulated, meaning symptoms of the disorder might be reversible.

The central tenet of the theory, published in the March issue of Brain Research Reviews, is that autism is a developmental disorder caused by impaired regulation of the locus coeruleus, a bundle of neurons in the brain stem that processes sensory signals from all areas of the body.

The new theory stems from decades of anecdotal observations that some autistic children seem to improve when they have a fever, only to regress when the fever ebbs. A 2007 study in the journal Pediatrics took a more rigorous look at fever and autism, observing autistic children during and after fever episodes and comparing their behavior with autistic children who didn’t have fevers. This study documented that autistic children experience behavior changes during fever.

“On a positive note, we are talking about a brain region that is not irrevocably altered. It gives us hope that, with novel therapies, we will eventually be able to help people with autism,” says theory co-author Mark F. Mehler, M.D., chairman of neurology and director of the Institute for Brain Disorders and Neural Regeneration at Einstein.

Autism is a complex developmental disability that affects a person’s ability to communicate and interact with others. It usually appears during the first three years of life. Autism is called a “spectrum disorder” since it affects individuals differently and to varying degrees. It is estimated that one in every 150 American children has some degree of autism.

Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. “The LC-NA system is the only brain system involved both in producing fever and controlling behavior,” says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.

The locus coeruleus has widespread connections to brain regions that process sensory information. It secretes most of the brain’s noradrenaline, a neurotransmitter that plays a key role in arousal mechanisms, such as the “fight or flight” response. It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another). Poor attentional focusing is a defining characteristic of autism.

“What is unique about the locus coeruleus is that it activates almost all higher-order brain centers that are involved in complex cognitive tasks,” says Dr. Mehler.

Drs. Purpura and Mehler hypothesize that in autism, the LC-NA system is dysregulated by the interplay of environment, genetic, and epigenetic factors (chemical substances both within as well as outside the genome that regulate the expression of genes).  They believe that stress plays a central role in dysregulation of the LC-NA system, especially in the latter stages of prenatal development when the fetal brain is particularly vulnerable.

As evidence, the researchers point to a 2008 study, published in the Journal of Autism and Developmental Disorders, that found a higher incidence of autism among children whose mothers had been exposed to hurricanes and tropical storms during pregnancy. Maternal exposure to severe storms at mid-gestation resulted in the highest prevalence of autism.

Drs. Purpura and Mehler believe that, in autistic children, fever stimulates the LC-NA system, temporarily restoring its normal regulatory function. “This could not happen if autism was caused by a lesion or some structural abnormality of the brain,” says Dr. Purpura.

“This gives us hope that we will eventually be able to do something for people with autism,” he adds.

The researchers do not advocate fever therapy (fever induced by artificial means), which would be an overly broad, and perhaps even dangerous, remedy. Instead, they say, the future of autism treatment probably lies in drugs that selectively target certain types of noradrenergic brain receptors or, more likely, in epigenetic therapies targeting genes of the LC-NA system.

“If the locus coeruleus is impaired in autism, it is probably because tens or hundreds, maybe even thousands, of genes are dysregulated in subtle and complex ways,” says Dr. Mehler.  “The only way you can reverse this process is with epigenetic therapies, which, we are beginning to learn, have the ability to coordinate very large integrated gene networks.”

“The message here is one of hope but also one of caution,” Dr. Mehler adds. “You can’t take a complex neuropsychiatric disease that has escaped our understanding for 50 years and in one fell swoop have a therapy that is going to reverse it — that’s folly. On the other hand, we now have clues to the neurobiology, the genetics, and the epigenetics of autism. To move forward, we need to invest more money in basic science to look at the genome and the epigenome in a more focused way.”

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The paper by Drs. Mehler and Purpura, “Autism, fever, epigenetics and the locus coeruleus,” was published in the March issue of Brain Research Reviews.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation’s premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island – which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein – the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.aecom.yu.edu.

Fish show autism-like gene expression in water with psychoactive pharmaceuticals

Results may suggest environmental trigger for autism, but only in genetically predisposed individuals

Psychoactive medications in water affect the gene expression profiles of fathead minnows in a way that mimics the gene expression patterns associated with autism spectrum disorder in genetically susceptible humans, according to research published June 6 in the open access journal PLoS ONE. These results suggest a potential environmental trigger for autism spectrum disorder in this vulnerable population, the authors write.

The researchers, led by Michael A. Thomas of Idaho State University, exposed the fish to three psychoactive pharmaceuticals – fluoxetine, a selective serotonin reuptake inhibitor, or SSR1; venlafaxine, a serotonin-norepinephrine reuptake inhibitor, and carbamazepine, used to control seizures – at concentrations comparable to the highest estimated environmental levels.

They found that the only gene expression patterns affected were those associated with idiopathic autism spectrum disorders, caused by genetic susceptibility interacting with unknown environmental triggers. These results suggest that exposure to environmental psychoactive pharmaceuticals may play a role in the development of autism spectrum disorder in genetically predisposed individuals.

Lead researcher Michael A. Thomas remarks, “While others have envisioned a causal role for psychotropic drugs in idiopathic autism, we were astonished to find evidence that this might occur at very low dosages, such as those found in aquatic systems.”

Bacteria in the gut of autistic children different from non-autistic children

 

The underlying reason autism is often associated with gastrointestinal problems is an unknown, but new results to be published in the online journal mBio® on January 10 reveal that the guts of autistic children differ from other children in at least one important way: many children with autism harbor a type of bacteria in their guts that non-autistic children do not. The study was conducted by Brent Williams and colleagues at the Mailman School of Public Health at Columbia University.

Earlier work has revealed that autistic individuals with gastrointestinal symptoms often exhibit inflammation and other abnormalities in their upper and lower intestinal tracts. However, scientists do not know what causes the inflammation or how the condition relates to the developmental disorders that characterize autism. The research results appearing in mBio® indicate the communities of microorganisms that reside in the gut of autistic children with gastrointestinal problems are different than the communities of non-autistic children. Whether or not these differences are a cause or effect of autism remains to be seen.

“The relationship between different microorganisms and the host and the outcomes for disease and development is an exciting issue,” says Christine A. Biron, the Brintzenhoff Professor of Medical Science at Brown University and editor of the study. “This paper is important because it starts to advance the question of how the resident microbes interact with a disorder that is poorly understood.”

Bacteria belonging to the group Sutterella represented a relatively large proportion of the microorganisms found in 12 of 23 tissue samples from the guts of autistic children, but these organisms were not detected in any samples from non-autistic children. Why this organism is present only in autistic kids with gastrointestinal problems and not in unaffected kids is unclear.

Sutterella has been associated with gastrointestinal diseases below the diaphragm, and whether it’s a pathogen or not is still not clear,” explains Jorge Benach, Chairman of the Department of Microbiology at Stony Brook University and a reviewer of the report. “It is not a very well-known bacterium.”

In children with autism, digestive problems can be quite serious and can contribute to behavioral problems, making it difficult for doctors and therapists to help their patients. Autism, itself, is poorly understood, but the frequent linkage between this set of developmental disorders and problems in the gut is even less so.

Benach says the study was uniquely powerful because they used tissue samples from the guts of patients. “Most work that has been done linking the gut microbiome with autism has been done with stool samples,” says Benach, but the microorganisms shed in stool don’t necessarily represent the microbes that line the intestinal wall. “What may show up in a stool sample may be different from what is directly attached to the tissue,” he says.

Tissue biopsy samples require surgery to acquire and represent a difficult process for the patient, facts that underscore the seriousness of the gastrointestinal problems many autistic children and their families must cope with.

Benach emphasizes that the study is statistically powerful, but future work is needed to determine what role Sutterella plays, if any, in the problems in the gut. “It is an observation that needs to be followed through,” says Benach.

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mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.

The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM’s mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide