“Research aimed at improving early detection of autism has largely focused on measurement of social and communication development,” said Dr. Rebecca Landa, study author and director of the Center for Autism and Related Disorders at Kennedy Krieger Institute. “However, disruption in early motor development may also provide important clues about developmental disorders such as autism.”

On May 17 in Toronto, Dr. Landa will present this and other new research on motor delay and how it impacts development of language and social skills. The spring International Meeting for Autism Research is an annual scientific meeting providing international researchers with an opportunity to share their findings on ASD.

Before Dr. Landa’s current study, the head-lag text has not been used to diagnose ASD. Her team assessed infants in a “pull-to-sit” task, a simple measure of postural control in infants. Typically developing infants achieve this type of postural control by four months of age.

Dr. Landa’s team studied two groups of infants. The first group consisted of 40 infants, ages 5.6 to 10 months, considered to be at high genetic risk because a sibling had autism. Dr. Landa and her team examined their ability to maintain head alignment when being carefully, yet firmly, pulled by the arms from lying flat on his/her back to a sitting position. Infants were scored according to whether their head maintained alignment with the spine, or was in front of the spine, during the task. Lack of this head control indicated head lag.

The second group examined six-month-olds at a single point in time for the presence of head lag. Dr. Landa and her team found that 75% (n =15) of high-risk infants exhibited head lag, compared to 33% (n =7) of low-risk infants, further supporting that head lag is more likely in infants at risk of developing ASD. “Our findings show that the evaluation of motor skills should be incorporated with other behavioral assessments to yield insights into the very earliest signs of autism,” said Dr. Landa.

“While previous research shows that motor impairments are linked to social and communication deficits in older children with autism, the field is just starting to examine this in younger children,” said Dr. Landa. “Our initial research suggests that motor delays may have an important impact on child development.”

Building on the head lag research, Dr. Landa’s team conducted a separate longitudinal study with 14-, 24- and 36-month-old children at high and low risk of developing ASD. The study found that motor delay becomes increasingly evident as children with ASD near their third birthday, yet not all children with ASD experience motor delay. Results showed that children with ASD who experience motor delays are more severely impaired by three years of age than children with ASD with no motor delays.

“While more research is needed to examine why not all children with ASD experience motor delay, the results of our studies examining motor development add to the body of research demonstrating that early detection and intervention for infants later diagnosed with autism is possible and remains crucial to minimize delays and improve outcomes,” said Dr. Landa.

To reach Dr. Landa’s team at the Kennedy Krieger Institute follow this LINK.

Candida Yeast

According to Henry Butt, M.D. of the University of Melbourne, a person’s general health depends largely on how well his or her body is able to absorb the byproducts of naturally present “gut flora.” Changes to our internal physical environment, especially persistent ones, can cause a variety of gastro-intestinal symptoms, such as diarrhea or abdominal distention. Patients with autism seem to be prone to such GI issues, which may be caused by an overabundance of yeast. According to some schools of thought, elevated yeast levels can cause a variety of autism-like symptoms, including increased sensory defensiveness, inappropriate laughter, and inattention. To date, however, there has been no proof that an elevated yeast level actually causes autism, and the etiology of autism remains unknown.

Ultimately, what Dr. Butt’s research shows is that while we are not yet able to pinpoint the causes of autism, we are reaching a point where we are able to ascertain whether or not secondary treatments, such as diet modification, are able to lessen some of the symptoms associated with autism. By additional outside factors that contribute to autism-like behaviors, we will perhaps be one step closer to finding the ultimate cause of this very prevalent disease.

An abstract of the lecture he presented at the 2011 ARMS Global Autism Conference can be found in HERE.

For more information on the validity of dietary changes and their effect on autism, please see the Mayo Clinic articles on autism and candida cleanse diets.

Recent discoveries in epigenetics could soon make a clinical difference for children with attention-deficit/hyperactivity disorder, autism spectrum disorder, and other conditions, according to an expert.

The implications go beyond targeting treatment for an individual child in your practice based on a specific genetic mutation, Dr. Hakon Hakonarson, director of the center for applied genomics at the Children’s Hospital of Philadelphia, said at a pediatric update sponsored by Miami Children’s Hospital. Recent advances point to gene alterations that modify shared pathways, so the potential for wider application beyond ADHD and ASD — such as unexpected discoveries related to pediatric neuroblastoma — is a real possibility.

Dr. Hakonarson is a member of ICare4Autism’s Advisory Council and will be speaking about the gene networks underlying autism targeted for therapeutic intervention at the upcoming ICare4Autism International Autism Conference being held in Israel.

Hakon Hakonarson, M.D., Ph.D., is an associate professor of Pediatrics at The University of Pennsylvania School of Medicine.  He is a physician-scientist and director of The Children’s Hospital of Philadelphia’s Center for Applied Genomics (CAG), a high-throughput highly automated genotyping facility founded to identify the genetic causes of complex medical disorders in children, such as autism and cancer, with the objective of developing new therapies.

Dr. Hakonarson has an extensive track record in human genetics and has developed an international reputation amongst his peers. He has served previously in several senior posts in the biopharmaceutical industry, including as the director of Inflammatory and Pharmacogenomics Research and the vice president of Clinical Sciences and Development and CSO.

Dr. Hakonarson has also been the principal and co-principal investigator on several NIH-sponsored grants, and he has published numerous high-impact papers on genomic discoveries and their translations in some of the most prestigious scientific medical journals, including Nature, Nature Genetics and The New England Journal of Medicine.

Time Magazine listed Dr. Hakonarson’s autism gene discovery reported in Nature, 2009, among the top 10 medical breakthroughs of that year. With over ten years of experience in pioneering genomics research and genome-wide mapping and association studies, Dr. Hakonarson has intimate knowledge of the complexities of large-scale genomics projects and has put together the necessary infrastructure and workflow processes to unravel these complexities.

ICare4Autism Founder and President, Joshua Weinstein with Dr. W. Ted Brown

The Fragile X Syndrome is the most common inherited cause of intellectual disability. Fragile X has a population incidence of approximately 1 in 4,000 affected (full-mutation) males, 1 in 6,000 affected females, 1 in 700 premutation carrier males and 1 in 260 carrier females. This disorder typically causes moderate to severe intellectual deficiency in affected males, and milder deficiency in affected females.  It is associated with autism or PDD-NOS in about 50% of affected males, and most affected individuals evidence some autistic-like behaviors. 

Fragile X syndrome is considered to be the most common known single gene cause of autism. It is estimated that Fragile X accounts for 2-4% of intellectual deficiency overall, and is second to Down syndrome, which is not inherited, as a genetic cause of intellectual deficiency. The fragile X mutation results in the lack of expression of the Fragile X Protein (FMRP), an mRNA finding protein, which results in overexpression of the glutamate (stimulatory) and under-expression of the GABA (inhibitory) pathways in the brain.

Current experimental treatment trails are being carried out in Fragile X and in autism with glutamate receptor blockers and GABA stimulatory drugs.  The underlying defects in neurochemical pathways in both conditions appear to have much in common, involving the ERK, mTOR and PI3K signaling pathways.

Dr. W. Ted Brown will be speaking at the upcoming ICare4Autism International Conference on Autism, in Israel, about the relationship between Fragile X syndrome and autism.

W. Ted Brown, MD, PhD, is the Director of the New York State Institute for Basic Research (IBR) in Developmental Disabilities, Chair of the IBR Department of Human Genetics and Director of the IBR Jervis Clinic.  He is a fellow of the American College of Medical Genetics and Professor at the State University of New York- Downstate Medical Center in Brooklyn.

In 1991, he was appointed the Director of IBR’s Jervis Clinic and in 2005 became IBR’s Director. He is the author of more than 350 publications.  At IBR, he began research focused on the Fragile X syndrome, which was then newly recognized and is now considered to be the most common inherited cause of intellectual deficiency or mental retardation. At IBR, he established a DNA diagnostic and molecular laboratory. He developed a screening and prenatal testing program for Fragile X.

His work on Fragile X has ranged from clinical studies relating to phenotype, to family inheritance studies, to mouse model development, and to basic molecular research. His current research is focused on autism genetics and the Fragile X syndrome.

Dr. Hollander will be speaking at the upcoming ICare4Autism International Autism Conference on the Neuropsychopharmacology of Oxytocin and Inflammation in ASD.  He is also receiving Global Autism Research Award for his breakthrough research in autism treatment at the ICare4Autism Fundraising Gala on Thursday, 7th of June, 2012.

The research, which included 37 high-functioning adults with, mainly diagnosed with Asperger’s syndrome, followed participants for 12 weeks. Taking fluoxetine doubled the chances that a patient would show overall improvement, measured by their clinicians. Half of the participants taking fluoxetine had significant reductions in obsessive-compulsive symptoms, compared with 8% taking placebo.

“Repetitive behavior is a core symptom of the illness,” says lead author Dr. Eric Hollander, medical director of the Autism and Obsessive-Compulsive Spectrum Program at Montefiore Medical Center in New York, explaining that “from a very early age, these children have rituals and routines. For example, they like to line up their toys and they get very bent out of shape if there is any deviation.”

A previous, larger study of a similar medication, citalopram, in children with autism did not find a reduction in repetitive behaviors, but the drug did reduce irritability and was superior to placebo among children who had the highest levels of irritability. Irritability can sometimes lead to repetitive behaviors because people wit autism often engage in these activities to self soothe.

Both fluoxetine and citalopram belong to a class of antidepressants known as selective serotonin reuptake inhibitors, or SSRIs. Prior research on SSRIs in people with autism has also looked at fluvoxamine and found a reduction in repetitive behavior in adults but not children. It is not known if the differences between these studies are due to differences between the medications or other factors.

Obsessive behaviors may also arise in people with autism in response to the stress or discomfort of unpredictable situations. “Many of these individuals have expectations for what’s going to happen, and if there is an unexpected deviation, they experience a lot of discomfort and then they do all these kinds of behaviors,” says Hollander. That’s why people with autism may obsessively avoid locations where they previously experienced discomfort, for example, or they may engage in a repetitive habit like washing, checking, counting, touching or tapping.

When taking fluoxetine, Hollander says, “Patients acknowledge experiencing less discomfort. They’re more able to go outside their comfort zone and to better resist their habits and rituals.” One participant in Hollander’s study was previously too anxious to take the subway or eat in a restaurant, but, when taking fluoxetine, was able to tolerate these unpredictable environments.

Hollander notes that the findings were statistically significant and clinically meaningful. “The clinicians could tell that people were doing better not only in terms of OCD symptoms but overall distress and ability to function.”

Read more: http://healthland.time.com/2011/12/05/prozac-may-reduce-symptoms-of-autism-in-adults/#ixzz1toOkty7N

Eyal Ben-David and Sagiv Shifman, Hebrew University of Jerusalem

It is widely understood that different genes interact with environmental factors to influence autism, but new research finds a common ground as the various genes involved in autism appear to influence special processes in the brain.

Autism is influenced by many different genes, and different genes are involved in different individuals, making it hard to find the common genetic ground between patients.

Now, research conducted at the Hebrew University of Jerusalem has shown that the different genes involved in autism tend to be involved in specific processes in the brain. This can explain similarities in the behavioral symptoms of different people with autism, but also the large spectrum of behaviors observed in different individuals with autism.

The Hebrew University research, conducted by Dr. Sagiv Shifman and his doctoral student Eyal Ben-David of the Department of Genetics at the Alexander Silberman Institute of Life Sciences, has potential implications for early diagnosis as well as for treatment of autism in the future.

Dr. Shifman’s areas of interest are the genetics of schizophrenia and autism and genetics of variation in gene expression.  He will be speaking about this research “Shared neuronal pathways affected by common and rare variants in autism spectrum disorders” at ICare4Autism’s upcoming International Autism Conference in Jerusalem.

The mission of the Hebrew University project was to test the contribution of rare genetic mutations, as well as the genetic variations which are common in the population, and to see whether these different types of genetic risk factors are related. Instead of testing individual genes, the researchers chose to study gene collections, in an attempt to understand general pathways involved in autism.

Based on genetic data from thousands of families with autistic children, the researchers studied the contribution of different groups of genes to autism.

To their surprise, they found – when looking at mutations found in autism as well as thousands of common gene variants that are more frequently seen in individuals with autism – that these mutations and variations are located in specific functional groups.

When looking at families with one individual with autism (sporadic cases), and in families where there is more than one affected individual (multiplex cases), the same variants were seen acting in both cases. These groups of genes are highly active in the first year of life, and are involved in processes of learning, memory, and sensory perception.

The Hebrew University scientists believe that their work could pave the way for large-scale genetic scans in the future that could allow for early diagnosis of autism. Further, the results of their study provide a ray of hope that by concentrating on specific gene groups, it will one day be possible to design drugs which could alleviate symptom

Ben-David E, Shifman S (2012) Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders. PLoS Genet 8(3):e1002556. doi:10.1371/journal.pgen.1002556

http://medicalxpress.com/news/2012-05-genetic-disrupted-autistic-brain.html

Genetic variation caused by mutation leading to autism spectrum disorders is well established, and research has repeatedly implicated “de novo” (new) mutations, those that show up for the first time in affected children, as being especially pertinent. Identification of the specific genes connected to autism may lead to vital advances in the diagnosis and treatment of autism spectrum disorders. The current study, led by Dr. Michael Wigler from Cold Spring Harbor Laboratory, used gene sequencing methods to look at nearly 350 families with healthy children and children on the autistic spectrum, part of the larger Simons Simplex Collection. Specifically, the researchers looked for mutations that were present in the children but not in their parents.

The researchers found that autism is linked with the types of new mutations that are likely to disrupt the function of a gene. By disrupting one of the pair of healthy genes that we normally inherit, such mutations alter “gene dosage.” There was double the incidence of such mutations in the affected child than in the healthy child, but little to no difference in the overall incidence of much more common types of mutations. The results also showed that children with older parents have more new mutations. This is in line with other recent reports and possibly explains why older parents are more likely to have children on the autism spectrum. “More generally, this work and the work preceding it point to the importance of new mutations and gene dosage in so-called complex genetic disorders,” says Dr. Wigler.

The study also identified many new autism candidate genes, and these genes showed a strong overlap with genes linked to the pathway involved in fragile X syndrome, one of the best studied cognitive-behavioral disorders in humans. “We observe strong statistical evidence for the link between autism and fragile X syndrome, first suggested by study coauthors Dr. Jennifer Darnell and Dr. Robert Darnell, in a paper they published in Cell last year,” explains Dr. Wigler. “Our finding has important implications for therapy and shows that autism is in large part a molecular disorder of neuroplasticity, the mechanisms by which our nervous system adapts to change.”

Sources:

Ivan Iossifov, Michael Ronemus, Dan Levy, Zihua Wang, Inessa Hakker, Julie Rosenbaum, Boris Yamrom, Yoon-ha Lee, Giuseppe Narzisi, Anthony Leotta, Jude Kendall, Ewa Grabowska, Beicong Ma, Steven Marks, Linda Rodgers, Asya Stepansky, Jennifer Troge, Peter Andrews, Mitchell Bekritsky, Kith Pradhan, Elena Ghiban, Melissa Kramer, Jennifer Parla, Ryan Demeter, Lucinda L. Fulton, Robert S. Fulton, Vincent J. Magrini, Kenny Ye, Jennifer C. Darnell, Robert B. Darnell, Elaine R. Mardis, Richard K. Wilson, Michael C. Schatz, W. Richard McCombie, Michael Wigler. De Novo Gene Disruptions in Children on the Autistic Spectrum. Neuron, 2012; 74 (2): 285 DOI:10.1016/j.neuron.2012.04.009

Cold Spring Harbor Laboratory (2012, April 25). A striking link is found between the Fragile-X gene and mutations that cause autism. ScienceDaily. Retrieved April 27, 2012, from http://www.sciencedaily.com­/releases/2012/04/120425140359.html

Philip Landrigan, MD, MSc, a world-renowned leader in children’s environmental health and Director of the Children’s Environmental Health Center (CEHC) at Mount Sinai School of Medicine, co-authored the editorial, entitled “A Research Strategy to Discover the Environmental Causes of Autism and Neurodevelopmental Disabilities,” along with Luca Lambertini, PhD, MPH, MSc, Assistant Professor of Preventive Medicine at Mount Sinai and Linda Birnbaum, Director of the National Institute OF Environmental Health Sciences.

The National Academy of Sciences reports that 3 percent of all neurobehavioral disorders in children, such as autism spectrum disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), are caused by toxic exposures in the environment and that another 25 percent are caused by interactions between environmental factors and genetics. But the precise environmental causes are not yet known. While genetic research has demonstrated that ASD and certain other neurodevelopmental disorders have a strong hereditary component, many believe that environmental causes may also play a role – and Mount Sinai is leading an effort to understand the role of these toxins in a condition that now affects between 400,000 and 600,000 of the 4 million children born in the United States each year.

“A large number of the chemicals in widest use have not undergone even minimal assessment of potential toxicity and this is of great concern,” says Dr. Landrigan. “Knowledge of environmental causes of neurodevelopmental disorders is critically important because they are potentially preventable.”

CEHC developed the list of ten chemicals found in consumer products that are suspected to contribute to autism and learning disabilities to guide a research strategy to discover potentially preventable environmental causes. The top ten chemicals are:

1. Lead
2. Methylmercury
3. PCBs
4. Organophosphate pesticides
5. Organochlorine pesticides
6. Endocrine disruptors
7. Automotive exhaust
8. Polycyclic aromatic hydrocarbons
9. Brominated flame retardants
10. Perfluorinated compounds

In addition to the editorial, there were four papers published which also call for increased research to identify the possible environmental causes of autism in America’s children.

Source: Mount Sinai Hospital

Furthermore, this kind of research could lead to better treatments for a subset of children with elevated levels of certain compounds in their urine, said James Woods, a researcher at the University of Washington who worked with Battelle researchers on the project.

While the study was relatively small, including 76 boys, Nick Heyer, a senior research scientist at Battelle’s Seattle lab, who worked on the study and said he’s hopeful it can be replicated on a larger scale and lead to a widely available screening test for babies.

“If it can detect increased risk of autism at age 1, that would be fantastic,” he said. “It’s the only biomarker (test) I’m aware of that could be done non-invasively and fairly inexpensively.

“I’m really pretty optimistic and excited about getting it retested.”

Heyer said he is trying to incorporate the urine test into a study that will include 1,200 mothers who have autistic children and are pregnant again. The researchers would follow the new babies’ development through age 3. He’s also working with a laboratory in South Korea to reproduce the study in a larger group.

The test looks for elevated levels of compounds called porphyrins and costs between $50 and $100. Woods said the cost would come down if the test were used frequently to screen babies.

Woods said everybody has the compounds in their urine, but some of the children in the study had clearly elevated levels.

The study included only boys, who are much more likely to have autism than girls, but the test likely would work for both genders based on other research, Woods said.

Heyer said there’s been speculation that elevated porphyrin levels are connected to mercury exposure in children with autism, but the research team found no link to increased exposure to mercury, leaving open the question of why the compounds are higher in some children with autism.

“I’m not a supporter of the concept that this is due to mercury exposure,” he said. “There’s no evidence in my mind that that should be the reason for this.”

Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, et al. 2010 Urinary Porphyrin Excretion in Neurotypical and Autistic Children. Environ Health Perspect 118(10): doi:10.1289/ehp.0901713

Overall, they found autism had been diagnosed in 10 percent to 11 percent of full siblings and 5 percent to 7 percent of half-siblings.

The new finding may not be a surprise – given that half-siblings share about 25 percent of their genes – but provides new clues to how autism is inherited.

The study included more than 5,000 U.S. families enrolled in a nationwide autism registry in which there was a child with autism and at least one other sibling. Included were 619 families with at least one maternal half-sibling, meaning the children shared the same mother but not the same father. The researchers compared autism recurrence among the half-siblings to the rate among the full siblings.

The researchers also looked at half-siblings in a group of St. Louis families to try to replicate the findings from the larger study.

“We found that autism risk for half-siblings is about half of what it is for full siblings,” principal investigator Dr. John Constantino, director of child and adolescent psychiatry at the Washington University School of Medicine in St. Louis and psychiatrist-in-chief at St. Louis Children’s Hospital, said in a university news release.

“Most of the half-siblings we studied had the same mothers. Given that half of the risk of transmission was lost and half was preserved among those maternal half-siblings, mothers and fathers appear to be transmitting risk equally in families in which autism recurs,” Constantino said.

The findings also suggest that in many families, the transmission of autism from parents to children is the result of the effects of many genes, with each contributing a small proportion of the risk, he said.

The study was published online April 16 in the journal Molecular Psychiatry.

Sources:

J N Constantino, A Todorov, C Hilton, P Law, Y Zhang, E Molloy, R Fitzgerald, D Geschwind. Autism recurrence in half siblings: strong support for genetic mechanisms of transmission in ASD. Molecular Psychiatry, 2012; DOI:10.1038/mp.2012.9

Washington University in St. Louis (2012, April 17). Study of half siblings provides genetic clues to autism. ScienceDaily. Retrieved April 23, 2012, from http://www.sciencedaily.com­/releases/2012/04/120417143849.htm