The Abrahams lab works to understand the “whys” and “hows” in the Autism Spectrum Disorders and to use these insights to achieve better patient outcomes. Dr. Abrahams has identified DNA variants that increase risk for disease and discovered how some of these impact brain structure and function. Ongoing work is poised to take these insights back to the clinic and improve quality of life for patients and families.

All of the work that they accomplish begins and ends in the clinic. The Abrahams team is always actively recruiting patients (and family members) to participate in genetic studies. If you are interested in being part of their study, you can contact them directly for more information.

Widely sought by instititutions nationwide, he chose to come to Einstein and now he is choosing to speak at ICare4Autism’s upcoming August Conference Autism: A Global Perspective. This is the second time that we have invited Dr. Abrahams to speak after the rave reviews of his last speaking engagement at our Jun 6^th conference in 2011.

Dr. Abrahams speaks from a history of personal patient interaction and detailed experiments with a protein called Cntnap2. He writes that, “convergent lines of evidence support involvement of Contactin Associated Protein-Like 2 (CNTNAP2), a Neurexin family member, in the ASDs and related disorders of cognition.” The Abrahams lab explores the biological mechanisms by which mutations in CNTNAP2 may cause disease. They characterized animals in which the murine homolog is deleted.

Cntnap2 KO mice were found to have behavioral abnormalities reminiscent of core deficits observed in patients. Mutant mice were also seen to be hyperactive and show spontaneous epileptic seizures, both primary reactions in autistic patients. Treatment with the FDA approved drug risperidone alleviated a subset of behaviors in mutant mice. Dr. Abrahams will discuss further possible treatments and elaborate on the numerous successes that his team has encountered at Einstein.

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.

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

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

Diagnosing autism is a complex and subjective process. With the recent rise in incidence to 1 in 88 children, has been partially attributed to improving diagnostic measures but there is still a need for accurate and widely deployable methods for screening and diagnosis.

Dennis Wall, associate professor of pathology and director of computational biology initiative at the Center for Biomedical Informatics at Harvard Medical School, has been working on this problem and has discovered a highly accurate strategy that could dramatically reduce the complexity and time of forming a diagnosis.

Wall has been developing a system to detect autism rapidly and with high accuracy. His system combines a small set of questions and a short home video of the subject, to enable rapid online assessments. This method could reduce the time for autism diagnosis by nearly 95 percent and could be integrated simply into routine child screening procedures and could reach the population at risk that have previously been short on diagnosis.

“We believe this approach will make it possible for more children to be accurately diagnosed during the early critical period when behavioral therapies are most effective,” said Wall.

This research will be published April 10 online in Translational Psychiatry.

Current diagnostic measures can take up to three hours to complete and must be administered by a trained clinician. There can be a delay of more than a year between initial warning signs and diagnosis because of the waiting times to see a clinical professional who can administer the tests and deliver the formal diagnosis, Wall said.

Using machine learning techniques, an artificial intelligence method where machines are trained to make decisions, Wall and his team discovered that just seven questions were sufficient to diagnose autism with nearly 100 percent accuracy compared to the full 93-question exam.

They validated the accuracy of the seven question survey against answer sets from more than 1,600 individuals from the Simons Foundation and more than 300 individuals from the Boston Autism Consortium.

Wall believes these results have tremendous potential to move a substantial percentage of the effort into a mobilized electronic health framework with broad reach and applications.

“This approach is the first attempt to retrospectively analyze large data repositories to derive a highly accurate, but significantly abbreviated classification tool,” said Wall, who is also associate professor of pathology at Beth Israel Deaconess Medical Center. “This kind of rapid assessment should provide valuable contributions to the diagnostic process moving forward and help lead to faster screening and earlier treatment,” he said.

Wall has made a survey and video site that is currently available to the public for free to continue evaluating the effectiveness of the new shortened approach and is working on ways to mobilize the overall approach to expand its reach.

Sources:

http://www.nature.com/tp/journal/v2/n4/full/tp201210a.html

http://medicalxpress.com/news/2012-04-web-based-tool-fast-accurate-autism.html

http://www.sciencedaily.com/releases/2012/04/120410111554.htm

S100B Protein

A recent study showed that 36% of children with an Autism diagnosis had significantly higher serum S100B protein levels than healthy controls and that those with severe autism had significantly higher serum S100B protein than children with mild to moderate autism. 

The study was looking at levels to determine autoimmunity in Autism.  Elevated S100B levels in biological fluids (CSF, blood, urine, saliva, amniotic fluid) are regarded as a biomarker of pathological conditions, including perinatal brain distress, acute brain injury, brain tumors, neuroinflammatory/neurodegenerative disorders, psychiatric disorders. In the majority of these conditions, high S100B levels indicate cell damage when standard diagnostic procedures do not reveal anything.

The study’s authors explain that S100B, “is a calcium-binding protein that is produced primarily by astrocytes. Increased serum S100B protein levels reflect neurological damage. Autoimmunity may have a role in the pathogenesis of autism in some patients. Autoantibodies may cross the blood–brain barrier and combine with brain tissue antigens, forming immune complexes and resulting in neurological damage… Furthermore, S100B protein may act as a cytokine and in vitro studies have shown that, at high levels, S100B protein can induce the neuronal expression and secretion of proinflammatory IL-6. Elevated levels of S100B have been detected in the CSF of MS patients during acute phases or exacerbations of the disease, and it has therefore been proposed that elevated S100B protein may be indicative of active cell injury and can reflect an axonal and glial pathology.”

The researchers concluded that S100B protein levels were elevated in children with autism and significantly correlated to autistic severity. They believe this may indicate the presence of an underlying neuropathological condition in those with autism.  They did not find a correlation to the levels and autoimmunity but recommend further research is required to investigate the possible link between serum S100B protein levels and other autoantibodies, which are possible indicators of autoimmunity to central nervous system in autism.

The article A lack of association between elevated serum levels of S100B protein and autoimmunity in autistic children was published in the Journal of Neuroinflammation.

Here are some of the top discoveries in Autism research released in 2012 to date;

Obesity during Pregnancy Raises Risk of Autism: Obese mothers were found to be 67% more likely than mothers of normal weight to have a child with autism, and they were more than twice as likely to have a child with another developmental disorder.

Not a Breakthrough but a Turning Point – Researchers Connect Gene Mutation to Autism Risk: A recent study of hundreds of families with autism has discovered that spontaneous mutations can take place in a parent’s sperm or egg cells that result in an increased risk of autism, and fathers are four times more likely than mothers to pass these mutations on to their children. The researchers discovered that new mutations occurred four times more frequently in sperm cells than in egg cells, and the older the father, the more likely he was to have sperm with these spontaneous mutations.

Severity of Autism Linked to Length of Pregnancy: Research suggests normal term children born with autism have less severe symptoms than children with autism who are born pre-term or several weeks late.

Autism Research Identifies Gene Abnormalities: Researchers found that genetic mechanisms that normally regulate the number of cortical neurons are abnormal in those with Autism and that the genes that control the number of brain cells did not behave in the standard way.  This probably leads to too many brain cells in some locations, such as prefrontal cortex, but perhaps too few in other regions of cortex as well.

Those with Autism have Higher Perceptual Capacity: A study revealed that people with autism have a greater than normal capacity for processing information. The research may explain way some with autism excel in highly technical fields.

Mouse Model explores Role of Serotonin in Autism:VanderbiltUniversity researchers used mice to explore how altered brain serotonin levels during development may produce long-lasting changes in behavior and impact the risk for autism. The researchers conclude that a lack of serotonin during development may lead to long-standing changes in the way the brain is wired.

New Study looks at Autism and Social Touch: A new study offers insight into why some people do not respond to physical touch and how families affected by autism may learn to show affection without overwhelming an child with autism’s senses. Yale neuroscientists imaged the brain activity of young adults while exposing them to different types of social touch.

Prenatal Exposure to Solvents Could Be Linked to Autism: According to an exploratory study exposures to lacquer, varnish and xylene occurred more often in the parents of children with Autism Spectrum Disorder compared to the parents of unaffected children.

Rare Bone Disorder Illuminates Potential Cause of Autism: A new study has found that mice with a genetic defect that models human MHE show symptoms of the three defining characteristics of autism: social impairment, language deficits, and repetitive behavior. The study used a mouse model of MHE to investigate cognitive function and points to the amygdala as the region of the brain causing symptoms of autism.

Deficiency in Mirror Neuron System Connected to Autism: Scientists found that the mirror neuron system in the ASD individuals became less activated when watching the gestures, compared to the control group. This finding adds to the evidence that deficits in mirror neuron system functioning contribute to the social deficits in ASD.

Study Shows Increased ASDs in Recent Immigrants: A study shows that children of immigrant parents particularly mothers who migrated just before or during pregnancy are disproportionately more likely to develop autism with intellectual disability. This link seems to be related to the timing of the migration rather than complications in childbirth.

Low Birth Weight Linked to Autism Spectrum Disorders: After studying 3,715 pairs of twins the researchers found that lower birth weight more than tripled the risk for autism spectrum disorder in identical twin pairs in which one twin had ASD and the other did not.

Another Autism Suspect Eliminated: Mercury: Mercury levels in urine did not differ between children with autism and controls, even after the figures were adjusted for factors such as urine concentration and body mass. The team also found no difference in the levels of other heavy metals such as lithium, manganese, and copper.

Gene Mutation in Autism Causes Hypersensitivity: A study has found that the loss of a specific mutated gene in the auditory cortical neurons – the powerhouses of the sound-processing center – causes hypersensitive to sound.

Researchers find Uncommon Bacteria in Children with Autism: Researchers atColumbiaUniversity have found that an uncommon bacterium exists in the walls of intestines of children with autism, but not those who do not have autism.

Study Finds Autism Linked to Parental Age: A study of Danish families found that children born to a parent over age 35 are at greater risk of developing an autism spectrum disorder — but the researchers are confused as why this is and why the risk is the same whether just one or both parents are older.

Autism Causes: Another Suspect Eliminated: One of the many potential causes of autism, smoking during pregnancy, has been ruled out after a large population-based study inSweden. Overall, 19.8 percent of the children with ASD were exposed to maternal smoking during pregnancy, compared to 18.4 percent of control children.

Biological Marker for Autism Possibly Found: A recent study using a mouse model of autism proposes abnormalities in the immune system could be linked to pervasive developmental disorders. The research proposes that heightened levels of an APP fragment circulating in the blood could explain the abnormalities in immune cell populations and function – both of which are seen in some autism patients.

While the researchers are quick to point out that their study doesn’t conclude that obesity during pregnancy causes autism but that their findings raise a red flag and warrant further research.

Researchers at the University of California, Davis, looked at 1,004 children aged 2 to 5 years enrolled in the CHARGE (Childhood Autism Risks from Genetics and the Environment) study from 2003 to 2010.

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Obese mothers were 67% more likely than mothers of normal weight and with no metabolic disorders to have a child with autism, and they were more than twice as likely to have a child with another developmental disorder — a delay in speech delay, perhaps, or a failure to reach developmental milestones at the appropriate age.

Mothers of children who were not developing typically were more likely to be obese: 21.5% of mothers of children with autism and 23.8% of mothers of children with developmental delays were obese, versus 14.3% of moms of typically developing children.

“Our findings raise concerns that these maternal conditions may be associated with neurodevelopmental problems in children and therefore could have serious public health implications.” the study authors wrote in their report published today in the journal Pediatrics.

“It’s hard to say if they’re linked,” said study author Irva Hertz-Picciotto, professor of public health sciences at the University of California at Davis. “It might be there’s some environmental factor that contributes both to the obesity epidemic and to the rise in autism cases. Or it could be the increase in obesity is, in fact, contributing to the increase in autism. But it’s certainly not going to account for all of it.”

Hertz-Picciotto and colleagues have also linked autism to poor maternal nutrition, antidepressant use and closely spaced pregnancies.

How obesity and diabetes during pregnancy might predispose the developing fetus autism is unclear, but theories include overexposure to glucose, insulin and inflammation.

“This study doesn’t tell you anything about the origin of autism. What it does tell you are things associated with autism,” said Dr. Susan Hyman, associate professor of pediatrics at the University of Rochester Medical Center. “We would not advocate treating the hypothetical causes of autism, but we would recommend women of childbearing years to eat healthy and exercise and take care of themselves, not only for the fetus but so they can see their children grow up.”

Hyman said autism is a complex condition thought to emerge from an interaction of multiple genetic and environmental influences.

Dr. Ari Brown, an Austin, Texas-based pediatrician, said the study is one more piece in the puzzle of autism spectrum disorders, a collection of conditions with varying symptoms and, quite likely, multiples causes.

“I think we’re just beginning to unravel some of the mysteries of autism spectrum disorders. And I don’t think we’re going to find just one answer because it’s not just one disease,” Brown said. “But it’s really important for women prior to do a preconception visit with their doctor and talk about attaining ideal body weight prior to becoming pregnant. Being overweight or obese can lead to a variety of health problems for mom and baby.”

We have known for many years that autism is more common in boys than girls. Latest CDC figures show that as much as 5 times as many boys are diagnosed with autism than girls. The disorder appears different in the sexes, and these differences may have important implications for both diagnosis and treatment.

There is currently no adequate explanation for this imbalance in the sex ratio, but Dr. Peter Szatmari, a professor and the head of the Division of Child and Adolescent Psychiatry in the Department of Psychiatry and Behavioral Neurosciences at McMaster University believes that something could be protecting girls from developing ASD and other developmental disorders. That factor could be hormone levels in utero, epigenetic factors that turn autism susceptibility genes “on” and “off” during development, or the fact that young girls have in general better social skills than boys and so need a bigger “dose” of what causes ASD to cross that threshold to being impaired.

Dr Szatmari explains “It is possible that those possible protective factors, once identified and understood, could play an important role in pointing toward new treatments and interventions that capitalize on those protective factors and so make a real difference to long-term outcomes.”

The clinical expression of autism is also different in boys. Generally speaking, girls with autism have greater learning disabilities and more problems academically than boys.

Higher-functioning girls with ASD are may be missed by clinicians who are not experts in diagnosis, Dr Szatmari states. There is some evidence that among this subgroup, girls have better social skills than higher-functioning boys with ASD and so are not diagnosed as readily. Although, the symptoms of ASD can appear as extreme shyness or anxiety in girls, masking that they may not be responsive to the social cues of others.

Girls on the autism spectrum have fewer repetitive behaviors such as rocking and spinning and less sensory sensitivity than boys with ASD. Since these signs are subtle, doctors may not recognize the disorder. Diagnosis at a later age reduces the chances of early treatment, which is understood to provide a better outcome.

Some evidence suggests that girls with ASD are bullied less often than boys. They appear to blend in more easily with their peers and are less often the victim of bullying by other girls.

Understanding these differences both biologically and experientially holds the promise of improving the long-term outcome of all children with ASD. Most important, clinicians need to be sensitive to how the disorder shows up in girls so that those affected can receive early intervention as soon as possible.

Three new studies, published in the journal Nature, suggest mutations in parts of genes that code for proteins play a significant role in autism.

Scientists have been debating the relative influence of inherited risk and environmental factors in autism for decades, and few today doubt that there is a strong genetic component.

Genetic mistakes can occur across the genetic code, and many are harmless, however they can cause major issues when they occur in parts of the genome needed for brain development. Some experts say an intensified search for rare mutations could uncover enough of these to account for 15 percent to 20 percent of all autism cases and give researchers a chance to see patterns and some possible mechanisms to explain what goes wrong.

The research teams – led by Mark Daly of the Broad Institute at Harvard and Massachusetts Institute of Technology, Dr. Matthew State of Yale University and Evan Eichler of the University of Washington in Seattle – also identified several hundred new suspect genes that could eventually lead to new targets for autism treatments.

“These studies aren’t so much a breakthrough, because we knew this was coming,” said Jonathan Sebat, a professor of psychiatry and cellular and molecular medicine at the University of California, San Diego, who was not a part of the research teams. “But I’d say it’s a turning point. We now have a reliable way forward, and I think it’s fair to expect that we will find 20, 30, maybe more such mutations in the next year or two.”

They looked specifically to see where these spontaneously occurring genetic mistakes were coming from: the father’s sperm or the mother’s egg cells.

The researchers discovered that new mutations occurred four times more frequently in sperm cells than in egg cells, and the older the father, the more likely he was to have sperm with these spontaneous mutations.

Joseph Buxbaum, director of the Seaver Autism Center at Mount Sinai School of Medicine in New York and a co-author of one of the studies believes one possible reason for this is that men make sperm every day, and this high turnover rate increases the chance for errors to occur in the genetic code that could be passed on to their offspring.

“It tells us that sperm production is an imperfect process,” Buxbaum said.

“It’s primarily driven by a dad’s age. That makes sense. As you get older, there are more and more chances for problems.”

He said these findings support other studies that show older fathers have a slightly increased risk of having a child with an autism spectrum disorder.